National Library of Energy BETA

Sample records for lung cancer incidence

  1. Residential radon and lung cancer incidence in a Danish cohort

    SciTech Connect (OSTI)

    Braeuner, Elvira V.; Andersen, Claus E.; Sorensen, Mette; Jovanovic Andersen, Zorana; Center for Epidemiology Screening, Department of Public Health, University of Copenhagen ; Gravesen, Peter; Ulbak, Kaare; Hertel, Ole; Pedersen, Camilla; Overvad, Kim; Tjonneland, Anne; Raaschou-Nielsen, Ole

    2012-10-15

    High-level occupational radon exposure is an established risk factor for lung cancer. We assessed the long-term association between residential radon and lung cancer risk using a prospective Danish cohort using 57,053 persons recruited during 1993-1997. We followed each cohort member for cancer occurrence until 27 June 2006, identifying 589 lung cancer cases. We traced residential addresses from 1 January 1971 until 27 June 2006 and calculated radon at each of these addresses using information from central databases regarding geology and house construction. Cox proportional hazards models were used to estimate incidence rate ratios (IRR) and 95% confidence intervals (CI) for lung cancer risk associated with residential radon exposure with and without adjustment for sex, smoking variables, education, socio-economic status, occupation, body mass index, air pollution and consumption of fruit and alcohol. Potential effect modification by sex, traffic-related air pollution and environmental tobacco smoke was assessed. Median estimated radon was 35.8 Bq/m{sup 3}. The adjusted IRR for lung cancer was 1.04 (95% CI: 0.69-1.56) in association with a 100 Bq/m{sup 3} higher radon concentration and 1.67 (95% CI: 0.69-4.04) among non-smokers. We found no evidence of effect modification. We find a positive association between radon and lung cancer risk consistent with previous studies but the role of chance cannot be excluded as these associations were not statistically significant. Our results provide valuable information at the low-level radon dose range.

  2. Role of curative radiotherapy in the treatment of lung cancer. [Clinical factors effecting efficacy and incidence of complications

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    Coy, P.; Kennelly, G.M.

    1980-02-15

    From 1963 to 1974, 141 patients with lung cancer were treated with curative intent in the A. Maxwell Evans Clinic in Vancouver. The clinical presentation, age and sex distribution, histology, and reasons for surgery not being carried out are examined. The results of this treatment are presented. An attempt has been made to isolate a group of patients who have a better prognosis so that treatment selection can be improved. Hemoptysis, cough, dyspnea, and incidental finding on routine chest x-ray were the most common manner of presentation. Thirty-four percent of the patients were over 70 years of age and 13% were women. The crude overall three- and five-year survival rates were 18 and 10% (19 and 9% in the men, 17 and 14% in the women). Patients presenting with dyspnea had a better survival than those presenting with cough and hemoptysis. Patients with lesions less than 3 cm in diameter had a 28% three-year survival, compared with 14% for lesions greater than 5 cm in diameter. The three- and five-year survival rates in patients over 70 years of age were 23 and 17% respectively. The response to treatment and the survival were better in the patients with squamous cell carcinoma. Twenty-two percent were alive at three years and 12% at five years as compared with 9 and 5% for other histologies. Fifty-four percent of the 35 patients with a complete response and with squamous cell carcinoma were alive at three years, compared with only 8% of the 12 patients with other histologies who showed a complete response.

  3. Early Lung Cancer Detection Program

    Broader source: Energy.gov [DOE]

    Since 2000, DOE has made screening for occupational lung cancer with low-dose helical computed tomography (CT) scans available to workers at high risk for lung cancer. Because former workers undertook essential activities to fulfill the Department's mission, many of them were at risk for lung cancer.

  4. Cancer incidence in the Love Canal area

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    Janerich, D.T.; Burnett, W.S.; Feck, G.; Hoff, M.; Nasca, P.; Polednak, A.P.; Greenwald, P.; Vianna, N.

    1981-06-01

    Data from the New York Cancer Registry show no evidence for higher cancer rates associated with residence near the Love Canal toxic waste burial site in comparison with the entire state outside of New York City. Rates of liver cancer, lymphoma, and leukemia, which were selected for special attention, were not consistently elevated. Among the other cancers studied, a higher rate was noted only for respiratory cancer, but it was not consistent across age groups and appeared to be related to a high rate for the entire city of Niagara Falls. There was no evidence that the lung cancer rate was associated with the toxic wastes buried at the dump site.

  5. Structures of Lung Cancer-Derived EGFR Mutants and Inhibitor...

    Office of Scientific and Technical Information (OSTI)

    Structures of Lung Cancer-Derived EGFR Mutants and Inhibitor Complexes: Mechanism of ... Citation Details In-Document Search Title: Structures of Lung Cancer-Derived EGFR Mutants ...

  6. Molecular Markers of Lung Cancer in MAYAK Workers

    SciTech Connect (OSTI)

    Steven A. Belinsky, PhD

    2007-02-15

    The molecular mechanisms that result in the elevated risk for lung cancer associated with exposure to radiation have not been well characterized. Workers from the MAYAK nuclear enterprise are an ideal cohort in which to study the molecular epidemiology of cancer associated with radiation exposure and to identify the genes targeted for inactivation that in turn affect individual risk for radiation-induced lung cancer. Epidemiology studies of the MAYAK cohort indicate a significantly higher frequency for adenocarcinoma and squamous cell carcinoma (SCC) in workers than in a control population and a strong correlation between these tumor types and plutonium exposure. Two hypotheses will be evaluated through the proposed studies. First, radiation exposure targets specific genes for inactivation by promoter methylation. This hypothesis is supported by our recent studies with the MAYAK population that demonstrated the targeting of the p16 gene for inactivation by promoter methylation in adenocarcinomas from workers (1). Second, genes inactivated in tumors can serve as biomarkers for lung cancer risk in a cancer-free population of workers exposed to plutonium. Support for this hypothesis is based on exciting preliminary results of our nested, case-control study of persons from the Colorado cohort. In that study, a panel of methylation markers for predicting lung cancer risk is being evaluated in sputum samples from incident lung cancer cases and controls. The first hypothesis will be tested by determining the prevalence for promoter hypermethylation of a panel of genes shown to play a critical role in the development of either adenocarcinoma and/or SCC associated with tobacco. Our initial studies on adenocarcinoma in MAYAK workers will be extended to evaluate methylation of the PAX5 {alpha}, PAX5 {beta}, H-cadherin, GATA5, and bone morphogenesis 3B (BMP3B) genes in the original sample set described under Preliminary studies. In addition, studies will be initiated in SCC from workers and controls to identify genes targeted for inactivation by plutonium in this other common histologic form of lung cancer. We will examine methylation of the p16, O{sup 6}-methylguanine-DNA methyl-transferase (MGMT), and death associated protein kinase genes ([DAP-K], evaluated previously in adenocarcinomas) as well as the new genes being assessed in the adenocarcinomas. The second hypothesis will be tested in a cross-sectional study of cancer-free workers exposed to plutonium and an unexposed population. A cohort of 700 cancer-free workers and 700 unexposed persons is being assembled, exposures are being defined, and induced sputum collected at initial entry into the study and approximately 1-year later. Exposed and unexposed persons will be matched by 5-year age intervals and smoking status (current and former). The frequency for methylation of four genes that show the greatest difference in prevalence in tumors from workers and controls will be determined in exfoliated cells within sputum. These studies will extend those in primary tumors to determine whether difference in prevalence for individual or multiple genes are detected in sputum samples from high-risk subjects exposed to plutonium. Follow-up of this cohort offers the opportunity to validate these endpoints and future biomarkers as true markers for lung cancer risk.

  7. A reevaluation of cancer incidence near the Three Mile Island nuclear plant: The collision of evidence and assumptions

    SciTech Connect (OSTI)

    Wing, S.; Richardson, D.; Armstrong, D.; Crawford-Brown, D.

    1997-01-01

    Previous studies concluded that there was no evidence that the 1979 nuclear accident at Three Mile Island (TMI) affected cancer incidence in the surrounding area; however, there were logical and methodological problems in earlier reports that led us to reconsider data previously collected. A 10-mile area around TMI was divided into 69 study tracts, which were assigned radiation dose estimates based on radiation readings and models of atmospheric dispersion. Incident cancers from 1975 to 1985 were ascertained from hospital records and assigned to study tracts. Associations between accident doses and incidence rates of leukemia, lung cancer, and all cancer were assessed using relative dose estimates calculated by the earlier investigators. Adjustments were made for age, sex, socioeconomic characteristics, and preaccident variation in incidence. Considering a 2-year latency, the estimated percent increase per dose unit {plus_minus} standard error was 0.020 {plus_minus} 0.012 for all cancer, 0.082 {plus_minus} 0.032 for lung cancer, and 0.116 {plus_minus} 0.067 for leukemia. Adjustment for socioeconomic variables increased the estimates to 0.034 {plus_minus} 0.013, 0.103 {plus_minus} 0.035, and 0.139 {plus_minus} 0.073 for all cancer, lung cancer, and leukemia, respectively. Associations were generally larger considering a 5-year latency, but were based on smaller numbers of cases. Results support the hypothesis that radiation doses are related to increased cancer incidence around TMI. The analysis avoids medical detection bias, but suffers from inaccurate dose classification; therefore, results may underestimate the magnitude of the association between radiation and cancer incidence. These associations would not be expected, based on previous estimates of near-background levels of radiation exposure following the accident. 35 refs., 3 tabs.

  8. Second cancer incidence risk estimates using BEIR VII models for standard and complex external beam radiotherapy for early breast cancer

    SciTech Connect (OSTI)

    Donovan, E. M.; James, H.; Bonora, M.; Yarnold, J. R.; Evans, P. M.

    2012-10-15

    Purpose: To compare organ specific cancer incidence risks for standard and complex external beam radiotherapy (including cone beam CT verification) following breast conservation surgery for early breast cancer.Method: Doses from breast radiotherapy and kilovoltage cone beam CT (CBCT) exposures were obtained from thermoluminescent dosimeter measurements in an anthropomorphic phantom in which the positions of radiosensitive organs were delineated. Five treatment deliveries were investigated: (i) conventional tangential field whole breast radiotherapy (WBRT), (ii) noncoplanar conformal delivery applicable to accelerated partial beast irradiation (APBI), (iii) two-volume simultaneous integrated boost (SIB) treatment, (iv) forward planned three-volume SIB, and (v) inverse-planned three volume SIB. Conformal and intensity modulated radiotherapy methods were used to plan the complex treatments. Techniques spanned the range from simple methods appropriate for patient cohorts with a low cancer recurrence risk to complex plans relevant to cohorts with high recurrence risk. Delineated organs at risk included brain, salivary glands, thyroid, contralateral breast, left and right lung, esophagus, stomach, liver, colon, and bladder. Biological Effects of Ionizing Radiation (BEIR) VII cancer incidence models were applied to the measured mean organ doses to determine lifetime attributable risk (LAR) for ages at exposure from 35 to 80 yr according to radiotherapy techniques, and included dose from the CBCT imaging. Results: All LAR decreased with age at exposure and were lowest for brain, thyroid, liver, and bladder (<0.1%). There was little dependence of LAR on radiotherapy technique for these organs and for colon and stomach. LAR values for the lungs for the three SIB techniques were two to three times those from WBRT and APBI. Uncertainties in the LAR models outweigh any differences in lung LAR between the SIB methods. Constraints in the planning of the SIB methods ensured that contralateral breast doses and LAR were comparable to WBRT, despite their added complexity. The smaller irradiated volume of the ABPI plan contributed to a halving of LAR for contralateral breast compared with the other plan types. Daily image guided radiotherapy (IGRT) for a left breast protocol using kilovoltage CBCT contributed <10% to LAR for the majority of organs, and did not exceed 22% of total organ dose. Conclusions: Phantom measurements and calculations of LAR from the BEIR VII models predict that complex breast radiotherapy techniques do not increase the theoretical risk of second cancer incidence for organs distant from the treated breast, or the contralateral breast where appropriate plan constraints are applied. Complex SIB treatments are predicted to increase the risk of second cancer incidence in the lungs compared to standard whole breast radiotherapy; this is outweighed by the threefold reduction in 5 yr local recurrence risk for patients of high risk of recurrence, and young age, from the use of radiotherapy. APBI may have a favorable impact on risk of second cancer in the contralateral breast and lung for older patients at low risk of recurrence. Intensive use of IGRTincreased the estimated values of LAR but these are dominated by the effect of the dose from the radiotherapy, and any increase in LAR from IGRT is much lower than the models' uncertainties.

  9. Investigation of excess thyroid cancer incidence in Los Alamos County

    SciTech Connect (OSTI)

    Athas, W.F.

    1996-04-01

    Los Alamos County (LAC) is home to the Los Alamos National Laboratory, a U.S. Department of Energy (DOE) nuclear research and design facility. In 1991, the DOE funded the New Mexico Department of Health to conduct a review of cancer incidence rates in LAC in response to citizen concerns over what was perceived as a large excess of brain tumors and a possible relationship to radiological contaminants from the Laboratory. The study found no unusual or alarming pattern in the incidence of brain cancer, however, a fourfold excess of thyroid cancer was observed during the late-1980`s. A rapid review of the medical records for cases diagnosed between 1986 and 1990 failed to demonstrate that the thyroid cancer excess had resulted from enhanced detection. Surveillance activities subsequently undertaken to monitor the trend revealed that the excess persisted into 1993. A feasibility assessment of further studies was made, and ultimately, an investigation was conducted to document the epidemiologic characteristics of the excess in detail and to explore possible causes through a case-series records review. Findings from the investigation are the subject of this report.

  10. Cancer incidence among residents of the Three Mile Island accident area: 1982-1995

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    Han, Yueh-Ying; Youk, Ada O.; Sasser, Howell; Talbott, Evelyn O.

    2011-11-15

    Background: The Pennsylvania Department of Health established a registry of the Three Mile Island (TMI) nuclear power plant accident in 1979. Over 93% of the population present on the day of the accident within a 5-mile radius was enrolled and interviewed. We used the registry to investigate the potential cancer risk from low-dose radiation exposure among the TMI population. Methods: Cancer incidence data among the TMI cohort were available from 1982 to 1995. Because more than 97% of the population were white and few cancer cases were reported for those younger than 18 years of age, we included whites of age 18 years and older (10,446 men and 11,048 women) for further analyses. Cox regression models were used to estimate the relative risk (RR) per 0.1 m Sv and 95% confident interval (CI) of cancer by radiation-related exposures. The cancers of interest were all malignant neoplasms, cancer of bronchus, trachea, and lung, cancer of lymphatic and hematopoietic tissues, leukemia, and female breast. Results: Among men and women, there was no evidence of an increased risk for all malignant neoplasms among the TMI cohort exposed to higher maximum and likely {gamma} radiation (RR=1.00, 95% CI=0.97, 1.01 and RR=0.99, 95% CI=0.94, 1.03, respectively) after adjusting for age, gender, education, smoking, and background radiation. Elevation in risk was noted for cancer of the bronchus, trachea, and lung in relation to higher background radiation exposure (RR=1.45, 95% CI=1.02-2.05 at 8.0-8.8 {mu}R/h compared to 5.2-7.2 {mu}R/h). An increased risk of leukemia was found among men exposed to higher maximum and likely {gamma} radiation related to TMI exposure during the ten days following the accident (RR=1.15, 95% CI=1.04, 1.29 and RR=1.36, 95% CI=1.08, 1.71, respectively). This relationship was not found in women. Conclusion: Increased cancer risks from low-level radiation exposure within the TMI cohort were small and mostly statistically non-significant. However, additional follow-up on this population is warranted, especially to explore the increased risk of leukemia found in men.

  11. SU-E-T-208: Incidence Cancer Risk From the Radiation Treatment for Acoustic Neuroma Patient

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    Kim, D; Chung, W; Shin, D; Yoon, M

    2014-06-01

    Purpose: The present study aimed to compare the incidence risk of a secondary cancer from therapeutic doses in patients receiving intensitymodulated radiotherapy (IMRT), volumetric modulated arc therapy (VMAT), and stereotactic radiosurgery (SRS). Methods: Four acoustic neuroma patients were treated with IMRT, VMAT, or SRS. Their incidnece excess relative risk (ERR), excess absolute risk (EAR), and lifetime attributable risk (LAR) were estimated using the corresponding therapeutic doses measured at various organs by radio-photoluminescence glass dosimeters (RPLGD) placed inside a humanoid phantom. Results: When a prescription dose was delivered in the planning target volume of the 4 patients, the average organ equivalent doses (OED) at the thyroid, lung, normal liver, colon, bladder, prostate (or ovary), and rectum were measured. The OED decreased as the distance from the primary beam increased. The thyroid received the highest OED compared to other organs. A LAR were estimated that more than 0.03% of AN patients would get radiation-induced cancer. Conclusion: The tyroid was highest radiation-induced cancer risk after radiation treatment for AN. We found that LAR can be increased by the transmitted dose from the primary beam. No modality-specific difference in radiation-induced cancer risk was observed in our study.

  12. Frizzled-8 as a putative therapeutic target in human lung cancer

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    Wang, Hua-qing; Department of Medical Oncology, Tianjin Medical University Cancer Hospital, Tianjin 300060 ; Xu, Mei-lin; Ma, Jie; Zhang, Yi; Xie, Cong-hua

    2012-01-06

    Highlights: Black-Right-Pointing-Pointer Fzd-8 is over-expressed in human lung cancer. Black-Right-Pointing-Pointer shRNA knock-down of Fzd-8 inhibits proliferation and Wnt pathway in lung cancer cells. Black-Right-Pointing-Pointer shRNA knock-down of Fzd-8 suppresses tumor growth in vivo. Black-Right-Pointing-Pointer shRNA knock-down Fzd-8 sensitizes lung cancer cells to chemotherapy Taxotere. -- Abstract: Lung cancer is the leading cause of cancer related deaths worldwide. It is necessary to better understand the molecular mechanisms involved in lung cancer in order to develop more effective therapeutics for the treatment of this disease. Recent reports have shown that Wnt signaling pathway is important in a number of cancer types including lung cancer. However, the role of Frizzled-8 (Fzd-8), one of the Frizzled family of receptors for the Wnt ligands, in lung cancer still remains to be elucidated. Here in this study we showed that Fzd-8 was over-expressed in human lung cancer tissue samples and cell lines. To investigate the functional importance of the Fzd-8 over-expression in lung cancer, we used shRNA to knock down Fzd-8 mRNA in lung cancer cells expressing the gene. We observed that Fzd-8 shRNA inhibited cell proliferation along with decreased activity of Wnt pathway in vitro, and also significantly suppressed A549 xenograft model in vivo (p < 0.05). Furthermore, we found that knocking down Fzd-8 by shRNA sensitized the lung cancer cells to chemotherapy Taxotere. These data suggest that Fzd-8 is a putative therapeutic target for human lung cancer and over-expression of Fzd-8 may be important for aberrant Wnt activation in lung cancer.

  13. Receptor tyrosine kinase EphA5 is a functional molecular target in human lung cancer

    SciTech Connect (OSTI)

    Staquicini, Fernanda I.; Qian, Ming D.; Salameh, Ahmad; Dobroff, Andrey S.; Edwards, Julianna K.; Cimino, Daniel F.; Moeller, Benjamin J.; Kelly, Patrick; Nunez, Maria I.; Tang, Ximing; Liu, Diane D.; Lee, J. Jack; Hong, Waun Ki; Ferrara, Fortunato; Bradbury, Andrew R. M.; Lobb, Roy R.; Edelman, Martin J.; Sidman, Richard L.; Wistuba, Ignacio I.; Arap, Wadih; Pasqualini, Renata

    2015-03-20

    Lung cancer is often refractory to radiotherapy, but molecular mechanisms of tumor resistance remain poorly defined. Here we show that the receptor tyrosine kinase EphA5 is specifically overexpressed in lung cancer and is involved in regulating cellular responses to genotoxic insult. In the absence of EphA5, lung cancer cells displayed a defective G1/S cell cycle checkpoint, were unable to resolve DNA damage, and became radiosensitive. Upon irradiation, EphA5 was transported into the nucleus where it interacted with activated ATM (ataxia-telangiectasia mutated) at sites of DNA repair. In conclusion, we demonstrate that a new monoclonal antibody against human EphA5 sensitized lung cancer cells and human lung cancer xenografts to radiotherapy and significantly prolonged survival, thus suggesting the likelihood of translational applications.

  14. Receptor tyrosine kinase EphA5 is a functional molecular target in human lung cancer

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Staquicini, Fernanda I.; Qian, Ming D.; Salameh, Ahmad; Dobroff, Andrey S.; Edwards, Julianna K.; Cimino, Daniel F.; Moeller, Benjamin J.; Kelly, Patrick; Nunez, Maria I.; Tang, Ximing; et al

    2015-03-20

    Lung cancer is often refractory to radiotherapy, but molecular mechanisms of tumor resistance remain poorly defined. Here we show that the receptor tyrosine kinase EphA5 is specifically overexpressed in lung cancer and is involved in regulating cellular responses to genotoxic insult. In the absence of EphA5, lung cancer cells displayed a defective G1/S cell cycle checkpoint, were unable to resolve DNA damage, and became radiosensitive. Upon irradiation, EphA5 was transported into the nucleus where it interacted with activated ATM (ataxia-telangiectasia mutated) at sites of DNA repair. In conclusion, we demonstrate that a new monoclonal antibody against human EphA5 sensitized lungmore » cancer cells and human lung cancer xenografts to radiotherapy and significantly prolonged survival, thus suggesting the likelihood of translational applications.« less

  15. Low-Dose Spiral CT Scans for Early Lung Cancer Detection

    Broader source: Energy.gov [DOE]

    Low-dose spiral computed tomography (CT) scanning is a noninvasive medical imaging test that has been used for the early detection of lung cancer for over 16 years (Sone et al. 1998; Henschke et.al. 1999).

  16. Radiotherapy in Small-Cell Lung Cancer: Lessons Learned and Future Directions

    SciTech Connect (OSTI)

    Slotman, Ben J.; Senan, Suresh

    2011-03-15

    Although chemotherapy is an essential component in the treatment of small-cell lung cancer, improvements in survival in the past two decades have been mainly achieved by the appropriate application of radiotherapy. The aim of the present study was to review the key developments in thoracic radiotherapy and prophylactic cranial radiotherapy and to discuss the rationale behind key ongoing studies in small-cell lung cancer.

  17. Structures of Lung Cancer-Derived EGFR Mutants and Inhibitor Complexes:

    Office of Scientific and Technical Information (OSTI)

    Mechanism of Activation and Insights into Differential Inhibitor Sensitivity (Journal Article) | SciTech Connect Structures of Lung Cancer-Derived EGFR Mutants and Inhibitor Complexes: Mechanism of Activation and Insights into Differential Inhibitor Sensitivity Citation Details In-Document Search Title: Structures of Lung Cancer-Derived EGFR Mutants and Inhibitor Complexes: Mechanism of Activation and Insights into Differential Inhibitor Sensitivity Authors: Yun, C.H. ; Boggon, T.J. ; Li, Y.

  18. Lung Cancer Survival Prediction using Ensemble Data Mining on Seer Data

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Agrawal, Ankit; Misra, Sanchit; Narayanan, Ramanathan; Polepeddi, Lalith; Choudhary, Alok

    2012-01-01

    We analyze the lung cancer data available from the SEER program with the aim of developing accurate survival prediction models for lung cancer. Carefully designed preprocessing steps resulted in removal/modification/splitting of several attributes, and 2 of the 11 derived attributes were found to have significant predictive power. Several supervised classification methods were used on the preprocessed data along with various data mining optimizations and validations. In our experiments, ensemble voting of five decision tree based classifiers and meta-classifiers was found to result in the best prediction performance in terms of accuracy and area under the ROC curve. We have developedmore » an on-line lung cancer outcome calculator for estimating the risk of mortality after 6 months, 9 months, 1 year, 2 year and 5 years of diagnosis, for which a smaller non-redundant subset of 13 attributes was carefully selected using attribute selection techniques, while trying to retain the predictive power of the original set of attributes. Further, ensemble voting models were also created for predicting conditional survival outcome for lung cancer (estimating risk of mortality after 5 years of diagnosis, given that the patient has already survived for a period of time), and included in the calculator. The on-line lung cancer outcome calculator developed as a result of this study is available at http://info.eecs.northwestern.edu:8080/LungCancerOutcomeCalculator/.« less

  19. Inhibitory effect of Disulfiram/copper complex on non-small cell lung cancer cells

    SciTech Connect (OSTI)

    Duan, Lincan; Shen, Hongmei; Zhao, Guangqiang; Yang, Runxiang; Cai, Xinyi; Zhang, Lijuan; Jin, Congguo; Huang, Yunchao

    2014-04-18

    Highlights: Disulfiram and copper synergistically inhibit lung cancer cell proliferation. Lung cancer cell colony formation ability is inhibited by Disulfiram/copper. Disulfiram/copper increases the sensitivity of cisplatin to lung cancer cells. Lung cancer stem cells are specifically targeted by Disulfiram/copper complex. - Abstract: Non-small cell lung cancer (NSCLC) is the most common cause of cancer-related death in both men and women worldwide. Recently, Disulfiram has been reported to be able to inhibit glioblastoma, prostate, or breast cancer cell proliferation. In this study, the synergistic effect of Disulfiram and copper on NSCLC cell growth was investigated. Inhibition of cancer cell proliferation was detected by 1-(4,5-Dimethylthiazol-2-yl)-3,5-diphenylformazan (MTT) assay and cell cycle analysis. Liquid colony formation and tumor spheroid formation assays were used to evaluate their effect on cancer cell clonogenicity. Real-time PCR was performed to test the mRNA level of cancer stem cell related genes. We found that Disulfiram or copper alone did not potently inhibit NSCLC cell proliferation in vitro. However, the presence of copper significantly enhanced inhibitory effect of Disulfiram on NSCLC cell growth, indicating a synergistic effect between Disulfiram and copper. Cell cycle analysis showed that Disulfiram/copper complex caused NSCLC cell cycle arrest in G2/M phase. Furthermore, Disulfiram/copper significantly increased the sensitivity of cisplatin in NSCLC cells tested by MTT assay. Liquid colony formation assay revealed that copper dramatically increased the inhibitory effect of Disulfiram on NSCLC cell colony forming ability. Disulfiram combined with copper significantly attenuated NSCLC cell spheroid formation and recuded the mRNA expression of lung cancer stem cell related genes. Our data suggest that Disulfiram/copper complex alone or combined with other chemotherapy is a potential therapeutic strategy for NSCLC patients.

  20. Lung Radiofrequency Ablation for the Treatment of Unresectable Recurrent Non-Small-Cell Lung Cancer After Surgical Intervention

    SciTech Connect (OSTI)

    Kodama, Hiroshi, E-mail: h-kodama@clin.medic.mie-u.ac.jp; Yamakado, Koichiro; Takaki, Haruyuki; Kashima, Masataka; Uraki, Junji; Nakatsuka, Atsuhiro [Mie University School of Medicine, Department of Radiology (Japan); Takao, Motoshi [Mie University School of Medicine, Department of Thoracic Surgery (Japan); Taguchi, Osamu [Mie University School of Medicine, Department of Internal Medicine (Japan); Yamada, Tomomi [Mie University School of Medicine, Department of Translational Medicine (Japan); Takeda, Kan [Mie University School of Medicine, Department of Radiology (Japan)

    2012-06-15

    Purpose: A retrospective evaluation was done of clinical utility of lung radiofrequency (RF) ablation in recurrent non-small-cell lung cancer (NSCLC) after surgical intervention. Methods: During May 2003 to October 2010, 44 consecutive patients (26 male and 18 female) received curative lung RF ablation for 51 recurrent NSCLC (mean diameter 1.7 {+-} 0.9 cm, range 0.6 to 4.0) after surgical intervention. Safety, tumor progression rate, overall survival, and recurrence-free survival were evaluated. Prognostic factors were evaluated in multivariate analysis. Results: A total of 55 lung RF sessions were performed. Pneumothorax requiring pluerosclerosis (n = 2) and surgical suture (n = 1) were the only grade 3 or 4 adverse events (5.5%, 3 of 55). During mean follow-up of 28.6 {+-} 20.3 months (range 1 to 98), local tumor progression was found in 5 patients (11.4%, 5 of 44). The 1-, 3-, and 5-year overall survival rates were 97.7, 72.9, and 55.7%, respectively. The 1- and 3-year recurrence-free survival rates were 76.7 and 41.1%, respectively. Tumor size and sex were independent significant prognostic factors in multivariate analysis. The 5-year survival rates were 73.3% in 18 women and 60.5% in 38 patients who had small tumors measuring {<=}3 cm. Conclusion: Our results suggest that lung RF ablation is a safe and useful therapeutic option for obtaining long-term survival in treated patients.

  1. Arsenic methylation and lung and bladder cancer in a case-control study in northern Chile

    SciTech Connect (OSTI)

    Melak, Dawit; Ferreccio, Catterina; Kalman, David; Parra, Roxana; Acevedo, Johanna; Prez, Liliana; Corts, Sandra; Smith, Allan H.; Yuan, Yan; Liaw, Jane; Steinmaus, Craig

    2014-01-15

    In humans, ingested inorganic arsenic is metabolized to monomethylarsenic (MMA) then to dimethylarsenic (DMA), although this process is not complete in most people. The trivalent form of MMA is highly toxic in vitro and previous studies have identified associations between the proportion of urinary arsenic as MMA (%MMA) and several arsenic-related diseases. To date, however, relatively little is known about its role in lung cancer, the most common cause of arsenic-related death, or about its impacts on people drinking water with lower arsenic concentrations (e.g., < 200 ?g/L). In this study, urinary arsenic metabolites were measured in 94 lung and 117 bladder cancer cases and 347 population-based controls from areas in northern Chile with a wide range of drinking water arsenic concentrations. Lung cancer odds ratios adjusted for age, sex, and smoking by increasing tertiles of %MMA were 1.00, 1.91 (95% confidence interval (CI), 0.993.67), and 3.26 (1.766.04) (p-trend < 0.001). Corresponding odds ratios for bladder cancer were 1.00, 1.81 (1.063.11), and 2.02 (1.153.54) (p-trend < 0.001). In analyses confined to subjects only with arsenic water concentrations < 200 ?g/L (median = 60 ?g/L), lung and bladder cancer odds ratios for subjects in the upper tertile of %MMA compared to subjects in the lower two tertiles were 2.48 (1.085.68) and 2.37 (1.015.57), respectively. Overall, these findings provide evidence that inter-individual differences in arsenic metabolism may be an important risk factor for arsenic-related lung cancer, and may play a role in cancer risks among people exposed to relatively low arsenic water concentrations. - Highlights: Urine arsenic metabolites were measured in cancer cases and controls from Chile. Higher urine %MMA values were associated with increased lung and bladder cancer. %MMA-cancer associations were seen at drinking water arsenic levels < 200 ?g/L.

  2. Lung cancer-derived Dickkopf1 is associated with bone metastasis and the mechanism involves the inhibition of osteoblast differentiation

    SciTech Connect (OSTI)

    Chu, Tianqing; Teng, Jiajun; Jiang, Liyan; Zhong, Hua; Han, Baohui

    2014-01-17

    Highlights: DKK1 level was associated with NSCLC bone metastases. Lung tumor cells derived DKK1 inhibited osteoblast differentiation. Lung tumor cells derived DKK1 modulates ?-catenin and RUNX2. -- Abstract: Wnt/?-catenin signaling and Dickkopf1 (DKK1) play important roles in the progression of lung cancer, which preferably metastasizes to skeleton. But the role of them in bone dissemination is poorly understood. This study aims to define the role of DKK1 in lung cancer bone metastases and investigate the underlying mechanism. Our results demonstrated that DKK1 over-expression was a frequent event in non-small-cell lung cancer (NSCLC) blood samples, and serous DKK1 level was much higher in bone metastatic NSCLC compared to non-bone metastatic NSCLC. We also found that conditioned medium from DKK1 over-expressing lung cancer cells inhibited the differentiation of osteoblast, determined by alkaline phosphatase activity and osteocalcin secretion, whereas the conditioned medium from DKK1 silencing lung cancer cells exhibited the opposite effects. Mechanistically, DKK1 reduced the level of ?-catenin and RUNX2, as well as inhibiting the nuclear translocation of ?-catenin. Taken together, these results suggested that lung cancer-produced DKK1 may be an important mechanistic link between NSCLC and bone metastases, and targeting DKK1 may be an effective method to treat bone metastase of NSCLC.

  3. Prognostic Factors in Stereotactic Body Radiotherapy for Non-Small-Cell Lung Cancer

    SciTech Connect (OSTI)

    Matsuo, Yukinori, E-mail: ymatsuo@kuhp.kyoto-u.ac.j [Department of Radiation Oncology and Image-Applied Therapy, Graduate School of Medicine, Kyoto University, Kyoto (Japan); Shibuya, Keiko [Department of Radiation Oncology and Image-Applied Therapy, Graduate School of Medicine, Kyoto University, Kyoto (Japan); Nagata, Yasushi [Division of Radiation Oncology, Hiroshima University Hospital, Hiroshima (Japan); Takayama, Kenji; Norihisa, Yoshiki; Mizowaki, Takashi; Narabayashi, Masaru; Sakanaka, Katsuyuki; Hiraoka, Masahiro [Department of Radiation Oncology and Image-Applied Therapy, Graduate School of Medicine, Kyoto University, Kyoto (Japan)

    2011-03-15

    Purpose: To investigate the factors that influence clinical outcomes after stereotactic body radiotherapy (SBRT) for non-small-cell lung cancer (NSCLC). Methods and Materials: A total of 101 consecutive patients who underwent SBRT with 48 Gy in 4 fractions for histologically confirmed Stage I NSCLC were enrolled in this study. Factors including age, maximal tumor diameter, sex, performance status, operability, histology, and overall treatment time were evaluated with regard to local progression (LP), disease progression (DP), and overall survival (OS) using the Cox proportional hazards model. Prognostic models were built with recursive partitioning analysis. Results: Three-year OS was 58.6% with a median follow-up of 31.4 months. Cumulative incidence rates of LP and DP were 13.2% and 40.8% at 3 years, respectively. Multivariate analysis demonstrated that tumor diameter was a significant factor in all endpoints of LP, DP, and OS. Other significant factors were age in DP and sex in OS. Recursive partitioning analysis indicated a condition for good prognosis (Class I) as follows: female or T1a (tumor diameter {<=}20 mm). When the remaining male patients with T1b-2a (>20 mm) were defined as Class II, 3-year LP, DP, and OS were 6.8%, 23.6%, and 69.9% in recursive partitioning analysis Class I, respectively, whereas these values were 19.9%, 58.3%, and 47.1% in Class II. The differences between the classes were statistically significant. Conclusions: Tumor diameter and sex were the most significant factors in SBRT for NSCLC. T1a or female patients had good prognosis.

  4. Residential Mobility and Lung Cancer Risk: Data-Driven Exploration Using Internet Sources

    SciTech Connect (OSTI)

    Yoon, Hong-Jun; Tourassi, Georgia; Xu, Songhua

    2015-01-01

    Frequent relocation has been linked to health decline, particularly with respect to emotional and psychological wellbeing. In this paper we investigate whether there is an association between frequent relocation and lung cancer risk. For the initial investigation we leverage two online data sources to collect cancer and control subjects using web crawling and tailored text mining. The two data sources share different strengths and weaknesses in terms of the amount of detail, population representation, and sample size. One data source includes online obituaries. The second data source includes augmented LinkedIn profiles. For each data source, the subjects spatiotemporal history is reconstructed from the available information provided in the obituaries and from the education and work experience provided in the LinkedIn profiles. The study shows that lung cancer subjects have higher mobility frequency than the control group. This trend is consistent for both data sources.

  5. Combined therapeutic potential of nuclear receptors with receptor tyrosine kinase inhibitors in lung cancer

    SciTech Connect (OSTI)

    Wairagu, Peninah M.; Park, Kwang Hwa; Kim, Jihye; Choi, Jong-Whan; Kim, Hyun-Won; Yeh, Byung-Il; Jung, Soon-Hee; Yong, Suk-Joong; Jeong, Yangsik

    2014-05-09

    Highlights: The 48 NR genes and 48 biological anti-cancer targets are profiled in paired-cells. Growth inhibition by NR ligands or TKIs is target receptor level-dependent. T0901317 with gefitinib/PHA665752 shows additive growth inhibition in lung cells. - Abstract: Cancer heterogeneity is a big hurdle in achieving complete cancer treatment, which has led to the emergence of combinational therapy. In this study, we investigated the potential use of nuclear receptor (NR) ligands for combinational therapy with other anti-cancer drugs. We first profiled all 48 NRs and 48 biological anti-cancer targets in four pairs of lung cell lines, where each pair was obtained from the same patient. Two sets of cell lines were normal and the corresponding tumor cell lines while the other two sets consisted of primary versus metastatic tumor cell lines. Analysis of the expression profile revealed 11 NRs and 15 cancer targets from the two pairs of normal versus tumor cell lines, and 9 NRs and 9 cancer targets from the primary versus metastatic tumor cell lines had distinct expression patterns in each category. Finally, the evaluation of nuclear receptor ligand T0901317 for liver X receptor (LXR) demonstrated its combined therapeutic potential with tyrosine kinase inhibitors. The combined treatment of cMET inhibitor PHA665752 or EGFR inhibitor gefitinib with T0901317 showed additive growth inhibition in both H2073 and H1993 cells. Mechanistically, the combined treatment suppressed cell cycle progression by inhibiting cyclinD1 and cyclinB expression. Taken together, this study provides insight into the potential use of NR ligands in combined therapeutics with other biological anti-cancer drugs.

  6. Appraisal of selected epidemiologic issues from studies of lung cancer among uranium and hard rock miners

    SciTech Connect (OSTI)

    Petersen, G R; Sever, L E

    1982-04-01

    An extensive body of published information about lung cancer among uranium miners was reviewed and diverse information, useful in identifying important issues but not in resolving them was found. Measuring exposure and response; thresholds of exposure; latency or the period from first mining experience to death; effort to predict excess risk of death, using a model; effects of smoking and radon daughter exposure on the histology of lung tumors; and the interplay of factors on the overall risk of death were all examined. The general concept of thresholds; that is, an exposure level below which risk does not increase was considered. The conclusion is that it should be possible to detect and estimate an epidemiologic threshold when the cohorts have been followed to the death of all members. Issues concerning latency in the studies of uranium miners published to date were examined. It is believed that the induction-latent period for lung cancer among uranium miners may be: as little as 10 to more than 40 years; dependent on age at which exposure begins; exposure rate; and ethnicity or smoking habits. Although suggested as factual, their existence is uncertain. An effect due to the exposure rate may exist although it has not been factual, their existence is uncertain. An effect due to the exposure rate may exist although it has not been confirmed. The median induction-latent period appears to be in excess of the 15 years frequently cited for US uranium miner. A distinct pattern of shorter induction-latent periods with increasing age at first mining exposure is reported. The evidence for and against an unusual histologic pattern of lung cancers among uranium miners was examined. The ratio of epidermoid to small cell types was close to 1:2; the ratio in the general population is nearer 2:1. The histologic pattern warrants closer attention of pathologists and epidemiologists. (ERB) (ERB)

  7. SU-E-J-190: Characterization of Radiation Induced CT Number Changes in Tumor and Normal Lung During Radiation Therapy for Lung Cancer

    SciTech Connect (OSTI)

    Yang, C; Liu, F; Tai, A; Gore, E; Johnstone, C; Li, X

    2014-06-01

    Purpose: To measure CT number (CTN) changes in tumor and normal lung as a function of radiation therapy (RT) dose during the course of RT delivery for lung cancer using daily IGRT CT images and single respiration phase CT images. Methods: 4D CT acquired during planning simulation and daily 3D CT acquired during daily IGRT for 10 lung cancer cases randomly selected in terms of age, caner type and stage, were analyzed using an in-house developed software tool. All patients were treated in 2 Gy fractions to primary tumors and involved nodal regions. Regions enclosed by a series of isodose surfaces in normal lung were delineated. The obtained contours along with target contours (GTVs) were populated to each singlephase planning CT and daily CT. CTN in term of Hounsfield Unit (HU) of each voxel in these delineated regions were collectively analyzed using histogram, mean, mode and linear correlation. Results: Respiration induced normal lung CTN change, as analyzed from single-phase planning CTs, ranged from 9 to 23 (2) HU for the patients studied. Normal lung CTN change was as large as 50 (12) HU over the entire treatment course, was dose and patient dependent and was measurable with dose changes as low as 1.5 Gy. For patients with obvious tumor volume regression, CTN within the GTV drops monotonically as much as 10 (1) HU during the early fractions with a total dose of 20 Gy delivered. The GTV and CTN reductions are significantly correlated with correlation coefficient >0.95. Conclusion: Significant RT dose induced CTN changes in lung tissue and tumor region can be observed during even the early phase of RT delivery, and may potentially be used for early prediction of radiation response. Single respiration phase CT images have dramatically reduced statistical noise in ROIs, making daily dose response evaluation possible.

  8. CDK-associated Cullin 1 promotes cell proliferation with activation of ERK1/2 in human lung cancer A549 cells

    SciTech Connect (OSTI)

    Chen, Tian Jun; Gao, Fei; Yang, Tian; Thakur, Asmitanand; Ren, Hui; Li, Yang; Zhang, Shuo; Wang, Ting; Chen, Ming Wei

    2013-07-19

    Highlights: CDK-associated Cullin 1 (CAC1) expression increases in human lung carcinoma. CAC1 promotes the proliferation of lung cancer A549 cells. CAC1 promotes human lung cancer A549 cell proliferation with activation of ERK1/2. -- Abstract: Lung cancer is one of the most common causes of cancer-related death in the world, but the mechanisms remain unknown. In this study, we investigated the expression of CDK-associated Cullin 1 (CAC1) in lung cancer, the effect of CAC1 on the proliferation of human lung cancer A549 cells, and the activation of signaling pathways of mitogen-activated protein kinases (MAPKs). Results showed that CAC1 expression was higher levels in human lung carcinoma than normal lung tissue, and CAC1 siRNA reduced the proliferation of lung cancer A549 cells by decreasing cell activity and cell division in vitro. The proportion of cells treated with CAC1 siRNA increased in the G1 phase and decreased in the S and G2/M phase, indicative of G1 cell cycle arrest. Furthermore, the proportions of early/late apoptosis in lung cancer A549 cells were enhanced with CAC1 siRNA treatment. It was also found that activation of extracellular signal-regulated protein kinase (ERK) and p38 signaling pathways were involved in the proliferation of A549 cells. After CAC1 siRNA treatment, p-ERK1/2 levels decreased, and meanwhile p-p38 level increased, A549 cell proliferation increased when ERK1/2 signaling is activated by PMA. Our findings demonstrated that CAC1 promoted the proliferation of human lung cancer A549 cells with activation of ERK1/2 signaling pathways, suggesting a potential cure target for treatment of human lung cancer.

  9. Silencing of poly(ADP-ribose) glycohydrolase sensitizes lung cancer cells to radiation through the abrogation of DNA damage checkpoint

    SciTech Connect (OSTI)

    Nakadate, Yusuke; Department of Bioengineering, Graduate School of Engineering, Osaka City University, 3-3-138 Sugimoto, Sumiyoshi-ku, Osaka 558-8585 ; Kodera, Yasuo; Kitamura, Yuka; Tachibana, Taro; Tamura, Tomohide; Koizumi, Fumiaki

    2013-11-29

    Highlights: Radiosensitization by PARG silencing was observed in multiple lung cancer cells. PAR accumulation was enhanced by PARG silencing after DNA damage. Radiation-induced G2/M arrest and checkpoint activation were impaired by PARG siRNA. -- Abstract: Poly(ADP-ribose) glycohydrolase (PARG) is a major enzyme that plays a role in the degradation of poly(ADP-ribose) (PAR). PARG deficiency reportedly sensitizes cells to the effects of radiation. In lung cancer, however, it has not been fully elucidated. Here, we investigated whether PARG siRNA contributes to an increased radiosensitivity using 8 lung cancer cell lines. Among them, the silencing of PARG induced a radiosensitizing effect in 5 cell lines. Radiation-induced G2/M arrest was largely suppressed by PARG siRNA in PC-14 and A427 cells, which exhibited significantly enhanced radiosensitivity in response to PARG knockdown. On the other hand, a similar effect was not observed in H520 cells, which did not exhibit a radiosensitizing effect. Consistent with a cell cycle analysis, radiation-induced checkpoint signals were not well activated in the PC-14 and A427 cells when treated with PARG siRNA. These results suggest that the increased sensitivity to radiation induced by PARG knockdown occurs through the abrogation of radiation-induced G2/M arrest and checkpoint activation in lung cancer cells. Our findings indicate that PARG could be a potential target for lung cancer treatments when used in combination with radiotherapy.

  10. On the interplay effects with proton scanning beams in stage III lung cancer

    SciTech Connect (OSTI)

    Li, Yupeng; Kardar, Laleh; Liao, Li; Lim, Gino; Li, Xiaoqiang; Li, Heng; Zhu, Ronald X.; Sahoo, Narayan; Gillin, Michael; Zhang, Xiaodong; Cao, Wenhua; Chang, Joe Y.; Liao, Zhongxing; Komaki, Ritsuko; Cox, James D.

    2014-02-15

    Purpose: To assess the dosimetric impact of interplay between spot-scanning proton beam and respiratory motion in intensity-modulated proton therapy (IMPT) for stage III lung cancer. Methods: Eleven patients were sampled from 112 patients with stage III nonsmall cell lung cancer to well represent the distribution of 112 patients in terms of target size and motion. Clinical target volumes (CTVs) and planning target volumes (PTVs) were defined according to the authors' clinical protocol. Uniform and realistic breathing patterns were considered along with regular- and hypofractionation scenarios. The dose contributed by a spot was fully calculated on the computed tomography (CT) images corresponding to the respiratory phase that the spot is delivered, and then accumulated to the reference phase of the 4DCT to generate the dynamic dose that provides an estimation of what might be delivered under the influence of interplay effect. The dynamic dose distributions at different numbers of fractions were compared with the corresponding 4D composite dose which is the equally weighted average of the doses, respectively, computed on respiratory phases of a 4DCT image set. Results: Under regular fractionation, the average and maximum differences in CTV coverage between the 4D composite and dynamic doses after delivery of all 35 fractions were no more than 0.2% and 0.9%, respectively. The maximum differences between the two dose distributions for the maximum dose to the spinal cord, heart V40, esophagus V55, and lung V20 were 1.2 Gy, 0.1%, 0.8%, and 0.4%, respectively. Although relatively large differences in single fraction, correlated with small CTVs relative to motions, were observed, the authors' biological response calculations suggested that this interfractional dose variation may have limited biological impact. Assuming a hypofractionation scenario, the differences between the 4D composite and dynamic doses were well confined even for single fraction. Conclusions: Despite the presence of interplay effect, the delivered dose may be reliably estimated using the 4D composite dose. In general the interplay effect may not be a primary concern with IMPT for lung cancers for the authors' institution. The described interplay analysis tool may be used to provide additional confidence in treatment delivery.

  11. Cytogenetic damage in lymphocytes of patients undergoing therapy for small cell lung cancer and ovarian carcinoma

    SciTech Connect (OSTI)

    Padjas, Anna; Lesisz, Dominika; Lankoff, Anna; Banasik, Anna; Lisowska, Halina; Bakalarz, Robert; Gozdz, Stanislaw; Wojcik, Andrzej . E-mail: awojcik@pu.kielce.pl

    2005-12-01

    The level of cytogenetic damage in peripheral blood lymphocytes of patients undergoing chemotherapy has been analyzed incisively 20 years ago. The results showed that the highest level of cytogenetic damage was observed at the end of therapy. In recent years, the doses of anticancer drugs were intensified thanks to the discovery of colony stimulating factors. Therefore, it was interesting to analyze the kinetics of micronuclei formation in lymphocytes of patients undergoing modern chemotherapy. The frequencies of micronuclei were measured in lymphocytes of 6 patients with small cell lung cancer treated with a combination of cisplatin and etoposide and 7 patients with ovarian carcinoma treated with a combination of taxol and cisplatin. 3 patients with lung cancer received radiotherapy in addition to chemotherapy. Micronuclei were analyzed in lymphocytes collected before the start of therapy and 1 day before each following cycle of chemotherapy. The micronucleus frequencies were compared with the kinetics of leukocyte counts. The micronucleus frequencies showed an interindividual variability. On average, the frequencies of micronuclei increased during the first half of therapy and declined thereafter, reaching, in some patients with ovarian carcinoma, values below the pre-treatment level. Leukocyte counts decreased strongly at the beginning of therapy with an upward trend at the end. We suggest that the decline of micronuclei was due to repopulation of lymphocytes and acquired drug resistance.

  12. SU-E-T-170: Evaluation of Rotational Errors in Proton Therapy Planning of Lung Cancer

    SciTech Connect (OSTI)

    Rana, S; Zhao, L; Ramirez, E; Singh, H; Zheng, Y

    2014-06-01

    Purpose: To investigate the impact of rotational (roll, yaw, and pitch) errors in proton therapy planning of lung cancer. Methods: A lung cancer case treated at our center was used in this retrospective study. The original plan was generated using two proton fields (posterior-anterior and left-lateral) with XiO treatment planning system (TPS) and delivered using uniform scanning proton therapy system. First, the computed tomography (CT) set of original lung treatment plan was re-sampled for rotational (roll, yaw, and pitch) angles ranged from ?5 to +5, with an increment of 2.5. Second, 12 new proton plans were generated in XiO using the 12 re-sampled CT datasets. The same beam conditions, isocenter, and devices were used in new treatment plans as in the original plan. All 12 new proton plans were compared with original plan for planning target volume (PTV) coverage and maximum dose to spinal cord (cord Dmax). Results: PTV coverage was reduced in all 12 new proton plans when compared to that of original plan. Specifically, PTV coverage was reduced by 0.03% to 1.22% for roll, by 0.05% to 1.14% for yaw, and by 0.10% to 3.22% for pitch errors. In comparison to original plan, the cord Dmax in new proton plans was reduced by 8.21% to 25.81% for +2.5 to +5 pitch, by 5.28% to 20.71% for +2.5 to +5 yaw, and by 5.28% to 14.47% for ?2.5 to ?5 roll. In contrast, cord Dmax was increased by 3.80% to 3.86% for ?2.5 to ?5 pitch, by 0.63% to 3.25% for ?2.5 to ?5 yaw, and by 3.75% to 4.54% for +2.5 to +5 roll. Conclusion: PTV coverage was reduced by up to 3.22% for rotational error of 5. The cord Dmax could increase or decrease depending on the direction of rotational error, beam angles, and the location of lung tumor.

  13. Comparative Effectiveness of 5 Treatment Strategies for Early-Stage Non-Small Cell Lung Cancer in the Elderly

    SciTech Connect (OSTI)

    Shirvani, Shervin M.; Jiang, Jing; Chang, Joe Y.; Welsh, James W.; Gomez, Daniel R.; Swisher, Stephen; Buchholz, Thomas A.; Smith, Benjamin D.

    2012-12-01

    Purpose: The incidence of early-stage non-small cell lung cancer (NSCLC) among older adults is expected to increase because of demographic trends and computed tomography-based screening; yet, optimal treatment in the elderly remains controversial. Using the Surveillance, Epidemiology, and End Results (SEER)-Medicare cohort spanning 2001-2007, we compared survival outcomes associated with 5 strategies used in contemporary practice: lobectomy, sublobar resection, conventional radiation therapy, stereotactic ablative radiation therapy (SABR), and observation. Methods and Materials: Treatment strategy and covariates were determined in 10,923 patients aged {>=}66 years with stage IA-IB NSCLC. Cox regression, adjusted for patient and tumor factors, compared overall and disease-specific survival for the 5 strategies. In a second exploratory analysis, propensity-score matching was used for comparison of SABR with other options. Results: The median age was 75 years, and 29% had moderate to severe comorbidities. Treatment distribution was lobectomy (59%), sublobar resection (11.7%), conventional radiation (14.8%), observation (12.6%), and SABR (1.1%). In Cox regression analysis with a median follow-up time of 3.2 years, SABR was associated with the lowest risk of death within 6 months of diagnosis (hazard ratio [HR] 0.48; 95% confidence interval [CI] 0.38-0.63; referent is lobectomy). After 6 months, lobectomy was associated with the best overall and disease-specific survival. In the propensity-score matched analysis, survival after SABR was similar to that after lobectomy (HR 0.71; 95% CI 0.45-1.12; referent is SABR). Conventional radiation and observation were associated with poor outcomes in all analyses. Conclusions: In this population-based experience, lobectomy was associated with the best long-term outcomes in fit elderly patients with early-stage NSCLC. Exploratory analysis of SABR early adopters suggests efficacy comparable with that of surgery in select populations. Evaluation of these therapies in randomized trials is urgently needed.

  14. Complications associated with brachytherapy alone or with laser in lung cancer

    SciTech Connect (OSTI)

    Khanavkar, B.; Stern, P.; Alberti, W.; Nakhosteen, J.A. )

    1991-05-01

    Relatively little has been reported about destruction through brachytherapy of mucosa-perforating and extraluminary tumors with probable large vessel involvement causing major hemorrhagic or fistular complications. We report 12 patients subjected to laser and brachytherapy for centrally occluding lung cancer, whom we have periodically followed up from June 1986 until they died. Although all laser procedures were free from complications, necrotic cavitation in five cases, two of which were accompanied by large bronchoesophageal fistulas, and massive fatal hemoptysis occurred in six. Minor complications included radiation mucositis (two), noncritical mucosal scarring (two), and cough (four). Characteristics that will identify patients at risk of developing fatal hemoptysis and fistulas should be better defined by imaging and endoscopic techniques. In such cases, modifying the protocol or using alternative procedures should be considered. Minor complications, such as cough, can be avoided by using topical steroid therapy (eg, beclomethasone dipropionate).

  15. Impact of Four-Dimensional Computed Tomography Pulmonary Ventilation Imaging-Based Functional Avoidance for Lung Cancer Radiotherapy

    SciTech Connect (OSTI)

    Yamamoto, Tokihiro; Kabus, Sven; Berg, Jens von; Lorenz, Cristian; Keall, Paul J.

    2011-01-01

    Purpose: To quantify the dosimetric impact of four-dimensional computed tomography (4D-CT) pulmonary ventilation imaging-based functional treatment planning that avoids high-functional lung regions. Methods and Materials: 4D-CT ventilation images were created from 15 non-small-cell lung cancer patients using deformable image registration and quantitative analysis of the resultant displacement vector field. For each patient, anatomic and functional plans were created for intensity-modulated radiotherapy (IMRT) and volumetric modulated arc therapy (VMAT). Consistent beam angles and dose-volume constraints were used for all cases. The plans with Radiation Therapy Oncology Group (RTOG) 0617-defined major deviations were modified until clinically acceptable. Functional planning spared the high-functional lung, and anatomic planning treated the lungs as uniformly functional. We quantified the impact of functional planning compared with anatomic planning using the two- or one-tailed t test. Results: Functional planning led to significant reductions in the high-functional lung dose, without significantly increasing other critical organ doses, but at the expense of significantly degraded the planning target volume (PTV) conformity and homogeneity. The average reduction in the high-functional lung mean dose was 1.8 Gy for IMRT (p < .001) and 2.0 Gy for VMAT (p < .001). Significantly larger changes occurred in the metrics for patients with a larger amount of high-functional lung adjacent to the PTV. Conclusion: The results of the present study have demonstrated the impact of 4D-CT ventilation imaging-based functional planning for IMRT and VMAT for the first time. Our findings indicate the potential of functional planning in lung functional avoidance for both IMRT and VMAT, particularly for patients who have high-functional lung adjacent to the PTV.

  16. A high incidence of BRCA1 mutations in 20 breast-ovarian cancer families

    SciTech Connect (OSTI)

    Serova, O.; Montagna, M.; Sylla, B.

    1996-01-01

    We have analyzed 20 breast-ovarian cancer families, the majority of which show positive evidence of linkage to chromosome 17q12, for germ-line mutations in the BRCA1 gene. BRCA1 mutations cosegregating with breast and ovarian cancer susceptibility were identified in 16 families, including 1 family with a case of male breast cancer. Nine of these mutations have not been reported previously. The majority of mutations were found to generate a premature stop codon leading to the formation of a truncated BRCA1 protein of 2%-88% of the expected normal length. Two mutations altered the RING finger domain. Sequencing of genomic DNA led to the identification of a mutation in the coding region of BRCA1 in 12 families, and cDNA analysis revealed an abnormal or missing BRCA1 transcript in 4 of the 8 remaining families. A total of eight mutations were associated with a reduced quantity of BRCA1 transcript. We were unable to detect BRCA1 mutations in 4 of the 20 families, but only 1 of these was clearly linked to BRCA1. It is expected that the majority of clear examples of the breast-ovarian cancer syndrome will be associated with germ-line mutations in the coding region of BRCA1. 30 refs., 4 figs., 3 tabs.

  17. Method of using 5,10,15,20-tetrakis(carboxyphenyl)porphine for detecting cancers of the lung

    DOE Patents [OSTI]

    Cole, D.A.; Moody, D.C. III; Ellinwood, L.E.; Klein, M.G.

    1992-11-10

    A method is described for using tetra-aryl porphyrins for and, in particular, 5,10,15,20-tetrakis(4-carboxyphenyl)porphine as a fluorescent tracer for cancers of the lung, and as a radiotracer therefor as a complex with [sup 67]Cu. The latter complex also provides a source of beta radiation for selective destruction of lung malignancies as well as gamma radiation useful for image analysis of the lungs by single photon emission computed tomography, as an example, both in vivo. Copper-64 may be substituted for the [sup 67]Cu if only radiotracer characteristics are of interest. This lighter isotope of copper is a positron emitter, and positron emission tomography techniques can be used to locate the malignant tissue mass. 1 figure.

  18. Predictive Parameters of CyberKnife Fiducial-less (XSight Lung) Applicability for Treatment of Early Non-Small Cell Lung Cancer: A Single-Center Experience

    SciTech Connect (OSTI)

    Bahig, Houda; Campeau, Marie-Pierre; Vu, Toni; Doucet, Robert; Bliveau Nadeau, Dominic; Fortin, Bernard; Roberge, David; Lambert, Louise; Carrier, Jean-Franois; Filion, Edith

    2013-11-01

    Purpose: To determine which parameters allow for CyberKnife fiducial-less tumor tracking in stereotactic body radiation therapy (SBRT) for early-stage non-small cell lung cancer. Methods and Materials: A total of 133 lung SBRT patients were preselected for direct soft-tissue tracking based on manufacturer recommendations (peripherally located tumors ?1.5 cm with a dense appearance) and staff experience. Patients underwent a tumor visualization test to verify adequate detection by the tracking system (orthogonal radiographs). An analysis of potential predictors of successful tumor tracking was conducted looking at: tumor stage, size, histology, tumor projection on the vertebral column or mediastinum, distance to the diaphragm, lung-to-soft tissue ratio, and patient body mass index. Results: Tumor visualization was satisfactory for 88 patients (66%) and unsatisfactory for 45 patients (34%). Median time to treatment start was 6 days in the success group (range, 2-18 days) and 15 days (range, 3-63 days) in the failure group. A stage T2 (P=.04), larger tumor size (volume of 15.3 cm{sup 3} vs 6.5 cm{sup 3} in success and failure group, respectively) (P<.0001), and higher tumor density (0.86 g/cm{sup 3} vs 0.79 g/cm{sup 3}) were predictive of adequate detection. There was a 63% decrease in failure risk with every 1-cm increase in maximum tumor dimension (relative risk for failure = 0.37, CI=0.23-0.60, P=.001). A diameter of 3.6 cm predicted a success probability of 80%. Histology, lung-to-soft tissue ratio, distance to diaphragm, patient's body mass index, and tumor projection on vertebral column and mediastinum were not found to be predictive of success. Conclusions: Tumor size, volume, and density were the most predictive factors of a successful XSight Lung tumor tracking. Tumors >3.5 cm have ?80% chance of being adequately visualized and therefore should all be considered for direct tumor tracking.

  19. Individualized Radical Radiotherapy of Non-Small-Cell Lung Cancer Based on Normal Tissue Dose Constraints: A Feasibility Study

    SciTech Connect (OSTI)

    Baardwijk, Angela van Bosmans, Geert; Boersma, Liesbeth; Wanders, Stofferinus; Dekker, Andre; Dingemans, Anne Marie C.; Bootsma, Gerben; Geraedts, Wiel; Pitz, Cordula; Simons, Jean; Lambin, Philippe; Ruysscher, Dirk de

    2008-08-01

    Purpose: Local recurrence is a major problem after (chemo-)radiation for non-small-cell lung cancer. We hypothesized that for each individual patient, the highest therapeutic ratio could be achieved by increasing total tumor dose (TTD) to the limits of normal tissues, delivered within 5 weeks. We report first results of a prospective feasibility trial. Methods and Materials: Twenty-eight patients with medically inoperable or locally advanced non-small-cell lung cancer, World Health Organization performance score of 0-1, and reasonable lung function (forced expiratory volume in 1 second > 50%) were analyzed. All patients underwent irradiation using an individualized prescribed TTD based on normal tissue dose constraints (mean lung dose, 19 Gy; maximal spinal cord dose, 54 Gy) up to a maximal TTD of 79.2 Gy in 1.8-Gy fractions twice daily. No concurrent chemoradiation was administered. Toxicity was scored using the Common Terminology Criteria for Adverse Events criteria. An {sup 18}F-fluoro-2-deoxy-glucose-positron emission tomography-computed tomography scan was performed to evaluate (metabolic) response 3 months after treatment. Results: Mean delivered dose was 63.0 {+-} 9.8 Gy. The TTD was most often limited by the mean lung dose (32.1%) or spinal cord (28.6%). Acute toxicity generally was mild; only 1 patient experienced Grade 3 cough and 1 patient experienced Grade 3 dysphagia. One patient (3.6%) died of pneumonitis. For late toxicity, 2 patients (7.7%) had Grade 3 cough or dyspnea; none had severe dysphagia. Complete metabolic response was obtained in 44% (11 of 26 patients). With a median follow-up of 13 months, median overall survival was 19.6 months, with a 1-year survival rate of 57.1%. Conclusions: Individualized maximal tolerable dose irradiation based on normal tissue dose constraints is feasible, and initial results are promising.

  20. Assessment of interpatient heterogeneity in tumor radiosensitivity for nonsmall cell lung cancer using tumor-volume variation data

    SciTech Connect (OSTI)

    Chvetsov, Alexei V. Schwartz, Jeffrey L.; Mayr, Nina; Yartsev, Slav

    2014-06-15

    Purpose: In our previous work, the authors showed that a distribution of cell surviving fractionsS{sub 2} in a heterogeneous group of patients could be derived from tumor-volume variation curves during radiotherapy for head and neck cancer. In this research study, the authors show that this algorithm can be applied to other tumors, specifically in nonsmall cell lung cancer. This new application includes larger patient volumes and includes comparison of data sets obtained at independent institutions. Methods: Our analysis was based on two data sets of tumor-volume variation curves for heterogeneous groups of 17 patients treated for nonsmall cell lung cancer with conventional dose fractionation. The data sets were obtained previously at two independent institutions by using megavoltage computed tomography. Statistical distributions of cell surviving fractionsS{sub 2} and clearance half-lives of lethally damaged cells T{sub 1/2} have been reconstructed in each patient group by using a version of the two-level cell population model of tumor response and a simulated annealing algorithm. The reconstructed statistical distributions of the cell surviving fractions have been compared to the distributions measured using predictive assays in vitro. Results: Nonsmall cell lung cancer presents certain difficulties for modeling surviving fractions using tumor-volume variation curves because of relatively large fractional hypoxic volume, low gradient of tumor-volume response, and possible uncertainties due to breathing motion. Despite these difficulties, cell surviving fractionsS{sub 2} for nonsmall cell lung cancer derived from tumor-volume variation measured at different institutions have similar probability density functions (PDFs) with mean values of 0.30 and 0.43 and standard deviations of 0.13 and 0.18, respectively. The PDFs for cell surviving fractions S{sub 2} reconstructed from tumor volume variation agree with the PDF measured in vitro. Conclusions: The data obtained in this work, when taken together with the data obtained previously for head and neck cancer, suggests that the cell surviving fractionsS{sub 2} can be reconstructed from the tumor volume variation curves measured during radiotherapy with conventional fractionation. The proposed method can be used for treatment evaluation and adaptation.

  1. Stereotactic Ablative Radiation Therapy as First Local Therapy for Lung Oligometastases From Colorectal Cancer: A Single-Institution Cohort Study

    SciTech Connect (OSTI)

    Filippi, Andrea Riccardo; Badellino, Serena; Ceccarelli, Manuela; Guarneri, Alessia; Franco, Pierfrancesco; Monagheddu, Chiara; Spadi, Rosella; Ragona, Riccardo; Racca, Patrizia; Ricardi, Umberto

    2015-03-01

    Purpose: To estimate stereotactic ablative radiation therapy (SABR) efficacy and its potential role as an alternative to surgery for the treatment of lung metastases from colorectal cancer. Methods and Materials: Forty consecutive patients who received SABR as first local therapy at the time of lung progression were included, from 2004 to 2014. The primary study endpoint was overall survival. Secondary endpoints were progression-free survival and safety. Results: A single nodule was treated in 26 patients (65%), 2 nodules in 10 patients (25%), 3 in 3 patients (7.5%), and 4 in 1 patient (2.5%), for a total of 59 lesions. The median delivered biological effective dose was 96 Gy, in 1 to 8 daily fractions. Median follow-up time was 20 months (range, 3-72 months). Overall survival rates at 1, 2, and 5 years were, respectively, 84%, 73%, and 39%, with 14 patients (35%) dead. Median overall survival was 46 months. Progression occurred in 25 patients (62.5%), at a median interval of 8 months; failure at SABR site was observed in 3 patients (7.5%). Progression-free survival rates were 49% and 27% at 1 and 2 years, respectively. Discussion: The results of this retrospective exploratory analysis suggest safety and efficacy of SABR in patients affected with colorectal cancer lung oligometastases and urge inclusion of SABR in prospective clinical trials.

  2. Impact of Neoadjuvant Radiation on Survival in Stage III Non-Small-Cell Lung Cancer

    SciTech Connect (OSTI)

    Koshy, Matthew, E-mail: mkoshy@umm.ed [Department of Radiation Oncology, University of Maryland School of Medicine and University of Maryland Marlene and Stewart Greenebaum Cancer Center, Baltimore, MD (United States); Goloubeva, Olga; Suntharalingam, Mohan [Department of Radiation Oncology, University of Maryland School of Medicine and University of Maryland Marlene and Stewart Greenebaum Cancer Center, Baltimore, MD (United States)

    2011-04-01

    Purpose: The role of surgery in Stage III non-small-cell lung cancer (NSCLC) is controversial. This study was undertaken to assess the impact of neoadjuvant radiation therapy for Stage III NSCLC. Methods and Materials: This was a retrospective study from the Surveillance, Epidemiology, and End Results (SEER) database that included patients who were 18 years and older with NSCLC classified as Stage III and who underwent definitive therapy from 1988 to 2004. Patients were characterized by type of treatment received. Survival functions were estimated by the Kaplan-Meier method, and Cox regression model was used to analyze trends in overall (OS) and cause-specific survival (CSS). Results: A total of 48,131 patients were selected, with a median follow-up of 10 months (range, 0-203 months). By type of treatment, the 3-year OS was 10% with radiation therapy (RT), 37% with surgery (S), 34% with surgery and postoperative radiation (S-RT), and 45% with neoadjuvant radiation followed by surgery (Neo-RT) (p = 0.0001). Multivariable Cox model identified sex, race, laterality, T stage, N stage, and type of treatment as factors affecting survival. Estimated hazard ratios (HR) adjusted for other variables in regression model showed the types of treatment: S (HR, 1.3; 95% confidence interval [CI], 1.2-1.4), S-RT (HR, 1.2; 95% CI, 1.1-1.3), and RT (HR, 2.3; 95% CI, 2.15-2.53) were associated with significantly worse overall survival when compared with Neo-RT (p = 0.0001). Conclusion: This population based study demonstrates that patients with Stage III NSCLC receiving Neo-RT had significantly improved overall survival when compared with other treatment groups.

  3. Rapid Disease Progression With Delay in Treatment of Non-Small-Cell Lung Cancer

    SciTech Connect (OSTI)

    Mohammed, Nasiruddin [Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, MI (United States); Kestin, Larry Llyn, E-mail: lkestin@beaumont.ed [Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, MI (United States); Grills, Inga Siiner; Battu, Madhu; Fitch, Dwight Lamar [Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, MI (United States); Wong, Ching-yee Oliver [Department of Nuclear Medicine, William Beaumont Hospital, Royal Oak, MI (United States); Margolis, Jeffrey Harold [Department of Medical Oncology, William Beaumont Hospital, Royal Oak, MI (United States); Chmielewski, Gary William; Welsh, Robert James [Department of Thoracic Surgery, William Beaumont Hospital, Royal Oak, MI (United States)

    2011-02-01

    Purpose: To assess rate of disease progression from diagnosis to initiation of treatment for Stage I-IIIB non-small-cell lung cancer (NSCLC). Methods and Materials: Forty patients with NSCLC underwent at least two sets of computed tomography (CT) and 18-fluorodeoxyglucose positron emission tomography (PET) scans at various time intervals before treatment. Progression was defined as development of any new lymph node involvement, site of disease, or stage change. Results: Median time interval between first and second CT scans was 13.4 weeks, and between first and second PET scans was 9.0 weeks. Median initial primary maximum tumor dimension (MTD) was 3.5 cm (0.6-8.5 cm) with a median standardized uptake value (SUV) of 13.0 (1.7-38.5). The median MTD increased by a median of 1.0 cm (mean, 1.6 cm) between scans for a median relative MTD increase of 35% (mean, 59%). Nineteen patients (48%) progressed between scans. Rate of any progression was 13%, 31%, and 46% at 4, 8, and 16 weeks, respectively. Upstaging occurred in 3%, 13%, and 21% at these intervals. Distant metastasis became evident in 3%, 13%, and 13% after 4, 8, and 16 weeks, respectively. T and N stage were associated with progression, whereas histology, grade, sex, age, and maximum SUV were not. At 3 years, overall survival for Stage III patients with vs. without progression was 18% vs. 67%, p = 0.05. Conclusions: With NSCLC, treatment delay can lead to disease progression. Diagnosis, staging, and treatment initiation should be expedited. After 4-8 weeks of delay, complete restaging should be strongly considered.

  4. Method of using 5,10,15,20-tetrakis(carboxyphenyl)porphine for detecting cancers of the lung

    DOE Patents [OSTI]

    Cole, Dean A. (60 San Juan St., Los Alamos, NM 87544); Moody, III, David C. (402 Pine Tree La., Boulder, CO 80304); Ellinwood, L. Edward (694 Sperber La., Grand Junction, CO 81506); Klein, M. Gerard (715 Victor Dr., Grand Junction, CO 81506)

    1992-01-01

    Method using tetra-aryl porphyrins for and, in particular, 5,10,15,20-tetrakis(4-carboxyphenyl)porphine as a fluorescent tracer for cancers of the lung, and as a radiotracer therefor as a complex with .sup.67 Cu. The latter complex also provides a source of beta radiation for selective destruction of lung malignancies as well as gamma radiation useful for image analysis of the situs thereof by single photon emission computed tomography, as an example, both in vivo. Copper-64 may be substituted for the .sup.67 Cu if only radiotracer characteristics are of interest. This lighter isotope of copper is a positron emitter, and positron emission tomography techniques cna be used to locate the malignant tissue mass.

  5. Method using 5,10,15,20-tetrakis(4-carboxyphenyl)porphine for treating cancers of the lung

    DOE Patents [OSTI]

    Cole, Dean A. (Germantown, MD); Moody, III, David C. (Superior, CO); Ellinwood, L. Edward (Grand Junction, CO); Klein, M. Gerard (Grand Junction, CO)

    1995-01-01

    Method using tetra-aryl porphyrins for and, in particular, 5,10,15,20-tetrakis(4-carboxyphenyl)porphine as a fluorescent tracer for cancers of the lung, and as a radiotracer therefor as a complex with .sup.67 Cu. The latter complex also provides a source of beta radiation for selective destruction of lung malignancies as well as gamma radiation useful for image analysis of the situs thereof by single photon emission computed tomography, as an example, both in vivo. Copper-64 may be substituted for the .sup.67 Cu if only radiotracer characteristics are of interest. This lighter isotope of copper is a positron emitter, and positron emission tomography techniques can be used to locate the malignant tissue mass.

  6. Factors Affecting the Risk of Brain Metastasis in Small Cell Lung Cancer With Surgery: Is Prophylactic Cranial Irradiation Necessary for Stage I-III Disease?

    SciTech Connect (OSTI)

    Gong Linlin; Wang, Q.I.; Zhao Lujun; Yuan Zhiyong; Li Ruijian; Wang Ping

    2013-01-01

    Purpose: The use of prophylactic cranial irradiation (PCI) in small cell lung cancer (SCLC) with surgical resection has not been fully identified. This study undertook to assess the factors affecting the risk of brain metastases in patients with stage I-III SCLC after surgical resection. The implications of PCI treatment for these patients are discussed. Methods and Materials: One hundred twenty-six patients treated with surgical resection for stage I-III SCLC from January 1998-December 2009 were retrospectively analyzed to elucidate the risk factors of brain metastases. Log-rank test and Cox regression model were used to determine the risk factors of brain metastases. Results: The median survival time for this patient population was 34 months, and the 5-year overall survival rate was 34.9%. For the whole group, 23.0% (29/126) of the patients had evidence of metastases to brain. Pathologic stage not only correlated with overall survival but also significantly affected the risk of brain metastases. The 5-year survival rates for patients with pathologic stages I, II, and III were 54.8%, 35.6%, and 14.1%, respectively (P=.001). The frequency of brain metastases in patients with pathologic stages I, II, and III were 6.25% (2/32), 28.2% (11/39), and 29.1% (16/55) (P=.026), respectively. A significant difference in brain metastases between patients with complete resection and incomplete resection was also observed (20.5% vs 42.9%, P=.028). The frequency of brain metastases was not found to be correlated with age, sex, pathologic type, induction chemotherapy, adjuvant chemotherapy, or adjuvant radiation therapy. Conclusions: Stage I SCLC patients with complete resection had a low incidence of brain metastases and a favorable survival rate. Stage II-III disease had a higher incidence of brain metastases. Thus, PCI might have a role for stage II-III disease but not for stage I disease.

  7. Respiration-Correlated Image Guidance Is the Most Important Radiotherapy Motion Management Strategy for Most Lung Cancer Patients

    SciTech Connect (OSTI)

    Korreman, Stine, E-mail: korreman@ruc.dk [Department of Science, Systems and Models, Roskilde University, Roskilde (Denmark); Department of Radiation Oncology, The Finsen Centre, Rigshospitalet, Copenhagen (Denmark); Niels Bohr Institute, University of Copenhagen, Copenhagen (Denmark); Department of Human Oncology, University of Wisconsin School of Medicine and Public Health, Madison (United States); Persson, Gitte; Nygaard, Ditte [Department of Radiation Oncology, The Finsen Centre, Rigshospitalet, Copenhagen (Denmark); Brink, Carsten [Laboratory of Radiation Physics, Odense University Hospital, Odense (Denmark); Faculty of Health Sciences, University of Southern Denmark, Odense (Denmark); Juhler-Nottrup, Trine [Department of Oncology, Herlev Hospital, Copenhagen (Denmark)

    2012-07-15

    Purpose: The purpose of this study was to quantify the effects of four-dimensional computed tomography (4DCT), 4D image guidance (4D-IG), and beam gating on calculated treatment field margins in a lung cancer patient population. Materials and Methods: Images were acquired from 46 lung cancer patients participating in four separate protocols at three institutions in Europe and the United States. Seven patients were imaged using fluoroscopy, and 39 patients were imaged using 4DCT. The magnitude of respiratory tumor motion was measured. The required treatment field margins were calculated using a statistical recipe (van Herk M, et al. Int J Radiat Oncol Biol Phys 2000;474:1121-1135), with magnitudes of all uncertainties, except respiratory peak-to-peak displacement, the same for all patients, taken from literature. Required margins for respiratory motion management were calculated using the residual respiratory tumor motion for each patient for various motion management strategies. Margin reductions for respiration management were calculated using 4DCT, 4D-IG, and gated beam delivery. Results: The median tumor motion magnitude was 4.4 mm for the 46 patients (range 0-29.3 mm). This value corresponded to required treatment field margins of 13.7 to 36.3 mm (median 14.4 mm). The use of 4DCT, 4D-IG, and beam gating required margins that were reduced by 0 to 13.9 mm (median 0.5 mm), 3 to 5.2 mm (median 5.1 mm), and 0 to 7 mm (median 0.2 mm), respectively, to a total of 8.5 to 12.4 mm (median 8.6 mm). Conclusion: A respiratory management strategy for lung cancer radiotherapy including planning on 4DCT scans and daily image guidance provides a potential reduction of 37% to 47% in treatment field margins. The 4D image guidance strategy was the most effective strategy for >85% of the patients.

  8. Phase 1 Study of Dose Escalation in Hypofractionated Proton Beam Therapy for Non-Small Cell Lung Cancer

    SciTech Connect (OSTI)

    Gomez, Daniel R., E-mail: dgomez@mdanderson.org [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Gillin, Michael [Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States)] [Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Liao, Zhongxing [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States)] [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Wei, Caimiao [Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States)] [Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Lin, Steven H.; Swanick, Cameron; Alvarado, Tina; Komaki, Ritsuko; Cox, James D.; Chang, Joe Y. [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States)] [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States)

    2013-07-15

    Background: Many patients with locally advanced non-small cell lung cancer (NSCLC) cannot undergo concurrent chemotherapy because of comorbidities or poor performance status. Hypofractionated radiation regimens, if tolerable, may provide an option to these patients for effective local control. Methods and Materials: Twenty-five patients were enrolled in a phase 1 dose-escalation trial of proton beam therapy (PBT) from September 2010 through July 2012. Eligible patients had histologically documented lung cancer, thymic tumors, carcinoid tumors, or metastatic thyroid tumors. Concurrent chemotherapy was not allowed, but concurrent treatment with biologic agents was. The dose-escalation schema comprised 15 fractions of 3 Gy(relative biological effectiveness [RBE])/fraction, 3.5 Gy(RBE)/fraction, or 4 Gy(RBE)/fraction. Dose constraints were derived from biologically equivalent doses of standard fractionated treatment. Results: The median follow-up time for patients alive at the time of analysis was 13 months (range, 8-28 months). Fifteen patients received treatment to hilar or mediastinal lymph nodes. Two patients experienced dose-limiting toxicity possibly related to treatment; 1 received 3.5-Gy(RBE) fractions and experienced an in-field tracheoesophageal fistula 9 months after PBT and 1 month after bevacizumab. The other patient received 4-Gy(RBE) fractions and was hospitalized for bacterial pneumonia/radiation pneumonitis 4 months after PBT. Conclusion: Hypofractionated PBT to the thorax delivered over 3 weeks was well tolerated even with significant doses to the lungs and mediastinal structures. Phase 2/3 trials are needed to compare the efficacy of this technique with standard treatment for locally advanced NSCLC.

  9. SU-F-BRF-12: Investigating Dosimetric Effects of Inter-Fraction Deformation in Lung Cancer Stereotactic Body Radiotherapy (SBRT)

    SciTech Connect (OSTI)

    Jia, J; Tian, Z; Gu, X; Yan, H; Jia, X; Jiang, S

    2014-06-15

    Purpose: We studied dosimetric effects of inter-fraction deformation in lung stereotactic body radiotherapy (SBRT), in order to investigate the necessity of adaptive re-planning for lung SBRT treatments. Methods: Six lung cancer patients with different treatment fractions were retrospectively investigated. All the patients were immobilized and localized with a stereotactic body frame and were treated under cone-beam CT (CBCT) image guidance at each fraction. We calculated the actual delivered dose of the treatment plan using the up-to-date patient geometry of each fraction, and compared the dose with the intended plan dose to investigate the dosimetric effects of the inter-fraction deformation. Deformable registration was carried out between the treatment planning CT and the CBCT of each fraction to obtain deformed planning CT for more accurate dose calculations of the delivered dose. The extent of the inter-fraction deformation was also evaluated by calculating the dice similarity coefficient between the delineated structures on the planning CT and those on the deformed planning CT. Results: The average dice coefficients for PTV, spinal cord, esophagus were 0.87, 0.83 and 0.69, respectively. The volume of PTV covered by prescription dose was decreased by 23.78% on average for all fractions and all patients. For spinal cord and esophagus, the volumes covered by the constraint dose were increased by 4.57% and 3.83%. The maximum dose was also increased by 4.11% for spinal cord and 4.29% for esophagus. Conclusion: Due to inter-fraction deformation, large deterioration was found in both PTV coverage and OAR sparing, which demonstrated the needs for adaptive re-planning of lung SBRT cases to improve target coverage while reducing radiation dose to nearby normal tissues.

  10. PR-Set7 is degraded in a conditional Cul4A transgenic mouse model of lung cancer

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Wang, Yang; Xu, Zhidong; Mao, Jian -Hua; Hsieh, David; Au, Alfred; Jablons, David M.; Li, Hui; You, Lian

    2015-06-01

    Background and objective. Maintenance of genomic integrity is essential to ensure normal organismal development and to prevent diseases such as cancer. PR-Set7 (also known as Set8) is a cell cycle regulated enzyme that catalyses monomethylation of histone 4 at Lys20 (H4K20me1) to promote chromosome condensation and prevent DNA damage. Recent studies show that CRL4CDT2-mediated ubiquitylation of PR-Set7 leads to its degradation during S phase and after DNA damage. This might occur to ensure appropriate changes in chromosome structure during the cell cycle or to preserve genome integrity after DNA damage. Methods. We developed a new model of lung tumor developmentmore » in mice harboring a conditionally expressed allele of Cul4A. We have therefore used a mouse model to demonstrate for the first time that Cul4A is oncogenic in vivo. With this model, staining of PR-Set7 in the preneoplastic and tumor lesions in AdenoCre-induced mouse lungs was performed. Meanwhile we identified higher protein level changes of γ-tubulin and pericentrin by IHC. Results. The level of PR-Set7 down-regulated in the preneoplastic and adenocarcinomous lesions following over-expression of Cul4A. We also identified higher levels of the proteins pericentrin and γ-tubulin in Cul4A mouse lungs induced by AdenoCre. Conclusion. PR-Set7 is a direct target of Cul4A for degradation and involved in the formation of lung tumors in the conditional Cul4A transgenic mouse model.« less

  11. Modeling Local Control After Hypofractionated Stereotactic Body Radiation Therapy for Stage I Non-Small Cell Lung Cancer: A Report From the Elekta Collaborative Lung Research Group

    SciTech Connect (OSTI)

    Ohri, Nitin; Werner-Wasik, Maria; Grills, Inga S.; Belderbos, Jose; Hope, Andrew; Yan Di; Kestin, Larry L.; Guckenberger, Matthias; Sonke, Jan-Jakob; Bissonnette, Jean-Pierre; Xiao, Ying

    2012-11-01

    Purpose: Hypofractionated stereotactic body radiation therapy (SBRT) has emerged as an effective treatment option for early-stage non-small cell lung cancer (NSCLC). Using data collected by the Elekta Lung Research Group, we generated a tumor control probability (TCP) model that predicts 2-year local control after SBRT as a function of biologically effective dose (BED) and tumor size. Methods and Materials: We formulated our TCP model as follows: TCP = e{sup [BED10-c Asterisk-Operator L-TCD50]/k} Division-Sign (1 + e{sup [BED10-c Asterisk-Operator L-TCD50]/k}), where BED10 is the biologically effective SBRT dose, c is a constant, L is the maximal tumor diameter, and TCD50 and k are parameters that define the shape of the TCP curve. Least-squares optimization with a bootstrap resampling approach was used to identify the values of c, TCD50, and k that provided the best fit with observed actuarial 2-year local control rates. Results: Data from 504 NSCLC tumors treated with a variety of SBRT schedules were available. The mean follow-up time was 18.4 months, and 26 local recurrences were observed. The optimal values for c, TCD50, and k were 10 Gy/cm, 0 Gy, and 31 Gy, respectively. Thus, size-adjusted BED (sBED) may be defined as BED minus 10 times the tumor diameter (in centimeters). Our TCP model indicates that sBED values of 44 Gy, 69 Gy, and 93 Gy provide 80%, 90%, and 95% chances of tumor control at 2 years, respectively. When patients were grouped by sBED, the model accurately characterized the relationship between sBED and actuarial 2-year local control (r=0.847, P=.008). Conclusion: We have developed a TCP model that predicts 2-year local control rate after hypofractionated SBRT for early-stage NSCLC as a function of biologically effective dose and tumor diameter. Further testing of this model with additional datasets is warranted.

  12. Survival and Quality of Life After Stereotactic or 3D-Conformal Radiotherapy for Inoperable Early-Stage Lung Cancer

    SciTech Connect (OSTI)

    Widder, Joachim; Postmus, Douwe; Ubbels, Jan F.; Wiegman, Erwin M.; Langendijk, Johannes A.

    2011-11-15

    Purpose: To investigate survival and local recurrence after stereotactic ablative radiotherapy (SABR) or three-dimensional conformal radiotherapy (3D-CRT) administered for early-stage primary lung cancer and to investigate longitudinal changes of health-related quality of life (HRQOL) parameters after either treatment. Methods and Materials: Two prospective cohorts of inoperable patients with T1-2N0M0 primary lung tumors were analyzed. Patients received 70 Gy in 35 fractions with 3D-CRT or 60 Gy in three to eight fractions with SABR. Global quality of life (GQOL), physical functioning (PF), and patient-rated dyspnea were assessed using the respective dimensions of European Organization for Research and Treatment of Cancer Core Questionnaire-C30 and LC13. HRQOL was analyzed using multivariate linear mixed-effects modeling, survival and local control (LC) using the Kaplan-Meier method, Cox proportional hazards analysis, and Fine and Gray multivariate competing risk analysis as appropriate. Results: Overall survival (OS) was better after SABR compared with 3D-CRT with a HR of 2.6 (95% confidence interval [CI]: 1.5-4.8; p < 0.01). 3D-CRT conferred a subhazard ratio for LC of 5.0 (95% CI: 1.7-14.7; p < 0.01) compared with SABR. GQOL and PF were stable after SABR (p = 0.21 and p = 0.62, respectively). Dyspnea increased after SABR by 3.2 out of 100 points (95% CI: 1.0-5.3; p < 0.01), which is clinically insignificant. At 1 year, PF decreased by an excess of 8.7 out of 100 points (95% CI: 2.8-14.7; p < 0.01) after 3D-CRT compared with SABR. Conclusion: In this nonrandomized comparison of two prospective cohorts of medically inoperable patients with Stage I lung cancer, OS and LC were better after SABR. GQOL, PF, and patient-rated dyspnea were stable after SABR, whereas PF decreased after 3D-CRT approaching clinical significance already at 1 year.

  13. SU-E-J-52: Dosimetric Benefit of Adaptive Re-Planning in Lung Cancer Stereotactic Body Radiotherapy (SBRT)

    SciTech Connect (OSTI)

    Jia, J; Tian, Z; Gu, X; Yan, H; Jiang, S; Jia, X

    2014-06-01

    Purpose: To investigate the dosimetric benefit of adaptive re-planning for lung stereotactic body radiotherapy(SBRT). Methods: Five lung cancer patients with SBRT treatment were retrospectively investigated. Our in-house supercomputing online re-planning environment (SCORE) was used to realize the re-planning process. First a deformable image registration was carried out to transfer contours from treatment planning CT to each treatment CBCT. Then an automatic re-planning using original plan DVH guided fluence-map optimization is performed to get a new plan for the up-to-date patient geometry. We compared the re-optimized plan to the original plan projected on the up-to-date patient geometry in critical dosimetric parameters, such as PTV coverage, spinal cord maximum and volumetric constraint dose, esophagus maximum and volumetric constraint dose. Results: The average volume of PTV covered by prescription dose for all patients was improved by 7.56% after the adaptive re-planning. The volume of the spinal cord receiving 14.5Gy and 23Gy (V14.5, V23) decreased by 1.48% and 0.68%, respectively. For the esophagus, the volume receiving 19.5Gy (V19.5) reduced by 1.37%. Meanwhile, the maximum dose dropped off by 2.87% for spinal cord and 4.80% for esophagus. Conclusion: Our experimental results demonstrate that adaptive re-planning for lung SBRT has the potential to minimize the dosimetric effect of inter-fraction deformation and thus improve target coverage while reducing the risk of toxicity to nearby normal tissues.

  14. Estimates of the gene frequency of BRCA1 and its contribution to breast and ovarian cancer incidence

    SciTech Connect (OSTI)

    Ford, D.; Easton, D.F.; Peto, J.

    1995-12-01

    The majority of multiple-case families that segregate both breast and ovarian cancer in a dominant fashion are due to mutations in the BRCA1 gene on chromosome 17q. In this paper, we have combined penetrance estimates for BRCA1 with the results of two population-based genetic epidemiological studies to estimate the gene frequency of BRCA1. On the assumption that the excess risk of ovarian cancer in first degree relatives of breast cancer patients and the breast cancer excess in relatives of ovarian cancer patients are both entirely accounted for by BRCA1, we estimate that the BRCA1 gene frequency is 0.0006 (95% confidence interval [0.0002-0.001]) and that the proportion of breast cancer cases in the general population due to BRCA1 is 5.3% below age 40 years, 2.2% between ages 40 and 49 years, and 1.1% between ages 50 and 70 years. The corresponding estimates for ovarian cancer are 5.7%, 4.6%, and 2.1%, respectively. Our results suggest that the majority of breast cancer families with less than four cases and no ovarian cancer are not due to rare highly penetrant genes such as BRCA1 but are more likely to be due either to chance or to more common genes of lower penetrance. 22 refs., 3 tabs.

  15. Association Between White Blood Cell Count Following Radiation Therapy With Radiation Pneumonitis in Non-Small Cell Lung Cancer

    SciTech Connect (OSTI)

    Tang, Chad; Gomez, Daniel R. [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Wang, Hongmei [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou (China); Levy, Lawrence B. [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Zhuang, Yan [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Xu, Ting; Nguyen, Quynh; Komaki, Ritsuko [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Liao, Zhongxing, E-mail: zliao@mdanderson.org [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States)

    2014-02-01

    Purpose: Radiation pneumonitis (RP) is an inflammatory response to radiation therapy (RT). We assessed the association between RP and white blood cell (WBC) count, an established metric of systemic inflammation, after RT for non-small cell lung cancer. Methods and Materials: We retrospectively analyzed 366 patients with non-small cell lung cancer who received ?60 Gy as definitive therapy. The primary endpoint was whether WBC count after RT (defined as 2 weeks through 3 months after RT completion) was associated with grade ?3 or grade ?2 RP. Median lung volume receiving ?20 Gy (V{sub 20}) was 31%, and post-RT WBC counts ranged from 1.7 to 21.2 10{sup 3} WBCs/?L. Odds ratios (ORs) associating clinical variables and post-RT WBC counts with RP were calculated via logistic regression. A recursive-partitioning algorithm was used to define optimal post-RT WBC count cut points. Results: Post-RT WBC counts were significantly higher in patients with grade ?3 RP than without (P<.05). Optimal cut points for post-RT WBC count were found to be 7.4 and 8.0 10{sup 3}/?L for grade ?3 and ?2 RP, respectively. Univariate analysis revealed significant associations between post-RT WBC count and grade ?3 (n=46, OR=2.6, 95% confidence interval [CI] 1.4?4.9, P=.003) and grade ?2 RP (n=164, OR=2.0, 95% CI 1.2?3.4, P=.01). This association held in a stepwise multivariate regression. Of note, V{sub 20} was found to be significantly associated with grade ?2 RP (OR=2.2, 95% CI 1.2?3.4, P=.01) and trended toward significance for grade ?3 RP (OR=1.9, 95% CI 1.0-3.5, P=.06). Conclusions: Post-RT WBC counts were significantly and independently associated with RP and have potential utility as a diagnostic or predictive marker for this toxicity.

  16. Radiobiologic comparison of helical tomotherapy, intensity modulated radiotherapy, and conformal radiotherapy in treating lung cancer accounting for secondary malignancy risks

    SciTech Connect (OSTI)

    Komisopoulos, Georgios; Mavroidis, Panayiotis; Rodriguez, Salvador; Stathakis, Sotirios; Papanikolaou, Nikos; Nikiforidis, Georgios C.; Sakellaropoulos, Georgios C.

    2014-01-01

    The aim of the present study is to examine the importance of using measures to predict the risk of inducing secondary malignancies in association with the clinical effectiveness of treatment plans in terms of tumor control and normal tissue complication probabilities. This is achieved by using radiobiologic parameters and measures, which may provide a closer association between clinical outcome and treatment delivery. Overall, 4 patients having been treated for lung cancer were examined. For each of them, 3 treatment plans were developed based on the helical tomotherapy (HT), multileaf collimator-based intensity modulated radiation therapy (IMRT), and 3-dimensional conformal radiation therapy (CRT) modalities. The different plans were evaluated using the complication-free tumor control probability (p{sub +}), the overall probability of injury (p{sub I}), the overall probability of control/benefit (p{sub B}), and the biologically effective uniform dose (D{sup }). These radiobiologic measures were used to develop dose-response curves (p-D{sup } diagram), which can help to evaluate different treatment plans when used in conjunction with standard dosimetric criteria. The risks for secondary malignancies in the heart and the contralateral lung were calculated for the 3 radiation modalities based on the corresponding dose-volume histograms (DVHs) of each patient. Regarding the overall evaluation of the different radiation modalities based on the p{sub +} index, the average values of the HT, IMRT, and CRT are 67.3%, 61.2%, and 68.2%, respectively. The corresponding average values of p{sub B} are 75.6%, 70.5%, and 71.0%, respectively, whereas the average values of p{sub I} are 8.3%, 9.3%, and 2.8%, respectively. Among the organs at risk (OARs), lungs show the highest probabilities for complications, which are 7.1%, 8.0%, and 1.3% for the HT, IMRT, and CRT modalities, respectively. Similarly, the biologically effective prescription doses (D{sub B}{sup }) for the HT, IMRT, and CRT modalities are 64.0, 60.9, and 60.8 Gy, respectively. Regarding the risk for secondary cancer, for the heart, the lowest average risk is produced by IMRT (0.10%) compared with the HT (0.17%) and CRT (0.12%) modalities, whereas the 3 radiation modalities show almost equivalent results regarding the contralateral lung (0.8% for HT, 0.9% for IMRT, and 0.9% for CRT). The use of radiobiologic parameters in the evaluation of different treatment plans and estimation of their expected clinical outcome is shown to provide very useful clinical information. The radiobiologic analysis of the response probabilities showed that different radiation modalities appear to be more effective in different patient geometries and target sizes and locations. Furthermore, there is not a clear pattern between the plans that appear to be more effective for the treatment and the risk of secondary malignancy. It seems that radiobiologically based treatment planning taking into account the risk of secondary cancer can be established as an effective clinical tool for a more clinically relevant treatment optimization.

  17. Influence of radiation therapy on the lung-tissue in breast cancer patients: CT-assessed density changes and associated symptoms

    SciTech Connect (OSTI)

    Rotstein, S.; Lax, I.; Svane, G. )

    1990-01-01

    The relative electron density of lung tissue was measured from computer tomography (CT) slices in 33 breast cancer patients treated by various techniques of adjuvant radiotherapy. The measurements were made before radiotherapy, 3 months and 9 months after completion of radiation therapy. The changes in lung densities at 3 months and 9 months were compared to radiation induced radiological (CT) findings. In addition, subjective symptoms such as cough and dyspnoea were assessed before and after radiotherapy. It was observed that the mean of the relative electron density of lung tissue varied from 0.25 when the whole lung was considered to 0.17 when only the anterior lateral quarter of the lung was taken into account. In patients with positive radiological (CT) findings the mean lung density of the anterior lateral quarter increased 2.1 times 3 months after radiotherapy and was still increased 1.6 times 6 months later. For those patients without findings, in the CT pictures the corresponding values were 1.2 and 1.1, respectively. The standard deviation of the pixel values within the anterior lateral quarter of the lung increased 3.8 times and 3.2 times at 3 months and 9 months, respectively, in the former group, as opposed to 1.2 and 1.1 in the latter group. Thirteen patients had an increase in either cough or dyspnoea as observed 3 months after completion of radiotherapy. In eleven patients these symptoms persisted 6 months later. No significant correlation was found between radiological findings and subjective symptoms. However, when three different treatment techniques were compared among 29 patients the highest rate of radiological findings was observed in patients in which the largest lung volumes received the target dose. A tendency towards an increased rate of subjective symptoms was also found in this group.

  18. Precision Hypofractionated Radiation Therapy in Poor Performing Patients With Non-Small Cell Lung Cancer: Phase 1 Dose Escalation Trial

    SciTech Connect (OSTI)

    Westover, Kenneth D.; Loo, Billy W.; Gerber, David E.; Iyengar, Puneeth; Choy, Hak; Diehn, Maximilian; Hughes, Randy; Schiller, Joan; Dowell, Jonathan; Wardak, Zabi; Sher, David; Christie, Alana; Xie, Xian-Jin; Corona, Irma; Sharma, Akanksha; Wadsworth, Margaret E.; Timmerman, Robert

    2015-09-01

    Purpose: Treatment regimens for locally advanced non-small cell lung cancer (NSCLC) give suboptimal clinical outcomes. Technological advancements such as radiation therapy, the backbone of most treatment regimens, may enable more potent and effective therapies. The objective of this study was to escalate radiation therapy to a tumoricidal hypofractionated dose without exceeding the maximally tolerated dose (MTD) in patients with locally advanced NSCLC. Methods and Materials: Patients with stage II to IV or recurrent NSCLC and Eastern Cooperative Oncology Group performance status of 2 or greater and not candidates for surgical resection, stereotactic radiation, or concurrent chemoradiation were eligible. Highly conformal radiation therapy was given to treat intrathoracic disease in 15 fractions to a total of 50, 55, or 60 Gy. Results: Fifty-five patients were enrolled: 15 at the 50-Gy, 21 at the 55-Gy, and 19 at the 60-Gy dose levels. A 90-day follow-up was completed in each group without exceeding the MTD. With a median follow-up of 12.5 months, there were 93 grade ≥3 adverse events (AEs), including 39 deaths, although most AEs were considered related to factors other than radiation therapy. One patient from the 55- and 60-Gy dose groups developed grade ≥3 esophagitis, and 5, 4, and 4 patients in the respective dose groups experienced grade ≥3 dyspnea, but only 2 of these AEs were considered likely related to therapy. There was no association between fraction size and toxicity (P=.24). The median overall survival was 6 months with no significant differences between dose levels (P=.59). Conclusions: Precision hypofractionated radiation therapy consisting of 60 Gy in 15 fractions for locally advanced NSCLC is generally well tolerated. This treatment regimen could provide patients with poor performance status a potent alternative to chemoradiation. This study has implications for the cost effectiveness of lung cancer therapy. Additional studies of long-term safety and efficacy of this therapy are warranted.

  19. Correlation of Clinical and Dosimetric Factors With Adverse Pulmonary Outcomes in Children After Lung Irradiation

    SciTech Connect (OSTI)

    Venkatramani, Rajkumar; Kamath, Sunil; Wong, Kenneth; Malvar, Jemily; Sposto, Richard; Goodarzian, Fariba; Freyer, David R.; Keens, Thomas G.; and others

    2013-08-01

    Purpose: To identify the incidence and the risk factors for pulmonary toxicity in children treated for cancer with contemporary lung irradiation. Methods and Materials: We analyzed clinical features, radiographic findings, pulmonary function tests, and dosimetric parameters of children receiving irradiation to the lung fields over a 10-year period. Results: We identified 109 patients (75 male patients). The median age at irradiation was 13.8 years (range, 0.04-20.9 years). The median follow-up period was 3.4 years. The median prescribed radiation dose was 21 Gy (range, 0.4-64.8 Gy). Pulmonary toxic chemotherapy included bleomycin in 58.7% of patients and cyclophosphamide in 83.5%. The following pulmonary outcomes were identified and the 5-year cumulative incidence after irradiation was determined: pneumonitis, 6%; chronic cough, 10%; pneumonia, 35%; dyspnea, 11%; supplemental oxygen requirement, 2%; radiographic interstitial lung disease, 40%; and chest wall deformity, 12%. One patient died of progressive respiratory failure. Post-irradiation pulmonary function tests available from 44 patients showed evidence of obstructive lung disease (25%), restrictive disease (11%), hyperinflation (32%), and abnormal diffusion capacity (12%). Thoracic surgery, bleomycin, age, mean lung irradiation dose (MLD), maximum lung dose, prescribed dose, and dosimetric parameters between V{sub 22} (volume of lung exposed to a radiation dose ≥22 Gy) and V{sub 30} (volume of lung exposed to a radiation dose ≥30 Gy) were significant for the development of adverse pulmonary outcomes on univariate analysis. MLD, maximum lung dose, and V{sub dose} (percentage of volume of lung receiving the threshold dose or greater) were highly correlated. On multivariate analysis, MLD was the sole significant predictor of adverse pulmonary outcome (P=.01). Conclusions: Significant pulmonary dysfunction occurs in children receiving lung irradiation by contemporary techniques. MLD rather than prescribed dose should be used to perform risk stratification of patients receiving lung irradiation.

  20. Designing Targets for Elective Nodal Irradiation in Lung Cancer Radiotherapy: A Planning Study

    SciTech Connect (OSTI)

    Kepka, Lucyna; Tatro, Daniel; Moran, Jean M.; Quint, Leslie E.; Hayman, James A.; Ten Haken, Randall K.; Kong Fengming

    2009-04-01

    Purpose: To assess doses received by mediastinal and hilar lymph node stations (LNS) delineated according to published recommendations when 'standard' two-dimensional (2D) elective fields are applied and to assess doses to critical structures when fields are designed using 2D and three-dimensional (3D) treatment planning for elective irradiation. Methods and Materials: LNS were delineated on axial CT scans according to existing recommendations. For each case and tumor location, 2D anteroposterior-posteroanterior (AP-PA) elective fields were applied using the AP-PA CT topograms. From the 2D portal fields, 3D dose distributions were then calculated to particular LNS. Next, 3D plans were prepared for elective nodal irradiation for tumors of different lobes. Doses for critical structures were compared for 2D and 3D plans. Results: LNS 1/2R, 1/2L, 3A, 3P, 5, 6, and 8 were not adequately covered in a substantial part of plans by standard 2D portals when guidelines for delineation were strictly followed. The magnitude of the lack of coverage increased with margin application. There was a trend for a higher yet probably still safe dose delivered to lung for 3D plans compared with 2D plans with a prescription dose of 45 Gy. Conclusions: 2D fields did not entirely cover LNS delineated according to the recommendations for 3D techniques. A strict adherence to these guidelines may lead to larger portals than traditionally constructed using 2D methods. Some modifications for clinical implementation are discussed.

  1. Geophysical variables and behavior: LIII. Epidemiological considerations for incidence of cancer and depression in areas of frequent UFO reports

    SciTech Connect (OSTI)

    Persinger, M.A.

    1988-12-01

    Luminous phenomena and anomalous physical forces have been hypothesized to be generated by focal tectonic strain fields that precede earthquakes. If these geophysical processes exist, then their spatial and temporal density should be greatest during periods of protracted, localized UFO reports; they might be used as dosimetric indicators. Contemporary epidemiological data concerning the health risks of power frequency electromagnetic fields and radon gas levels (expected correlates of certain tectonic strain fields), suggest that increased incidence (odds ratios greater 1:3) of brain tumors and leukemia should be evident within flap areas. In addition the frequency of variants of temporal lobe lability, psychological depression and posttraumatic stress should be significantly elevated. UFO field investigators, because they have repeated, intermittent close proximity to these fields, are considered to be a particularly high risk population for these disorders. 22 references.

  2. Brachial Plexopathy in Apical Non-Small Cell Lung Cancer Treated With Definitive Radiation: Dosimetric Analysis and Clinical Implications

    SciTech Connect (OSTI)

    Eblan, Michael J.; Corradetti, Michael N.; Lukens, J. Nicholas; Xanthopoulos, Eric; Mitra, Nandita; Christodouleas, John P.; Grover, Surbhi; Fernandes, Annemarie T.; Langer, Corey J.; Evans, Tracey L.; Stevenson, James; Rengan, Ramesh; Apisarnthanarax, Smith

    2013-01-01

    Purpose: Data are limited on the clinical significance of brachial plexopathy in patients with apical non-small cell lung cancers (NSCLC) treated with definitive radiation therapy. We report the rates of radiation-induced brachial plexopathy (RIBP) and tumor-related brachial plexopathy (TRBP) and associated dosimetric parameters in apical NSCLC patients. Methods and Materials: Charts of NSCLC patients with primary upper lobe or superiorly located nodal disease who received {>=}50 Gy of definitive conventionally fractionated radiation or chemoradiation were retrospectively reviewed for evidence of brachial plexopathy and categorized as RIBP, TRBP, or trauma-related. Dosimetric data were gathered on ipsilateral brachial plexuses (IBP) contoured according to Radiation Therapy Oncology Group atlas guidelines. Results: Eighty patients were identified with a median follow-up and survival time of 17.2 and 17.7 months, respectively. The median prescribed dose was 66.6 Gy (range, 50.4-84.0), and 71% of patients received concurrent chemotherapy. RIBP occurred in 5 patients with an estimated 3-year rate of 12% when accounting for competing risk of death. Seven patients developed TRBP (estimated 3-year rate of 13%), comprising 24% of patients who developed locoregional failures. Grade 3 brachial plexopathy was more common in patients who experienced TRBP than RIBP (57% vs 20%). No patient who received {<=}78 Gy to the IBP developed RIBP. On multivariable competing risk analysis, IBP V76 receiving {>=}1 cc, and primary tumor failure had the highest hazard ratios for developing RIBP and TRBP, respectively. Conclusions: RIBP is a relatively uncommon complication in patients with apical NSCLC tumors receiving definitive doses of radiation, while patients who develop primary tumor failures are at high risk for developing morbid TRBP. These findings suggest that the importance of primary tumor control with adequate doses of radiation outweigh the risk of RIBP in this population of patients.

  3. Use of Stereotactic Radiosurgery for Brain Metastases From Non-Small Cell Lung Cancer in the United States

    SciTech Connect (OSTI)

    Halasz, Lia M.; Weeks, Jane C.; Neville, Bridget A.; Taback, Nathan; Punglia, Rinaa S.

    2013-02-01

    Purpose: The indications for treatment of brain metastases from non-small cell lung cancer (NSCLC) with stereotactic radiosurgery (SRS) remain controversial. We studied patterns, predictors, and cost of SRS use in elderly patients with NSCLC. Methods and Materials: Using the Surveillance, Epidemiology, and End Results-Medicare (SEER-Medicare) database, we identified patients with NSCLC who were diagnosed with brain metastases between 2000 and 2007. Our cohort included patients treated with radiation therapy and not surgical resection as initial treatment for brain metastases. Results: We identified 7684 patients treated with radiation therapy within 2 months after brain metastases diagnosis, of whom 469 (6.1%) cases had billing codes for SRS. Annual SRS use increased from 3.0% in 2000 to 8.2% in 2005 and varied from 3.4% to 12.5% by specific SEER registry site. After controlling for clinical and sociodemographic characteristics, we found SRS use was significantly associated with increasing year of diagnosis, specific SEER registry, higher socioeconomic status, admission to a teaching hospital, no history of participation in low-income state buy-in programs (a proxy for Medicaid eligibility), no extracranial metastases, and longer intervals from NSCLC diagnosis. The average cost per patient associated with radiation therapy was 2.19 times greater for those who received SRS than for those who did not. Conclusions: The use of SRS in patients with metastatic NSCLC increased almost 3-fold from 2000 to 2005. In addition, we found significant variations in SRS use across SEER registries and socioeconomic quartiles. National practice patterns in this study suggested both a lack of consensus and an overall limited use of the approach among elderly patients before 2008.

  4. ATM Polymorphisms Predict Severe Radiation Pneumonitis in Patients With Non-Small Cell Lung Cancer Treated With Definitive Radiation Therapy

    SciTech Connect (OSTI)

    Xiong, Huihua; Liao, Zhongxing; Liu, Zhensheng; Xu, Ting; Wang, Qiming; Liu, Hongliang; Komaki, Ritsuko; Gomez, Daniel; Wang, Li-E; Wei, Qingyi

    2013-03-15

    Purpose: The ataxia telangiectasia mutated (ATM) gene mediates detection and repair of DNA damage. We investigated associations between ATM polymorphisms and severe radiation-induced pneumonitis (RP). Methods and Materials: We genotyped 3 potentially functional single nucleotide polymorphisms (SNPs) of ATM (rs1801516 [D1853N/5557G>A], rs189037 [-111G>A] and rs228590) in 362 patients with non-small cell lung cancer (NSCLC), who received definitive (chemo)radiation therapy. The cumulative severe RP probabilities by genotypes were evaluated using the Kaplan-Meier analysis. The associations between severe RP risk and genotypes were assessed by both logistic regression analysis and Cox proportional hazard model with time to event considered. Results: Of 362 patients (72.4% of non-Hispanic whites), 56 (15.5%) experienced grade ≥3 RP. Patients carrying ATM rs189037 AG/GG or rs228590 TT/CT genotypes or rs189037G/rs228590T/rs1801516G (G-T-G) haplotype had a lower risk of severe RP (rs189037: GG/AG vs AA, adjusted hazard ratio [HR] = 0.49, 95% confidence interval [CI], 0.29-0.83, P=.009; rs228590: TT/CT vs CC, HR=0.57, 95% CI, 0.33-0.97, P=.036; haplotype: G-T-G vs A-C-G, HR=0.52, 95% CI, 0.35-0.79, P=.002). Such positive findings remained in non-Hispanic whites. Conclusions: ATM polymorphisms may serve as biomarkers for susceptibility to severe RP in non-Hispanic whites. Large prospective studies are required to confirm our findings.

  5. Risk of Hippocampal Metastases in Small Cell Lung Cancer Patients at Presentation and After Cranial Irradiation: A Safety Profile Study for Hippocampal Sparing During Prophylactic or Therapeutic Cranial Irradiation

    SciTech Connect (OSTI)

    Kundapur, Vijayananda; Ellchuk, Tasha; Ahmed, Shahid; Gondi, Vinai

    2015-03-15

    Purpose: Neurocognitive impairment (NI) in patients with small cell lung cancer (SCLC) after whole brain radiation treatment (WBRT) is a significant cause of morbidity. Hippocampal avoidance (HA) during WBRT may mitigate or prevent NI in such patients. However, this has not been tested in SCLC patients. The estimated risk of metastases in the HA region (HM) in patients with SCLC at diagnosis or after WBRT is unknown. Our study aimed to determine the risk of HM in patients with SCLC and to assess correlated clinical factors. Methods and Materials: Patients with SCLC who experienced brain metastases (BM) at presentation (de novo) or after WBRT treated at the Saskatoon Cancer Centre between 2005 and 2012 were studied. Relevant neuroimaging was independently reviewed by a neuroradiologist. HM was defined as metastases within 5 mm of the hippocampus. Logistic regression analysis was performed to assess correlation between various clinical variables and HM. Results: Seventy eligible patients were identified. Of 59 patients presenting with de novo BM, 3 patients (5%, 95% confidence interval [CI]: 0%-10.7%) had HM. Collectively there were 359 (range, 1-33) de novo BM with 3 (0.8%, 95% CI: 0%-1.7%) HM deposits. Twenty patients experienced progression of metastatic disease in the brain after WBRT. Of the 20 patients, only 1 patient (5%, 95% CI: 0%-14.5%) experienced HM. On logistic regression, no factors significantly correlated with HM. Conclusion: The overall incidence of HM before or after WBRT in SCLC patients is low, providing preliminary support for the safety of HA during planned clinical trials of HA-WBRT for SCLC.

  6. Early prediction of tumor recurrence based on CT texture changes after stereotactic ablative radiotherapy (SABR) for lung cancer

    SciTech Connect (OSTI)

    Mattonen, Sarah A.; Palma, David A.; Department of Oncology, The University of Western Ontario, London, Ontario N6A 4L6; Division of Radiation Oncology, London Regional Cancer Program, London, Ontario N6A 4L6 ; Haasbeek, Cornelis J. A.; Senan, Suresh; Ward, Aaron D.

    2014-03-15

    Purpose: Benign computed tomography (CT) changes due to radiation induced lung injury (RILI) are common following stereotactic ablative radiotherapy (SABR) and can be difficult to differentiate from tumor recurrence. The authors measured the ability of CT image texture analysis, compared to more traditional measures of response, to predict eventual cancer recurrence based on CT images acquired within 5 months of treatment. Methods: A total of 24 lesions from 22 patients treated with SABR were selected for this study: 13 with moderate to severe benign RILI, and 11 with recurrence. Three-dimensional (3D) consolidative and ground-glass opacity (GGO) changes were manually delineated on all follow-up CT scans. Two size measures of the consolidation regions (longest axial diameter and 3D volume) and nine appearance features of the GGO were calculated: 2 first-order features [mean density and standard deviation of density (first-order texture)], and 7 second-order texture features [energy, entropy, correlation, inverse difference moment (IDM), inertia, cluster shade, and cluster prominence]. For comparison, the corresponding response evaluation criteria in solid tumors measures were also taken for the consolidation regions. Prediction accuracy was determined using the area under the receiver operating characteristic curve (AUC) and two-fold cross validation (CV). Results: For this analysis, 46 diagnostic CT scans scheduled for approximately 3 and 6 months post-treatment were binned based on their recorded scan dates into 25 month and 58 month follow-up time ranges. At 25 months post-treatment, first-order texture, energy, and entropy provided AUCs of 0.790.81 using a linear classifier. On two-fold CV, first-order texture yielded 73% accuracy versus 76%77% with the second-order features. The size measures of the consolidative region, longest axial diameter and 3D volume, gave two-fold CV accuracies of 60% and 57%, and AUCs of 0.72 and 0.65, respectively. Conclusions: Texture measures of the GGO appearance following SABR demonstrated the ability to predict recurrence in individual patients within 5 months of SABR treatment. Appearance changes were also shown to be more accurately predictive of recurrence, as compared to size measures within the same time period. With further validation, these results could form the substrate for a clinically useful computer-aided diagnosis tool which could provide earlier salvage of patients with recurrence.

  7. Risk Factors for Brain Metastases in Locally Advanced Non-Small Cell Lung Cancer With Definitive Chest Radiation

    SciTech Connect (OSTI)

    Ji, Zhe; Bi, Nan; Wang, Jingbo; Hui, Zhouguang; Xiao, Zefen; Feng, Qinfu; Zhou, Zongmei; Chen, Dongfu; Lv, Jima; Liang, Jun; Fan, Chengcheng; Liu, Lipin; Wang, Luhua

    2014-06-01

    Purpose: We intended to identify risk factors that affect brain metastases (BM) in patients with locally advanced non-small cell lung cancer (LA-NSCLC) receiving definitive radiation therapy, which may guide the choice of selective prevention strategies. Methods and Materials: The characteristics of 346 patients with stage III NSCLC treated with thoracic radiation therapy from January 2008 to December 2010 in our institution were retrospectively reviewed. BM rates were analyzed by the Kaplan-Meier method. Multivariate Cox regression analysis was performed to determine independent risk factors for BM. Results: The median follow-up time was 48.3 months in surviving patients. A total of 74 patients (21.4%) experienced BM at the time of analysis, and for 40 (11.7%) of them, the brain was the first site of failure. The 1-year and 3-year brain metastasis rates were 15% and 28.1%, respectively. In univariate analysis, female sex, age ≤60 years, non-squamous cell carcinoma, T3-4, N3, >3 areas of lymph node metastasis, high lactate dehydrogenase and serum levels of tumor markers (CEA, NSE, CA125) before treatment were significantly associated with BM (P<.05). In multivariate analysis, age ≤60 years (P=.004, hazard ratio [HR] = 0.491), non-squamous cell carcinoma (P=.000, HR=3.726), NSE >18 ng/mL (P=.008, HR=1.968) and CA125 ≥ 35 U/mL (P=.002, HR=2.129) were independent risk factors for BM. For patients with 0, 1, 2, and 3 to 4 risk factors, the 3-year BM rates were 7.3%, 18.9%, 35.8%, and 70.3%, respectively (P<.001). Conclusions: Age ≤60 years, non-squamous cell carcinoma, serum NSE >18 ng/mL, and CA125 ≥ 35 U/mL were independent risk factors for brain metastasis. The possibilities of selectively using prophylactic cranial irradiation in higher-risk patients with LA-NSCLC should be further explored in the future.

  8. Predictors of Individual Tumor Local Control After Stereotactic Radiosurgery for Non-Small Cell Lung Cancer Brain Metastases

    SciTech Connect (OSTI)

    Garsa, Adam A.; Badiyan, Shahed N.; DeWees, Todd; Simpson, Joseph R.; Huang, Jiayi; Drzymala, Robert E.; Barani, Igor J.; Dowling, Joshua L.; Rich, Keith M.; Chicoine, Michael R.; Kim, Albert H.; Leuthardt, Eric C.; Robinson, Clifford G.

    2014-10-01

    Purpose: To evaluate local control rates and predictors of individual tumor local control for brain metastases from non-small cell lung cancer (NSCLC) treated with stereotactic radiosurgery (SRS). Methods and Materials: Between June 1998 and May 2011, 401 brain metastases in 228 patients were treated with Gamma Knife single-fraction SRS. Local failure was defined as an increase in lesion size after SRS. Local control was estimated using the Kaplan-Meier method. The Cox proportional hazards model was used for univariate and multivariate analysis. Receiver operating characteristic analysis was used to identify an optimal cutpoint for conformality index relative to local control. A P value <.05 was considered statistically significant. Results: Median age was 60 years (range, 27-84 years). There were 66 cerebellar metastases (16%) and 335 supratentorial metastases (84%). The median prescription dose was 20 Gy (range, 14-24 Gy). Median overall survival from time of SRS was 12.1 months. The estimated local control at 12 months was 74%. On multivariate analysis, cerebellar location (hazard ratio [HR] 1.94, P=.009), larger tumor volume (HR 1.09, P<.001), and lower conformality (HR 0.700, P=.044) were significant independent predictors of local failure. Conformality index cutpoints of 1.4-1.9 were predictive of local control, whereas a cutpoint of 1.75 was the most predictive (P=.001). The adjusted Kaplan-Meier 1-year local control for conformality index ≥1.75 was 84% versus 69% for conformality index <1.75, controlling for tumor volume and location. The 1-year adjusted local control for cerebellar lesions was 60%, compared with 77% for supratentorial lesions, controlling for tumor volume and conformality index. Conclusions: Cerebellar tumor location, lower conformality index, and larger tumor volume were significant independent predictors of local failure after SRS for brain metastases from NSCLC. These results warrant further investigation in a prospective setting.

  9. Clinically Meaningful Differences in Patient-Reported Outcomes With Amifostine in Combination With Chemoradiation for Locally Advanced Non-Small-Cell Lung Cancer: An Analysis of RTOG 9801

    SciTech Connect (OSTI)

    Sarna, Linda [University of California, Los Angeles, CA (United States)], E-mail: lsarna@sonnet.ucla.edu; Swann, Suzanne [Radiation Therapy Oncology Group, Philadelphia, PA (United States); Langer, Corey [Fox Chase Cancer Center, Philadelphia, PA (United States); Werner-Wasik, Maria [Thomas Jefferson University, Jefferson Medical College, Philadelphia, PA (United States); Nicolaou, Nicos [Fox Chase Cancer Center, Philadelphia, PA (United States); Komaki, Ritsuko [M.D. Anderson Cancer Center, Houston, TX (United States); Machtay, Mitchell [Thomas Jefferson University, Jefferson Medical College, Philadelphia, PA (United States); Byhardt, Roger [Medical College of Wisconsin, Milwaukee, WI (United States); Wasserman, Todd [Washington University, St. Louis, MO (United States); Movsas, Benjamin [Henry Ford Health System, Detroit, MI (United States)

    2008-12-01

    Purpose: The purpose of this study is to analyze changes in quality of life (QOL) and symptoms from pretreatment to 6 weeks posttreatment in a Phase III randomized study (Radiation Therapy Oncology Group 9801) of amifostine (AM) vs. no AM in patients with Stages II-III non-small-cell lung cancer receiving paclitaxel and carboplatin as induction and then concurrently with hyperfractionated radiation therapy (RT). Methods and Materials: One hundred thirty-eight patients with baseline and 6-week posttreatment QOL data were analyzed. There were no significant differences in baseline demographics between those who did and did not have QOL data. The QOL and symptoms were assessed by using the European Organization for Research and Treatment of Cancer (EORTC) Global QOL and Pain subscales and the EORTC-Lung Cancer-13 symptom tool. Clinically relevant changes in QOL were characterized by 10-point differences in individual scores pre/post treatment. A daily diary of patient-rated difficulty swallowing and a weekly physician-rated dysphagia log (using National Cancer Institute Common Toxicity Criteria) were completed during treatment. Weight loss was monitored. Differences in outcomes were examined according to smoking status, alcohol use, and sex. Results: Patients receiving AM reported significantly greater pain reduction after chemoradiation (34% vs. no AM, 21%), less difficulty swallowing during chemoradiation, and less weight loss than patients not receiving AM. However, physician-rated assessments of dysphagia were not significantly different by treatment arm. There were no other significant changes in QOL or symptoms according to treatment arm, smoking status, alcohol use, or sex. Conclusions: Patient evaluations of difficulty swallowing and pain suggest benefits from AM use that are distinct from clinician-rated assessments.

  10. Functional Promoter Variant rs2868371 of HSPB1 Is Associated With Risk of Radiation Pneumonitis After Chemoradiation for Non-Small Cell Lung Cancer

    SciTech Connect (OSTI)

    Pang, Qingsong; Department of Radiation Oncology and Lung Cancer Center, Tianjin Medical University Cancer Institute and Hospital, Key Laboratory of Cancer Prevention and Therapy, Tianjin ; Wei, Qingyi; Xu, Ting; Yuan, Xianglin; Lopez Guerra, Jose Luis; Levy, Lawrence B.; Liu, Zhensheng; Gomez, Daniel R.; Zhuang, Yan; Wang, Li-E.; Mohan, Radhe; Komaki, Ritsuko; Liao, Zhongxing

    2013-04-01

    Purpose: To date, no biomarkers have been found to predict, before treatment, which patients will develop radiation pneumonitis (RP), a potentially fatal toxicity, after chemoradiation for lung cancer. We investigated potential associations between single nucleotide polymorphisms (SNPs) in HSPB1 and risk of RP after chemoradiation for non-small cell lung cancer (NSCLC). Methods and Materials: Subjects were patients with NSCLC treated with chemoradiation at 1 institution. The training data set comprised 146 patients treated from 1999 to July 2004; the validation data set was 125 patients treated from August 2004 to March 2010. We genotyped 2 functional SNPs of HSPB1 (rs2868370 and rs2868371) from all patients. We used Kaplan-Meier analysis to assess the risk of grade ≥2 or ≥3 RP in both data sets and a parametric log-logistic survival model to evaluate the association of HSPB1 genotypes with that risk. Results: Grade ≥3 RP was experienced by 13% of those with CG/GG and 29% of those with CC genotype of HSPB1 rs2868371 in the training data set (P=.028); corresponding rates in the validation data set were 2% CG/GG and 14% CC (P=.02). Univariate and multivariate analysis confirmed the association of CC of HSPB1 rs2868371 with higher risk of grade ≥3 RP than CG/GG after adjustment for sex, age, performance status, and lung mean dose. This association was validated both in the validation data set and with Harrell's C statistic. Conclusions: The CC genotype of HSPB1 rs2868371 was associated with severe RP after chemoradiation for NSCLC.

  11. Isotoxic Dose Escalation in the Treatment of Lung Cancer by Means of Heterogeneous Dose Distributions in the Presence of Respiratory Motion

    SciTech Connect (OSTI)

    Baker, Mariwan; Nielsen, Morten [Laboratory of Radiation Physics, Odense University Hospital, Odense (Denmark); Hansen, Olfred [Department of Oncology, Odense University Hospital, Odense (Denmark); Jahn, Jonas Westberg [Laboratory of Radiation Physics, Odense University Hospital, Odense (Denmark); Korreman, Stine [Department of Radiation Oncology, Copenhagen University Hospital, Copenhagen (Denmark); Brink, Carsten, E-mail: carsten.brink@ouh.regionsyddanmark.dk [Laboratory of Radiation Physics, Odense University Hospital, Odense (Denmark); Institute of Clinical Research, University of Southern Denmark, Odense (Denmark)

    2011-11-01

    Purpose: To test, in the presence of intrafractional respiration movement, a margin recipe valid for a homogeneous and conformal dose distribution and to test whether the use of smaller margins combined with heterogeneous dose distributions allows an isotoxic dose escalation when respiratory motion is considered. Methods and Materials: Twenty-three Stage II-III non-small-cell lung cancer patients underwent four-dimensional computed tomography scanning. The gross tumor volume and clinical target volume (CTV) were outlined in the mid-ventilation phase. The CTV-to-planning target volume (PTV) margin was calculated by use of a standard margin recipe and the patient-specific respiration pattern. Standard three-dimensional treatment plans were generated and recalculated on the remaining respiration phases. The planning was repeated for a CTV-to-PTV margin decreased by 2.5 and 5 mm relative to the initial margin in all directions. Time-averaged dose-volume histograms (four-dimensional dose-volume histograms) were calculated to evaluate the CTV-to-PTV margin. Finally, the dose was escalated in the plans with decreased PTV such that the mean lung dose (predictor of radiation-induced pneumonitis) was equal to mean lung dose in the plan by use of the initially calculated margin. Results: A reduction of the standard margin by 2.5 mm compared with the recipe resulted in too low of a minimum dose for some patients. A combination of dose escalation and use of heterogeneous dose distribution was able to increase the minimum dose to the target by approximately 10% and 20% for a CTV-to-PTV margin reduction of 2.5 mm and 5.0 mm, respectively. Conclusion: The margin recipe is valid for intrafractional respiration-induced tumor motions. It is possible to increase the dose to the target without increased mean lung dose with an inhomogeneous dose distribution.

  12. Stereotactic Body Radiotherapy Versus Surgery for Medically Operable Stage I Non-Small-Cell Lung Cancer: A Markov Model-Based Decision Analysis

    SciTech Connect (OSTI)

    Louie, Alexander V.; Rodrigues, George; Palma, David A.; Cao, Jeffrey Q.; Yaremko, Brian P.; Malthaner, Richard; Mocanu, Joseph D.

    2011-11-15

    Purpose: To compare the quality-adjusted life expectancy and overall survival in patients with Stage I non-small-cell lung cancer (NSCLC) treated with either stereotactic body radiation therapy (SBRT) or surgery. Methods and Materials: We constructed a Markov model to describe health states after either SBRT or lobectomy for Stage I NSCLC for a 5-year time frame. We report various treatment strategy survival outcomes stratified by age, sex, and pack-year history of smoking, and compared these with an external outcome prediction tool (Adjuvant{exclamation_point} Online). Results: Overall survival, cancer-specific survival, and other causes of death as predicted by our model correlated closely with those predicted by the external prediction tool. Overall survival at 5 years as predicted by baseline analysis of our model is in favor of surgery, with a benefit ranging from 2.2% to 3.0% for all cohorts. Mean quality-adjusted life expectancy ranged from 3.28 to 3.78 years after surgery and from 3.35 to 3.87 years for SBRT. The utility threshold for preferring SBRT over surgery was 0.90. Outcomes were sensitive to quality of life, the proportion of local and regional recurrences treated with standard vs. palliative treatments, and the surgery- and SBRT-related mortalities. Conclusions: The role of SBRT in the medically operable patient is yet to be defined. Our model indicates that SBRT may offer comparable overall survival and quality-adjusted life expectancy as compared with surgical resection. Well-powered prospective studies comparing surgery vs. SBRT in early-stage lung cancer are warranted to further investigate the relative survival, quality of life, and cost characteristics of both treatment paradigms.

  13. SU-E-T-606: A Novel Integrated VMAT/IMRT Technique For the Treatment of Non-Small Cell Lung Cancer

    SciTech Connect (OSTI)

    Zhao, N; Yang, R; Wang, J

    2014-06-01

    Purpose: To investigate a novel Integrated VMAT/IMRT technique which combines volumetric modulated arc therapy (VMAT) and intensity modulated radiation therapy (IMRT) for non-small cell lung cancer (NSCLC). Methods: 2 partial arcs VMAT, 5-field IMRT and Integrated VMAT/IMRT plans were created for 17 patients with NSCLC. The Integrated VMAT/IMRT technique consisted of 2 partial VMAT arcs and 5 IMRT fields. The dose distribution of planning target volume (PTV) and organs at risk (OARs) for Integrated VMAT/IMRT was compared with IMRT and VMAT. The monitor units (MUs) and treatment delivery time were also evaluated. For each plan, a dry run was performed to assess the dosimetric accuracy with MatriXX from IBA. Results: Integrated VMAT/IMRT significantly improved the target conformity and homogeneity. The V30 of normal lung for Integrated plans was significantly lower than IMRT plans (8.4% vs 9.2%; p<0.05). The V5 and mean lung dose (MLD) of normal lung for Integrated plans were 9.8% and 4.6% lower than VMAT plans (p<0.05). The maximum dose of spinal cord for Integrated plans was 4.9 Gy lower than IMRT plans (p<0.05). The mean delivery time of IMRT, VMAT and Integrated plans was 280 s, 114 s, and 327 s, respectively. The mean MUs needed for IMRT, VMAT and Integrated plans were 933, 512, and 737, respectively. The gamma pass rates were beyond 90% at the 3%/3 mm criteria when the gantry angles were set to 0 for pretreatment verification. Conclusion: Integrated VMAT/IMRT technique significantly reduced V5, V10 and MLD of normal lung compared with VMAT, and the irradiated volume of the OARs receiving medium to high dose with fewer MUs compared with IMRT. Integrated VMAT/IMRT technique can be a feasible radiotherapy technique with better plan quality and accurately delivered on the linear accelerator. Ruijie Yang was funded by the grant project: National Natural Science Foundation of China (No. 81071237). Other authors have no competing interest for this work.

  14. SU-E-J-265: Practical Issues and Solutions in Reconstructing and Using 4DCT for Radiotherapy Planning of Lung Cancer

    SciTech Connect (OSTI)

    Lu, W; Feigenberg, S; Yi, B; Lasio, G; Prado, K; D'Souza, W

    2014-06-01

    Purpose: To report practical issues and solutions in reconstructing and using 4DCT to account for respiratory motion in radiotherapy planning. Methods: Quiet breathing 4DCT was used to account for respiratory motion for patients with lung or upper abdomen tumor. A planning CT and a 4DCT were acquired consecutively with a Philips Brilliance CT scanner and Varian RPM System. The projections were reconstructed into 10 phases. In Pinnacle RTP system, we contour a GTV in each phase and unite all 10 GTVs as ITV. The ITV is then mapped to the planning CT. We describe practical issues, their causes, our solutions and reasoning during this process. Results: In 6 months, 9 issues were reported for 8 patients with lung cancer. For two patients, part of the GTV (?50% and 10%) in planning CT fell outside the ITV in 4DCT. There was a 7 mm variation in first patient back position because less restricted immobilization had to be used. The second discrepancy was due to moderate variation in breathing amplitude. We extended the ITV to include the GTV since both variations may likely happen during treatment. A LUL tumor showed no motion due to a 10-s long no-breathing period. An RLL tumor appeared double due to an abnormally deeper breath at the tumor region. We repeated 4DCT reiterating the importance of quiet, regular breathing. One patient breathed too light to generate RPM signal. Two issues (no motion in lung, incomplete images in 90% phase) were due to incorrect tag positions. Two unexplainable errors disappeared when repeating reconstruction. In summary, 5 issues were patient-related and 4 were technique issues. Conclusion: Improving breathing regularity avoided large artifacts in 4DCT. One needs to closely monitor patient breathing. For uncontrollable variations, larger PTVs are necessary which requires appropriate communication between physics and the treating physician.

  15. Critical dose and toxicity index of organs at risk in radiotherapy: Analyzing the calculated effects of modified dose fractionation in nonsmall cell lung cancer

    SciTech Connect (OSTI)

    Pedicini, Piernicola; Strigari, Lidia; Benassi, Marcello; Caivano, Rocchina; Fiorentino, Alba; Nappi, Antonio; Salvatore, Marco; Storto, Giovanni

    2014-04-01

    To increase the efficacy of radiotherapy for nonsmall cell lung cancer (NSCLC), many schemes of dose fractionation were assessed by a new toxicity index (I), which allows one to choose the fractionation schedules that produce less toxic treatments. Thirty-two patients affected by non resectable NSCLC were treated by standard 3-dimensional conformal radiotherapy (3DCRT) with a strategy of limited treated volume. Computed tomography datasets were employed to re plan by simultaneous integrated boost intensity-modulated radiotherapy (IMRT). The dose distributions from plans were used to test various schemes of dose fractionation, in 3DCRT as well as in IMRT, by transforming the dose-volume histogram (DVH) into a biological equivalent DVH (BDVH) and by varying the overall treatment time. The BDVHs were obtained through the toxicity index, which was defined for each of the organs at risk (OAR) by a linear quadratic model keeping an equivalent radiobiological effect on the target volume. The less toxic fractionation consisted in a severe/moderate hyper fractionation for the volume including the primary tumor and lymph nodes, followed by a hypofractionation for the reduced volume of the primary tumor. The 3DCRT and IMRT resulted, respectively, in 4.7% and 4.3% of dose sparing for the spinal cord, without significant changes for the combined-lungs toxicity (p < 0.001). Schedules with reduced overall treatment time (accelerated fractionations) led to a 12.5% dose sparing for the spinal cord (7.5% in IMRT), 8.3% dose sparing for V{sub 20} in the combined lungs (5.5% in IMRT), and also significant dose sparing for all the other OARs (p < 0.001). The toxicity index allows to choose fractionation schedules with reduced toxicity for all the OARs and equivalent radiobiological effect for the tumor in 3DCRT, as well as in IMRT, treatments of NSCLC.

  16. Stereotactic Body Radiation Therapy Can Be Used Safely to Boost Residual Disease in Locally Advanced Non-Small Cell Lung Cancer: A Prospective Study

    SciTech Connect (OSTI)

    Feddock, Jonathan; Arnold, Susanne M.; Department of Medical Oncology, University of Kentucky, Lexington, Kentucky ; Shelton, Brent J.; Sinha, Partha; Conrad, Gary; Chen, Li; Rinehart, John; McGarry, Ronald C.

    2013-04-01

    Purpose: To report the results of a prospective, single-institution study evaluating the feasibility of conventional chemoradiation (CRT) followed by stereotactic body radiation therapy (SBRT) as a means of dose escalation for patients with stage II-III non-small cell lung cancer (NSCLC) with residual disease. Methods and Materials: Patients without metastatic disease and with radiologic evidence of limited residual disease (?5 cm) within the site of the primary tumor and good or complete nodal responses after standard CRT to a target dose of 60 Gy were considered eligible. The SBRT boost was done to achieve a total combined dose biological equivalent dose >100 Gy to the residual primary tumor, consisting of 10 Gy 2 fractions (20 Gy total) for peripheral tumors, and 6.5 Gy 3 fractions (19.5 Gy total) for medial tumors using the Radiation Therapy Oncology Group protocol 0813 definitions. The primary endpoint was the development of grade ?3 radiation pneumonitis (RP). Results: After a median follow-up of 13 months, 4 patients developed acute grade 3 RP, and 1 (2.9%) developed late and persistent grade 3 RP. No patients developed grade 4 or 5 RP. Mean lung dose, V2.5, V5, V10, and V20 values were calculated for the SBRT boost, and none were found to significantly predict for RP. Only advancing age (P=.0147), previous smoking status (P=.0505), and high CRT mean lung dose (P=.0295) were significantly associated with RP development. At the time of analysis, the actuarial local control rate at the primary tumor site was 82.9%, with only 6 patients demonstrating recurrence. Conclusions: Linear accelerator-based SBRT for dose escalation of limited residual NSCLC after definitive CRT was feasible and did not increase the risk for toxicity above that for standard radiation therapy.

  17. SU-E-T-452: Impact of Respiratory Motion On Robustly-Optimized Intensity-Modulated Proton Therapy to Treat Lung Cancers

    SciTech Connect (OSTI)

    Liu, W; Schild, S; Bues, M [Mayo Clinic Arizona, Phoenix, AZ (United States); Liao, Z; Sahoo, N [MD Anderson Cancer Center, Houston, TX (United States); Park, P [Scottsdale, GA (United States); Li, H [M.D. Anderson Cancer Center, Houston, TX (United States); Li, Y [Varian Medical Systems, Houston, TX (United States); Li, X; Shen, J [Mayo Clinic Arizona, Phoenix, AA (United States); Anand, A [Mayo Clinic Arizona, Phoenix (United States); Dong, L [Scripps Proton Therapy Center, San Diego, CA (United States); Zhu, X; Mohan, R [UT MD Anderson Cancer Center, Houston, TX (United States)

    2014-06-01

    Purpose: We compared conventionally optimized intensity-modulated proton therapy (IMPT) treatment plans against the worst-case robustly optimized treatment plans for lung cancer. The comparison of the two IMPT optimization strategies focused on the resulting plans' ability to retain dose objectives under the influence of patient set-up, inherent proton range uncertainty, and dose perturbation caused by respiratory motion. Methods: For each of the 9 lung cancer cases two treatment plans were created accounting for treatment uncertainties in two different ways: the first used the conventional Method: delivery of prescribed dose to the planning target volume (PTV) that is geometrically expanded from the internal target volume (ITV). The second employed the worst-case robust optimization scheme that addressed set-up and range uncertainties through beamlet optimization. The plan optimality and plan robustness were calculated and compared. Furthermore, the effects on dose distributions of the changes in patient anatomy due to respiratory motion was investigated for both strategies by comparing the corresponding plan evaluation metrics at the end-inspiration and end-expiration phase and absolute differences between these phases. The mean plan evaluation metrics of the two groups were compared using two-sided paired t-tests. Results: Without respiratory motion considered, we affirmed that worst-case robust optimization is superior to PTV-based conventional optimization in terms of plan robustness and optimality. With respiratory motion considered, robust optimization still leads to more robust dose distributions to respiratory motion for targets and comparable or even better plan optimality [D95% ITV: 96.6% versus 96.1% (p=0.26), D5% - D95% ITV: 10.0% versus 12.3% (p=0.082), D1% spinal cord: 31.8% versus 36.5% (p =0.035)]. Conclusion: Worst-case robust optimization led to superior solutions for lung IMPT. Despite of the fact that robust optimization did not explicitly account for respiratory motion it produced motion-resistant treatment plans. However, further research is needed to incorporate respiratory motion into IMPT robust optimization.

  18. Poster Thur Eve 62: A Retrospective Assessment of the Prevalence and Dosimetric Effect of Lateral Electron Disequilibrium in a Population of Lung Cancer Patients Treated by Stereotactic Body Radiation Therapy

    SciTech Connect (OSTI)

    Disher, Brandon; Wade, Laura; Hajdok, George; Gaede, Stewart; Battista, Jerry J.; Palma, David

    2014-08-15

    Stereotactic Body Radiation Therapy (SBRT) is a treatment option for early stage non-small cell lung cancer (NSCLC). SBRT uses tightly conformed megavoltage (MV) x-ray beams to ablate the tumour. However, small MV x-ray fields may produce lateral electron disequilibrium (LED) within lung tissue, which can reduce the dose to tumour. The goal of this work is to estimate the prevalence of LED in NSCLC patients treated with SBRT, and determine dose effects for patients prone or averse to LED. Thirty NSCLC patients were randomly selected for analysis. 4-dimensional CT lung images were segmented into the right and left upper and lower lobes (RUL, RLL, LUL, LLL), and the right middle lobe. Dose calculations were performed using volume-modulated arc therapy in the Pinnacle{sup 3} TPS. Most tumours were located in the upper lobes (RUL 53%, LUL 27%) where density was significantly lower (RUL ?80846 HU vs. RLL ?74371 HU; LUL ?808 56 HU vs. LLL ?74670 HU; p<0.001). In general, the prevalence of LED increased with higher beam energy. Using 6MV photons, patients with a RUL tumour experienced moderate (81 %), and mild (19%) levels of LED. At 18MV, LED became more prominent with severe (50%) and moderate (50%) LED exhibited. Dosimetrically, for patients prone to LED, poorer target coverage (i.e. increased R100 by 20%) and improved lung sparing (i.e. reduced V20 by ?46%) was observed. The common location of lung cancers in the upper lobes, coupled with lower lung density, results in the potential occurrence of LED, which may underdose the tumour.

  19. Quantification of incidental mediastinal and hilar irradiation delivered during definitive stereotactic body radiation therapy for peripheral non-small cell lung cancer

    SciTech Connect (OSTI)

    Martin, Kate L.; Gomez, Jorge; Nazareth, Daryl P.; Warren, Graham W.; Singh, Anurag K.

    2012-07-01

    To determine the amount of incidental radiation dose received by the mediastinal and hilar nodes for patients with non-small cell lung cancer (NSCLC) treated with stereotactic body radiation therapy (SBRT). Fifty consecutive patients with NSCLC, treated using an SBRT technique, were identified. Of these patients, 38 had a prescription dose of 60 Gy in 20-Gy fractions and were eligible for analysis. For each patient, ipsilateral upper (level 2) and lower (level 4) paratracheal, and hilar (level 10) nodal regions were contoured on the planning computed tomography (CT) images. Using the clinical treatment plan, dose and volume calculations were performed retrospectively for each nodal region. SBRT to upper lobe tumors resulted in an average total ipsilateral mean dose of between 5.2 and 7.8 Gy for the most proximal paratracheal nodal stations (2R and 4R for right upper lobe lesions, 2L and 4L for left upper lobe lesions). SBRT to lower lobe tumors resulted in an average total ipsilateral mean dose of between 15.6 and 21.5 Gy for the most proximal hilar nodal stations (10R for right lower lobe lesions, 10 l for left lower lobe lesions). Doses to more distal nodes were substantially lower than 5 Gy. The often substantial incidental irradiation, delivered during SBRT for peripheral NSCLC of the lower lobes to the most proximal hilar lymph nodes may be therapeutic for low-volume, subclinical nodal disease. Treatment of peripheral upper lobe lung tumors delivers less incidental irradiation to the paratracheal lymph nodes with lower likelihood of therapeutic benefit.

  20. Predictive Treatment Management: Incorporating a Predictive Tumor Response Model Into Robust Prospective Treatment Planning for Non-Small Cell Lung Cancer

    SciTech Connect (OSTI)

    Zhang, Pengpeng; Yorke, Ellen; Hu, Yu-Chi; Mageras, Gig; Rimner, Andreas; Deasy, Joseph O.

    2014-02-01

    Purpose: We hypothesized that a treatment planning technique that incorporates predicted lung tumor regression into optimization, predictive treatment planning (PTP), could allow dose escalation to the residual tumor while maintaining coverage of the initial target without increasing dose to surrounding organs at risk (OARs). Methods and Materials: We created a model to estimate the geometric presence of residual tumors after radiation therapy using planning computed tomography (CT) and weekly cone beam CT scans of 5 lung cancer patients. For planning purposes, we modeled the dynamic process of tumor shrinkage by morphing the original planning target volume (PTV{sub orig}) in 3 equispaced steps to the predicted residue (PTV{sub pred}). Patients were treated with a uniform prescription dose to PTV{sub orig}. By contrast, PTP optimization started with the same prescription dose to PTV{sub orig} but linearly increased the dose at each step, until reaching the highest dose achievable to PTV{sub pred} consistent with OAR limits. This method is compared with midcourse adaptive replanning. Results: Initial parenchymal gross tumor volume (GTV) ranged from 3.6 to 186.5 cm{sup 3}. On average, the primary GTV and PTV decreased by 39% and 27%, respectively, at the end of treatment. The PTP approach gave PTV{sub orig} at least the prescription dose, and it increased the mean dose of the true residual tumor by an average of 6.0 Gy above the adaptive approach. Conclusions: PTP, incorporating a tumor regression model from the start, represents a new approach to increase tumor dose without increasing toxicities, and reduce clinical workload compared with the adaptive approach, although model verification using per-patient midcourse imaging would be prudent.

  1. Is Intermediate Radiation Dose Escalation With Concurrent Chemotherapy for Stage III NonSmall-Cell Lung Cancer Beneficial? A Multi-Institutional Propensity Score MatchedAnalysis

    SciTech Connect (OSTI)

    Rodrigues, George; Oberije, Cary; Senan, Suresh; Tsujino, Kayoko; Wiersma, Terry; Moreno-Jimenez, Marta; Kim, Tae Hyun; Marks, Lawrence B.; Rengan, Ramesh; De Petris, Luigi; Ramella, Sara; DeRuyck, Kim; De Dios, Nria Rodriguez; Warner, Andrew; Bradley, Jeffrey D.; Palma, David A.

    2015-01-01

    Purpose: The clinical benefits and risks of dose escalation (DE) for stage III nonsmall-cell lung cancer (NSCLC) remain uncertain despite the results from Radiation Therapy Oncology Group (RTOG) protocol 0617. There is significant heterogeneity of practice, with many clinicians prescribing intermediate dose levels between the 0617 study arms of 60 and 74Gy. This study investigated whether this strategy is associated with any survival benefits/risks by analyzing a large multi-institutional database. Methods and Materials: An individual patient database of stage III NSCLC patients treated with radical intent concurrent chemoradiation therapy was created (13 institutions, n=1274 patients). Patients were divided into 2 groups based on tumor Biological Effective Dose at 10 Gy (BED 10): those receiving standard dose (SD; n=552), consisting of 72Gy?BED 10?76.8Gy (eg 60-64Gy/30-32 fractions [fr]), and those receiving intermediate dose (ID; n=497), consisting of 76.8Gy64Gy/32 fr and <74Gy/37 fr), with lower-dose patients (n=225) excluded from consideration. Patients were then matched using propensity scores, leading to 2 matched groups of 196 patients. Outcomes were compared using various statistics including interquartile range (IQR), Kaplan-Meier curves, and adjusted Cox regression analysis. Results: Matched groups were found to be balanced except for N stage (more N3 disease in SD), median treatment year (SD in 2003; ID in 2007), platinum and taxane chemotherapy (SD in 28%; ID in 39%), and median follow-up (SD were 89months; ID were 40months). Median dose fractionation was 60Gy/30 fr in SD (BED 10 IQR: 72.0-75.5Gy) and 66Gy/33 fr (BED 10 IQR: 78.6-79.2Gy) in ID. Survival curves for SD and ID matched cohorts were statistically similar (P=.27); however, a nonstatistically significant trend toward better survival for ID was observed after 15months (median survival SD: 19.3months; ID: 21.0months). There was an increase in grades III to V lung toxicity associated with ID (13.0% vs 4.9%, respectively). Conclusions: No significant overall survival benefits were found with intermediate DE; however, more grade III or greater lung toxicity was observed. The separation of survival curves after 15months of follow-up suggests that a small overall survival improvement associated with intermediate DE cannot be excluded.

  2. Radiosensitizing Effects of Ectopic miR-101 on Non-Small-Cell Lung Cancer Cells Depend on the Endogenous miR-101 Level

    SciTech Connect (OSTI)

    Chen, Susie; Wang Hongyan; Ng, Wooi Loon; Curran, Walter J.; Wang Ya

    2011-12-01

    Purpose: Previously, we showed that ectopic miR-101 could sensitize human tumor cells to radiation by targeting ATM and DNA-PK catalytic subunit (DNA-PKcs) to inhibit DNA repair, as the endogenous miR-101 levels are low in tumors in general. However, the heterogeneity of human cancers may result in an exception. The purpose of this study was to test the hypothesis that a few tumor cell lines with a high level of endogenous miR-101 would prove less response to ectopic miR-101. Methods and Materials: Fourteeen non-small-cell lung cancer (NSCLC) cell lines and one immortalized non-malignant lung epithelial cell line (NL20) were used for comparing endogenous miR-101 levels by real-time reverse transcription-polymerase chain reaction. Based on the different miR-101 levels, four cell lines with different miR-101 levels were chosen for transfection with a green fluorescent protein-lentiviral plasmid encoding miR-101. The target protein levels were measured by using Western blotting. The radiosensitizing effects of ectopic miR-101 on these NSCLC cell lines were determined by a clonogenic assay and xenograft mouse model. Results: The endogenous miR-101 level was similar or lower in 13 NSCLC cell lines but was 11-fold higher in one cell line (H157) than in NL20 cells. Although ectopic miR-101 efficiently decreased the ATM and DNA-PKcs levels and increased the radiosensitization level in H1299, H1975, and A549 cells, it did not change the levels of the miR-101 targets or radiosensitivity in H157 cells. Similar results were observed in xenograft mice. Conclusions: A small number of NSCLC cell lines could have a high level of endogenous miR-101. The ectopic miR-101 was able to radiosensitize most NSCLC cells, except for the NSCLC cell lines that had a much higher endogenous miR-101 level. These results suggest that when we choose one miRNA as a therapeutic tool, the endogenous level of the miRNA in each tumor should be considered.

  3. Gamma Knife Stereotactic Radiosurgery as Salvage Therapy After Failure of Whole-Brain Radiotherapy in Patients With Small-Cell Lung Cancer

    SciTech Connect (OSTI)

    Harris, Sunit; Chan, Michael D.; Lovato, James F.; Ellis, Thomas L.; Tatter, Stephen B.; Bourland, J. Daniel; Munley, Michael T.; Guzman, Allan F. de; Shaw, Edward G.; Urbanic, James J.; McMullen, Kevin P.

    2012-05-01

    Purpose: Radiosurgery has been successfully used in selected cases to avoid repeat whole-brain irradiation (WBI) in patients with multiple brain metastases of most solid tumor histological findings. Few data are available for the use of radiosurgery for small-cell lung cancer (SCLC). Methods and Materials: Between November 1999 and June 2009, 51 patients with SCLC and previous WBI and new brain metastases were treated with GammaKnife stereotactic radiosurgery (GKSRS). A median dose of 18 Gy (range, 10-24 Gy) was prescribed to the margin of each metastasis. Patients were followed with serial imaging. Patient electronic records were reviewed to determine disease-related factors and clinical outcomes after GKSRS. Local and distant brain failure rates, overall survival, and likelihood of neurologic death were determined based on imaging results. The Kaplan-Meier method was used to determine survival and local and distant brain control. Cox proportional hazard regression was performed to determine strength of association between disease-related factors and survival. Results: Median survival time for the entire cohort was 5.9 months. Local control rates at 1 and 2 years were 57% and 34%, respectively. Distant brain failure rates at 1 and 2 years were 58% and 75%, respectively. Fifty-three percent of patients ultimately died of neurologic death. On multivariate analysis, patients with stable (hazard ratio [HR] = 2.89) or progressive (HR = 6.98) extracranial disease (ECD) had worse overall survival than patients without evidence of ECD (p = 0.00002). Concurrent chemotherapy improved local control (HR = 89; p = 0.006). Conclusions: GKSRS represents a feasible salvage option in patients with SCLC and brain metastases for whom previous WBI has failed. The status of patients' ECD is a dominant factor predictive of overall survival. Local control may be inferior to that seen with other cancer histological results, although the use of concurrent chemotherapy may help to improve this.

  4. Prognostic Impact of Radiation Therapy to the Primary Tumor in Patients With Non-small Cell Lung Cancer and Oligometastasis at Diagnosis

    SciTech Connect (OSTI)

    Lopez Guerra, Jose Luis [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States) [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Department of Radiation Oncology, Instituto Madrileno de Oncologia/Grupo IMO, Madrid (Spain); Gomez, Daniel, E-mail: dgomez@mdanderson.org [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States)] [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Zhuang, Yan; Hong, David S. [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States)] [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Heymach, John V. [Department of Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States)] [Department of Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Swisher, Stephen G. [Department of Thoracic Surgery, University of Texas MD Anderson Cancer Center, Houston, Texas (United States)] [Department of Thoracic Surgery, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Lin, Steven H.; Komaki, Ritsuko; Cox, James D.; Liao Zhongxing [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States)] [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States)

    2012-09-01

    Purpose: We investigated prognostic factors associated with survival in patients with non-small cell lung cancer (NSCLC) and oligometastatic disease at diagnosis, particularly the influence of local treatment to the primary site on prognosis. Methods and Materials: From January 2000 through June 2011, 78 consecutive patients with oligometastatic NSCLC (<5 metastases) at diagnosis underwent definitive chemoradiation therapy ({>=}45 Gy) to the primary site. Forty-four of these patients also received definitive local treatment for the oligometastases. Survival outcomes were estimated using the Kaplan-Meier method, and risk factors were identified by univariate and multivariate analyses. Results: Univariate Cox proportional hazard analysis revealed better overall survival (OS) for those patients who received at least 63 Gy of radiation to the primary site (P=.002), received definitive local treatment for oligometastasis (P=.041), had a Karnofsky performance status (KPS) score >80 (P=.007), had a gross tumor volume {<=}124 cm{sup 3} (P=.002), had adenocarcinoma histology (P=.002), or had no history of respiratory disease (P=.016). On multivariate analysis, radiation dose, performance status, and tumor volume retained significance (P=.004, P=.006, and P<.001, respectively). The radiation dose also maintained significance when patients with and without brain metastases were analyzed separately. Conclusions: Tumor volume, KPS, and receipt of at least 63 Gy to the primary tumor are associated with improved OS in patients with oligometastatic NSCLC at diagnosis. Our results suggest that a subset of such patients may benefit from definitive local therapy.

  5. Impact of Weight Change During the Course of Concurrent Chemoradiation Therapy on Outcomes in Stage IIIB Non-Small Cell Lung Cancer Patients: Retrospective Analysis of 425 Patients

    SciTech Connect (OSTI)

    Topkan, Erkan; Parlak, Cem; Selek, Ugur

    2013-11-15

    Purpose: We retrospectively investigated the impact of weight change (WC) during concurrent chemoradiation therapy (C-CRT) on clinical outcomes of stage 3B non-small cell lung cancer (NSCLC) patients. Methods and Materials: A total of 425 patients treated with C-CRT were included. All patients received 60 to 66 Gy of thoracic radiation therapy concurrently with 1 to 3 cycles of platinum-based chemotherapy. Pre- and posttreatment weight measurements on first and last days of C-CRT were used for WC. Patients were divided into 2 groups: group 1 = weight loss (WL); group 2 = weight preservation/gain (WP) for comparative analyses. Results: Following C-CRT, 252 patients (59.3%) experienced WL, while 89 patients (20.9%) and 84 patients (19.8%) showed WP or WG. At median 24.2 months of follow-up, 142 patients (33.4%) were alive (84 WP [48.6%] and 58 WL [23.0%]), and 58 (13.6%) of them were free of disease progression (41 [23.7%] for WP and 17 [6.7%] for WL). Median overall survival (OS), locoregional progression-free survival (LRPFS), progression-free survival (PFS), and distant metastases-free survival (DMFS) for the entire population were 22.8, 14.4, 10.6, and 11.7 months, respectively. Intergroup comparisons between WP and WL cohorts revealed significantly superior OS, LRPFS, PFS, and DMFS in WP patients (P<.05 for each). On multivariate analyses, only WL and advanced T stage were associated with poor prognosis (P<.05). Conclusions: Present results in 425 stage 3B NSCLC patients demonstrated that WL during C-CRT is strongly associated with inferior survival outcomes compared to WP. This emerging finding might be useful by forming an encouraging basis for future investigations in facilitating a way to improve the outcomes of these patients experiencing WL during C-CRT.

  6. HSPB1 Gene Polymorphisms Predict Risk of Mortality for US Patients After Radio(chemo)therapy for Non-Small Cell Lung Cancer

    SciTech Connect (OSTI)

    Xu Ting; Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas ; Wei Qingyi; Lopez Guerra, Jose Luis; Department of Radiation Oncology, Instituto Madrileno de Oncologia Wang Lie; Liu Zhensheng; Gomez, Daniel; O'Reilly, Michael; Lin, Steven Hsesheng; Zhuang Yan; Levy, Lawrence B.; Mohan, Radhe; Zhou Honghao; Liao Zhongxing

    2012-10-01

    Purpose: We investigated potential associations between single-nucleotide polymorphisms (SNPs) in the heat shock protein beta-1 (HSPB1) gene and overall survival in US patients with non-small cell lung cancer (NSCLC). Methods and Materials: Using available genomic DNA samples from 224 patients with NSCLC treated with definitive radio(chemo)therapy, we genotyped 2 SNPs of HSPB1 (NCBI SNP nos. rs2868370 and rs2868371). We used both Kaplan-Meier cumulative probability and Cox proportional hazards analyses to evaluate the effect of HSPB1 genotypes on survival. Results: Our cohort consisted of 117 men and 107 women, mostly white (79.5%), with a median age of 70 years. The median radiation dose was 66 Gy (range, 63-87.5 Gy), and 183 patients (82%) received concurrent platinum-based chemotherapy. The most common genotype of the rs2868371 SNP was CC (61%). Univariate and multivariate analyses showed that this genotype was associated with poorer survival than CG and GG genotypes (univariate hazard ratio [HR] = 1.39, 95% confidence interval [CI], 1.02-1.90; P=.037; multivariate HR = 1.39; 95% CI, 1.01-1.92; P=.045). Conclusions: Our results showed that the CC genotype of HSPB1 rs2868371 was associated with poorer overall survival in patients with NSCLC after radio(chemo)therapy, findings that contradict those of a previous study of Chinese patients. Validation of our findings with larger numbers of similar patients is needed, as are mechanical and clinical studies to determine the mechanism underlying these associations.

  7. Phase II Study of Accelerated High-Dose Radiotherapy With Concurrent Chemotherapy for Patients With Limited Small-Cell Lung Cancer: Radiation Therapy Oncology Group Protocol 0239

    SciTech Connect (OSTI)

    Komaki, Ritsuko; Paulus, Rebecca; Ettinger, David S.; Videtic, Gregory M.M.; Bradley, Jeffrey D.; Glisson, Bonnie S.; Sause, William T.; Curran, Walter J.; Choy, Hak

    2012-07-15

    Purpose: To investigate whether high-dose thoracic radiation given twice daily during cisplatin-etoposide chemotherapy for limited small-cell lung cancer (LSCLC) improves survival, acute esophagitis, and local control rates relative to findings from Intergroup trial 0096 (47%, 27%, and 64%). Patients and Methods: Patients were accrued over a 3-year period from 22 US and Canadian institutions. Patients with LSCLC and good performance status were given thoracic radiation to 61.2 Gy over 5 weeks (daily 1.8-Gy fractions on days 1-22, then twice-daily 1.8-Gy fractions on days 23-33). Cisplatin (60 mg/m{sup 2} IV) was given on day 1 and etoposide (120 mg/m{sup 2} IV) on days 1-3 and days 22-24, followed by 2 cycles of cisplatin plus etoposide alone. Patients who achieved complete response were offered prophylactic cranial irradiation. Endpoints included overall and progression-free survival; severe esophagitis (Common Toxicity Criteria v 2.0) and treatment-related fatalities; response (Response Evaluation Criteria in Solid Tumors); and local control. Results: Seventy-two patients were accrued from June 2003 through May 2006; 71 were evaluable (median age 63 years; 52% female; 58% Zubrod 0). Median survival time was 19 months; at 2 years, the overall survival rate was 36.6% (95% confidence interval [CI] 25.6%-47.7%), and progression-free survival 19.7% (95% CI 11.4%-29.6%). Thirteen patients (18%) experienced severe acute esophagitis, and 2 (3%) died of treatment-related causes; 41% achieved complete response, 39% partial response, 10% stable disease, and 6% progressive disease. The local control rate was 73%. Forty-three patients (61%) received prophylactic cranial irradiation. Conclusions: The overall survival rate did not reach the projected goal; however, rates of esophagitis were lower, and local control higher, than projected. This treatment strategy is now one of three arms of a prospective trial of chemoradiation for LSCLC (Radiation Therapy Oncology Group 0538/Cancer and Leukemia Group B 30610).

  8. Do Angiotensin-Converting Enzyme Inhibitors Reduce the Risk of Symptomatic Radiation Pneumonitis in Patients With Non-Small Cell Lung Cancer After Definitive Radiation Therapy? Analysis of a Single-Institution Database

    SciTech Connect (OSTI)

    Wang, Hongmei [Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, P.R. of China (China); Liao, Zhongxing, E-mail: zliao@mdanderson.org [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Zhuang, Yan; Xu, Ting; Nguyen, Quynh-Nhu; Levy, Lawrence B.; O'Reilly, Michael [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Gold, Kathryn A. [Department of Thoracic Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Gomez, Daniel R. [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States)

    2013-12-01

    Purpose: Preclinical studies have suggested that angiotensin-converting enzyme inhibitors (ACEIs) can mitigate radiation-induced lung injury. We sought here to investigate possible associations between ACEI use and the risk of symptomatic radiation pneumonitis (RP) among patients undergoing radiation therapy (RT) for nonsmall cell lung cancer (NSCLC). Methods and Materials: We retrospectively identified patients who received definitive radiation therapy for stages I to III NSCLC between 2004 and 2010 at a single tertiary cancer center. Patients must have received a radiation dose of at least 60 Gy for a single primary lung tumor and have had imaging and dosimetric data available for analysis. RP was quantified according to Common Terminology Criteria for Adverse Events, version 3.0. A Cox proportional hazard model was used to assess potential associations between ACEI use and risk of symptomatic RP. Results: Of 413 patients analyzed, 65 were using ACEIs during RT. In univariate analysis, the rate of RP grade ?2 seemed lower in ACEI users than in nonusers (34% vs 46%), but this apparent difference was not statistically significant (P=.06). In multivariate analysis of all patients, ACEI use was not associated with the risk of symptomatic RP (hazard ratio [HR] = 0.66; P=.07) after adjustment for sex, smoking status, mean lung dose (MLD), and concurrent carboplatin and paclitaxel chemotherapy. Subgroup analysis showed that ACEI use did have a protective effect from RP grade ?2 among patients who received a low (?20-Gy) MLD (P<.01) or were male (P=.04). Conclusions: A trend toward reduction in symptomatic RP among patients taking ACEIs during RT for NSCLC was not statistically significant on univariate or multivariate analyses, although certain subgroups may benefit from use (ie, male patients and those receiving low MLD). The evidence at this point is insufficient to establish whether the use of ACEIs does or does not reduce the risk of RP.

  9. Incidents of Security Concern

    SciTech Connect (OSTI)

    Atencio, Julian J.

    2014-05-01

    This presentation addresses incidents of security concern and an incident program for addressing them. It addresses the phases of an inquiry, and it divides incidents into categories based on severity and interest types based on whether security, management, or procedural interests are involved. A few scenarios are then analyzed according to these breakdowns.

  10. Activation of protein kinase B (PKB/Akt) and risk of lung cancer among rural women in India who cook with biomass fuel

    SciTech Connect (OSTI)

    Roychoudhury, Sanghita; Mondal, Nandan Kumar; Mukherjee, Sayali; Dutta, Anindita; Siddique, Shabana; Ray, Manas Ranjan

    2012-02-15

    The impact of indoor air pollution (IAP) from biomass fuel burning on the risk of carcinogenesis in the airways has been investigated in 187 pre-menopausal women (median age 34 years) from eastern India who cooked exclusively with biomass and 155 age-matched control women from same locality who cooked with cleaner fuel liquefied petroleum gas. Compared with control, Papanicolau-stained sputum samples showed 3-times higher prevalence of metaplasia and 7-times higher prevalence of dysplasia in airway epithelial cell (AEC) of biomass users. Immunocytochemistry showed up-regulation of phosphorylated Akt (p-Akt{sup ser473} and p-Akt{sup thr308}) proteins in AEC of biomass users, especially in metaplastic and dysplastic cells. Compared with LPG users, biomass-using women showed marked rise in reactive oxygen species (ROS) generation and depletion of antioxidant enzyme, superoxide dismutase (SOD) indicating oxidative stress. There were 25 times more particulate pollutants (PM{sub 10} and PM{sub 2.5}), 72% more nitrogen dioxide and 4-times more particulate-laden benzo(a)pyrene, but no change in sulfur dioxide in indoor air of biomass-using households, and high performance liquid chromatography estimated 6-fold rise in the concentration of benzene metabolite trans,trans-muconic acid (t,t-MA) in urine of biomass users. Metaplasia and dysplasia, p-Akt expression and ROS generation were positively associated with PM and t,t-MA levels. It appears that cumulative exposure to biomass smoke increases the risk of lung carcinogenesis via oxidative stress-mediated activation of Akt signal transduction pathway. -- Highlights: ? Carcinogenesis in airway cells was examined in biomass and LPG using women. ? Metaplasia and dysplasia of epithelial cells were more prevalent in biomass users. ? Change in airway cytology was associated with oxidative stress and Akt activation. ? Biomass users had greater exposure to respirable PM, B(a)P and benzene. ? Cooking with biomass increases cancer risk in the airways via Akt activation.

  11. Does Response to Induction Chemotherapy Predict Survival for Locally Advanced Non-Small-Cell Lung Cancer? Secondary Analysis of RTOG 8804/8808

    SciTech Connect (OSTI)

    McAleer, Mary Frances; Moughan, Jennifer M.S.; Byhardt, Roger W.; Cox, James D.; Sause, William T.; Komaki, Ritsuko

    2010-03-01

    Purpose: Induction chemotherapy (ICT) improves survival compared with radiotherapy (RT) alone in locally advanced non-small-cell lung cancer (LANSCLC) patients with good prognostic factors. Concurrent chemoradiotherapy (CCRT) is superior to ICT followed by RT. The question arises whether ICT response predicts the outcome of patients subsequently treated with CCRT or RT. Methods and Materials: Between 1988 and 1992, 194 LANSCLC patients were treated prospectively with ICT (two cycles of vinblastine and cisplatin) and then CCRT (cisplatin plus 63 Gy for 7 weeks) in the Radiation Therapy Oncology Group 8804 trial (n = 30) or ICT and then RT (60 Gy/6 wk) on Radiation Therapy Oncology Group 8808 trial (n = 164). Of the 194 patients, 183 were evaluable and 141 had undergone a postinduction assessment. The overall survival (OS) of those with complete remission (CR) or partial remission (PR) was compared with that of patients with stable disease (SD) or progressive disease (PD) after ICT. Results: Of the 141 patients, 6, 30, 99, and 6 had CR, PR, SD, and PD, respectively. The log-rank test showed a significant difference (p <0.0001) in OS when the response groups were compared (CR/PR vs. SD/PD). On univariate and multivariate analyses, a trend was seen toward a response to ICT with OS (p = 0.097 and p = 0.06, respectively). A squamous histologic type was associated with worse OS on univariate and multivariate analyses (p = 0.031 and p = 0.018, respectively). SD/PD plus a squamous histologic type had a hazard ratio of 2.25 vs. CR/PR plus a nonsquamous histologic type (p = 0.007) on covariate analysis. Conclusion: The response to ICT was associated with a significant survival difference when the response groups were compared. A response to ICT showed a trend toward, but was not predictive of, improved OS in LANSCLC patients. Patients with SD/PD after ICT and a squamous histologic type had the poorest OS. These data suggest that patients with squamous LANSCLC might benefit from immediate RT or CCRT.

  12. The Impact of Extent and Location of Mediastinal Lymph Node Involvement on Survival in Stage III Non-Small Cell Lung Cancer Patients Treated With Definitive Radiotherapy

    SciTech Connect (OSTI)

    Fernandes, Annemarie T.; Mitra, Nandita; Xanthopoulos, Eric; Evans, Tracey; Stevenson, James; Langer, Corey; Kucharczuk, John C.; Lin, Lilie; Rengan, Ramesh

    2012-05-01

    Purpose: Several surgical series have identified subcarinal, contralateral, and multilevel nodal involvement as predictors of poor overall survival in patients with Stage III non-small-cell lung cancer (NSCLC) treated with definitive resection. This retrospective study evaluates the impact of extent and location of mediastinal lymph node (LN) involvement on survival in patients with Stage III NSCLC treated with definitive radiotherapy. Methods and Materials: We analyzed 106 consecutive patients with T1-4 N2-3 Stage III NSCLC treated with definitive radiotherapy at University of Pennsylvania between January 2003 and February 2009. For this analysis, mediastinal LN stations were divided into four mutually exclusive groups: supraclavicular, ipsilateral mediastinum, contralateral mediastinum, and subcarinal. Patients' conditions were then analyzed according to the extent of involvement and location of mediastinal LN stations. Results: The majority (88%) of patients received sequential or concurrent chemotherapy. The median follow-up time for survivors was 32.6 months. By multivariable Cox modeling, chemotherapy use (hazard ratio [HR]: 0.21 [95% confidence interval (CI): 0.07-0.63]) was associated with improved overall survival. Increasing primary tumor [18F]-fluoro-2-deoxy-glucose avidity (HR: 1.11 [CI: 1.06-1.19]), and subcarinal involvement (HR: 2.29 [CI: 1.11-4.73]) were significant negative predictors of overall survival. On univariate analysis, contralateral nodal involvement (HR: 0.70 [CI: 0.33-1.47]), supraclavicular nodal involvement (HR: 0.78 [CI: 0.38-1.67]), multilevel nodal involvement (HR: 0.97 [CI: 0.58-1.61]), and tumor size (HR: 1.04 [CI: 0.94-1.14]) did not predict for overall survival. Patients with subcarinal involvement also had lower rates of 2-year nodal control (51.2% vs. 74.9%, p = 0.047) and 2-year distant control (28.4% vs. 61.2%, p = 0.043). Conclusions: These data suggest that the factors that determine oncologic outcome in Stage III NSCLC patients treated with definitive radiotherapy are distinct from those observed in patients who undergo surgical resection. The ultimate efficacy of radiation in locally advanced NSCLC is dependent on the intrinsic biology of the tumor.

  13. Modeling the Risk of Radiation-Induced Acute Esophagitis for Combined Washington University and RTOG Trial 93-11 Lung Cancer Patients

    SciTech Connect (OSTI)

    Huang, Ellen X.; Bradley, Jeffrey D.; El Naqa, Issam [Department of Radiation Oncology, Washington University School of Medicine, St Louis, MO (United States); Hope, Andrew J.; Lindsay, Patricia E. [Princess Margaret Hospital, Toronto, ON (Canada); Bosch, Walter R.; Matthews, John W. [Department of Radiation Oncology, Washington University School of Medicine, St Louis, MO (United States); Sause, William T. [Department of Radiation Oncology, LDS Hospital, Salt Lake City, UT (United States); Graham, Mary V. [Department of Radiation Oncology, Phelps County Regional Hospital, Rolla, MO (United States); Deasy, Joseph O., E-mail: deasyj@mskcc.org [Department of Medical Physics, Memorial Sloan-Kettering Cancer Center, New York, NY (United States)

    2012-04-01

    Purpose: To construct a maximally predictive model of the risk of severe acute esophagitis (AE) for patients who receive definitive radiation therapy (RT) for non-small-cell lung cancer. Methods and Materials: The dataset includes Washington University and RTOG 93-11 clinical trial data (events/patients: 120/374, WUSTL = 101/237, RTOG9311 = 19/137). Statistical model building was performed based on dosimetric and clinical parameters (patient age, sex, weight loss, pretreatment chemotherapy, concurrent chemotherapy, fraction size). A wide range of dose-volume parameters were extracted from dearchived treatment plans, including Dx, Vx, MOHx (mean of hottest x% volume), MOCx (mean of coldest x% volume), and gEUD (generalized equivalent uniform dose) values. Results: The most significant single parameters for predicting acute esophagitis (RTOG Grade 2 or greater) were MOH85, mean esophagus dose (MED), and V30. A superior-inferior weighted dose-center position was derived but not found to be significant. Fraction size was found to be significant on univariate logistic analysis (Spearman R = 0.421, p < 0.00001) but not multivariate logistic modeling. Cross-validation model building was used to determine that an optimal model size needed only two parameters (MOH85 and concurrent chemotherapy, robustly selected on bootstrap model-rebuilding). Mean esophagus dose (MED) is preferred instead of MOH85, as it gives nearly the same statistical performance and is easier to compute. AE risk is given as a logistic function of (0.0688 Asterisk-Operator MED+1.50 Asterisk-Operator ConChemo-3.13), where MED is in Gy and ConChemo is either 1 (yes) if concurrent chemotherapy was given, or 0 (no). This model correlates to the observed risk of AE with a Spearman coefficient of 0.629 (p < 0.000001). Conclusions: Multivariate statistical model building with cross-validation suggests that a two-variable logistic model based on mean dose and the use of concurrent chemotherapy robustly predicts acute esophagitis risk in combined-data WUSTL and RTOG 93-11 trial datasets.

  14. SU-E-T-481: Dosimetric Comparison of Acuros XB and Anisotropic Analytic Algorithm with Commercial Monte Carlo Based Dose Calculation Algorithm for Stereotactic Body Radiation Therapy of Lung Cancer

    SciTech Connect (OSTI)

    Cao, M; Tenn, S; Lee, C; Yang, Y; Lamb, J; Agazaryan, N; Lee, P; Low, D

    2014-06-01

    Purpose: To evaluate performance of three commercially available treatment planning systems for stereotactic body radiation therapy (SBRT) of lung cancer using the following algorithms: Boltzmann transport equation based algorithm (AcurosXB AXB), convolution based algorithm Anisotropic Analytic Algorithm (AAA); and Monte Carlo based algorithm (XVMC). Methods: A total of 10 patients with early stage non-small cell peripheral lung cancer were included. The initial clinical plans were generated using the XVMC based treatment planning system with a prescription of 54Gy in 3 fractions following RTOG0613 protocol. The plans were recalculated with the same beam parameters and monitor units using AAA and AXB algorithms. A calculation grid size of 2mm was used for all algorithms. The dose distribution, conformity, and dosimetric parameters for the targets and organs at risk (OAR) are compared between the algorithms. Results: The average PTV volume was 19.6mL (range 4.247.2mL). The volume of PTV covered by the prescribed dose (PTV-V100) were 93.972.00%, 95.072.07% and 95.102.97% for XVMC, AXB and AAA algorithms, respectively. There was no significant difference in high dose conformity index; however, XVMC predicted slightly higher values (p=0.04) for the ratio of 50% prescription isodose volume to PTV (R50%). The percentage volume of total lungs receiving dose >20Gy (LungV20Gy) were 4.032.26%, 3.862.22% and 3.852.21% for XVMC, AXB and AAA algorithms. Examination of dose volume histograms (DVH) revealed small differences in targets and OARs for most patients. However, the AAA algorithm was found to predict considerable higher PTV coverage compared with AXB and XVMC algorithms in two cases. The dose difference was found to be primarily located at the periphery region of the target. Conclusion: For clinical SBRT lung treatment planning, the dosimetric differences between three commercially available algorithms are generally small except at target periphery. XVMC and AXB algorithms are recommended for accurate dose estimation at tissue boundaries.

  15. Predicting Pneumonitis Risk: A Dosimetric Alternative to Mean Lung Dose

    SciTech Connect (OSTI)

    Tucker, Susan L.; Mohan, Radhe; Liengsawangwong, Raweewan; Martel, Mary K.; Liao Zhongxing

    2013-02-01

    Purpose: To determine whether the association between mean lung dose (MLD) and risk of severe (grade {>=}3) radiation pneumonitis (RP) depends on the dose distribution pattern to normal lung among patients receiving 3-dimensional conformal radiation therapy for non-small-cell lung cancer. Methods and Materials: Three cohorts treated with different beam arrangements were identified. One cohort (2-field boost [2FB]) received 2 parallel-opposed (anteroposterior-posteroanterior) fields per fraction initially, followed by a sequential boost delivered using 2 oblique beams. The other 2 cohorts received 3 or 4 straight fields (3FS and 4FS, respectively), ie, all fields were irradiated every day. The incidence of severe RP was plotted against MLD in each cohort, and data were analyzed using the Lyman-Kutcher-Burman (LKB) model. Results: The incidence of grade {>=}3 RP rose more steeply as a function of MLD in the 2FB cohort (N=120) than in the 4FS cohort (N=138), with an intermediate slope for the 3FS group (N=99). The estimated volume parameter from the LKB model was n=0.41 (95% confidence interval, 0.15-1.0) and led to a significant improvement in fit (P=.05) compared to a fit with volume parameter fixed at n=1 (the MLD model). Unlike the MLD model, the LKB model with n=0.41 provided a consistent description of the risk of severe RP in all three cohorts (2FB, 3FS, 4FS) simultaneously. Conclusions: When predicting risk of grade {>=}3 RP, the mean lung dose does not adequately take into account the effects of high doses. Instead, the effective dose, computed from the LKB model using volume parameter n=0.41, may provide a better dosimetric parameter for predicting RP risk. If confirmed, these findings support the conclusion that for the same MLD, high doses to small lung volumes ('a lot to a little') are worse than low doses to large volumes ('a little to a lot').

  16. Incidents of Security Concern

    Office of Environmental Management (EM)

    NOT MEASUREMENT SENSITIVE DOE-STD-1210-2012 September 2012 DOE STANDARD Incidents of Security Concern U.S. Department of Energy AREA SANS Washington, D.C. 20585 DISTRIBUTION STATEMENT A. Approved for public release; distribution is unlimited. DOE-STD-1210-2012 INTENTIONALLY BLANK DOE-STD-1210-2012 TABLE OF CONTENTS PARAGRAPH PAGE FOREWORD ................................................................................................................................ IV INCIDENTS OF SECURITY

  17. July 2013 Cyber Incident

    Broader source: Energy.gov [DOE]

    The Department of Energy (DOE) has confirmed a cyber incident that occurred at the end of July and resulted in the unauthorized disclosure of federal employee Personally Identifiable Information ...

  18. January 2013 Cyber Incident

    Broader source: Energy.gov [DOE]

    The Department of Energy (DOE) has confirmed a recent cyber incident that occurred in mid-January 2013 which targeted the Headquarters' network and resulted in the unauthorized disclosure of...

  19. Incidents of Security Concern

    Broader source: Directives, Delegations, and Requirements [Office of Management (MA)]

    2004-03-17

    Sets forth requirements for the DOE Incidents of Security Concern Program, including timely identification and notification of, response to, inquiry into, reporting of, and closure actions for incidents of security concern. Cancels Chapter VII of DOE O 470.1; DOE N 471.3; and Chapter IV of DOE M 471.2-1B (Note: Paragraphs 1 and 2 of Chapter III remain in effect.) Canceled by DOE O 470.4.

  20. Nonbreast Second Malignancies After Treatment of Primary Breast Cancer

    SciTech Connect (OSTI)

    Yadav, Budhi S. Sharma, Suresh C.; Patel, Firuza D.; Ghoshal, Sushmita; Kapoor, Rakesh; Kumar, Rajinder

    2009-04-01

    Purpose: To determine the incidence and risk factors for nonbreast second malignancies (NBSMs) in women after treatment for primary breast cancer. Methods and Materials: Between January 1985 and December 1995, a total of 1,084 breast cancer patients were analyzed for NBSMs. Detailed analysis was carried out for age, family history, disease stage, radiation therapy, chemotherapy, hormone therapy, other clinical/pathologic characteristics, and site of NBSMs. The Cox proportional hazard regression model was used to estimate the relative risk of NBSMs. Results: Median follow-up was 12 years. In total, 33 cases of NBSMs were noted in 29 patients. The overall incidence of NBSM was 3%, and the median time for NBSMs was 7 years. The most common NBSMs were gynecologic (22 patients), gastrointestinal (4 patients), head and neck (3 patients), hematologic (2 patients), lung (1 patient), and thyroid (1 patient). The NBSMs rate at 12 years was 2.4% for both mastectomy and radiation therapy groups. In the subset of patients less than 45 years of age at the time of treatment, the NBSMs rate was 0.7% as compared with 4.6% in patients more than 45 years of age (p = 0.001). Statistically significant higher incidences of endometrial and ovarian cancer were seen in patients with hormonal therapy (5.2%) as compared with patients without hormonal therapy (1.8%, p = 0.002). Women with a family history of breast cancer had a higher incidence (6%) of endometrial and ovarian malignancy compared with women without such a history (2.1%, p = 0.003). Chemotherapy did not affect the risk of second malignancy. Conclusion: The most common NBSMs in this study were gynecologic. Family history of breast cancer was a high risk factor for NBSMs. No risk of NBSMs with radiotherapy was observed.

  1. A polysaccharide fraction of adlay seed (Coixlachryma-jobi L.) induces apoptosis in human non-small cell lung cancer A549 cells

    SciTech Connect (OSTI)

    Lu, Xiangyi; Liu, Wei; Wu, Junhua; Li, Mengxian [Key Laboratory of Food Nutrition and Safety, Ministry of Education, School of Food Engineering and Biotechnology, Tianjin University of Science and Technology, Tianjin 300457 (China)] [Key Laboratory of Food Nutrition and Safety, Ministry of Education, School of Food Engineering and Biotechnology, Tianjin University of Science and Technology, Tianjin 300457 (China); Wang, Juncheng; Wu, Jihui [School of Life Science, University of Science and Technology of China, Hefei 230022 (China)] [School of Life Science, University of Science and Technology of China, Hefei 230022 (China); Luo, Cheng, E-mail: Luo58@yahoo.com [Key Laboratory of Food Nutrition and Safety, Ministry of Education, School of Food Engineering and Biotechnology, Tianjin University of Science and Technology, Tianjin 300457 (China)] [Key Laboratory of Food Nutrition and Safety, Ministry of Education, School of Food Engineering and Biotechnology, Tianjin University of Science and Technology, Tianjin 300457 (China)

    2013-01-11

    Highlights: Black-Right-Pointing-Pointer A polysaccharide from adlay seed, its molecular mass, optical rotation and sugars was determined. Black-Right-Pointing-Pointer We demonstrated that a polysaccharide from adlay can induce apoptosis in cancer cells. Black-Right-Pointing-Pointer The polysaccharide inhibited the metabolism and proliferation of NSCLC A549 cells. Black-Right-Pointing-Pointer The polysaccharide may trigger apoptosis via the mitochondria-dependent pathway. -- Abstract: Different seed extracts from Coix lachryma-jobi (adlay seed) have been used for the treatment of various cancers in China, and clinical data support the use of these extracts for cancer therapy; however, their underlying molecular mechanisms have not been well defined. A polysaccharide fraction, designated as CP-1, was extracted from the C.lachryma-jobi L. var. using the ethanol subsiding method. CP-1 induced apoptosis in A549 cells in a dose-dependent manner, as determined by MTT assay. Apoptotic bodies were observed in the cells by scanning electronic microscopy. Apoptosis and DNA accumulation during S-phase of the cell cycle were determined by annexin V-FITC and PI staining, respectively, and measured by flow cytometry. CP-1 also extended the comet tail length on single cell gel electrophoresis, and disrupted the mitochondrial membrane potential. Further analysis by western blotting showed that the expression of caspase-3 and caspase-9 proteins was increased. Taken together, our results demonstrate that CP-1 is capable of inhibiting A549 cell proliferation and inducing apoptosis via a mechanism primarily involving the activation of the intrinsic mitochondrial pathway. The assay data suggest that in addition to its nutritional properties, CP-1 is a very promising candidate polysaccharide for the development of anti-cancer medicines.

  2. Incident Management | Department of Energy

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    Management Incident Management IC2 (004).jpg The Incident Management Program (IMP) focuses on: threat information sharing critical infrastructure protection active defense incident preparedness. The IMP reports all incidents to the United States Computer Emergency Readiness Team (US-CERT), fulfilling statutory requirements and ensuring a coordinated response to cyber attacks. Joint Cybersecurity Coordination Center (JC3) The Joint Cybersecurity Coordination Center (JC3) provides DOE with

  3. Effects of Respiratory Motion on Passively Scattered Proton Therapy Versus Intensity Modulated Photon Therapy for Stage III Lung Cancer: Are Proton Plans More Sensitive to Breathing Motion?

    SciTech Connect (OSTI)

    Matney, Jason; Park, Peter C. [Department of Radiation Physics, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); The University of Texas Graduate School of Biomedical Sciences, Houston, Texas (United States); Bluett, Jaques [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Chen, Yi Pei [Department of Radiation Physics, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); The University of Texas Graduate School of Biomedical Sciences, Houston, Texas (United States); Liu, Wei; Court, Laurence E. [Department of Radiation Physics, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Liao, Zhongxing [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Li, Heng [Department of Radiation Physics, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Mohan, Radhe, E-mail: rmohan@mdanderson.org [Department of Radiation Physics, University of Texas MD Anderson Cancer Center, Houston, Texas (United States)

    2013-11-01

    Purpose: To quantify and compare the effects of respiratory motion on paired passively scattered proton therapy (PSPT) and intensity modulated photon therapy (IMRT) plans; and to establish the relationship between the magnitude of tumor motion and the respiratory-induced dose difference for both modalities. Methods and Materials: In a randomized clinical trial comparing PSPT and IMRT, radiation therapy plans have been designed according to common planning protocols. Four-dimensional (4D) dose was computed for PSPT and IMRT plans for a patient cohort with respiratory motion ranging from 3 to 17 mm. Image registration and dose accumulation were performed using grayscale-based deformable image registration algorithms. The dosevolume histogram (DVH) differences (4D-3D [3D = 3-dimensional]) were compared for PSPT and IMRT. Changes in 4D-3D dose were correlated to the magnitude of tumor respiratory motion. Results: The average 4D-3D dose to 95% of the internal target volume was close to zero, with 19 of 20 patients within 1% of prescribed dose for both modalities. The mean 4D-3D between the 2 modalities was not statistically significant (P<.05) for all dosevolume histogram indices (mean SD) except the lung V5 (PSPT: +1.1% 0.9%; IMRT: +0.4% 1.2%) and maximum cord dose (PSPT: +1.5 2.9 Gy; IMRT: 0.0 0.2 Gy). Changes in 4D-3D dose were correlated to tumor motion for only 2 indices: dose to 95% planning target volume, and heterogeneity index. Conclusions: With our current margin formalisms, target coverage was maintained in the presence of respiratory motion up to 17 mm for both PSPT and IMRT. Only 2 of 11 4D-3D indices (lung V5 and spinal cord maximum) were statistically distinguishable between PSPT and IMRT, contrary to the notion that proton therapy will be more susceptible to respiratory motion. Because of the lack of strong correlations with 4D-3D dose differences in PSPT and IMRT, the extent of tumor motion was not an adequate predictor of potential dosimetric error caused by breathing motion.

  4. Tumor Volume Combined With Number of Positive Lymph Node Stations Is a More Important Prognostic Factor Than TNM Stage for Survival of Non-Small-Cell Lung Cancer Patients Treated With (Chemo)radiotherapy

    SciTech Connect (OSTI)

    Dehing-Oberije, Cary [Department of Radiotherapy, University Hospital Maastricht, University Maastricht, MAASTRO Clinic, Research Institute Growth and Development (GROW), Maastricht (Netherlands)], E-mail: cary.dehing@maastro.nl; Ruysscher, Dirk de; Weide, Hiska van der [Department of Radiotherapy, University Hospital Maastricht, University Maastricht, MAASTRO Clinic, Research Institute Growth and Development (GROW), Maastricht (Netherlands); Hochstenbag, Monique [Department of Pulmonology, University Hospital Maastricht, Maastricht (Netherlands); Bootsma, Gerben [Department of Pulmonology, Atrium Medical Centre, Heerlen (Netherlands); Geraedts, Wiel [Department of Pulmonology, Maasland Hospital, Sittard (Netherlands); Pitz, Cordula [Department of Pulmonology, Laurentius Hospital, Roermond (Netherlands); Simons, Jean [Department of Pulmonology, Sint Jans Hospital, Weert (Netherlands); Teule, Jaap [Department of Nuclear Medicine, University Hospital Maastricht, Maastricht (Netherlands); Rahmy, Ali [Department of Nuclear Medicine, Atrium Medical Centre, Heerlen (Netherlands); Thimister, Paul [Department of Nuclear Medicine, Maasland Hospital, Sittard (Netherlands); Steck, Harald [Siemens Medical Solutions, Malvern, PA (United States); Lambin, Philippe [Department of Radiotherapy, University Hospital Maastricht, University Maastricht, MAASTRO Clinic, Research Institute Growth and Development (GROW), Maastricht (Netherlands)

    2008-03-15

    Purpose: The current tumor, node, metastasis system needs refinement to improve its ability to predict survival of patients with non-small-cell lung cancer (NSCLC) treated with (chemo)radiation. In this study, we investigated the prognostic value of tumor volume and N status, assessed by using fluorodeoxyglucose-positron emission tomography (PET). Patients and Methods: Clinical data from 270 consecutive patients with inoperable NSCLC Stages I-IIIB treated radically with (chemo)radiation were collected retrospectively. Diagnostic imaging was performed using either integrated PET-computed tomography or computed tomography and PET separately. The Kaplan-Meier method, as well as Cox regression, was used to analyze data. Results: Univariate survival analysis showed that number of positive lymph node stations (PLNSs), as well as N stage on PET, was associated significantly with survival. The final multivariate Cox model consisted of number of PLNSs, gross tumor volume (i.e., volume of the primary tumor plus lymph nodes), sex, World Health Organization performance status, and equivalent radiation dose corrected for time; N stage was no longer significant. Conclusions: Number of PLNSs, assessed by means of fluorodeoxyglucose-PET, was a significant factor for survival of patients with inoperable NSCLC treated with (chemo)radiation. Risk stratification for this group of patients should be based on gross tumor volume, number of PLNSs, sex, World Health Organization performance status, and equivalent radiation dose corrected for time.

  5. A Phase 3 Trial of Whole Brain Radiation Therapy and Stereotactic Radiosurgery Alone Versus WBRT and SRS With Temozolomide or Erlotinib for Non-Small Cell Lung Cancer and 1 to 3 Brain Metastases: Radiation Therapy Oncology Group 0320

    SciTech Connect (OSTI)

    Sperduto, Paul W.; Wang, Meihua; Robins, H. Ian; Schell, Michael C.; Werner-Wasik, Maria; Komaki, Ritsuko; Souhami, Luis; Buyyounouski, Mark K.; Khuntia, Deepak; Demas, William; Shah, Sunjay A.; Nedzi, Lucien A.; Perry, Gad; Suh, John H.; Mehta, Minesh P.

    2013-04-01

    Background: A phase 3 Radiation Therapy Oncology Group (RTOG) study subset analysis demonstrated improved overall survival (OS) with the addition of stereotactic radiosurgery (SRS) to whole brain radiation therapy (WBRT) in non-small cell lung cancer (NSCLC) patients with 1 to 3 brain metastases. Because temozolomide (TMZ) and erlotinib (ETN) cross the blood-brain barrier and have documented activity in NSCLC, a phase 3 study was designed to test whether these drugs would improve the OS associated with WBRT + SRS. Methods and Materials: NSCLC patients with 1 to 3 brain metastases were randomized to receive WBRT (2.5 Gy 15 to 37.5 Gy) and SRS alone, versus WBRT + SRS + TMZ (75 mg/m{sup 2}/day 21 days) or ETN (150 mg/day). ETN (150 mg/day) or TMZ (150-200 mg/m{sup 2}/day 5 days/month) could be continued for as long as 6 months after WBRT + SRS. The primary endpoint was OS. Results: After 126 patients were enrolled, the study closed because of accrual limitations. The median survival times (MST) for WBRT + SRS, WBRT + SRS + TMZ, and WBRT + SRS + ETN were qualitatively different (13.4, 6.3, and 6.1 months, respectively), although the differences were not statistically significant. Time to central nervous system progression and performance status at 6 months were better in the WBRT + SRS arm. Grade 3 to 5 toxicity was 11%, 41%, and 49% in arms 1, 2, and 3, respectively (P<.001). Conclusion: The addition of TMZ or ETN to WBRT + SRS in NSCLC patients with 1 to 3 brain metastases did not improve survival and possibly had a deleterious effect. Because the analysis is underpowered, these data suggest but do not prove that increased toxicity was the cause of inferior survival in the drug arms.

  6. Functional Polymorphisms of Base Excision Repair Genes XRCC1 and APEX1 Predict Risk of Radiation Pneumonitis in Patients With Non-Small Cell Lung Cancer Treated With Definitive Radiation Therapy

    SciTech Connect (OSTI)

    Yin Ming; Liao Zhongxing; Liu Zhensheng; Wang, Li-E; Gomez, Daniel; Komaki, Ritsuko; Wei Qingyi

    2011-11-01

    Purpose: To explore whether functional single nucleotide polymorphisms (SNPs) of base-excision repair genes are predictors of radiation treatment-related pneumonitis (RP), we investigated associations between functional SNPs of ADPRT, APEX1, and XRCC1 and RP development. Methods and Materials: We genotyped SNPs of ADPRT (rs1136410 [V762A]), XRCC1 (rs1799782 [R194W], rs25489 [R280H], and rs25487 [Q399R]), and APEX1 (rs1130409 [D148E]) in 165 patients with non-small cell lung cancer (NSCLC) who received definitive chemoradiation therapy. Results were assessed by both Logistic and Cox regression models for RP risk. Kaplan-Meier curves were generated for the cumulative RP probability by the genotypes. Results: We found that SNPs of XRCC1 Q399R and APEX1 D148E each had a significant effect on the development of Grade {>=}2 RP (XRCC1: AA vs. GG, adjusted hazard ratio [HR] = 0.48, 95% confidence interval [CI], 0.24-0.97; APEX1: GG vs. TT, adjusted HR = 3.61, 95% CI, 1.64-7.93) in an allele-dose response manner (Trend tests: p = 0.040 and 0.001, respectively). The number of the combined protective XRCC1 A and APEX1 T alleles (from 0 to 4) also showed a significant trend of predicting RP risk (p = 0.001). Conclusions: SNPs of the base-excision repair genes may be biomarkers for susceptibility to RP. Larger prospective studies are needed to validate our findings.

  7. Definitive Chemoradiation Therapy Following Surgical Resection or Radiosurgery Plus Whole-Brain Radiation Therapy in Non-Small Cell Lung Cancer Patients With Synchronous Solitary Brain Metastasis: A Curative Approach

    SciTech Connect (OSTI)

    Parlak, Cem; Mertsoylu, Hüseyin; Güler, Ozan Cem; Onal, Cem; Topkan, Erkan

    2014-03-15

    Purpose/Objectives: The aim of this study was to evaluate the impact of definitive thoracic chemoradiation therapy following surgery or stereotactic radiosurgery (SRS) and whole-brain radiation therapy (WBRT) on the outcomes of patients with non-small cell lung cancer (NSCLC) with synchronous solitary brain metastasis (SSBM). Methods and Materials: A total of 63 NSCLC patients with SSBM were retrospectively evaluated. Patients were staged using positron emission tomography-computed tomography in addition to conventional staging tools. Thoracic radiation therapy (TRT) with a total dose of 66 Gy in 2 Gy fractions was delivered along with 2 cycles of cisplatin-based chemotherapy following either surgery plus 30 Gy of WBRT (n=33) or SRS plus 30 Gy of WBRT (n=30) for BM. Results: Overall, the treatment was well tolerated. All patients received planned TRT, and 57 patients (90.5%) were also able to receive 2 cycles of chemotherapy. At a median follow-up of 25.3 months (7.1-52.1 months), the median months of overall, locoregional progression-free, neurological progression-free, and progression-free survival were 28.6, 17.7, 26.4, and 14.6, respectively. Both univariate and multivariate analyses revealed that patients with a T1-T2 thoracic disease burden (P=.001), a nodal stage of N0-N1 (P=.003), and no weight loss (P=.008) exhibited superior survival. Conclusions: In the present series, surgical and radiosurgical treatments directed toward SSBM in NSCLC patients were equally effective. The similarities between the present survival outcomes and those reported in other studies for locally advanced NSCLC patients indicate the potentially curative role of definitive chemoradiation therapy for highly selected patients with SSBM.

  8. Cyber Security Incident Management Manual

    Broader source: Directives, Delegations, and Requirements [Office of Management (MA)]

    2009-01-08

    The manual establishes minimum requirements for a structured cyber security incident detection and management process for detecting, identifying, categorizing, containing, reporting, and mitigating cyber security incidents involving DOE information and information systems operated by DOE or by contractors on behalf of the Department. No cancellations. Admin Chg 1 dated 9-1-09.

  9. Cyber Security Incident Management Manual

    Broader source: Directives, Delegations, and Requirements [Office of Management (MA)]

    2009-01-08

    The manual establishes minimum requirements for a structured cyber security incident detection and management process for detecting, identifying, categorizing, containing, reporting, and mitigating cyber security incidents involving DOE information and information systems operated by DOE or by contractors on behalf of the Department. No cancellations.

  10. Reporting Incidents Of Security Concern

    Broader source: Directives, Delegations, and Requirements [Office of Management (MA)]

    2001-04-03

    To enhance the Department of Energy (DOE) Incidents of Security Concern Reporting Program through more consistent reporting, better information tracking, and interactive coordination. DOE N 251.54, dated 07/08/03, extends this directive until 07/08/04. Cancels Deputy Secretary Glauthier memorandum, subject: Reporting Security Incidents, dated 9-7-99.

  11. Cyber Security Incident Management Manual

    Broader source: Directives, Delegations, and Requirements [Office of Management (MA)]

    2009-01-08

    The manual establishes minimum requirements for a structured cyber security incident detection and management process for detecting, identifying, categorizing, containing, reporting, and mitigating cyber security incidents involving DOE information and information systems operated by DOE or by contractors on behalf of the Department. Admin Chg 1 dated 9-1-09; Admin Chg 2 dated 12-22-09. Canceled by DOE O 205.1B.

  12. LANL responds to radiological incident

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    LANL responds to radiological incident LANL responds to radiological incident Multiple tests indicate no health risks to public or employees. August 27, 2012 Aerial view of the Los Alamos Neutron Science Center(LANSCE). Aerial view of the Los Alamos Neutron Science Center (LANSCE). The contamination poses no danger to the public. The Laboratory is investigating the inadvertent spread of Technetium 99 by employees and contractors at the Lujan Neutron Scattering Center August 27, 2012-The

  13. Cyber Incidents Involving Control Systems

    SciTech Connect (OSTI)

    Robert J. Turk

    2005-10-01

    The Analysis Function of the US-CERT Control Systems Security Center (CSSC) at the Idaho National Laboratory (INL) has prepared this report to document cyber security incidents for use by the CSSC. The description and analysis of incidents reported herein support three CSSC tasks: establishing a business case; increasing security awareness and private and corporate participation related to enhanced cyber security of control systems; and providing informational material to support model development and prioritize activities for CSSC. The stated mission of CSSC is to reduce vulnerability of critical infrastructure to cyber attack on control systems. As stated in the Incident Management Tool Requirements (August 2005) ''Vulnerability reduction is promoted by risk analysis that tracks actual risk, emphasizes high risk, determines risk reduction as a function of countermeasures, tracks increase of risk due to external influence, and measures success of the vulnerability reduction program''. Process control and Supervisory Control and Data Acquisition (SCADA) systems, with their reliance on proprietary networks and hardware, have long been considered immune to the network attacks that have wreaked so much havoc on corporate information systems. New research indicates this confidence is misplaced--the move to open standards such as Ethernet, Transmission Control Protocol/Internet Protocol, and Web technologies is allowing hackers to take advantage of the control industry's unawareness. Much of the available information about cyber incidents represents a characterization as opposed to an analysis of events. The lack of good analyses reflects an overall weakness in reporting requirements as well as the fact that to date there have been very few serious cyber attacks on control systems. Most companies prefer not to share cyber attack incident data because of potential financial repercussions. Uniform reporting requirements will do much to make this information available to Department of Homeland Security (DHS) and others who require it. This report summarizes the rise in frequency of cyber attacks, describes the perpetrators, and identifies the means of attack. This type of analysis, when used in conjunction with vulnerability analyses, can be used to support a proactive approach to prevent cyber attacks. CSSC will use this document to evolve a standardized approach to incident reporting and analysis. This document will be updated as needed to record additional event analyses and insights regarding incident reporting. This report represents 120 cyber security incidents documented in a number of sources, including: the British Columbia Institute of Technology (BCIT) Industrial Security Incident Database, the 2003 CSI/FBI Computer Crime and Security Survey, the KEMA, Inc., Database, Lawrence Livermore National Laboratory, the Energy Incident Database, the INL Cyber Incident Database, and other open-source data. The National Memorial Institute for the Prevention of Terrorism (MIPT) database was also interrogated but, interestingly, failed to yield any cyber attack incidents. The results of this evaluation indicate that historical evidence provides insight into control system related incidents or failures; however, that the limited available information provides little support to future risk estimates. The documented case history shows that activity has increased significantly since 1988. The majority of incidents come from the Internet by way of opportunistic viruses, Trojans, and worms, but a surprisingly large number are directed acts of sabotage. A substantial number of confirmed, unconfirmed, and potential events that directly or potentially impact control systems worldwide are also identified. Twelve selected cyber incidents are presented at the end of this report as examples of the documented case studies (see Appendix B).

  14. Chemical incident economic impact analysis methodology. (Technical...

    Office of Scientific and Technical Information (OSTI)

    Chemical incident economic impact analysis methodology. Citation Details In-Document Search Title: Chemical incident economic impact analysis methodology. You are accessing a...

  15. The Department's Cyber Security Incident Management Program,...

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    The Department's Cyber Security Incident Management Program, IG-0787 The Department's Cyber Security Incident Management Program, IG-0787 The Department of Energy operates numerous...

  16. Lung pair phantom

    DOE Patents [OSTI]

    Olsen, P.C.; Gordon, N.R.; Simmons, K.L.

    1993-11-30

    The present invention is a material and method of making the material that exhibits improved radiation attenuation simulation of real lungs, i.e., an ``authentic lung tissue`` or ALT phantom. Specifically, the ALT phantom is a two-part polyurethane medium density foam mixed with calcium carbonate, potassium carbonate if needed for K-40 background, lanthanum nitrate, acetone, and a nitrate or chloride form of a radionuclide. This formulation is found to closely match chemical composition and linear attenuation of real lungs. The ALT phantom material is made according to established procedures but without adding foaming agents or preparing thixotropic concentrate and with a modification for ensuring uniformity of density of the ALT phantom that is necessary for accurate simulation. The modification is that the polyurethane chemicals are mixed at a low temperature prior to pouring the polyurethane mixture into the mold.

  17. Lung pair phantom

    DOE Patents [OSTI]

    Olsen, Peter C. (West Richland, WA); Gordon, N. Ross (Kennewick, WA); Simmons, Kevin L. (Kennewick, WA)

    1993-01-01

    The present invention is a material and method of making the material that exhibits improved radiation attenuation simulation of real lungs, i.e., an "authentic lung tissue" or ALT phantom. Specifically, the ALT phantom is a two-part polyurethane medium density foam mixed with calcium carbonate, potassium carbonate if needed for K-40 background, lanthanum nitrate, acetone, and a nitrate or chloride form of a radionuclide. This formulation is found to closely match chemical composition and linear attenuation of real lungs. The ALT phantom material is made according to established procedures but without adding foaming agents or preparing thixotropic concentrate and with a modification for ensuring uniformity of density of the ALT phantom that is necessary for accurate simulation. The modification is that the polyurethane chemicals are mixed at a low temperature prior to pouring the polyurethane mixture into the mold.

  18. Chapter_11_Incidents_of_Security_Concern

    Office of Environmental Management (EM)

    1 Incidents of Security Concern This chapter covers the DOE HQ implementation of DOE Order 470.4B, Safeguards and Security Program, Attachment 5, Incidents of Security Concern. AU-42 manages the HQ Security Incidents Program. Incidents of Security Concern (henceforth referred to as Incidents) are actions, inactions, or events that are believed to: * Pose threats to national security interests and/or DOE assets * Create potentially serious or dangerous security situations * Significantly affect

  19. JC3 Incident Reporting | Department of Energy

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    Management » JC3 Incident Reporting JC3 Incident Reporting technology-785742_960_720.jpg JC3 Incident Reporting Procedures U.S. Department of Energy Facilities/Contractors Only DOE O 205.1-B Chg 2 4.(c)(13) DEPARTMENT OF ENERGY CYBER SECURITY PROGRAM requires a defined "process for incident reporting that requires all cyber security incidents involving information or information systems, including privacy breaches, under DOE or DOE contractor control must be identified, mitigated,

  20. Analysis of lung tumor initiation and progression in transgenic mice for Cre-inducible overexpression of Cul4A gene

    SciTech Connect (OSTI)

    Wang, Yang; Xu, Zhidong; Mao, Jian -Hua; Hung, Ming -Szu; Hsieh, David; Au, Alfred; Jablons, David M.; You, Liang

    2015-06-08

    Background: Lung cancer is the leading cause of morbidity and death worldwide. Although the available lung cancer animal models have been informative and further propel our understanding of human lung cancer, they still do not fully recapitulate the complexities of human lung cancer. The pathogenesis of lung cancer remains highly elusive because of its aggressive biologic nature and considerable heterogeneity, compared to other cancers. The association of Cul4A amplification with aggressive tumor growth and poor prognosis has been suggested. Our previous study suggested that Cul4A is oncogenic in vitro, but its oncogenic role in vivo has not been studied. Methods: Viral delivery approaches have been used extensively to model cancer in mouse models. In our experiments, we used Cre-recombinase induced overexpression of the Cul4A gene in transgenic mice to study the role of Cul4A on lung tumor initiation and progression and have developed a new model of lung tumor development in mice harboring a conditionally expressed allele of Cul4A. Results: Here we show that the use of a recombinant adenovirus expressing Cre-recombinase (AdenoCre) to induce Cul4A overexpression in the lungs of mice allows controls of the timing and multiplicity of tumor initiation. Following our mouse models, we are able to study the potential role of Cul4A in the development and progression in pulmonary adenocarcinoma as well. Conclusion: Our findings indicate that Cul4A is oncogenic in vivo, and this mouse model is a tool in understanding the mechanisms of Cul4A in human cancers and for testing experimental therapies targeting Cul4A.

  1. Analysis of lung tumor initiation and progression in transgenic mice for Cre-inducible overexpression of Cul4A gene

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Wang, Yang; Xu, Zhidong; Mao, Jian -Hua; Hung, Ming -Szu; Hsieh, David; Au, Alfred; Jablons, David M.; You, Liang

    2015-06-08

    Background: Lung cancer is the leading cause of morbidity and death worldwide. Although the available lung cancer animal models have been informative and further propel our understanding of human lung cancer, they still do not fully recapitulate the complexities of human lung cancer. The pathogenesis of lung cancer remains highly elusive because of its aggressive biologic nature and considerable heterogeneity, compared to other cancers. The association of Cul4A amplification with aggressive tumor growth and poor prognosis has been suggested. Our previous study suggested that Cul4A is oncogenic in vitro, but its oncogenic role in vivo has not been studied. Methods:more » Viral delivery approaches have been used extensively to model cancer in mouse models. In our experiments, we used Cre-recombinase induced overexpression of the Cul4A gene in transgenic mice to study the role of Cul4A on lung tumor initiation and progression and have developed a new model of lung tumor development in mice harboring a conditionally expressed allele of Cul4A. Results: Here we show that the use of a recombinant adenovirus expressing Cre-recombinase (“AdenoCre”) to induce Cul4A overexpression in the lungs of mice allows controls of the timing and multiplicity of tumor initiation. Following our mouse models, we are able to study the potential role of Cul4A in the development and progression in pulmonary adenocarcinoma as well. Conclusion: Our findings indicate that Cul4A is oncogenic in vivo, and this mouse model is a tool in understanding the mechanisms of Cul4A in human cancers and for testing experimental therapies targeting Cul4A.« less

  2. Dose impact in radiographic lung injury following lung SBRT: Statistical analysis and geometric interpretation

    SciTech Connect (OSTI)

    Yu, Victoria; Kishan, Amar U.; Cao, Minsong; Low, Daniel; Lee, Percy; Ruan, Dan

    2014-03-15

    Purpose: To demonstrate a new method of evaluating dose response of treatment-induced lung radiographic injury post-SBRT (stereotactic body radiotherapy) treatment and the discovery of bimodal dose behavior within clinically identified injury volumes. Methods: Follow-up CT scans at 3, 6, and 12 months were acquired from 24 patients treated with SBRT for stage-1 primary lung cancers or oligometastic lesions. Injury regions in these scans were propagated to the planning CT coordinates by performing deformable registration of the follow-ups to the planning CTs. A bimodal behavior was repeatedly observed from the probability distribution for dose values within the deformed injury regions. Based on a mixture-Gaussian assumption, an Expectation-Maximization (EM) algorithm was used to obtain characteristic parameters for such distribution. Geometric analysis was performed to interpret such parameters and infer the critical dose level that is potentially inductive of post-SBRT lung injury. Results: The Gaussian mixture obtained from the EM algorithm closely approximates the empirical dose histogram within the injury volume with good consistency. The average Kullback-Leibler divergence values between the empirical differential dose volume histogram and the EM-obtained Gaussian mixture distribution were calculated to be 0.069, 0.063, and 0.092 for the 3, 6, and 12 month follow-up groups, respectively. The lower Gaussian component was located at approximately 70% prescription dose (35 Gy) for all three follow-up time points. The higher Gaussian component, contributed by the dose received by planning target volume, was located at around 107% of the prescription dose. Geometrical analysis suggests the mean of the lower Gaussian component, located at 35 Gy, as a possible indicator for a critical dose that induces lung injury after SBRT. Conclusions: An innovative and improved method for analyzing the correspondence between lung radiographic injury and SBRT treatment dose has been demonstrated. Bimodal behavior was observed in the dose distribution of lung injury after SBRT. Novel statistical and geometrical analysis has shown that the systematically quantified low-dose peak at approximately 35 Gy, or 70% prescription dose, is a good indication of a critical dose for injury. The determined critical dose of 35 Gy resembles the critical dose volume limit of 30 Gy for ipsilateral bronchus in RTOG 0618 and results from previous studies. The authors seek to further extend this improved analysis method to a larger cohort to better understand the interpatient variation in radiographic lung injury dose response post-SBRT.

  3. The Medical Aspects of Radiation Incidents, 3rd Edition

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    ... Depending on the dosedose rate and volume of lung irradiated, acute radiation pneumonitis may develop, characterized by dry cough and dyspnea. Fibrosis of the lung, which causes ...

  4. ORISE: Incident Command System (ICS) Training

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Incident Command System (ICS) Training The Oak Ridge Institute for Science and Education (ORISE) supports the emergency response community by promoting interagency cooperation and...

  5. Nuclear Incident Team | National Nuclear Security Administration

    National Nuclear Security Administration (NNSA)

    Incident Team | National Nuclear Security Administration Facebook Twitter Youtube Flickr RSS People Mission Managing the Stockpile Preventing Proliferation Powering the Nuclear ...

  6. Researchers correlate incidences of rheumatoid arthritis and...

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Researchers correlate incidences of rheumatoid arthritis and giant cell arteritis with solar cycles By John Greenwald June 15, 2015 Tweet Widget Google Plus One Share on Facebook A...

  7. Incident Prevention, Warning, and Response (IPWAR) Manual

    Broader source: Directives, Delegations, and Requirements [Office of Management (MA)]

    2004-09-30

    This Manual defines a structured, cohesive, and consistent process for performing incident prevention, warning, and response for DOE's Federal information systems and is consistent with the requirements of Federal laws, Executive orders, national security directives, and other regulations. The Manual also provides requirements and implementation instructions for the Department's Incident Prevention, Warning and Response process, and supplements DOE O 205.1, Department of Energy Cyber Security Management Program, dated 3-21-03. DOE N 205.17 cancels this manual. This manual cancels DOE N 205.4, Handling Cyber Security Alerts and Advisories and Reporting Cyber Security Incidents, dated 3/18/2002.

  8. Researchers correlate incidences of rheumatoid arthritis and...

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    increased incidents of RA and GCA to be in periodic concert with the cycle of magnetic activity of the sun. During the solar cycle, dramatic changes that can affect space...

  9. Establishing and operating an incident response team

    SciTech Connect (OSTI)

    Padgett, K.M.

    1992-01-01

    Occurrences of improprieties dealing with computer usage are on the increase. They range all the way from misuse by employees to international computer telecommunications hacking. In addition, natural disasters and other disasters such as catastrophic fires may also fall into the same category. These incidents, like any other breach of acceptable behavior, may or may not involve actual law breaking. A computer incident response team should be created as a first priority. This report discusses the establishment and operation of a response team.

  10. Establishing and operating an incident response team

    SciTech Connect (OSTI)

    Padgett, K.M.

    1992-09-01

    Occurrences of improprieties dealing with computer usage are on the increase. They range all the way from misuse by employees to international computer telecommunications hacking. In addition, natural disasters and other disasters such as catastrophic fires may also fall into the same category. These incidents, like any other breach of acceptable behavior, may or may not involve actual law breaking. A computer incident response team should be created as a first priority. This report discusses the establishment and operation of a response team.

  11. Use of 4-Dimensional Computed Tomography-Based Ventilation Imaging to Correlate Lung Dose and Function With Clinical Outcomes

    SciTech Connect (OSTI)

    Vinogradskiy, Yevgeniy, E-mail: yevgeniy.vinogradskiy@ucdenver.edu [Department of Radiation Oncology, University of Colorado School of Medicine, Aurora, Colorado (United States)] [Department of Radiation Oncology, University of Colorado School of Medicine, Aurora, Colorado (United States); Castillo, Richard [Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States)] [Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Castillo, Edward [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States) [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Department of Computational and Applied Mathematics, Rice University, Houston, Texas (United States); Tucker, Susan L. [Departments of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States)] [Departments of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Liao, Zhongxing [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States)] [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Guerrero, Thomas [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States) [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Department of Computational and Applied Mathematics, Rice University, Houston, Texas (United States); Martel, Mary K. [Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States)] [Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States)

    2013-06-01

    Purpose: Four-dimensional computed tomography (4DCT)-based ventilation is an emerging imaging modality that can be used in the thoracic treatment planning process. The clinical benefit of using ventilation images in radiation treatment plans remains to be tested. The purpose of the current work was to test the potential benefit of using ventilation in treatment planning by evaluating whether dose to highly ventilated regions of the lung resulted in increased incidence of clinical toxicity. Methods and Materials: Pretreatment 4DCT data were used to compute pretreatment ventilation images for 96 lung cancer patients. Ventilation images were calculated using 4DCT data, deformable image registration, and a density-change based algorithm. Dosevolume and ventilation-based dose function metrics were computed for each patient. The ability of the dosevolume and ventilation-based dosefunction metrics to predict for severe (grade 3+) radiation pneumonitis was assessed using logistic regression analysis, area under the curve (AUC) metrics, and bootstrap methods. Results: A specific patient example is presented that demonstrates how incorporating ventilation-based functional information can help separate patients with and without toxicity. The logistic regression significance values were all lower for the dosefunction metrics (range P=.093-.250) than for their dosevolume equivalents (range, P=.331-.580). The AUC values were all greater for the dosefunction metrics (range, 0.569-0.620) than for their dosevolume equivalents (range, 0.500-0.544). Bootstrap results revealed an improvement in model fit using dosefunction metrics compared to dosevolume metrics that approached significance (range, P=.118-.155). Conclusions: To our knowledge, this is the first study that attempts to correlate lung dose and 4DCT ventilation-based function to thoracic toxicity after radiation therapy. Although the results were not significant at the .05 level, our data suggests that incorporating ventilation-based functional imaging can improve prediction for radiation pneumonitis. We present an important first step toward validating the use of 4DCT-based ventilation imaging in thoracic treatment planning.

  12. Metabolite signatures in hydrophilic extracts of mouse lungs exposed to cigarette smoke revealed by 1H NMR metabolomics investigation

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Hu, Jian Z.; Wang, Xuan; Feng, Ju; Webb-Robertson, Bobbie-Jo M.; Waters, Katrina M.; Tilton, Susan C.; Pounds, Joel G.; Corley, Richard A.; Liu, Maili; Hu, Mary Y.

    2015-05-12

    Herein, 1H-NMR metabolomics are carried out to evaluate the changes of metabolites in lungs of mice exposed to cigarette smoke. It is found that the concentrations of adenosine derivatives (i.e. ATP, ADP and AMP), inosine and uridine are significantly fluctuated in the lungs of mice exposed to cigarette smoke compared with those of controls regardless the mouse is obese or regular weight. The decreased ATP, ADP, AMP and elevated inosine predict that the deaminases in charge of adenosine derivatives to inosine derivatives conversion are altered in lungs of mice exposed to cigarette smoke. Transcriptional analysis reveals that the concentrations ofmore » adenosine monophosphate deaminase and adenosine deaminase are different in the lungs of mice exposed to cigarette smoke, confirming the prediction from metabolomics studies. We also found, for the first time, that the ratio of glycerophosphocholine (GPC) to phosphocholine (PC) is significantly increased in the lungs of obese mice compared with regular weight mice. The ratio of GPC/PC is further elevated in the lungs of obese group by cigarette smoke exposure. Since GPC/PC ratio is a known biomarker for cancer, these results may suggest that obese group is more susceptible to lung cancer when exposed to cigarette smoke.« less

  13. Leukemia, lymphoma and multiple myeloma mortality (19501999) and incidence (19691999) in the Eldorado uranium workers cohort

    SciTech Connect (OSTI)

    Zablotska, Lydia B.; Lane, Rachel S.D.; Frost, Stanley E.; Thompson, Patsy A.

    2014-04-01

    Uranium workers are chronically exposed to low levels of radon decay products (RDP) and gamma (?) radiation. Risks of leukemia from acute and high doses of ?-radiation are well-characterized, but risks from lower doses and dose-rates and from RDP exposures are controversial. Few studies have evaluated risks of other hematologic cancers in uranium workers. The purpose of this study was to analyze radiation-related risks of hematologic cancers in the cohort of Eldorado uranium miners and processors first employed in 19321980 in relation to cumulative RDP exposures and ?-ray doses. The average cumulative RDP exposure was 100.2 working level months and the average cumulative whole-body ?-radiation dose was 52.2 millisievert. We identified 101 deaths and 160 cases of hematologic cancers in the cohort. Overall, male workers had lower mortality and cancer incidence rates for all outcomes compared with the general Canadian male population, a likely healthy worker effect. No statistically significant association between RDP exposure or ?-ray doses, or a combination of both, and mortality or incidence of any hematologic cancer was found. We observed consistent but non-statistically significant increases in risks of chronic lymphocytic leukemia (CLL) and Hodgkin lymphoma (HL) incidence and non-Hodgkin lymphoma (NHL) mortality with increasing ?-ray doses. These findings are consistent with recent studies of increased risks of CLL and NHL incidence after ?-radiation exposure. Further research is necessary to understand risks of other hematologic cancers from low-dose exposures to ?-radiation. - Highlights: We analyzed long-term follow-up for hematologic cancers of the Eldorado uranium workers. Workers were exposed to a unique combination of radon decay products (RDP) and gamma (?) ray doses. Exposures to RDP and ?-ray doses were not associated with significantly increased risks of cancers. Radiation risks of chronic lymphocytic leukemia (CLL) and Hodgkin lymphoma were increased. Study findings provide additional support for radiation-related risks of CLL.

  14. Real-Time Tumor Tracking in the Lung Using an Electromagnetic Tracking System

    SciTech Connect (OSTI)

    Shah, Amish P.; Kupelian, Patrick A.; Waghorn, Benjamin J.; Willoughby, Twyla R.; Rineer, Justin M.; Maon, Rafael R.; Vollenweider, Mark A.; Meeks, Sanford L.

    2013-07-01

    Purpose: To describe the first use of the commercially available Calypso 4D Localization System in the lung. Methods and Materials: Under an institutional review board-approved protocol and an investigational device exemption from the US Food and Drug Administration, the Calypso system was used with nonclinical methods to acquire real-time 4-dimensional lung tumor tracks for 7 lung cancer patients. The aims of the study were to investigate (1) the potential for bronchoscopic implantation; (2) the stability of smooth-surface beacon transponders (transponders) after implantation; and (3) the ability to acquire tracking information within the lung. Electromagnetic tracking was not used for any clinical decision making and could only be performed before any radiation delivery in a research setting. All motion tracks for each patient were reviewed, and values of the average displacement, amplitude of motion, period, and associated correlation to a sinusoidal model (R{sup 2}) were tabulated for all 42 tracks. Results: For all 7 patients at least 1 transponder was successfully implanted. To assist in securing the transponder at the tumor site, it was necessary to implant a secondary fiducial for most transponders owing to the transponder's smooth surface. For 3 patients, insertion into the lung proved difficult, with only 1 transponder remaining fixed during implantation. One patient developed a pneumothorax after implantation of the secondary fiducial. Once implanted, 13 of 14 transponders remained stable within the lung and were successfully tracked with the tracking system. Conclusions: Our initial experience with electromagnetic guidance within the lung demonstrates that transponder implantation and tracking is achievable though not clinically available. This research investigation proved that lung tumor motion exhibits large variations from fraction to fraction within a single patient and that improvements to both transponder and tracking system are still necessary to create a clinical daily-use system to assist with actual lung radiation therapy.

  15. Pretreatment [{sup 18}F]-fluoro-2-deoxy-glucose Positron Emission Tomography Maximum Standardized Uptake Value as Predictor of Distant Metastasis in Early-Stage Non-Small Cell Lung Cancer Treated With Definitive Radiation Therapy: Rethinking the Role of Positron Emission Tomography in Personalizing Treatment Based on Risk Status

    SciTech Connect (OSTI)

    Nair, Vimoj J.; MacRae, Robert; Sirisegaram, Abby; Pantarotto, Jason R.

    2014-02-01

    Purpose: The aim of this study was to determine whether the preradiation maximum standardized uptake value (SUV{sub max}) of the primary tumor for [{sup 18}F]-fluoro-2-deoxy-glucose positron emission tomography (FDG-PET) has a prognostic significance in patients with Stage T1 or T2N0 non-small cell lung cancer (NSCLC) treated with curative radiation therapy, whether conventional or stereotactic body radiation therapy (SBRT). Methods and Materials: Between January 2007 and December 2011, a total of 163 patients (180 tumors) with medically inoperable histologically proven Stage T1 or T2N0 NSCLC and treated with radiation therapy (both conventional and SBRT) were entered in a research ethics board approved database. All patients received pretreatment FDG-PET / computed tomography (CT) at 1 institution with consistent acquisition technique. The medical records and radiologic images of these patients were analyzed. Results: The overall survival at 2 years and 3 years for the whole group was 76% and 67%, respectively. The mean and median SUV{sub max} were 8.1 and 7, respectively. Progression-free survival at 2 years with SUV{sub max} <7 was better than that of the patients with tumor SUV{sub max} ?7 (67% vs 51%; P=.0096). Tumors with SUV{sub max} ?7 were associated with a worse regional recurrence-free survival and distant metastasis-free survival. In the multivariate analysis, SUV{sub max} ?7 was an independent prognostic factor for distant metastasis-free survival. Conclusion: In early-stage NSCLC managed with radiation alone, patients with SUV{sub max} ?7 on FDG-PET / CT scan have poorer outcomes and high risk of progression, possibly because of aggressive biology. There is a potential role for adjuvant therapies for these high-risk patients with intent to improve outcomes.

  16. Headquarters Facilities Master Security Plan - Chapter 11, Incidents...

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    1, Incidents of Security Concern Headquarters Facilities Master Security Plan - Chapter 11, Incidents of Security Concern 2016 Headquarters Facilities Master Security Plan - ...

  17. Aging Impacts Transcriptome but not Genome of Hormone-dependentBreast Cancers

    SciTech Connect (OSTI)

    Yau, Christina; Fedele, Vita; Roydasgupta, Ritu; Fridlyand, Jane; Hubbard, Alan; Gray, Joe W.; Chew, Karen; Dairkee, Shanaz H.; Moore, DanH.; Schittulli, Francesco; Tommasi, Stefania; Paradiso, Angelo; Albertson, Donna G.; Benz, Christopher C.

    2007-10-09

    Age is one of the most important risk factors for human malignancies, including breast cancer; in addition, age-at-diagnosis has been shown to be an independent indicator of breast cancer prognosis. However, except for inherited forms of breast cancer, there is little genetic or epigenetic understanding of the biological basis linking aging with sporadic breast cancer incidence and its clinical behavior.

  18. Jefferson Lab Leadership Council - Dr. Allison Lung

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Associate Director, Dr. Allison Lung Allison Lung Associate Director, 12 GeV Upgrade Project Allison Lung was appointed the assistant director for the Thomas Jefferson National Accelerator Facility in October 2002. As assistant director, Lung is responsible for formulating and leading the JLab Continual Improvement Program, and responding to requests from JLab stakeholders. She organizes support and documentation for funding campaigns and collaborates closely with the lab director in matters

  19. Risk of Salivary Gland Cancer After Childhood Cancer: A Report From the Childhood Cancer Survivor Study

    SciTech Connect (OSTI)

    Boukheris, Houda; Stovall, Marilyn; Gilbert, Ethel S.; Stratton, Kayla L.; Smith, Susan A.; Weathers, Rita; Hammond, Sue; Mertens, Ann C.; Donaldson, Sarah S.; Armstrong, Gregory T.; Robison, Leslie L.; Neglia, Joseph P.; Inskip, Peter D.

    2013-03-01

    Purpose: To evaluate effects of radiation therapy, chemotherapy, cigarette smoking, and alcohol consumption on the risk of second primary salivary gland cancer (SGC) in the Childhood Cancer Survivor Study (CCSS). Methods and Materials: Standardized incidence ratios (SIR) and excess absolute risks (EAR) of SGC in the CCSS were calculated using incidence rates from Surveillance, Epidemiology, and End Results population-based cancer registries. Radiation dose to the salivary glands was estimated based on medical records. Poisson regression was used to assess risks with respect to radiation dose, chemotherapy, smoking, and alcohol consumption. Results: During the time period of the study, 23 cases of SGC were diagnosed among 14,135 childhood cancer survivors. The mean age at diagnosis of the first primary cancer was 8.3 years, and the mean age at SGC diagnosis was 24.8 years. The incidence of SGC was 39-fold higher in the cohort than in the general population (SIR = 39.4; 95% CI = 25.4-57.8). The EAR was 9.8 per 100,000 person-years. Risk increased linearly with radiation dose (excess relative risk = 0.36/Gy; 95% CI = 0.06-2.5) and remained elevated after 20 years. There was no significant trend of increasing risk with increasing dose of chemotherapeutic agents, pack-years of cigarette smoking, or alcohol intake. Conclusion: Although the cumulative incidence of SGC was low, childhood cancer survivors treated with radiation experienced significantly increased risk for at least 2 decades after exposure, and risk was positively associated with radiation dose. Results underscore the importance of long-term follow up of childhood cancer survivors for the development of new malignancies.

  20. Electrically floating, near vertical incidence, skywave antenna

    DOE Patents [OSTI]

    Anderson, Allen A.; Kaser, Timothy G.; Tremblay, Paul A.; Mays, Belva L.

    2014-07-08

    An Electrically Floating, Near Vertical Incidence, Skywave (NVIS) Antenna comprising an antenna element, a floating ground element, and a grounding element. At least part of said floating ground element is positioned between said antenna element and said grounding element. The antenna is separated from the floating ground element and the grounding element by one or more electrical insulators. The floating ground element is separated from said antenna and said grounding element by one or more electrical insulators.

  1. Joshua DeLung | Department of Energy

    Office of Environmental Management (EM)

    Joshua DeLung About Us Joshua DeLung Joshua DeLung is an Account Manager at ENC Marketing & Communications and the Executive Editor at Relatively Journalizing. Most Recent EnerG2 Develops New Approach to EV Energy Storage November 16 A Spin on Technology: Extracting Value from Wasted Heat November 12 Solar-Powered, School-Zone Safety November 8

  2. An Incident Management Preparedness and Coordination Toolkit

    SciTech Connect (OSTI)

    Koch, Daniel B; Payne, Patricia W

    2012-01-01

    Although the use of Geographic Information Systems (GIS) by centrally-located operations staff is well established in the area of emergency response, utilization by first responders in the field is uneven. Cost, complexity, and connectivity are often the deciding factors preventing wider adoption. For the past several years, Oak Ridge National Laboratory (ORNL) has been developing a mobile GIS solution using free and open-source software targeting the needs of front-line personnel. Termed IMPACT, for Incident Management Preparedness and Coordination Toolkit, this ORNL application can complement existing GIS infrastructure and extend its power and capabilities to responders first on the scene of a natural or man-made disaster.

  3. Toward in vivo lung's tissue incompressibility characterization for tumor motion modeling in radiation therapy

    SciTech Connect (OSTI)

    Shirzadi, Zahra; Sadeghi-Naini, Ali; Samani, Abbas

    2013-05-15

    Purpose: A novel technique is proposed to characterize lung tissue incompressibility variation during respiration. Estimating lung tissue incompressibility parameter variations resulting from air content variation throughout respiration is critical for computer assisted tumor motion tracking. Continuous tumor motion is a major challenge in lung cancer radiotherapy, especially with external beam radiotherapy. If not accounted for, this motion may lead to areas of radiation overdosage for normal tissue. Given the unavailability of imaging modality that can be used effectively for real-time lung tumor tracking, computer assisted approach based on tissue deformation estimation can be a good alternative. This approach involves lung biomechanical model where its fidelity depends on input tissue properties. This investigation shows that considering variable tissue incompressibility parameter is very important for predicting tumor motion accurately, hence improving the lung radiotherapy outcome. Methods: First, an in silico lung phantom study was conducted to demonstrate the importance of employing variable Poisson's ratio for tumor motion predication. After it was established that modeling this variability is critical for accurate tumor motion prediction, an optimization based technique was developed to estimate lung tissue Poisson's ratio as a function of respiration cycle time. In this technique, the Poisson's ratio and lung pressure value were varied systematically until optimal values were obtained, leading to maximum similarity between acquired and simulated 4D CT lung images. This technique was applied in an ex vivo porcine lung study where simulated images were constructed using the end exhale CT image and deformation fields obtained from the lung's FE modeling of each respiration time increment. To model the tissue, linear elastic and Marlow hyperelastic material models in conjunction with variable Poisson's ratio were used. Results: The phantom study showed that the tumor motion trajectory and its final locations obtained from simulations with and without considering tissue incompressibility variation were very different. For example, tumor displacements in the z direction were -11.23 and -38.10 mm obtained with the Marlow hyperelastic material model in conjunction with constant and variable Poisson's ratio, respectively. By comparing the acquired 4D-CT image sequence of the porcine lung with their image sequence counterparts obtained from the hyperelastic model with constant and variable Poisson's ratio, it was shown that using variable tissue incompressibility reduced errors significantly in tumor motion prediction. Conclusions: This investigation demonstrates the importance of incompressibility variation estimation and utilization for accurate tumor tracking in computer assisted lung external beam radiation therapy. An optimization framework was developed to estimate a Poisson's ratio function in terms of respiration cycle time using experimental image data of the lung. Utilizing this function along with respiratory system FE modeling may lead to more effective tumor targeting, hence potentially improving the outcome of lung external beam radiation therapy techniques. This is particularly true for stereotactic body radiation therapy where only one or a few fraction treatments are applied, precluding the possibility of averaging out dosimetric deviations introduced by the respiratory motion.

  4. Personnel Accountability for Non-COOP Incidents | Department of Energy

    Energy Savers [EERE]

    Personnel Accountability for Non-COOP Incidents Personnel Accountability for Non-COOP Incidents This document establishes reporting requirements for non-COOP incidents. PDF icon Personnel Accountability for Non-COOP Incidents Responsible Contacts Bruce Murray HR Policy Advisor E-mail bruce.murray@hq.doe.gov Phone 202-586-3372 More Documents & Publications Inspection Report: IG-0784 Audit Report: IG-0845 High-Energy, Low-Frequency Risk to the North American Bulk Power System (June 2010)

  5. Workplace Charging Challenge Partner: American Lung Association in Colorado

    Broader source: Energy.gov [DOE]

    The mission of the American Lung Association in Colorado (ALAC) is to improve lung health and prevent lung disease. Encouraging the use of plug-in electric vehicles is essential to improving local...

  6. Metabolite signatures in hydrophilic extracts of mouse lungs exposed to cigarette smoke revealed by 1H NMR metabolomics investigation

    SciTech Connect (OSTI)

    Hu, Jian Z.; Wang, Xuan; Feng, Ju; Webb-Robertson, Bobbie-Jo M.; Waters, Katrina M.; Tilton, Susan C.; Pounds, Joel G.; Corley, Richard A.; Liu, Maili; Hu, Mary Y.

    2015-05-12

    Herein, 1H-NMR metabolomics are carried out to evaluate the changes of metabolites in lungs of mice exposed to cigarette smoke. It is found that the concentrations of adenosine derivatives (i.e. ATP, ADP and AMP), inosine and uridine are significantly fluctuated in the lungs of mice exposed to cigarette smoke compared with those of controls regardless the mouse is obese or regular weight. The decreased ATP, ADP, AMP and elevated inosine predict that the deaminases in charge of adenosine derivatives to inosine derivatives conversion are altered in lungs of mice exposed to cigarette smoke. Transcriptional analysis reveals that the concentrations of adenosine monophosphate deaminase and adenosine deaminase are different in the lungs of mice exposed to cigarette smoke, confirming the prediction from metabolomics studies. We also found, for the first time, that the ratio of glycerophosphocholine (GPC) to phosphocholine (PC) is significantly increased in the lungs of obese mice compared with regular weight mice. The ratio of GPC/PC is further elevated in the lungs of obese group by cigarette smoke exposure. Since GPC/PC ratio is a known biomarker for cancer, these results may suggest that obese group is more susceptible to lung cancer when exposed to cigarette smoke.

  7. Response of Human Lung Epithelial Cells to Engineered Nanoparticles...

    Office of Scientific and Technical Information (OSTI)

    Response of Human Lung Epithelial Cells to Engineered Nanoparticles. Citation Details In-Document Search Title: Response of Human Lung Epithelial Cells to Engineered Nanoparticles. ...

  8. Recovery from chemical, biological, and radiological incidents :

    SciTech Connect (OSTI)

    Franco, David Oliver; Yang, Lynn I.; Hammer, Ann E.

    2012-06-01

    To restore regional lifeline services and economic activity as quickly as possible after a chemical, biological or radiological incident, emergency planners and managers will need to prioritize critical infrastructure across many sectors for restoration. In parallel, state and local governments will need to identify and implement measures to promote reoccupation and economy recovery in the region. This document provides guidance on predisaster planning for two of the National Disaster Recovery Framework Recovery Support Functions: Infrastructure Systems and Economic Recovery. It identifies key considerations for infrastructure restoration, outlines a process for prioritizing critical infrastructure for restoration, and identifies critical considerations for promoting regional economic recovery following a widearea disaster. Its goal is to equip members of the emergency preparedness community to systematically prioritize critical infrastructure for restoration, and to develop effective economic recovery plans in preparation for a widearea CBR disaster.

  9. Cellular morphometry of the bronchi of human and dog lungs

    SciTech Connect (OSTI)

    Robbins, E.S.

    1992-09-01

    Quantitative data of the human bronchial epithelial cells at possible risk for malignant transformation in lung cancer is crucial for accurate radon dosimetry and risk analysis. The locations and other parameters of the nuclei which may be damaged by [alpha] particles must be determined and compared in different airway generations, among smokers, non-smokers and ex-smokers, between men and women and in people of different ages. This proposal includes extended morphometric studies on electron micrographs of human epithelium of defined airway generations and in parallel on electron micrographs of the dog bronchial lining. The second part of this proposal describes studies to quantitate the cycling bronchial epithelial population(s) using proliferation markers and immunocytochemistry on frozen and paraffin sections and similar labeling of isolated bronchial epithelial cells sorted flow cytometry.

  10. Predicting the Risk of Secondary Lung Malignancies Associated With Whole-Breast Radiation Therapy

    SciTech Connect (OSTI)

    Ng, John; Shuryak, Igor; Xu Yanguang; Clifford Chao, K.S.; Brenner, David J.; Burri, Ryan J.

    2012-07-15

    Purpose: The risk of secondary lung malignancy (SLM) is a significant concern for women treated with whole-breast radiation therapy after breast-conserving surgery for early-stage breast cancer. In this study, a biologically based secondary malignancy model was used to quantify the risk of secondary lung malignancies (SLMs) associated with several common methods of delivering whole-breast radiation therapy (RT). Methods and Materials: Both supine and prone computed tomography simulations of 15 women with early breast cancer were used to generate standard fractionated and hypofractionated whole-breast RT treatment plans for each patient. Dose-volume histograms (DVHs) of the ipsilateral breast and lung were calculated for each patient on each plan. A model of spontaneous and radiation-induced carcinogenesis was used to determine the relative risks of SLMs for the different treatment techniques. Results: A higher risk of SLMs was predicted for supine breast irradiation when compared with prone breast irradiation for both the standard fractionation and hypofractionation schedules (relative risk [RR] = 2.59, 95% confidence interval (CI) = 2.30-2.88, and RR = 2.68, 95% CI = 2.39-2.98, respectively). No difference in risk of SLMs was noted between standard fractionation and hypofractionation schedules in either the supine position (RR = 1.05, 95% CI = 0.97-1.14) or the prone position (RR = 1.01, 95% CI = 0.88-1.15). Conclusions: Compared with supine whole-breast irradiation, prone breast irradiation is associated with a significantly lower predicted risk of secondary lung malignancy. In this modeling study, fractionation schedule did not have an impact on the risk of SLMs in women treated with whole-breast RT for early breast cancer.

  11. Computerized Accident Incident Reporting System | Department of Energy

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    Computerized Accident Incident Reporting System Computerized Accident Incident Reporting System CAIRS Database The Computerized Accident/Incident Reporting System is a database used to collect and analyze DOE and DOE contractor reports of injuries, illnesses, and other accidents that occur during DOE operations. CAIRS is a Government computer system and, as such, has security requirements that must be followed. Access to the database is open to DOE and DOE contractors. Additional information

  12. Cell migration or cytokinesis and proliferation? Revisiting the go or grow hypothesis in cancer cells in vitro

    SciTech Connect (OSTI)

    Garay, Tams; Juhsz, va; Molnr, Eszter; Eisenbauer, Maria; Czirk, Andrs; Dekan, Barbara; Lszl, Viktria; Hoda, Mir Alireza; Dme, Balzs; Tmr, Jzsef; Klepetko, Walter; Berger, Walter; Heged?s, Balzs

    2013-12-10

    The mortality of patients with solid tumors is mostly due to metastasis that relies on the interplay between migration and proliferation. The go or grow hypothesis postulates that migration and proliferation spatiotemporally excludes each other. We evaluated this hypothesis on 35 cell lines (12 mesothelioma, 13 melanoma and 10 lung cancer) on both the individual cell and population levels. Following three-day-long videomicroscopy, migration, proliferation and cytokinesis-length were quantified. We found a significantly higher migration in mesothelioma cells compared to melanoma and lung cancer while tumor types did not differ in mean proliferation or duration of cytokinesis. Strikingly, we found in melanoma and lung cancer a significant positive correlation between mean proliferation and migration. Furthermore, non-dividing melanoma and lung cancer cells displayed slower migration. In contrast, in mesothelioma there were no such correlations. Interestingly, negative correlation was found between cytokinesis-length and migration in melanoma. FAK activation was higher in melanoma cells with high motility. We demonstrate that the cancer cells studied do not defer proliferation for migration. Of note, tumor cells from various organ systems may differently regulate migration and proliferation. Furthermore, our data is in line with the observation of pathologists that highly proliferative tumors are often highly invasive. - Highlights: We investigated the go or grow hypothesis in human cancer cells in vitro. Proliferation and migration positively correlate in melanoma and lung cancer cells. Duration of cytokinesis and migration shows inverse correlation. Increased FAK activation is present in highly motile melanoma cells.

  13. NNSA Nuclear/Radiological Incident Response | National Nuclear...

    National Nuclear Security Administration (NNSA)

    Dec 1, 2008 The National Nuclear Security Administration (NNSA) has over 60 years of nuclear weapons experience in responding to nuclear and radiological accidents and incidents....

  14. ORISE: DeepwaterHorizon and Nuclear & Radiological Incidents

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    System's Incident Command System was utilized during the response, there were immense command and coordination challenges for the unified management team never before...

  15. The National Traffic Safety Summit Traffic Incident Management...

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Day - Registration 0900 to 1200 Staged Live Vehicle Crash University of Tulsa's Crash Reconstruction Research Consortium 1200 to 1300 Lunch 1300 to 1500 Traffic Incident...

  16. Model Recovery Procedure for Response to a Radiological Transportation Incident

    Broader source: Energy.gov [DOE]

    This Transportation Emergency Preparedness Program (TEPP) Model Recovery Procedure contains the recommended elements for developing and conducting recovery planning at transportation incident scene...

  17. Prevalence and contribution of BRCA1 mutations in breast cancer and ovarian cancer: Results from three US population-based case-control studies of ovarian cancer

    SciTech Connect (OSTI)

    Whittemore, A.S.; Gong, G.; Itnyre, J.

    1997-03-01

    We investigate the familial risks of cancers of the breast and ovary, using data pooled from three population-based case-control studies of ovarian cancer that were conducted in the United States. We base estimates of the frequency of mutations of BRCA1 (and possibly other genes) on the reported occurrence of breast cancer and ovarian cancer in the mothers and sisters of 922 women with incident ovarian cancer (cases) and in 922 women with no history of ovarian cancer (controls). Segregation analysis and goodness-of-fit testing of genetic models suggest that rare mutations (frequency .0014; 95% confidence interval .0002-.011) account for all the observed aggregation of breast cancer and ovarian cancer in these families. The estimated risk of breast cancer by age 80 years is 73.5% in mutation carriers and 6.8% in noncarriers. The corresponding estimates for ovarian cancer are 27.8% in carriers and 1.8% in noncarriers. For cancer risk in carriers, these estimates are lower than those obtained from families selected for high cancer prevalence. The estimated proportion of all U.S. cancer diagnoses, by age 80 years, that are due to germ-line BRCA1 mutations is 3.0% for breast cancer and 4.4% for ovarian cancer. Aggregation of breast cancer and ovarian cancer was less evident in the families of 169 cases with borderline ovarian cancers than in the families of cases with invasive cancers. Familial aggregation did not differ by the ethnicity of the probands, although the number of non-White and Hispanic cases (N = 99) was sparse. 14 refs., 3 figs., 6 tabs.

  18. Understanding the origins of human cancer

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Alexandrov, L. B.

    2015-12-04

    All cancers originate from a single cell that starts to behave abnormally, to divide uncontrollably, and, eventually, to invade adjacent tissues (1). The aberrant behavior of this single cell is due to somatic mutations—changes in the genomic DNA produced by the activity of different mutational processes (1). These various mutational processes include exposure to exogenous or endogenous mutagens, abnormal DNA editing, the incomplete fidelity of DNA polymerases, and failure of DNA repair mechanisms (2). Early studies that sequenced TP53, the most commonly mutated gene in human cancer, provided evidence that mutational processes leave distinct imprints of somatic mutations on themore » genome of a cancer cell (3). For example, C:G>A:T transversions predominate in smoking-associated lung cancer, whereas C:G>T:A transitions occurring mainly at dipyrimidines and CC:GG>TT:AA double-nucleotide substitutions are common in ultraviolet light–associated skin cancers. Moreover, these patterns of mutations matched the ones induced experimentally by tobacco mutagens and ultraviolet light, respectively, the major, known, exogenous carcinogenic influences in these cancer types, and demonstrated that examining patterns of mutations in cancer genomes can yield information about the mutational processes that cause human cancer (4).« less

  19. Linear dimensions and volumes of human lungs

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Hickman, David P.

    2012-03-30

    TOTAL LUNG Capacity is defined as “the inspiratory capacity plus the functional residual capacity; the volume of air contained in the lungs at the end of a maximal inspiration; also equals vital capacity plus residual volume” (from MediLexicon.com). Within the Results and Discussion section of their April 2012 Health Physics paper, Kramer et al. briefly noted that the lungs of their experimental subjects were “not fully inflated.” By definition and failure to obtain maximal inspiration, Kramer et. al. did not measure Total Lung Capacity (TLC). The TLC equation generated from this work will tend to underestimate TLC and does notmore » improve or update total lung capacity data provided by ICRP and others. Likewise, the five linear measurements performed by Kramer et. al. are only representative of the conditions of the measurement (i.e., not at-rest volume, but not fully inflated either). While there was significant work performed and the data are interesting, the data does not represent a maximal situation, a minimal situation, or an at-rest situation. Moreover, while interesting, the linear data generated by this study is limited by the conditions of the experiment and may not be fully comparative with other lung or inspiratory parameters, measures, or physical dimensions.« less

  20. Incident Management Preparedness and Coordination Toolkit

    Energy Science and Technology Software Center (OSTI)

    2013-04-01

    As with many professions, safety planners and first responders tend to be specialists in certain areas. To be truly useful, tools should be tailored to meet their specific needs. Thus, general software suites aimed at the professional geographic information system (GIS) community might not be the best solution for a first responder with little training in GIS terminology and techniques. On the other hand, commonly used web-based map viewers may not have the capability tomore » be customized for the planning, response, and recovery (PR&R) mission. Data formats should be open and foster easy information flow among local, state, and federal partners. Tools should be free or low-cost to address real-world budget constraints at the local level. They also need to work both with and without a network connection to be robust. The Incident Management Preparedness and Coordination Toolkit (IMPACT) can satisfy many of these needs while working in harmony with established systems at the local, state, and federal levels. The IMPACT software framework, termed the Geospatial Integrated Problem Solving Environment (GIPSE), organizes tasks, tools, and resources for the end user. It uses the concept of software wizards to both customize and extend its functionality. On the Tasks panel are a number of buttons used to initiate various operations. Similar to macros, these task buttons launch scripts that utilize the full functionality of the underlying foundational components such as the SQL spatial database and ORNL-developed map editor. The user is presented with a series of instruction pages which are implemented with HTML for interactivity. On each page are links which initiate specific actions such as creating a map showing various features. Additional tasks may be quickly programmed and added to the panel. The end user can customize the graphical interface to faciltate its use during an emergency. One of the major components of IMPACT is the ORNL Geospatial Viewer (OGV). It is used to provide various map displays for the Tasks and Maps panels. Unlike typical maps however, the OGV display is highly interactive and can be customized, automated, and animated to meet the needs of the user. It is also a means to both import and export geospatial data from or to existing GIS systems. The built-in simulation capability can be used as the basis of table-top exercises.« less

  1. Radiation-induced lung injury

    SciTech Connect (OSTI)

    Rosiello, R.A.; Merrill, W.W. )

    1990-03-01

    The use of radiation therapy is limited by the occurrence of the potentially fatal clinical syndromes of radiation pneumonitis and fibrosis. Radiation pneumonitis usually becomes clinically apparent from 2 to 6 months after completion of radiation therapy. It is characterized by fever, cough, dyspnea, and alveolar infiltrates on chest roentgenogram and may be difficult to differentiate from infection or recurrent malignancy. The pathogenesis is uncertain, but appears to involve both direct lung tissue toxicity and an inflammatory response. The syndrome may resolve spontaneously or may progress to respiratory failure. Corticosteroids may be effective therapy if started early in the course of the disease. The time course for the development of radiation fibrosis is later than that for radiation pneumonitis. It is usually present by 1 year following irradiation, but may not become clinically apparent until 2 years after radiation therapy. It is characterized by the insidious onset of dyspnea on exertion. It most often is mild, but can progress to chronic respiratory failure. There is no known successful treatment for this condition. 51 references.

  2. Discriminating electromagnetic radiation based on angle of incidence

    DOE Patents [OSTI]

    Hamam, Rafif E.; Bermel, Peter; Celanovic, Ivan; Soljacic, Marin; Yeng, Adrian Y. X.; Ghebrebrhan, Michael; Joannopoulos, John D.

    2015-06-16

    The present invention provides systems, articles, and methods for discriminating electromagnetic radiation based upon the angle of incidence of the electromagnetic radiation. In some cases, the materials and systems described herein can be capable of inhibiting reflection of electromagnetic radiation (e.g., the materials and systems can be capable of transmitting and/or absorbing electromagnetic radiation) within a given range of angles of incidence at a first incident surface, while substantially reflecting electromagnetic radiation outside the range of angles of incidence at a second incident surface (which can be the same as or different from the first incident surface). A photonic material comprising a plurality of periodically occurring separate domains can be used, in some cases, to selectively transmit and/or selectively absorb one portion of incoming electromagnetic radiation while reflecting another portion of incoming electromagnetic radiation, based upon the angle of incidence. In some embodiments, one domain of the photonic material can include an isotropic dielectric function, while another domain of the photonic material can include an anisotropic dielectric function. In some instances, one domain of the photonic material can include an isotropic magnetic permeability, while another domain of the photonic material can include an anisotropic magnetic permeability. In some embodiments, non-photonic materials (e.g., materials with relatively large scale features) can be used to selectively absorb incoming electromagnetic radiation based on angle of incidence.

  3. Microsoft Word - NNSS Incident Initial News Release.docx

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    January 29, 2013 Darwin.morgan@nnsa.doe.gov Incident at Nevada National Security Site LAS VEGAS, NV - Emergency responders are currently responding to an incident on the central portion of the Nevada National Security Site. More information will be released as it becomes available. -30- NSO-13-04

  4. Radiation pneumonitis in breast cancer patients treated with conservative surgery and radiation therapy

    SciTech Connect (OSTI)

    Lingos, T.I.; Recht, A.; Vicini, F.; Abner, A.; Silver, B.; Harris, J.R. )

    1991-07-01

    The likelihood of radiation pneumonitis and factors associated with its development in breast cancer patients treated with conservative surgery and radiation therapy have not been well established. To assess these, the authors retrospectively reviewed 1624 patients treated between 1968 and 1985. Median follow-up for patients without local or distant failure was 77 months. Patients were treated with either tangential fields alone (n = 508) or tangents with a third field to the supraclavicular (SC) or SC-axillary (AX) region (n = 1116). Lung volume treated in the tangential fields was generally limited by keeping the perpendicular distance (demagnified) at the isocenter from the deep field edges to the posterior chest wall (CLD) to 3 cm or less. Seventeen patients with radiation pneumonitis were identified (1.0%). Radiation pneumonitis was diagnosed when patients presented with cough (15/17, 88%), fever (9/17, 53%), and/or dyspnea (6/17, 35%) and radiographic changes (17/17) following completion of RT. Radiographic infiltrates corresponded to treatment portals in all patients, and in 12 of the 17 patients, returned to baseline within 1-12 months. Five patients had permanent scarring on chest X ray. No patient had late or persistent pulmonary symptoms. The incidence of radiation pneumonitis was correlated with the combined use of chemotherapy (CT) and a third field. Three percent (11/328) of patients treated with a 3-field technique who received chemotherapy developed radiation pneumonitis compared to 0.5% (6 of 1296) for all other patients (p = 0.0001). When patients treated with a 3-field technique received chemotherapy concurrently with radiation therapy, the incidence of radiation pneumonitis was 8.8% (8/92) compared with 1.3% (3/236) for those who received sequential chemotherapy and radiation therapy (p = 0.002).

  5. Incidence of Second Malignancies Among Patients Treated With Proton Versus Photon Radiation

    SciTech Connect (OSTI)

    Chung, Christine S., E-mail: chungc1@sutterhealth.org [Department of Radiation Oncology, Alta Bates Summit Medical Center, Berkeley, California (United States); Yock, Torunn I. [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Nelson, Kerrie [Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts (United States); Xu, Yang [Department of Health Care Policy, Harvard Medical School, Boston, Massachusetts (United States); Keating, Nancy L. [Department of Health Care Policy, Harvard Medical School, Boston, Massachusetts (United States); Department of General Internal Medicine, Brigham and Women's Hospital, Boston, Massachusetts (United States); Tarbell, Nancy J. [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Office of the Executive Dean, Harvard Medical School, Boston, Massachusetts (United States)

    2013-09-01

    Purpose: Proton radiation, when compared with photon radiation, allows delivery of increased radiation dose to the tumor while decreasing dose to adjacent critical structures. Given the recent expansion of proton facilities in the United States, the long-term sequelae of proton therapy should be carefully assessed. The objective of this study was to compare the incidence of second cancers in patients treated with proton radiation with a population-based cohort of matched patients treated with photon radiation. Methods and Materials: We performed a retrospective cohort study of 558 patients treated with proton radiation from 1973 to 2001 at the Harvard Cyclotron in Cambridge, MA and 558 matched patients treated with photon therapy in the Surveillance, Epidemiology, and End Results (SEER) Program cancer registry. Patients were matched by age at radiation treatment, sex, year of treatment, cancer histology, and site. The main outcome measure was the incidence of second malignancies after radiation. Results: We matched 558 proton patients with 558 photon patients from the Surveillance, Epidemiology, and End Results registry. The median duration of follow-up was 6.7 years (interquartile range, 7.4) and 6.0 years (interquartile range, 9.3) in the proton and photon cohorts, respectively. The median age at treatment was 59 years in each cohort. Second malignancies occurred in 29 proton patients (5.2%) and 42 photon patients (7.5%). After we adjusted for sex, age at treatment, primary site, and year of diagnosis, proton therapy was not associated with an increased risk of second malignancy (adjusted hazard ratio, 0.52 [95% confidence interval, 0.32-0.85]; P=.009). Conclusions: The use of proton radiation therapy was not associated with a significantly increased risk of secondary malignancies compared with photon therapy. Longer follow-up of these patients is needed to determine if there is a significant decrease in second malignancies. Given the limitations of the study, these results should be viewed as hypothesis generating.

  6. On using an adaptive neural network to predict lung tumor motion during respiration for radiotherapy applications

    SciTech Connect (OSTI)

    Isaksson, Marcus; Jalden, Joakim; Murphy, Martin J.

    2005-12-15

    In this study we address the problem of predicting the position of a moving lung tumor during respiration on the basis of external breathing signals--a technique used for beam gating, tracking, and other dynamic motion management techniques in radiation therapy. We demonstrate the use of neural network filters to correlate tumor position with external surrogate markers while simultaneously predicting the motion ahead in time, for situations in which neither the breathing pattern nor the correlation between moving anatomical elements is constant in time. One pancreatic cancer patient and two lung cancer patients with mid/upper lobe tumors were fluoroscopically imaged to observe tumor motion synchronously with the movement of external chest markers during free breathing. The external marker position was provided as input to a feed-forward neural network that correlated the marker and tumor movement to predict the tumor position up to 800 ms in advance. The predicted tumor position was compared to its observed position to establish the accuracy with which the filter could dynamically track tumor motion under nonstationary conditions. These results were compared to simplified linear versions of the filter. The two lung cancer patients exhibited complex respiratory behavior in which the correlation between surrogate marker and tumor position changed with each cycle of breathing. By automatically and continuously adjusting its parameters to the observations, the neural network achieved better tracking accuracy than the fixed and adaptive linear filters. Variability and instability in human respiration complicate the task of predicting tumor position from surrogate breathing signals. Our results show that adaptive signal-processing filters can provide more accurate tumor position estimates than simpler stationary filters when presented with nonstationary breathing motion.

  7. ORISE: REAC/TS Medical Management of Radiation Incidents

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    of Radiation Incidents As part of its primary mission for the U.S. Department of Energy (DOE), the Radiation Emergency Assistance CenterTraining Site (REACTS) at the Oak...

  8. Effect of Emergency Argon on FCF Operational Incidents

    SciTech Connect (OSTI)

    Charles Solbrig

    2011-12-01

    The following report presents analyses of operational incidents which are considered in the safety analysis of the FCF argon cell and the effect that the operability of the emergency argon system has on the course of these incidents. The purpose of this study is to determine if the emergency argon system makes a significant difference in ameliorating the course of these incidents. Six incidents were considered. The following three incidents were analyzed. These are: 1. Cooling failing on 2. Vacuum Pump Failing on 3. Argon Supplies Failing on. In the remaining three incidents, the emergency argon supply would have no effect on the course of these transients since it would not come on during these incidents. The transients are 1. Loss of Cooling 2. Loss of power (Differs from above by startup delay till the Diesel Generators come on.) 3. Cell rupture due to an earthquake or other cause. The analyses of the first three incidents are reported on in the next three sections. This report is issued realizing the control parameters used may not be optimum, and additional modeling must be done to model the inertia of refrigeration system, but the major conclusion concerning the need for the emergency argon system is still valid. The timing of some events may change with a more accurate model but the differences between the transients with and without emergency argon will remain the same. Some of the parameters assumed in the analyses are Makeup argon supply, 18 cfm, initiates when pressure is = -6 iwg., shuts off when pressure is = -3.1 iwg. 170,000 ft3 supply. Min 1/7th always available, can be cross connected to HFEF argon supply dewar. Emergency argon supply, 900 cfm, initiates when pressure is = -8 iwg. shuts off when pressure is =-4 iwg. reservoir 220 ft3, refilled when tank farm pressure reduces to 1050 psi which is about 110 ft3.

  9. Source term estimation during incident response to severe nuclear power

    Office of Scientific and Technical Information (OSTI)

    plant accidents (Technical Report) | SciTech Connect Source term estimation during incident response to severe nuclear power plant accidents Citation Details In-Document Search Title: Source term estimation during incident response to severe nuclear power plant accidents × You are accessing a document from the Department of Energy's (DOE) SciTech Connect. This site is a product of DOE's Office of Scientific and Technical Information (OSTI) and is provided as a public service. Visit OSTI to

  10. Radioactive Waste Issues in Major Nuclear Incidents | Department of Energy

    Energy Savers [EERE]

    Radioactive Waste Issues in Major Nuclear Incidents Radioactive Waste Issues in Major Nuclear Incidents S.Y. Chen*, Illinois Institute of Technology Abstract: Large amounts of radioactive waste had been generated in major nuclear accidents such as the Chernobyl nuclear accident in Ukraine of 1986 and the recent Fukushima nuclear accident in Japan of 2011. The wastes were generated due to the accidental releases of radioactive materials that resulted in widespread contamination throughout the

  11. Headquarters Facilities Master Security Plan- Chapter 11, Incidents of Security Concern

    Broader source: Energy.gov [DOE]

    2016 Headquarters Facilities Master Security Plan - Chapter 11, Incidents of Security Concern Describes DOE Headquarters procedures for reporting, investigating, and correcting Incidents of Security Concern.

  12. The Kauai Skin Cancer Study--1983 to 1992

    SciTech Connect (OSTI)

    Reizner, G.T. )

    1993-05-01

    The Kauai Skin Cancer Study began as a modest effort in 1983 to look at this island's skin cancer incidence. David Elpern MD, Kauai's only dermatologist at the time, was interested in the large number of these tumors in his practice. He first enlisted his office staff to help keep track of the numbers and type of these skin cancers. Along with this information, the basic demographic data on each patient was collected. These records became the first entries into what has become a decade-long project.

  13. PSM case history: Regulatory compliance can prevent catastrophic incidents

    SciTech Connect (OSTI)

    Kiihne, E.J.; Mannan, M. [RMT/Jones and Neuse, Inc., Austin, TX (United States)

    1995-12-31

    As mandated by the Clean Air Act Amendments of 1990, the Occupational Safety and Health Administration promulgated on February 24, 1992 the Process Safety Management (PSM) rule: 29 CFR 1910.119. The PSM rule represents a holistic program which requires facilities to develop, implement and practice 14 different elements. Each of the 14 elements are significant in the protection of health and safety of all employees and personnel working in and around the plant site. PSM programs developed in compliance with the PSM rule are expected to reduce the probability and consequence of occurrence of hazardous incidents. This paper presents a real life incident that occurred in a plant before a PSM program was put in place. A detailed description of the incident is provided with appropriate discussions of non compliance with the PSM rule. Finally, the paper provides a theoretical scenario where a fully operational PSM program would have prevented the incident. The case history and discussion provided in this paper also reinforces the concept of maintaining process and equipment integrity through multiple barriers of safety. A fully operational PSM program represents such a multiple barrier safety system.

  14. Violation of Laws, Losses, and Incidents of Security Concerns

    Broader source: Directives, Delegations, and Requirements [Office of Management (MA)]

    1992-09-15

    To set forth Department of Energy (DOE) procedures to assure timely and effective action relating to violations of criminal, laws, loses, and incidents of security concern to DOE. Cancels DOE O 5631.5. Canceled by DOE O 470.1 of 9-28-1995.

  15. EM-Led Radiological Incident Response Program Receives Honors

    Broader source: Energy.gov [DOE]

    A program led by EM’s Carlsbad Field Office (CBFO) that coordinates analytical capabilities throughout DOE for response to potential national radiological incidents recently received recognition for the best-in-track poster at a waste management conference earlier this year.

  16. NNSA Nuclear/Radiological Incident Response | National Nuclear Security

    National Nuclear Security Administration (NNSA)

    Administration Nuclear/Radiological Incident Response | National Nuclear Security Administration Facebook Twitter Youtube Flickr RSS People Mission Managing the Stockpile Preventing Proliferation Powering the Nuclear Navy Emergency Response Recapitalizing Our Infrastructure Countering Nuclear Terrorism About Our Programs Our History Who We Are Our Leadership Our Locations Budget Our Operations Library Bios Congressional Testimony Fact Sheets Newsletters Press Releases Photo Gallery Jobs

  17. Nested methylation-specific polymerase chain reaction cancer detection method

    DOE Patents [OSTI]

    Belinsky, Steven A.; Palmisano, William A.

    2007-05-08

    A molecular marker-based method for monitoring and detecting cancer in humans. Aberrant methylation of gene promoters is a marker for cancer risk in humans. A two-stage, or "nested" polymerase chain reaction method is disclosed for detecting methylated DNA sequences at sufficiently high levels of sensitivity to permit cancer screening in biological fluid samples, such as sputum, obtained non-invasively. The method is for detecting the aberrant methylation of the p16 gene, O 6-methylguanine-DNA methyltransferase gene, Death-associated protein kinase gene, RAS-associated family 1 gene, or other gene promoters. The method offers a potentially powerful approach to population-based screening for the detection of lung and other cancers.

  18. Method and apparatus for measuring lung density by Compton backscattering

    DOE Patents [OSTI]

    Loo, B.W.; Goulding, F.S.

    1988-03-11

    The density of the lung of a patient suffering from pulmonary edema is monitored by irradiating the lung by a single collimated beam of monochromatic photons and measuring the energies of photons compton back-scattered from the lung by a single high-resolution, high-purity germanium detector. A compact system geometry and a unique data extraction scheme are utilized to minimize systematic errors due to the presence of the chestwall and multiple scattering. 11 figs., 1 tab.

  19. Method and apparatus for measuring lung density by Compton backscattering

    DOE Patents [OSTI]

    Loo, Billy W. (Oakland, CA); Goulding, Frederick S. (Lafayette, CA)

    1991-01-01

    The density of the lung of a patient suffering from pulmonary edema is monitored by irradiating the lung by a single collimated beam of monochromatic photons and measuring the energies of photons Compton backscattered from the lung by a single high-resolution, high-purity germanium detector. A compact system geometry and a unique data extraction scheme are utilized to monimize systematic errors due to the presence of the chestwall and multiple scattering.

  20. Sex-specific differences in hyperoxic lung injury in mice: Implications for acute and chronic lung disease in humans

    SciTech Connect (OSTI)

    Lingappan, Krithika, E-mail: lingappa@bcm.edu [Department of Pediatrics, Section of Neonatology, Texas Children's Hospital, Baylor College of Medicine, 1102 Bates Avenue, MC: FC530.01, Houston, TX 77030 (United States); Jiang, Weiwu; Wang, Lihua; Couroucli, Xanthi I. [Department of Pediatrics, Section of Neonatology, Texas Children's Hospital, Baylor College of Medicine, 1102 Bates Avenue, MC: FC530.01, Houston, TX 77030 (United States); Barrios, Roberto [Department of Pathology and Genomic Medicine, The Methodist Hospital Physician Organization, 6565 Fannin Street, Suite M227, Houston, TX 77030 (United States); Moorthy, Bhagavatula [Department of Pediatrics, Section of Neonatology, Texas Children's Hospital, Baylor College of Medicine, 1102 Bates Avenue, MC: FC530.01, Houston, TX 77030 (United States)

    2013-10-15

    Sex-specific differences in pulmonary morbidity in humans are well documented. Hyperoxia contributes to lung injury in experimental animals and humans. The mechanisms responsible for sex differences in the susceptibility towards hyperoxic lung injury remain largely unknown. In this investigation, we tested the hypothesis that mice will display sex-specific differences in hyperoxic lung injury. Eight week-old male and female mice (C57BL/6J) were exposed to 72 h of hyperoxia (FiO{sub 2} > 0.95). After exposure to hyperoxia, lung injury, levels of 8-iso-prostaglandin F{sub 2} alpha (8-iso-PGF 2?) (LCMS/MS), apoptosis (TUNEL) and inflammatory markers (suspension bead array) were determined. Cytochrome P450 (CYP)1A expression in the lung was assessed using immunohistochemistry and western blotting. After exposure to hyperoxia, males showed greater lung injury, neutrophil infiltration and apoptosis, compared to air-breathing controls than females. Pulmonary 8-iso-PGF 2? levels were higher in males than females after hyperoxia exposure. Sexually dimorphic increases in levels of IL-6 (F > M) and VEGF (M > F) in the lungs were also observed. CYP1A1 expression in the lung was higher in female mice compared to males under hyperoxic conditions. Overall, our results support the hypothesis that male mice are more susceptible than females to hyperoxic lung injury and that differences in inflammatory and oxidative stress markers contribute to these sex-specific dimorphic effects. In conclusion, this paper describes the establishment of an animal model that shows sex differences in hyperoxic lung injury in a temporal manner and thus has important implications for lung diseases mediated by hyperoxia in humans. - Highlights: Male mice were more susceptible to hyperoxic lung injury than females. Sex differences in inflammatory markers were observed. CYP1A expression was higher in females after hyperoxia exposure.

  1. Optimization of leaf margins for lung stereotactic body radiotherapy using a flattening filter-free beam

    SciTech Connect (OSTI)

    Wakai, Nobuhide; Sumida, Iori; Otani, Yuki; Suzuki, Osamu; Seo, Yuji; Isohashi, Fumiaki; Yoshioka, Yasuo; Ogawa, Kazuhiko; Hasegawa, Masatoshi

    2015-05-15

    Purpose: The authors sought to determine the optimal collimator leaf margins which minimize normal tissue dose while achieving high conformity and to evaluate differences between the use of a flattening filter-free (FFF) beam and a flattening-filtered (FF) beam. Methods: Sixteen lung cancer patients scheduled for stereotactic body radiotherapy underwent treatment planning for a 7 MV FFF and a 6 MV FF beams to the planning target volume (PTV) with a range of leaf margins (?3 to 3 mm). Forty grays per four fractions were prescribed as a PTV D95. For PTV, the heterogeneity index (HI), conformity index, modified gradient index (GI), defined as the 50% isodose volume divided by target volume, maximum dose (Dmax), and mean dose (Dmean) were calculated. Mean lung dose (MLD), V20 Gy, and V5 Gy for the lung (defined as the volumes of lung receiving at least 20 and 5 Gy), mean heart dose, and Dmax to the spinal cord were measured as doses to organs at risk (OARs). Paired t-tests were used for statistical analysis. Results: HI was inversely related to changes in leaf margin. Conformity index and modified GI initially decreased as leaf margin width increased. After reaching a minimum, the two values then increased as leaf margin increased (V shape). The optimal leaf margins for conformity index and modified GI were ?1.1 0.3 mm (mean 1 SD) and ?0.2 0.9 mm, respectively, for 7 MV FFF compared to ?1.0 0.4 and ?0.3 0.9 mm, respectively, for 6 MV FF. Dmax and Dmean for 7 MV FFF were higher than those for 6 MV FF by 3.6% and 1.7%, respectively. There was a positive correlation between the ratios of HI, Dmax, and Dmean for 7 MV FFF to those for 6 MV FF and PTV size (R = 0.767, 0.809, and 0.643, respectively). The differences in MLD, V20 Gy, and V5 Gy for lung between FFF and FF beams were negligible. The optimal leaf margins for MLD, V20 Gy, and V5 Gy for lung were ?0.9 0.6, ?1.1 0.8, and ?2.1 1.2 mm, respectively, for 7 MV FFF compared to ?0.9 0.6, ?1.1 0.8, and ?2.2 1.3 mm, respectively, for 6 MV FF. With the heart inside the radiation field, the mean heart dose showed a V-shaped relationship with leaf margins. The optimal leaf margins were ?1.0 0.6 mm for both beams. Dmax to the spinal cord showed no clear trend for changes in leaf margin. Conclusions: The differences in doses to OARs between FFF and FF beams were negligible. Conformity index, modified GI, MLD, lung V20 Gy, lung V5 Gy, and mean heart dose showed a V-shaped relationship with leaf margins. There were no significant differences in optimal leaf margins to minimize these parameters between both FFF and FF beams. The authors results suggest that a leaf margin of ?1 mm achieves high conformity and minimizes doses to OARs for both FFF and FF beams.

  2. Researchers correlate incidences of rheumatoid arthritis and giant cell

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    arteritis with solar cycles | Princeton Plasma Physics Lab Researchers correlate incidences of rheumatoid arthritis and giant cell arteritis with solar cycles By John Greenwald June 15, 2015 Tweet Widget Google Plus One Share on Facebook A coronal mass ejection hurling plasma from the sun (Photo by NASA) A coronal mass ejection hurling plasma from the sun What began as a chat between husband and wife has evolved into an intriguing scientific discovery. The results, published in May in BMJ

  3. Researchers correlate incidences of rheumatoid arthritis and giant cell

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    arteritis with solar cycles | Princeton Plasma Physics Lab Researchers correlate incidences of rheumatoid arthritis and giant cell arteritis with solar cycles By John Greenwald June 15, 2015 Tweet Widget Google Plus One Share on Facebook A coronal mass ejection hurling plasma from the sun (Photo by NASA) A coronal mass ejection hurling plasma from the sun What began as a chat between husband and wife has evolved into an intriguing scientific discovery. The results, published in May in BMJ

  4. ORISE: Incident Management Training Put to Test in Gulf

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Incident Management Training Put to Test in Gulf ORISE emergency management staff provided critical support during Deepwater Horizon disaster On April 20, 2010, an explosion on the Deepwater Horizon oil rig in the Gulf of Mexico killed 11 people and touched off a massive offshore oil spill that continued for more than 12 weeks. U.S. Department of Energy and the Oak Ridge Institute for Science and Education emergency management personnel were among those who traveled to the Gulf to assist

  5. Incidents at nuclear power plants caused by the human factor

    SciTech Connect (OSTI)

    Mashin, V. A.

    2012-09-15

    Psychological analysis of the causes of incorrect actions by personnel is discussed as presented in the report 'Methodological guidelines for analyzing the causes of incidents in the operation of nuclear power plants.' The types of incorrect actions and classification of the root causes of errors by personnel are analyzed. Recommendations are made for improvements in the psychological analysis of causes of incorrect actions by personnel.

  6. ORISE: REAC/TS Medical Management of Radiation Incidents

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Medical Management of Radiation Incidents As part of its primary mission for the U.S. Department of Energy (DOE), the Radiation Emergency Assistance Center/Training Site (REAC/TS) at the Oak Ridge Institute for Science and Education (ORISE) is available 24 hours a day, seven days a week to consult with officials from any federal, state or local government agency; industries; international governments or organizations; or individuals needing assistance with the medical management of a radiation

  7. Chapter 27 -- Breast Cancer Genomics, Section VI, Pathology and Biological Markers of Invasive Breast Cancer

    SciTech Connect (OSTI)

    Spellman, Paul T.; Heiser, Laura; Gray, Joe W.

    2009-06-18

    Breast cancer is predominantly a disease of the genome with cancers arising and progressing through accumulation of aberrations that alter the genome - by changing DNA sequence, copy number, and structure in ways that that contribute to diverse aspects of cancer pathophysiology. Classic examples of genomic events that contribute to breast cancer pathophysiology include inherited mutations in BRCA1, BRCA2, TP53, and CHK2 that contribute to the initiation of breast cancer, amplification of ERBB2 (formerly HER2) and mutations of elements of the PI3-kinase pathway that activate aspects of epidermal growth factor receptor (EGFR) signaling and deletion of CDKN2A/B that contributes to cell cycle deregulation and genome instability. It is now apparent that accumulation of these aberrations is a time-dependent process that accelerates with age. Although American women living to an age of 85 have a 1 in 8 chance of developing breast cancer, the incidence of cancer in women younger than 30 years is uncommon. This is consistent with a multistep cancer progression model whereby mutation and selection drive the tumor's development, analogous to traditional Darwinian evolution. In the case of cancer, the driving events are changes in sequence, copy number, and structure of DNA and alterations in chromatin structure or other epigenetic marks. Our understanding of the genetic, genomic, and epigenomic events that influence the development and progression of breast cancer is increasing at a remarkable rate through application of powerful analysis tools that enable genome-wide analysis of DNA sequence and structure, copy number, allelic loss, and epigenomic modification. Application of these techniques to elucidation of the nature and timing of these events is enriching our understanding of mechanisms that increase breast cancer susceptibility, enable tumor initiation and progression to metastatic disease, and determine therapeutic response or resistance. These studies also reveal the molecular differences between cancer and normal that may be exploited to therapeutic benefit or that provide targets for molecular assays that may enable early cancer detection, and predict individual disease progression or response to treatment. This chapter reviews current and future directions in genome analysis and summarizes studies that provide insights into breast cancer pathophysiology or that suggest strategies to improve breast cancer management.

  8. Drum Involved in Idaho Incident Not Shippable to WIPP

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Contacts: Dennis Hurtt U.S. Department of Energy Carlsbad Field Office (505) 234-7327 Susan Scott Washington TRU Solutions LLC (505) 234-7204 (800) 493-9768 http://www.wipp.carlsbad.nm.us U.S. Department of Energy Carlsbad Field Office Waste Isolation Pilot Plant P.O. Box 3090 Carlsbad, New Mexico 88221 DOENews For Immediate Release Drum Involved in Idaho Incident Not Shippable to WIPP CARLSBAD, N.M., August 14, 2003, 4:05 p.m. (MDT) - As communicated by the U.S. Department of Energy, and

  9. Epithelialmesenchymal transition during oncogenic transformation induced by hexavalent chromium involves reactive oxygen species-dependent mechanism in lung epithelial cells

    SciTech Connect (OSTI)

    Ding, Song-Ze; Yang, Yu-Xiu; Li, Xiu-Ling; Michelli-Rivera, Audrey; Han, Shuang-Yin; Wang, Lei; Pratheeshkumar, Poyil; Wang, Xin; Lu, Jian; Yin, Yuan-Qin; Budhraja, Amit; Hitron, Andrew J.

    2013-05-15

    Hexavalent chromium [Cr(VI)] is an important human carcinogen associated with pulmonary diseases and lung cancer. Exposure to Cr(VI) induces DNA damage, cell morphological change and malignant transformation in human lung epithelial cells. Despite extensive studies, the molecular mechanisms remain elusive, it is also not known if Cr(VI)-induced transformation might accompany with invasive properties to facilitate metastasis. We aimed to study Cr(VI)-induced epithelialmesenchymal transition (EMT) and invasion during oncogenic transformation in lung epithelial cells. The results showed that Cr(VI) at low doses represses E-cadherin mRNA and protein expression, enhances mesenchymal marker vimentin expression and transforms the epithelial cell into fibroblastoid morphology. Cr(VI) also increases cell invasion and promotes colony formation. Further studies indicated that Cr(VI) uses multiple mechanisms to repress E-cadherin expression, including activation of E-cadherin repressors such as Slug, ZEB1, KLF8 and enhancement the binding of HDAC1 in E-cadherin gene promoter, but DNA methylation is not responsible for the loss of E-cadherin. Catalase reduces Cr(VI)-induced E-cadherin and vimentin protein expression, attenuates cell invasion in matrigel and colony formation on soft agar. These results demonstrate that exposure to a common human carcinogen, Cr(VI), induces EMT and invasion during oncogenic transformation in lung epithelial cells and implicate in cancer metastasis and prevention. - Graphical abstract: Epithelialmesenchymal transition during oncogenic transformation induced by hexavalent chromium involves reactive oxygen species-dependent mechanisms in lung epithelial cells. - Highlights: We study if Cr(VI) might induce EMT and invasion in epithelial cells. Cr(VI) induces EMT by altering E-cadherin and vimentin expression. It also increases cell invasion and promotes oncogenic transformation. Catalase reduces Cr(VI)-induced EMT, invasion and transformation.

  10. Accelerated cellular senescence phenotype of GAPDH-depleted human lung carcinoma cells

    SciTech Connect (OSTI)

    Phadke, Manali; Krynetskaia, Natalia; Mishra, Anurag; Krynetskiy, Evgeny; Jayne Haines Center for Pharmacogenomics, Temple University School of Pharmacy, Philadelphia, PA 19140

    2011-07-29

    Highlights: {yields} We examined the effect of glyceraldehyde 3-phosphate (GAPDH) depletion on proliferation of human carcinoma A549 cells. {yields} GAPDH depletion induces accelerated senescence in tumor cells via AMPK network, in the absence of DNA damage. {yields} Metabolic and genetic rescue experiments indicate that GAPDH has regulatory functions linking energy metabolism and cell cycle. {yields} Induction of senescence in LKB1-deficient lung cancer cells via GAPDH depletion suggests a novel strategy to control tumor cell proliferation. -- Abstract: Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) is a pivotal glycolytic enzyme, and a signaling molecule which acts at the interface between stress factors and the cellular apoptotic machinery. Earlier, we found that knockdown of GAPDH in human carcinoma cell lines resulted in cell proliferation arrest and chemoresistance to S phase-specific cytotoxic agents. To elucidate the mechanism by which GAPDH depletion arrests cell proliferation, we examined the effect of GAPDH knockdown on human carcinoma cells A549. Our results show that GAPDH-depleted cells establish senescence phenotype, as revealed by proliferation arrest, changes in morphology, SA-{beta}-galactosidase staining, and more than 2-fold up-regulation of senescence-associated genes DEC1 and GLB1. Accelerated senescence following GAPDH depletion results from compromised glycolysis and energy crisis leading to the sustained AMPK activation via phosphorylation of {alpha} subunit at Thr172. Our findings demonstrate that GAPDH depletion switches human tumor cells to senescent phenotype via AMPK network, in the absence of DNA damage. Rescue experiments using metabolic and genetic models confirmed that GAPDH has important regulatory functions linking the energy metabolism and the cell cycle networks. Induction of senescence in LKB1-deficient non-small cell lung cancer cells via GAPDH depletion suggests a novel strategy to control tumor cell proliferation.

  11. Mechanism-based inhibition of cancer metastasis with (?)-epigallocatechin gallate

    SciTech Connect (OSTI)

    Takahashi, Atsushi; Graduate School of Science and Engineering, Saitama University, Saitama 338-8570; Green Tea Laboratory, Saitama Prefectural Agriculture and Forestry Research Center, Saitama 358-0042 ; Watanabe, Tatsuro; Mondal, Anupom; Suzuki, Kaori; Kurusu-Kanno, Miki; Li, Zhenghao; Yamazaki, Takashi; Graduate School of Science and Engineering, Saitama University, Saitama 338-8570 ; Fujiki, Hirota; Suganuma, Masami

    2014-01-03

    Highlights: EGCG reduced cell motility of highly metastatic human lung cancer cells. EGCG increased cell stiffness of the cells, indicating the inhibition of phenotypes of EMT. EGCG inhibited expression of vimentin and Slug in the cells at the leading edge of scratch. Treatment of M?CD increased cell stiffness, and inhibited cell motility and vimentin expression. Inhibition of EMT phenotypes with EGCG is a mechanism-based inhibition of cancer metastasis. -- Abstract: Cell motility and cell stiffness are closely related to metastatic activity of cancer cells. (?)-Epigallocatechin gallate (EGCG) has been shown to inhibit spontaneous metastasis of melanoma cell line into the lungs of mice, so we studied the effects of EGCG on cell motility, cell stiffness, and expression of vimentin and Slug, which are molecular phenotypes of epithelialmesenchymal transition (EMT). Treatments of human non-small cell lung cancer cell lines H1299 and Lu99 with 50 and 100 ?M EGCG reduced cell motility to 67.5% and 43.7% in H1299, and 71.7% and 31.5% in Lu99, respectively in in vitro wound healing assay. Studies on cell stiffness using atomic force microscope (AFM) revealed that treatment with 50 ?M EGCG increased Youngs modulus of H1299 from 1.24 to 2.25 kPa and that of Lu99 from 1.29 to 2.28 kPa, showing a 2-fold increase in cell stiffness, i.e. rigid elasticity of cell membrane. Furthermore, treatment with 50 ?M EGCG inhibited high expression of vimentin and Slug in the cells at a leading edge of scratch. Methyl-?-cyclodextrin, a reagent to deplete cholesterol in plasma membrane, showed inhibition of EMT phenotypes similar that by EGCG, suggesting that EGCG induces inhibition of EMT phenotypes by alteration of membrane organization.

  12. SciSat AM: Stereo 03: Dosmetric evaluation of single versus multi-arc VMAT for lung SBRT

    SciTech Connect (OSTI)

    Karan, T; Taremi, M; Comsa, D; Allibhai, Z; Ryan, M; Le, K

    2014-08-15

    Five non-small cell lung cancer patients previously treated with stereotactic body radiation therapy using the VMAT (volumetric modulated arc therapy) technique were selected for this retrospective study. Plans were re-optimized using Pinnacle treatment planning system (v9.0, Philips Medical), with the basis for comparison a two-arc plan involving a 360 arc in addition to a 90 arc with a couch kick. Additionally a single 360 arc was optimized for comparison, as well as a partial arc covering ?230, avoiding the contralateral lung. All plans met target coverage criteria as dictated by RTOG0236. Plans were evaluated based on conformity, sparing of organs at risk and practical considerations of delivery. Conformity was best in the two-arc plan; however the decrease seen in one- and partial arc plans was not statistically significant as tested by the Wilcoxon rank sum test. The partial-arc plan resulted in the lowest esophagus and trachea dose and the highest heart dose, however none of the plans exceeded organ at risk tolerances for lung SBRT. Partial arcs resulted in plans with slightly cooler dose distributions, a decrease in low dose spillage and an overall lower mean lung dose. The decrease in treatment time was on average 36 and 40 seconds for single and partial arcs, respectively, with partial arcs requiring the lowest number of MUs. The slight decrease in conformity seen in one-arc plans is offset by an increase in efficiency (optimization and treatment time, MUs) making the implementation of a single or partial-arc treatment technique clinically desirable.

  13. A CAD system for nodule detection in low-dose lung CTs based on region growing and a new active contour model

    SciTech Connect (OSTI)

    Bellotti, R.; De Carlo, F.; Gargano, G.; Tangaro, S.; Cascio, D.; Catanzariti, E.; Cerello, P.; Cheran, S. C.; Delogu, P.; De Mitri, I.; Fulcheri, C.; Grosso, D.; Retico, A.; Squarcia, S.; Tommasi, E.; Golosio, Bruno

    2007-12-15

    A computer-aided detection (CAD) system for the selection of lung nodules in computer tomography (CT) images is presented. The system is based on region growing (RG) algorithms and a new active contour model (ACM), implementing a local convex hull, able to draw the correct contour of the lung parenchyma and to include the pleural nodules. The CAD consists of three steps: (1) the lung parenchymal volume is segmented by means of a RG algorithm; the pleural nodules are included through the new ACM technique; (2) a RG algorithm is iteratively applied to the previously segmented volume in order to detect the candidate nodules; (3) a double-threshold cut and a neural network are applied to reduce the false positives (FPs). After having set the parameters on a clinical CT, the system works on whole scans, without the need for any manual selection. The CT database was recorded at the Pisa center of the ITALUNG-CT trial, the first Italian randomized controlled trial for the screening of the lung cancer. The detection rate of the system is 88.5% with 6.6 FPs/CT on 15 CT scans (about 4700 sectional images) with 26 nodules: 15 internal and 11 pleural. A reduction to 2.47 FPs/CT is achieved at 80% efficiency.

  14. Diesel Exhaust Dispersion in a Phospholipid Lung Surfactant | Department of

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    Energy Exhaust Dispersion in a Phospholipid Lung Surfactant Diesel Exhaust Dispersion in a Phospholipid Lung Surfactant 2005 Diesel Engine Emissions Reduction (DEER) Conference Presentations and Posters PDF icon 2005_deer_wallace.pdf More Documents & Publications IN VITRO MUTAGENIC AND DNA AND CHROMOSOMAL DAMAGE ACTIVITY BY SURFACTANT DISPERSION OR SOLVENT EXTRACT OF A REFERENCE DIESEL EXHAUST PARTICULATE MATERIAL In Vitro Genotoxicity of Gasoline and Diesel Engine Vehicle Exhaust

  15. Response of Human Lung Epithelial Cells to Engineered Nanoparticles.

    Office of Scientific and Technical Information (OSTI)

    (Conference) | SciTech Connect Response of Human Lung Epithelial Cells to Engineered Nanoparticles. Citation Details In-Document Search Title: Response of Human Lung Epithelial Cells to Engineered Nanoparticles. Abstract not provided. Authors: Bachand, George ; Bachand, Marlene ; Brozik, Susan Marie ; Achyuthan, Komandoor ; Allen, Amy Publication Date: 2011-10-01 OSTI Identifier: 1120230 Report Number(s): SAND2011-7265C 482189 DOE Contract Number: DE-AC04-94AL85000 Resource Type: Conference

  16. Federal Response Assets for a Radioactive Dispersal Device Incident

    SciTech Connect (OSTI)

    Sullivan,T.

    2009-06-30

    If a large scale RDD event where to occur in New York City, the magnitude of the problem would likely exceed the capabilities of City and State to effectively respond to the event. New York State could request Federal Assistance if the United States President has not already made the decision to provide it. The United States Federal Government has a well developed protocol to respond to emergencies. The National Response Framework (NRF) describes the process for responding to all types of emergencies including RDD incidents. Depending on the location and type of event, the NRF involves appropriate Federal Agencies, e.g., Department of Homeland Security (DHS), the Department of Energy (DOE), Environmental Protection Agency (EPA), United States Coast Guard (USCG), Department of Defense (DOD), Department of Justice (DOJ), Department of Agriculture (USDA), and Nuclear Regulatory Commission (NRC). The Federal response to emergencies has been refined and improved over the last thirty years and has been tested on natural disasters (e.g. hurricanes and floods), man-made disasters (oil spills), and terrorist events (9/11). However, the system has never been tested under an actual RDD event. Drills have been conducted with Federal, State, and local agencies to examine the initial (early) phases of such an event (TopOff 2 and TopOff 4). The Planning Guidance for Protection and Recovery Following Radiological Dispersal Device (RDD) and Improvised Nuclear Device (IND) incidents issued by the Department of Homeland Security (DHS) in August 2008 has never been fully tested in an interagency exercise. Recently, another exercise called Empire 09 that was situated in Albany, New York was conducted. Empire 09 consists of 3 different exercises be held in May and June, 2009. The first exercise, May 2009, involved a table top exercise for phase 1 (0-48 hours) of the response to an RDD incident. In early June, a full-scale 3- day exercise was conducted for the mid-phase response (48 hours +). A few weeks later, a one day full-scale exercise was conducted for the late phase (recovery) response to an RDD event. The lessons learned from this study are not available as of June 30, 2009. The objective of this report is to review and summarize anticipated Federal and State response actions and the roles and responsibilities of various agencies (DHS, EPA, DOE, NY-DEP, NY-DEC) with respect to decontamination issues that would arise from a radiological dispersion device (RDD), e.g., dirty bomb attack. These issues arise in the late phase of the response (48 hours and beyond) after the area has been stabilized and forensic information has been obtained. Much of the information provided in this report is taken directly from published guidance that is readily available.

  17. Laser Incident Lessons Learned and Action List (Technical Report) | SciTech

    Office of Scientific and Technical Information (OSTI)

    Connect Laser Incident Lessons Learned and Action List Citation Details In-Document Search Title: Laser Incident Lessons Learned and Action List On Thursday November 19, 2015, LANL postdoc received an eye injury from a reflected, nonvisible laser beam (Class 4, pulsed, wavelength 800 nanometer). The setup is configured to split the laser output into two work areas in which qualified operators conduct research experiments. During this incident, the laser output beam was being projected to

  18. Fact Sheet Investigation of Incident at Waste Isolation Pilot Plant by

    Energy Savers [EERE]

    Technical Assessment Team | Department of Energy Fact Sheet Investigation of Incident at Waste Isolation Pilot Plant by Technical Assessment Team Fact Sheet Investigation of Incident at Waste Isolation Pilot Plant by Technical Assessment Team On February 14, 2014, an incident in Panel 7 Room 7 (P7R7) of the Waste Isolation Pilot Plant (WIPP) underground repository resulted in the release of radioactive material into the environment and contaminated 21 people with low-level radioactivity. The

  19. SU-E-J-185: Gated CBCT Imaging for Positioning Moving Lung Tumor in Lung SBRT Treatment

    SciTech Connect (OSTI)

    Li, X; Li, T; Zhang, Y; Burton, S; Karlovits, B; Clump, D; Heron, D; Huq, M

    2014-06-01

    Purpose: Lung stereo-tactic body radiotherapy(SBRT) treatment requires high accuracy of lung tumor positioning during treatment, which is usually accomplished by free breathing Cone-Beam computerized tomography (CBCT) scan. However, respiratory motion induced image artifacts in free breathing CBCT may degrade such positioning accuracy. The purpose of this study is to investigate the feasibility of gated CBCT imaging for lung SBRT treatment. Methods: Six Lung SBRT patients were selected for this study. The respiratory motion of the tumors ranged from 1.2cm to 3.5cm, and the gating windows for all patients were set between 35% and 65% of the respiratory phases. Each Lung SBRT patient underwent free-breathing CBCT scan using half-fan scan technique. The acquired projection images were transferred out for off-line analyses. An In-house semi-automatic algorithm was developed to trace the diaphragm movement from those projection images to acquire a patient's specific respiratory motion curve, which was used to correlate respiratory phases with each projection image. Afterwards, a filtered back-projection algorithm was utilized to reconstruct the gated CBCT images based on the projection images only within the gating window. Results: Target volumes determined by free breathing CBCT images were 71.9%72% bigger than the volume shown in gated CBCT image. On the contrary, the target volume differences between gated CBCT and planning CT images at exhale stage were 5.8%2.4%. The center to center distance of the targets shown in free breathing CBCT and gated CBCT images were 9.28.1mm. For one particular case, the superior boundary of the target was shifted 15mm between free breathing CBCT and gated CBCT. Conclusion: Gated CBCT imaging provides better representation of the moving lung tumor with less motion artifacts, and has the potential to improve the positioning accuracy in lung SBRT treatment.

  20. Urinary arsenic profiles and the risks of cancer mortality: A population-based 20-year follow-up study in arseniasis-endemic areas in Taiwan

    SciTech Connect (OSTI)

    Chung, Chi-Jung; Department of Medical Research, China Medical Hospital, Taichung, Taiwan ; Huang, Ya-Li; Huang, Yung-Kai; Wu, Meei-Maan; Chen, Shu-Yuan; Hsueh, Yu-Mei; School of Public Health, College of Public Health and Nutrition, Taipei Medical University, Taipei, Taiwan ; Chen, Chien-Jen

    2013-04-15

    Few studies investigated the association between chronic arsenic exposure and the mortality of cancers by estimating individual urinary arsenic methylation profiles. Therefore, we compared with the general population in Taiwan to calculate the standardized mortality ratio (SMR) in arseniasis-endemic area of Taiwan from 1996 to 2010 and evaluated the dose-response relationships between environmental arsenic exposure indices or urinary arsenic profiles and the mortality of cause-specific cancer. A cohort of 1563 residents was conducted and collected their urine sample and information regarding arsenic exposure from a questionnaire. All-cause death was identified using the National Death Registry of Taiwan. Urinary arsenic profiles were measured using high performance liquid chromatographyhydride generatoratomic absorption spectrometry. We used Cox proportional hazard models to evaluate the mortality risks. In results, 193 all-site cancer deaths, and 29, 71, 43 deaths respectively for liver, lung and bladder cancers were ascertained. The SMRs were significantly high in arseniasis-endemic areas for liver, lung, and bladder cancers. People with high urinary InAs% or low DMA% or low secondary methylation index (SMI) were the most likely to suffer bladder cancer after adjusting other risk factors. Even stopping exposure to arsenic from the artesian well water, the mortality rates of the residents were higher than general population. Finally, urinary InAs%, DMA% and SMI could be the potential biomarkers to predict the mortality risk of bladder cancer. -- Highlights: ? The SMRs were significantly high in arseniasis-endemic areas for liver, lung, and bladder cancers. ? People with high urinary InAs% were the most likely to suffer bladder cancer. ? People with low DMA% or low SMI were the most likely to suffer bladder cancer.

  1. Volumetric Image Guidance Using Carina vs Spine as Registration Landmarks for Conventionally Fractionated Lung Radiotherapy

    SciTech Connect (OSTI)

    Lavoie, Caroline; Higgins, Jane; Bissonnette, Jean-Pierre; Le, Lisa W.; Sun, Alexander; Brade, Anthony; Hope, Andrew; Cho, John; Bezjak, Andrea

    2012-12-01

    Purpose: To compare the relative accuracy of 2 image guided radiation therapy methods using carina vs spine as landmarks and then to identify which landmark is superior relative to tumor coverage. Methods and Materials: For 98 lung patients, 2596 daily image-guidance cone-beam computed tomography scans were analyzed. Tattoos were used for initial patient alignment; then, spine and carina registrations were performed independently. A separate analysis assessed the adequacy of gross tumor volume, internal target volume, and planning target volume coverage on cone-beam computed tomography using the initial, middle, and final fractions of radiation therapy. Coverage was recorded for primary tumor (T), nodes (N), and combined target (T+N). Three scenarios were compared: tattoos alignment, spine registration, and carina registration. Results: Spine and carina registrations identified setup errors {>=}5 mm in 35% and 46% of fractions, respectively. The mean vector difference between spine and carina matching had a magnitude of 3.3 mm. Spine and carina improved combined target coverage, compared with tattoos, in 50% and 34% (spine) to 54% and 46% (carina) of the first and final fractions, respectively. Carina matching showed greater combined target coverage in 17% and 23% of fractions for the first and final fractions, respectively; with spine matching, this was only observed in 4% (first) and 6% (final) of fractions. Carina matching provided superior nodes coverage at the end of radiation compared with spine matching (P=.0006), without compromising primary tumor coverage. Conclusion: Frequent patient setup errors occur in locally advanced lung cancer patients. Spine and carina registrations improved combined target coverage throughout the treatment course, but carina matching provided superior combined target coverage.

  2. Perfusion lung scan: an aid in detection of lymphangitic carcinomatosis

    SciTech Connect (OSTI)

    Bates, S.E.; Tranum, B.L.

    1982-07-15

    Lymphangitic carcinomatosis is usually a late manifestation of metastatic disease. The patient usually presents with cough or dyspnea, and the chest radiograph is often nondiagnostic. Two patients are presented who developed symptoms while on adjuvant chemotherapy. Both had abnormal perfusion lung scans. One had matching ventilation defects; the other a normal ventilation study. Biopsy revealed metastatic carcinoma; in one case tumor was seen in both the pulmonary lymphatics and arterioles; in the other, tumor was identified but the site could not be specified. The radionuclide lung scan is a technique which can speed diagnosis and institution of therapy in lymphangitic carcinomatosis.

  3. SU-E-T-351: Verification of Monitor Unit Calculation for Lung...

    Office of Scientific and Technical Information (OSTI)

    States Language: English Subject: 60 APPLIED LIFE SCIENCES; COMPUTERIZED TOMOGRAPHY; LUNGS; MONTE CARLO METHOD; RADIATION DOSES; RADIATION MONITORS; RADIOTHERAPY; SPATIAL...

  4. Cellular morphometry of the bronchi of human and dog lungs. Annual progress report, April 1, 1992--March 31, 1993

    SciTech Connect (OSTI)

    Robbins, E.S.

    1992-09-01

    Quantitative data of the human bronchial epithelial cells at possible risk for malignant transformation in lung cancer is crucial for accurate radon dosimetry and risk analysis. The locations and other parameters of the nuclei which may be damaged by {alpha} particles must be determined and compared in different airway generations, among smokers, non-smokers and ex-smokers, between men and women and in people of different ages. This proposal includes extended morphometric studies on electron micrographs of human epithelium of defined airway generations and in parallel on electron micrographs of the dog bronchial lining. The second part of this proposal describes studies to quantitate the cycling bronchial epithelial population(s) using proliferation markers and immunocytochemistry on frozen and paraffin sections and similar labeling of isolated bronchial epithelial cells sorted flow cytometry.

  5. Modifications of lung clearance mechanisms by acute influenza A infection

    SciTech Connect (OSTI)

    Levandowski, R.A.; Gerrity, T.R.; Garrard, C.S.

    1985-10-01

    Four volunteers with naturally acquired, culture-proved influenza A infection inhaled a radiolabeled aerosol to permit investigation of lung mucociliary clearance mechanisms during and after symptomatic illness. Mucus transport in the trachea was undetectable when monitored with an external multidetector probe within 48 hours of the onset of the illness, but was found at a normal velocity by 1 week in three of the four subjects. In two volunteers who coughed 23 to 48 times during the 4.5-hour observation period, whole lung clearance was as fast within the first 48 hours of illness as during health 3 months later in spite of the absence of measurable tracheal mucus transport. Conversely, in spite of the return 1 week later of mucus transport at velocities expected in the trachea, whole lung clearance for the 4.5-hour period was slowed in two volunteers who coughed less than once an hour. The data offer evidence that cough is important in maintaining lung clearance for at least several days after symptomatic influenza A infection when other mechanisms that depend on ciliary function are severely deficient.

  6. Hedgehog pathway regulators influence cervical cancer cell proliferation, survival and migration

    SciTech Connect (OSTI)

    Samarzija, Ivana; Beard, Peter

    2012-08-17

    Highlights: Black-Right-Pointing-Pointer Unknown cellular mutations complement papillomavirus-induced carcinogenesis. Black-Right-Pointing-Pointer Hedgehog pathway components are expressed by cervical cancer cells. Black-Right-Pointing-Pointer Hedgehog pathway activators and inhibitors regulate cervical cancer cell biology. Black-Right-Pointing-Pointer Cell immortalization by papillomavirus and activation of Hedgehog are independent. -- Abstract: Human papillomavirus (HPV) infection is considered to be a primary hit that causes cervical cancer. However, infection with this agent, although needed, is not sufficient for a cancer to develop. Additional cellular changes are required to complement the action of HPV, but the precise nature of these changes is not clear. Here, we studied the function of the Hedgehog (Hh) signaling pathway in cervical cancer. The Hh pathway can have a role in a number of cancers, including those of liver, lung and digestive tract. We found that components of the Hh pathway are expressed in several cervical cancer cell lines, indicating that there could exists an autocrine Hh signaling loop in these cells. Inhibition of Hh signaling reduces proliferation and survival of the cervical cancer cells and induces their apoptosis as seen by the up-regulation of the pro-apoptotic protein cleaved caspase 3. Our results indicate that Hh signaling is not induced directly by HPV-encoded proteins but rather that Hh-activating mutations are selected in cells initially immortalized by HPV. Sonic Hedgehog (Shh) ligand induces proliferation and promotes migration of the cervical cancer cells studied. Together, these results indicate pro-survival and protective roles of an activated Hh signaling pathway in cervical cancer-derived cells, and suggest that inhibition of this pathway may be a therapeutic option in fighting cervical cancer.

  7. Implementation of the National Incident Management System (NIMS)/Incident Command System (ICS) in the Federal Radiological Monitoring and Assessment Center(FRMAC) - Emergency Phase

    SciTech Connect (OSTI)

    NSTec Environmental Restoration

    2007-04-01

    Homeland Security Presidential Directive HSPD-5 requires all federal departments and agencies to adopt a National Incident Management System (NIMS)/Incident Command System (ICS) and use it in their individual domestic incident management and emergency prevention, preparedness, response, recovery, and mitigation programs and activities, as well as in support of those actions taken to assist state and local entities. This system provides a consistent nationwide template to enable federal, state, local, and tribal governments, private-sector, and nongovernmental organizations to work together effectively and efficiently to prepare for, prevent, respond to, and recover from domestic incidents, regardless of cause, size, or complexity, including acts of catastrophic terrorism. This document identifies the operational concepts of the Federal Radiological Monitoring and Assessment Center's (FRMAC) implementation of the NIMS/ICS response structure under the National Response Plan (NRP). The construct identified here defines the basic response template to be tailored to the incident-specific response requirements. FRMAC's mission to facilitate interagency environmental data management, monitoring, sampling, analysis, and assessment and link this information to the planning and decision staff clearly places the FRMAC in the Planning Section. FRMAC is not a mitigating resource for radiological contamination but is present to conduct radiological impact assessment for public dose avoidance. Field monitoring is a fact-finding mission to support this effort directly. Decisions based on the assessed data will drive public protection and operational requirements. This organizational structure under NIMS is focused by the mission responsibilities and interface requirements following the premise to provide emergency responders with a flexible yet standardized structure for incident response activities. The coordination responsibilities outlined in the NRP are based on the NIMS/ICS construct and Unified Command (UC) for management of a domestic incident. The NRP Nuclear/Radiological Incident Annex (NUC) further provides requirements and protocols for coordinating federal government capabilities to respond to nuclear/radiological Incidents of National Significance (INS) and other radiological incidents. When a FRMAC is established, it operates under the parameters of NIMS as defined in the NRP. FRMAC and its operations have been modified to reflect NIMS/ICS concepts and principles and to facilitate working in a Unified Command structure. FRMAC is established at or near the scene of the incident to coordinate radiological monitoring and assessment and is established in coordination with the U.S. Department of Homeland Security (DHS); the coordinating agency; other federal agencies; and state, local, and tribal authorities. However, regardless of the coordinating agency designation, U.S. Department of Energy (DOE) coordinates radiological monitoring and assessment activities for the initial phases of the offsite federal incident response through the Radiological Assistance Program (RAP) and FRMAC assets. Monitoring and assessment data are managed by FRMAC in an accountable, secure, and retrievable format. Monitoring data interpretations, including exposure rate contours, dose projections, and any requested radiological assessments are to be provided to the DHS; to the coordinating agency; and to state, local, and tribal government agencies.

  8. Elevated epidermal growth factor receptor binding in plutonium-induced lung tumors from dogs

    SciTech Connect (OSTI)

    Leung, F.C.; Bohn, L.R.; Dagle, G.E. )

    1991-04-01

    The objective of this study is to examine and characterize epidermal growth factor receptor (EGF-R) binding in inhaled plutonium-induced canine lung-tumor tissue and to compare it with that in normal canine lung tissue. Crude membrane preparations from normal and lung-tumor tissue from beagle dogs were examined in a radioreceptor assay, using {sup 125}I-labeled epidermal growth factor (EGF) as a ligand. Specific EGF receptor binding was determined in the presence of excess unlabeled EGF. We have examined EGF receptor binding in eight lung-tumor samples obtained from six dogs. Epidermal growth factor receptor binding was significantly greater in lung-tumor samples (31.38%) compared with that in normal lung tissue (3.76%). Scatchard plot analysis from the displacement assay revealed that there was no statistical difference in the binding affinity but significantly higher concentration of EGF-R sites in the lung-tumor tissue (619 fmol/mg) than in normal lung tissue (53 fmol/mg). The increase in EGF-R number in plutonium-induced dog lung tumors does not seem to correlate with increase in the initial lung burden exposure to plutonium. Our results demonstrate that there is a significant increase in EGF-R binding in inhaled plutonium-induced dog lung tumors.

  9. Bismuth 213 Cancer Treatment

    ScienceCinema (OSTI)

    None

    2013-05-28

    See how INL scientists are increasing supplies of radioactive medical isotopes to treat cancer. For more information about INL research, visit http://www.facebook.com/idahonationallaboratory.

  10. X-ray imaging with grazing-incidence microscopes developed for the LIL

    Office of Scientific and Technical Information (OSTI)

    program (Journal Article) | SciTech Connect X-ray imaging with grazing-incidence microscopes developed for the LIL program Citation Details In-Document Search Title: X-ray imaging with grazing-incidence microscopes developed for the LIL program This article describes x-ray imaging with grazing-incidence microscopes, developed for the experimental program carried out on the Ligne d'Integration Laser (LIL) facility [J. P. Le Breton et al., Inertial Fusion Sciences and Applications 2001

  11. Consideration of Dose Limits for Organs at Risk of Thoracic Radiotherapy: Atlas for Lung, Proximal Bronchial Tree, Esophagus, Spinal Cord, Ribs, and Brachial Plexus

    SciTech Connect (OSTI)

    Kong, Feng-Ming; Ritter, Timothy; Quint, Douglas J.; Senan, Suresh; Gaspar, Laurie E.; Komaki, Ritsuko U.; Hurkmans, Coen W.; Timmerman, Robert; Bezjak, Andrea; Bradley, Jeffrey D.; Movsas, Benjamin; Marsh, Lon; Okunieff, Paul; Choy, Hak; Curran, Walter J.

    2011-12-01

    Purpose: To review the dose limits and standardize the three-dimenional (3D) radiographic definition for the organs at risk (OARs) for thoracic radiotherapy (RT), including the lung, proximal bronchial tree, esophagus, spinal cord, ribs, and brachial plexus. Methods and Materials: The present study was performed by representatives from the Radiation Therapy Oncology Group, European Organization for Research and Treatment of Cancer, and Soutwestern Oncology Group lung cancer committees. The dosimetric constraints of major multicenter trials of 3D-conformal RT and stereotactic body RT were reviewed and the challenges of 3D delineation of these OARs described. Using knowledge of the human anatomy and 3D radiographic correlation, draft atlases were generated by a radiation oncologist, medical physicist, dosimetrist, and radiologist from the United States and reviewed by a radiation oncologist and medical physicist from Europe. The atlases were then critically reviewed, discussed, and edited by another 10 radiation oncologists. Results: Three-dimensional descriptions of the lung, proximal bronchial tree, esophagus, spinal cord, ribs, and brachial plexus are presented. Two computed tomography atlases were developed: one for the middle and lower thoracic OARs (except for the heart) and one focusing on the brachial plexus for a patient positioned supine with their arms up for thoracic RT. The dosimetric limits of the key OARs are discussed. Conclusions: We believe these atlases will allow us to define OARs with less variation and generate dosimetric data in a more consistent manner. This could help us study the effect of radiation on these OARs and guide high-quality clinical trials and individualized practice in 3D-conformal RT and stereotactic body RT.

  12. A preliminary regional PBPK model of lung metabolism for improving species dependent descriptions of 1,3-butadiene and its metabolites

    SciTech Connect (OSTI)

    Campbell, Jerry; Van Landingham, Cynthia; Crowell, Susan; Gentry, Robinan; Kaden, Debra; Fiebelkorn, Stacy; Loccisano, Anne; Clewell, Harvey

    2015-06-12

    1,3-Butadiene (BD), a volatile organic chemical (VOC), is used in synthetic rubber production and other industrial processes. It is detectable at low levels in ambient air as well as in tobacco smoke and gasoline vapors. Inhalation exposures to high concentrations of BD have been associated with lung cancer in both humans and experimental animals, although differences in species sensitivity have been observed. Metabolically active lung cells such as Pulmonary Type I and Type II epithelial cells and club cells (Clara cells)1 are potential targets of BD metabolite-induced toxicity. Metabolic capacities of these cells, their regional densities, and distributions vary throughout the respiratory tract as well as between species and cell types. Here we present a physiologically based pharmacokinetic (PBPK) model for BD that includes a regional model of lung metabolism, based on a previous model for styrene, to provide species-dependent descriptions of BD metabolism in the mouse, rat, and human. Since there are no in vivo data on BD pharmacokinetics in the human, the rat and mouse models were parameterized to the extent possible on the basis of in vitro metabolic data. Where it was necessary to use in vivo data, extrapolation from rat to mouse was performed to evaluate the level of uncertainty in the human model. A kidney compartment and description of downstream metabolism were also included in the model to allow for eventual use of available urinary and blood biomarker data in animals and humans to calibrate the model for estimation of BD exposures and internal metabolite levels. Results from simulated inhalation exposures to BD indicate that incorporation of differential lung region metabolism is important in describing species differences in pulmonary response and that these differences may have implications for risk assessments of human exposures to BD.

  13. A preliminary regional PBPK model of lung metabolism for improving species dependent descriptions of 1,3-butadiene and its metabolites

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Campbell, Jerry; Van Landingham, Cynthia; Crowell, Susan; Gentry, Robinan; Kaden, Debra; Fiebelkorn, Stacy; Loccisano, Anne; Clewell, Harvey

    2015-06-12

    1,3-Butadiene (BD), a volatile organic chemical (VOC), is used in synthetic rubber production and other industrial processes. It is detectable at low levels in ambient air as well as in tobacco smoke and gasoline vapors. Inhalation exposures to high concentrations of BD have been associated with lung cancer in both humans and experimental animals, although differences in species sensitivity have been observed. Metabolically active lung cells such as Pulmonary Type I and Type II epithelial cells and club cells (Clara cells)1 are potential targets of BD metabolite-induced toxicity. Metabolic capacities of these cells, their regional densities, and distributions vary throughoutmore » the respiratory tract as well as between species and cell types. Here we present a physiologically based pharmacokinetic (PBPK) model for BD that includes a regional model of lung metabolism, based on a previous model for styrene, to provide species-dependent descriptions of BD metabolism in the mouse, rat, and human. Since there are no in vivo data on BD pharmacokinetics in the human, the rat and mouse models were parameterized to the extent possible on the basis of in vitro metabolic data. Where it was necessary to use in vivo data, extrapolation from rat to mouse was performed to evaluate the level of uncertainty in the human model. A kidney compartment and description of downstream metabolism were also included in the model to allow for eventual use of available urinary and blood biomarker data in animals and humans to calibrate the model for estimation of BD exposures and internal metabolite levels. Results from simulated inhalation exposures to BD indicate that incorporation of differential lung region metabolism is important in describing species differences in pulmonary response and that these differences may have implications for risk assessments of human exposures to BD.« less

  14. Investigation of Incident at Waste Isolation Pilot Plant by Technical Assessment Team

    Energy Savers [EERE]

    Incident at Waste Isolation Pilot Plant by Technical Assessment Team March 2015 Overall Findings On February 14, 2014, an incident in Panel 7 Room 7 (P7R7) of the Waste Isolation Pilot Plant (WIPP) underground repository resulted in the release of radioactive material into the environment and contaminated 21 people with low-level radioactivity. The Technical Assessment Team (TAT) concluded that one drum, Drum 68660, was the source of radioactive contamination released during the February 14,

  15. Follow-up Audit of the Department's Cyber Security Incident Management Program, IG-0878

    Office of Environmental Management (EM)

    Department's Cyber Security Incident Management Program DOE/IG-0878 December 2012 U.S. Department of Energy Office of Inspector General Office of Audits & Inspections Department of Energy Washington, DC 20585 December 11, 2012 MEMORANDUM FOR THE SECRETARY FROM: Gregory H. Friedman Inspector General SUBJECT: INFORMATION: Audit Report on "Follow-up Audit of the Department's Cyber Security Incident Management Program" INTRODUCTION AND OBJECTIVE The Department of Energy operates

  16. Summary of canister overheating incident at the Carbon Tetrachloride Expedited Response Action site

    SciTech Connect (OSTI)

    Driggers, S.A.

    1994-03-10

    The granular activated carbon (GAC)-filled canister that overheated was being used to adsorb carbon tetrachloride vapors drawn from a well near the 216-Z-9 Trench, a subsurface disposal site in the 200 West Area of the Hanford Site. The overheating incident resulted in a band of discolored paint on the exterior surface of the canister. Although there was no other known damage to equipment, no injuries to operating personnel, and no releases of hazardous materials, the incident is of concern because it was not anticipated. It also poses the possibility of release of carbon tetrachloride and other hazardous vapors if the incident were to recur. All soil vapor extraction system (VES) operations were halted until a better understanding of the cause of the incident could be determined and controls implemented to reduce the possibility of a recurrence. The focus of this report and the intent of all the activities associated with understanding the overheating incident has been to provide information that will allow safe restart of the VES operations, develop operational limits and controls to prevent recurrence of an overheating incident, and safely optimize recovery of carbon tetrachloride from the ground.

  17. An association between the risk of ovarian cancer and rare HRAS1 alleles

    SciTech Connect (OSTI)

    Weitzel, J.N.; Patel, J.; Smith, D.M.

    1994-09-01

    The highly polymorphic HRAS1 minisatellite locus just downstream from the proto-oncogene H-ras-1 on chromosome 11p consists of four common progenitor alleles and several dozen rare alleles, which apparently derive from mutations of the progenitors. Mutant alleles of this locus represent a major risk factor for common types of cancer. Rare-sized HRAS1 alleles have been found more frequently in patients with carcinoma of the breast, colorectum, and urinary bladder and acute leukemia, compared to cancer-free controls. This highly significant association (p<1.001) results in a modest relative risk for patients with one rare allele, but the prevalence of this class of mutant alleles implies an important attributable risk: 1 in 11 cancers of the breast, colorectum, and bladder. Therefore, we performed a case-control study using conventional (Southern blot) and PCR-based methods to score HRAS1 alleles in the leukocyte DNA from 59 patients with ovarian cancer, and 51 cancer-free controls. Our preliminary data suggest an increased incidence of rare and intermediate HRAS1 alleles in caucasian ovarian cancer patients (13%) compared to cancer-free controls (4%). These results parallel the allele distribution seen in the large published series, and lend support for a significant association between rare HRAS1 alleles and ovarian cancer predisposition.

  18. Perfusion lung scan: an aid in detection of lymphangitic carcinomatosis

    SciTech Connect (OSTI)

    Bates, S.E.; Tranum, B.L.

    1982-07-15

    Lymphangitic carcinomatosis is usually a late manifestation of metastatic disease. The patient usually presents with cough or dyspnea, and the chest radiograph is often nondiagnostic. Two patients are presented who developed symptoms while on adjuvant chemotherapy. Both had abnormal perfusion lung scans. One had matching ventilation defects; the other a normal ventilation study. Biopsy revealed metastatic carcinoma; in one case tumor was seen in both the pulmonary lymphatics and arterioles; in technique which can speed diagnosis and institution of therapy in lymphangitic carcinomatosis.

  19. Over-expression of human endosulfatase-1 exacerbates cadmium-induced injury to transformed human lung cells in vitro

    SciTech Connect (OSTI)

    Zhang, Huiying; Department of Environmental and Molecular Toxicology, College of Agriculture and Life Sciences, NC State University, Raleigh, NC 27695 ; Newman, Donna R.; Bonner, James C.; Sannes, Philip L.

    2012-11-15

    Environmental exposure to cadmium is known to cause damage to alveolar epithelial cells of the lung, impair their capacity to repair, and result in permanent structural alterations. Cell surface heparan sulfate proteoglycans (HSPGs) can modulate cell responses to injury through their interactions with soluble effector molecules. These interactions are often sulfate specific, and the removal of sulfate groups from HS side chains could be expected to influence cellular injury, such as that caused by exposure to cadmium. The goal of this study was to define the role 6-O-sulfate plays in cellular responses to cadmium exposure in two pulmonary epithelial cancer cell lines (H292 and A549) and in normal human primary alveolar type II (hAT2) cells. Sulfate levels were modified by transduced transient over-expression of 6-O-endosulfatase (HSulf-1), a membrane-bound enzyme which specifically removes 6-O-sulfate groups from HSPG side chains. Results showed that cadmium decreased cell viability and activated apoptosis pathways at low concentrations in hAT2 cells but not in the cancer cells. HSulf-1 over-expression, on the contrary, decreased cell viability and activated apoptosis pathways in H292 and A549 cells but not in hAT2 cells. When combined with cadmium, HSulf-1 over-expression further decreased cell viability and exacerbated the activation of apoptosis pathways in the transformed cells but did not add to the toxicity in hAT2 cells. The finding that HSulf-1 sensitizes these cancer cells and intensifies the injury induced by cadmium suggests that 6-O-sulfate groups on HSPGs may play important roles in protection against certain environmental toxicants, such as heavy metals. -- Highlights: ? Primary human lung alveolar type 2 (hAT2) cells and H292 and A549 cells were used. ? Cadmium induced apoptosis in hAT2 cells but not in H292 or A549 cells. ? HSulf-1exacerbates apoptosis induced by cadmium in H292 and A549 but not hAT2 cells.

  20. Optimized Volumetric Modulated Arc Therapy Versus 3D-CRT for Early Stage Mediastinal Hodgkin Lymphoma Without Axillary Involvement: A Comparison of Second Cancers and Heart Disease Risk

    SciTech Connect (OSTI)

    Filippi, Andrea Riccardo; Ragona, Riccardo; Piva, Cristina; Scafa, Davide; Fiandra, Christian; Fusella, Marco; Giglioli, Francesca Romana; Lohr, Frank; Ricardi, Umberto

    2015-05-01

    Purpose: The purpose of this study was to evaluate the risks of second cancers and cardiovascular diseases associated with an optimized volumetric modulated arc therapy (VMAT) planning solution in a selected cohort of stage I/II Hodgkin lymphoma (HL) patients treated with either involved-node or involved-site radiation therapy in comparison with 3-dimensional conformal radiation therapy (3D-CRT). Methods and Materials: Thirty-eight patients (13 males and 25 females) were included. Disease extent was mediastinum alone (n=8, 21.1%); mediastinum plus unilateral neck (n=19, 50%); mediastinum plus bilateral neck (n=11, 29.9%). Prescription dose was 30 Gy in 2-Gy fractions. Only 5 patients had mediastinal bulky disease at diagnosis (13.1%). Anteroposterior 3D-CRT was compared with a multiarc optimized VMAT solution. Lung, breast, and thyroid cancer risks were estimated by calculating a lifetime attributable risk (LAR), with a LAR ratio (LAR{sub VMAT}-to-LAR{sub 3D-CRT}) as a comparative measure. Cardiac toxicity risks were estimated by calculating absolute excess risk (AER). Results: The LAR ratio favored 3D-CRT for lung cancer induction risk in mediastinal alone (P=.004) and mediastinal plus unilateral neck (P=.02) presentations. LAR ratio for breast cancer was lower for VMAT in mediastinal plus bilateral neck presentations (P=.02), without differences for other sites. For thyroid cancer, no significant differences were observed, regardless of anatomical presentation. A significantly lower AER of cardiac (P=.038) and valvular diseases (P<.0001) was observed for VMAT regardless of disease extent. Conclusions: In a cohort of patients with favorable characteristics in terms of disease extent at diagnosis (large prevalence of nonbulky presentations without axillary involvement), optimized VMAT reduced heart disease risk with comparable risks of thyroid and breast cancer, with an increase in lung cancer induction probability. The results are however strongly influenced by the different anatomical presentations, supporting an individualized approach.

  1. Low Dose Radiation Cancer Risks: Epidemiological and Toxicological Models

    SciTech Connect (OSTI)

    David G. Hoel, PhD

    2012-04-19

    The basic purpose of this one year research grant was to extend the two stage clonal expansion model (TSCE) of carcinogenesis to exposures other than the usual single acute exposure. The two-stage clonal expansion model of carcinogenesis incorporates the biological process of carcinogenesis, which involves two mutations and the clonal proliferation of the intermediate cells, in a stochastic, mathematical way. The current TSCE model serves a general purpose of acute exposure models but requires numerical computation of both the survival and hazard functions. The primary objective of this research project was to develop the analytical expressions for the survival function and the hazard function of the occurrence of the first cancer cell for acute, continuous and multiple exposure cases within the framework of the piece-wise constant parameter two-stage clonal expansion model of carcinogenesis. For acute exposure and multiple exposures of acute series, it is either only allowed to have the first mutation rate vary with the dose, or to have all the parameters be dose dependent; for multiple exposures of continuous exposures, all the parameters are allowed to vary with the dose. With these analytical functions, it becomes easy to evaluate the risks of cancer and allows one to deal with the various exposure patterns in cancer risk assessment. A second objective was to apply the TSCE model with varing continuous exposures from the cancer studies of inhaled plutonium in beagle dogs. Using step functions to estimate the retention functions of the pulmonary exposure of plutonium the multiple exposure versions of the TSCE model was to be used to estimate the beagle dog lung cancer risks. The mathematical equations of the multiple exposure versions of the TSCE model were developed. A draft manuscript which is attached provides the results of this mathematical work. The application work using the beagle dog data from plutonium exposure has not been completed due to the fact that the research project did not continue beyond its first year.

  2. SU-D-9A-07: Imaging Dose and Cancer Risk in Image-Guided Radiotherapy of Cancers

    SciTech Connect (OSTI)

    Zhou, L; Bai, S; Zhang, Y; Ming, X; Zhang, Y; Deng, J

    2014-06-01

    Purpose: To systematically evaluate the imaging doses and cancer risks associated with various imaging procedures involving ionizing radiation during image-guided radiotherapy of an increasingly large number of cancer patients. Methods: 141 patients (52 brain cases, 47 thoracic cases, 42 abdominal cases, aged 3 to 91 years old) treated between October 2009 and March 2010 were included in this IRB-approved retrospective study. During the whole radiotherapy course, each patient underwent at least one type of imaging procedures, i.e., kV portal, MV portal and kVCBCT, besides CT simulations. Based on Monte Carlo modeling and particle transport in human anatomy of various dimensions, the correlations between the radiation doses to the various organs-at-risk (OARs) at the head, the thoracic and the abdominal regions and one's weight, circumference, scan mAs and kVp have been obtained and used to estimate the radiation dose from a specific imaging procedure. The radiation-induced excess relative risk (ERR) was then estimated with BEIR VII formulism based on one's gender, age and radiation dose. 1+ ERR was reported in this study as relative cancer risk. Results: For the whole cohort of 141 patients, the mean imaging doses from various imaging procedures were 8.3 cGy to the brain, 10.5 cGy to the lungs and 19.2 cGy to the red bone marrow, respectively. Accordingly, the cancer risks were 1.140, 1.369 and 2.671, respectively. In comparison, MV portal deposited largest doses to the lungs while kVCBCT delivered the highest doses to the red bone marrow. Conclusion: The compiled imaging doses to a patient during his/her treatment course were patient-specific and site-dependent, varying from 1.2 to 263.5 cGy on average, which were clinically significant and should be included in the treatment planning and overall decision-making. Our results indicated the necessity of personalized imaging to maximize its clinical benefits while reducing the associated cancer risks. Sichuan University Scholarship.

  3. The founder mutations 185delAG and 5382insC in BRCA1 and 6174delT in BRCA2 appear in 60% of ovarian cancer and 30% of early-onset breast cancer patients among Ashkenazi women

    SciTech Connect (OSTI)

    Abeliovich, D.; Lerer, I.; Weinberg, N.

    1997-03-01

    The mutations 185delAG, 188del11, and 5382insC in the BRCA1 gene and 6174delT in the BRCA2 gene were analyzed in 199 Ashkenazi and 44 non-Ashkenazi Jewish unrelated patients with breast and/or ovarian cancer. Of the Jewish Ashkenazi women with ovarian cancer, 62% (13/21) had one of the target mutations, as did 30% (13/43) of women with breast cancer alone diagnosed before the age 40 years and 10% (15/141) of those with breast cancer diagnosed after the age 40 years. Age at ovarian cancer diagnosis was not associated with carrier status. Of 99 Ashkenazi patients with no family history of breast and/or ovarian cancer, 10% carried one of the mutations; in two of them the mutation was proved to be paternally transmitted. One non-Ashkenazi Jewish ovarian cancer patient from Iraq carried the 185delAG mutation. Individual mutation frequencies among breast cancer Ashkenazi patients were 6.7% for 185delAG, 2.2% for 5382insC, and 4.5% for 6174delT, among ovarian cancer patients; 185delAG and 6174delT were about equally common (33% and 29%, respectively), but no ovarian cancer patient carried the 5382insC. More mutations responsible for inherited breast and ovarian cancer probably remain to be found in this population, since 79% of high-incidence breast cancer families and 35% of high-incidence breast/ovarian cancer families had none of the three known founder mutations. 25 refs., 3 figs., 6 tabs.

  4. EP&R Standards Project Report: Technical Review of National Incident Management Standards

    SciTech Connect (OSTI)

    Stenner, Robert D.

    2007-04-24

    The importance and necessity for a fully developed and implemented National Incident Management System (NIMS) has been demonstrated in recent years by the impact of national events such as Hurricane Katrina in 2005. Throughout the history of emergency response to major disasters, especially when multiple response organizations are involved, there have been systemic problems in the consistency and uniformity of response operations. Identifying national standards that support the development and implementation of NIMS is key to helping solve these systemic problems. The NIMS seeks to provide uniformity and consistency for incident management by using common terminology and protocols that will enable responders to coordinate their efforts to ensure an efficient response.

  5. The effect of diet and exercise on incidence of 7,12

    Office of Scientific and Technical Information (OSTI)

    dimethylbenz(a)anthracene-induced mammary tumors in virgin BALB/c mice (Conference) | SciTech Connect The effect of diet and exercise on incidence of 7,12 dimethylbenz(a)anthracene-induced mammary tumors in virgin BALB/c mice Citation Details In-Document Search Title: The effect of diet and exercise on incidence of 7,12 dimethylbenz(a)anthracene-induced mammary tumors in virgin BALB/c mice The effects of rotating-drum treadmill exercise and diet on 7,12 dimethylbenz(a)anthracene

  6. A multiscale MDCT image-based breathing lung model with time-varying regional ventilation

    SciTech Connect (OSTI)

    Yin, Youbing, E-mail: youbing-yin@uiowa.edu [Department of Mechanical and Industrial Engineering, The University of Iowa, Iowa City, IA 52242 (United States) [Department of Mechanical and Industrial Engineering, The University of Iowa, Iowa City, IA 52242 (United States); IIHR-Hydroscience and Engineering, The University of Iowa, Iowa City, IA 52242 (United States); Department of Radiology, The University of Iowa, Iowa City, IA 52242 (United States); Choi, Jiwoong, E-mail: jiwoong-choi@uiowa.edu [Department of Mechanical and Industrial Engineering, The University of Iowa, Iowa City, IA 52242 (United States) [Department of Mechanical and Industrial Engineering, The University of Iowa, Iowa City, IA 52242 (United States); IIHR-Hydroscience and Engineering, The University of Iowa, Iowa City, IA 52242 (United States); Hoffman, Eric A., E-mail: eric-hoffman@uiowa.edu [Department of Radiology, The University of Iowa, Iowa City, IA 52242 (United States); Department of Biomedical Engineering, The University of Iowa, Iowa City, IA 52242 (United States); Department of Internal Medicine, The University of Iowa, Iowa City, IA 52242 (United States); Tawhai, Merryn H., E-mail: m.tawhai@auckland.ac.nz [Auckland Bioengineering Institute, The University of Auckland, Auckland (New Zealand); Lin, Ching-Long, E-mail: ching-long-lin@uiowa.edu [Department of Mechanical and Industrial Engineering, The University of Iowa, Iowa City, IA 52242 (United States) [Department of Mechanical and Industrial Engineering, The University of Iowa, Iowa City, IA 52242 (United States); IIHR-Hydroscience and Engineering, The University of Iowa, Iowa City, IA 52242 (United States)

    2013-07-01

    A novel algorithm is presented that links local structural variables (regional ventilation and deforming central airways) to global function (total lung volume) in the lung over three imaged lung volumes, to derive a breathing lung model for computational fluid dynamics simulation. The algorithm constitutes the core of an integrative, image-based computational framework for subject-specific simulation of the breathing lung. For the first time, the algorithm is applied to three multi-detector row computed tomography (MDCT) volumetric lung images of the same individual. A key technique in linking global and local variables over multiple images is an in-house mass-preserving image registration method. Throughout breathing cycles, cubic interpolation is employed to ensure C{sub 1} continuity in constructing time-varying regional ventilation at the whole lung level, flow rate fractions exiting the terminal airways, and airway deformation. The imaged exit airway flow rate fractions are derived from regional ventilation with the aid of a three-dimensional (3D) and one-dimensional (1D) coupled airway tree that connects the airways to the alveolar tissue. An in-house parallel large-eddy simulation (LES) technique is adopted to capture turbulent-transitional-laminar flows in both normal and deep breathing conditions. The results obtained by the proposed algorithm when using three lung volume images are compared with those using only one or two volume images. The three-volume-based lung model produces physiologically-consistent time-varying pressure and ventilation distribution. The one-volume-based lung model under-predicts pressure drop and yields un-physiological lobar ventilation. The two-volume-based model can account for airway deformation and non-uniform regional ventilation to some extent, but does not capture the non-linear features of the lung.

  7. CRADA Final Report: ErbB2 Targeted Cancer Therapeutics

    SciTech Connect (OSTI)

    Lupu, Ruth

    2002-08-27

    The aim of the study was to design novel therapeutic strategies for the treatment of carcinomas which overexpress the erbB-2 oncogene product and/or the activator (HRG). erbB-2 is a tyrosine kinase growth factor receptor, that overexpression of which in invasive breast, prostate, ovarian and lung carcinomas correlates with poor prognosis and poor overall survival. In breast carcinomas, erbB-2 is overexpressed in 25%-30% of the invasive phenotype and in 70% of ductal carcinomas in situ. On the other hand, the erbB-2 activator, heregulin (HRG) is expressed in about 30% of invasive breast carcinomas and it is highly expressed in other carcinoIl1as including, ovarian, lung, and prostate. Interestingly, only 6% of invasive breast carcinomas co-express both HRG and erbB-2. It is known today that tumors that overexpress erbB-2 are a leading cause of death, making erbB-2 and its activator HRG critical targets for therapy. Targeting both the receptors and the activator would be beneficial for a significant number of cancer patients. At the final stages of the project we had obtained significant improvements over the peptide quality but not significant improvements were made towards the generation of humanized monoclonal antibodies.

  8. Founding BRCA1 mutations in hereditary breast and ovarian cancer in southern Sweden

    SciTech Connect (OSTI)

    Johannsson, O.; Hakansson, S.; Johannson, U.

    1996-03-01

    Nine different germ-line mutations in the BRCA1 breast and ovarian cancer susceptibility gene were identified in 15 of 47 kindreds from southern Sweden, by use of SSCP and heteroduplex analysis of all exons and flanking intron region and by a protein-truncation test for exon 11, followed by direct sequencing. All but one of the mutations are predicted to give rise to premature translation termination and include seven frameshift insertions or deletions, a nonsense mutation, and a splice acceptor site mutation. The remaining mutation is a missense mutation (Cys61Gly) in the zinc-binding motif. Four novel Swedish founding mutations were identified: the nucleotide 2595 deletion A was found in five families, the C 1806 T nonsense mutation in three families, the 3166 insertion TGAGA in three families, and the nucleotide 1201 deletion 11 in two families. Analysis of the intragenic polymorphism D17S855 supports common origins of the mutations. Eleven of the 15 kindreds manifesting BRCA1 mutations were breast-ovarian cancer families, several of them with a predominant ovarian cancer phenotype. The set of 32 families in which no BRCA1 alterations were detected included 1 breast-ovarian cancer kindred manifesting clear linkage to the BRCA1 region and loss of the wild-type chromosome in associated tumors. Other tumor types found in BRCA1 mutation/haplotype carriers included prostatic, pancreas, skin, and lung cancer, a malignant melanoma, an oligodendroglioma, and a carcinosarcoma. In all, 12 of 16 kindreds manifesting BRCA1 mutation or linkage contained ovarian cancer, as compared with only 6 of the remaining 31 families (P < .001). The present study confirms the involvement of BRCA1 in disease predisposition for a subset of hereditary breast cancer families often characterized by ovarian cancers. 28 refs., 3 figs., 4 tabs.

  9. A Reanalysis of Curvature in the Dose Response for Cancer and Modifications by Age at Exposure Following Radiation Therapy for Benign Disease

    SciTech Connect (OSTI)

    Little, Mark P.; Stovall, Marilyn; Smith, Susan A.; Kleinerman, Ruth A.

    2013-02-01

    Purpose: To assess the shape of the dose response for various cancer endpoints and modifiers by age and time. Methods and Materials: Reanalysis of the US peptic ulcer data testing for heterogeneity of radiogenic risk by cancer endpoint (stomach, pancreas, lung, leukemia, all other). Results: There are statistically significant (P<.05) excess risks for all cancer and for lung cancer and borderline statistically significant risks for stomach cancer (P=.07), and leukemia (P=.06), with excess relative risks Gy{sup -1} of 0.024 (95% confidence interval [CI] 0.011, 0.039), 0.559 (95% CI 0.221, 1.021), 0.042 (95% CI -0.002, 0.119), and 1.087 (95% CI -0.018, 4.925), respectively. There is statistically significant (P=.007) excess risk of pancreatic cancer when adjusted for dose-response curvature. General downward curvature is apparent in the dose response, statistically significant (P<.05) for all cancers, pancreatic cancer, and all other cancers (ie, other than stomach, pancreas, lung, leukemia). There are indications of reduction in relative risk with increasing age at exposure (for all cancers, pancreatic cancer), but no evidence for quadratic variations in relative risk with age at exposure. If a linear-exponential dose response is used, there is no significant heterogeneity in the dose response among the 5 endpoints considered or in the speed of variation of relative risk with age at exposure. The risks are generally consistent with those observed in the Japanese atomic bomb survivors and in groups of nuclear workers. Conclusions: There are excess risks for various malignancies in this data set. Generally there is a marked downward curvature in the dose response and significant reduction in relative risk with increasing age at exposure. The consistency of risks with those observed in the Japanese atomic bomb survivors and in groups of nuclear workers implies that there may be little sparing effect of fractionation of dose or low-dose-rate exposure.

  10. Effects of coal combustion and gasification upon lung structure and function. Quarterly progress report

    SciTech Connect (OSTI)

    Hinton, Dr., David E.

    1980-12-12

    The effects on lungs of emissions from fluidized-bed combustion and coal gasification on man are being studied by inhalation experiments and intratracheal administration of fly ash to hamsters. The hamsters are sacrificed at 1, 3, 6, 9 and 30 days and the lungs examined by methods which are described. (LTN)

  11. Biomedical nuclear and X-ray imager using high-energy grazing incidence mirrors

    DOE Patents [OSTI]

    Ziock, Klaus-Peter; Craig, William W.; Hasegawa, Bruce; Pivovaroff, Michael J.

    2005-09-27

    Imaging of radiation sources located in a subject is explored for medical applications. The approach involves using grazing-incidence optics to form images of the location of radiopharmaceuticals administered to a subject. The optics are "true focusing" optics, meaning that they project a real and inverted image of the radiation source onto a detector possessing spatial and energy resolution.

  12. Solid state laser disk amplifer architecture: the normal-incidence stack

    DOE Patents [OSTI]

    Dane, C. Brent; Albrecht, Georg F.; Rotter, Mark D.

    2005-01-25

    Normal incidence stack architecture coupled with the development of diode array pumping enables the power/energy per disk to be increased, a reduction in beam distortions by orders of magnitude, a beam propagation no longer restricted to only one direction of polarization, and the laser becomes so much more amendable to robust packaging.

  13. 2D/3D registration algorithm for lung brachytherapy

    SciTech Connect (OSTI)

    Zvonarev, P. S.; Farrell, T. J.; Hunter, R.; Wierzbicki, M.; Hayward, J. E.; Sur, R. K.

    2013-02-15

    Purpose: A 2D/3D registration algorithm is proposed for registering orthogonal x-ray images with a diagnostic CT volume for high dose rate (HDR) lung brachytherapy. Methods: The algorithm utilizes a rigid registration model based on a pixel/voxel intensity matching approach. To achieve accurate registration, a robust similarity measure combining normalized mutual information, image gradient, and intensity difference was developed. The algorithm was validated using a simple body and anthropomorphic phantoms. Transfer catheters were placed inside the phantoms to simulate the unique image features observed during treatment. The algorithm sensitivity to various degrees of initial misregistration and to the presence of foreign objects, such as ECG leads, was evaluated. Results: The mean registration error was 2.2 and 1.9 mm for the simple body and anthropomorphic phantoms, respectively. The error was comparable to the interoperator catheter digitization error of 1.6 mm. Preliminary analysis of data acquired from four patients indicated a mean registration error of 4.2 mm. Conclusions: Results obtained using the proposed algorithm are clinically acceptable especially considering the complications normally encountered when imaging during lung HDR brachytherapy.

  14. SU-E-T-632: A Dosimetric Comparison of the 3D-CRT Planning of Chest Wall in Post-Mastectomy Breast Cancer Patients, with and Without Breast Board Setup

    SciTech Connect (OSTI)

    Muzaffar, Ambreen; Masood, Asif; Ullah, Haseeb; Mehmood, Kashif; Qasim, Uzma; Afridi, M. Ali; Khan, Salim; Hameed, Abdul

    2014-06-15

    Purpose: Breast boards are used in breast radiation which increases normal lung and heart doses, when supraclavicular field is included. Therefore, in this study through dose volume histogram (DVHs), lung and heart doses comparison was done between two different setups i.e. with and without breast board, for the treatment of left chest wall and supraclavicular fossa in postmastectomy left breast cancer. Methods: In this study, CT-Simulation scans of ten breast cancer patients were done with and without breast board, at Shifa International Hospitals Islamabad, to investigate the differences between the two different setups of the irradiation of left chest wall in terms of lung and heart doses. For immobilization, support under the neck, shoulders and arms was used. Precise PLAN 2.15 treatment planning system (TPS) was used for 3D-CRT planning. The total prescribed dose for both the plans was 5000 cGy/25 fractions. The chest wall was treated with a pair of tangential photon fields and the upper supraclavicular nodal regions were treated with an anterior photon field. A mono-isocentric technique was used to match the tangential fields with the anterior field at the isocentre. The dose volume histogram was used to compare the doses of heart and ipsilateral lung. Results: Both the plans of each patient were generated and compared. DVH results showed that for the same PTV dose coverage, plans without breast board resulted in a reduction of lung and heart doses compared with the plans with breast board. There was significant reductions in V20, V<25 and mean doses for lung and V<9 and mean doses for heart. Conclusion: In comparison of both the plans, setup without breast board significantly reduced the dose-volume of the ipsilateral lung and heart in left chest wall patients. Waived registration request has been submitted.

  15. Cell Senescence: Aging and Cancer

    ScienceCinema (OSTI)

    Campisi, Judith

    2013-05-29

    Scientists have identified a molecular cause behind the ravages of old age and in doing so have also shown how a natural process for fighting cancer in younger persons can actually promote cancer in older individuals.

  16. SU-E-T-524: Web-Based Radiation Oncology Incident Reporting and Learning System (ROIRLS)

    SciTech Connect (OSTI)

    Kapoor, R; Palta, J; Hagan, M; Grover, S; Malik, G

    2014-06-01

    Purpose: Describe a Web-based Radiation Oncology Incident Reporting and Learning system that has the potential to improve quality of care for radiation therapy patients. This system is an important facet of continuing effort by our community to maintain and improve safety of radiotherapy.Material and Methods: The VA National Radiation Oncology Program office has embarked on a program to electronically collect adverse events and near miss data of radiation treatment of over 25,000 veterans treated with radiotherapy annually. Software used for this program is deployed on the VAs intranet as a Website. All data entry forms (adverse event or near miss reports, work product reports) utilize standard causal, RT process step taxonomies and data dictionaries defined in AAPM and ASTRO reports on error reporting (AAPM Work Group Report on Prevention of Errors and ASTROs safety is no accident report). All reported incidents are investigated by the radiation oncology domain experts. This system encompasses the entire feedback loop of reporting an incident, analyzing it for salient details, and developing interventions to prevent it from happening again. The operational workflow is similar to that of the Aviation Safety Reporting System. This system is also synergistic with ROSIS and SAFRON. Results: The ROIRLS facilitates the collection of data that help in tracking adverse events and near misses and develop new interventions to prevent such incidents. The ROIRLS electronic infrastructure is fully integrated with each registered facility profile data thus minimizing key strokes and multiple entries by the event reporters. Conclusions: OIRLS is expected to improve the quality and safety of a broad spectrum of radiation therapy patients treated in the VA and fulfills our goal of Effecting Quality While Treating Safely The Radiation Oncology Incident Reporting and Learning System software used for this program has been developed, conceptualized and maintained by TSG Innovations Inc. and is deployed on the VA intranet as a Website. The Radiation Oncology Incident Reporting and Learning System software used for this program has been developed, conceptualized and maintained by TSG Innovations Inc. and is deployed on the VA intranet as a Website.

  17. Role of reactive nitrogen species generated via inducible nitric oxide synthase in vesicant-induced lung injury, inflammation and altered lung functioning

    SciTech Connect (OSTI)

    Sunil, Vasanthi R.; Shen, Jianliang; Patel-Vayas, Kinal; Gow, Andrew J.; Laskin, Jeffrey D.; Laskin, Debra L.

    2012-05-15

    Pulmonary toxicity induced by sulfur mustard and related vesicants is associated with oxidative stress. In the present studies we analyzed the role of reactive nitrogen species (RNS) generated via inducible nitric oxide synthase (iNOS) in lung injury and inflammation induced by vesicants using 2-chloroethyl ethyl sulfide (CEES) as a model. C57Bl/6 (WT) and iNOS ?/? mice were sacrificed 3 days or 14 days following intratracheal administration of CEES (6 mg/kg) or control. CEES intoxication resulted in transient (3 days) increases in bronchoalveolar lavage (BAL) cell and protein content in WT, but not iNOS ?/? mice. This correlated with expression of Ym1, a marker of oxidative stress in alveolar macrophages and epithelial cells. In contrast, in iNOS ?/? mice, Ym1 was only observed 14 days post-exposure in enlarged alveolar macrophages, suggesting that they are alternatively activated. This is supported by findings that lung tumor necrosis factor and lipocalin Lcn2 expression, mediators involved in tissue repair were also upregulated at this time in iNOS ?/? mice. Conversely, CEES-induced increases in the proinflammatory genes, monocyte chemotactic protein-1 and cyclooxygenase-2, were abrogated in iNOS ?/? mice. In WT mice, CEES treatment also resulted in increases in total lung resistance and decreases in compliance in response to methacholine, effects blunted by loss of iNOS. These data demonstrate that RNS, generated via iNOS play a role in the pathogenic responses to CEES, augmenting oxidative stress and inflammation and suppressing tissue repair. Elucidating inflammatory mechanisms mediating vesicant-induced lung injury is key to the development of therapeutics to treat mustard poisoning. -- Highlights: ? Lung injury, inflammation and oxidative stress are induced by the model vesicant CEES ? RNS generated via iNOS are important in the CEES-induced pulmonary toxicity ? iNOS ?/? mice are protected from CEES-induced lung toxicity and altered lung functioning.

  18. H-1 Nuclear Magnetic Resonance Metabolomics Analysis Identifies Novel Urinary Biomarkers for Lung Function

    SciTech Connect (OSTI)

    MCClay, Joseph L.; Adkins, Daniel E.; Isern, Nancy G.; O'Connell, Thomas M.; Wooten, Jan B.; Zedler, Barbara K.; Dasika, Madhukar S.; Webb, B. T.; Webb-Robertson, Bobbie-Jo M.; Pounds, Joel G.; Murrelle, Edward L.; Leppert, Mark F.; van den Oord, Edwin J.

    2010-06-04

    Chronic obstructive pulmonary disease (COPD), characterized by chronic airflow limitation, is a serious and growing public health concern. The major environmental risk factor for COPD is tobacco smoking, but the biological mechanisms underlying COPD are not well understood. In this study, we used proton nuclear magnetic resonance (1H-NMR) spectroscopy to identify and quantify metabolites associated with lung function in COPD. Plasma and urine were collected from 197 adults with COPD and from 195 adults without COPD. Samples were assayed using a 600 MHz NMR spectrometer, and the resulting spectra were analyzed against quantitative spirometric measures of lung function. After correcting for false discoveries and adjusting for covariates (sex, age, smoking) several spectral regions in urine were found to be significantly associated with baseline lung function. These regions correspond to the metabolites trigonelline, hippurate and formate. Concentrations of each metabolite, standardized to urinary creatinine, were associated with baseline lung function (minimum p-value = 0.0002 for trigonelline). No significant associations were found with plasma metabolites. Two of the three urinary metabolites positively associated with baseline lung function, i.e. hippurate and formate, are often related to gut microflora. This suggests that the microbiome composition is variable between individuals with different lung function. Alternatively, the nature and origins of all three associated metabolites may reflect lifestyle differences affecting overall health. Our results will require replication and validation, but demonstrate the utility of NMR metabolomics as a screening tool for identifying novel biomarkers of lung disease or disease risk.

  19. The cough response to ultrasonically nebulized distilled water in heart-lung transplantation patients

    SciTech Connect (OSTI)

    Higenbottam, T.; Jackson, M.; Woolman, P.; Lowry, R.; Wallwork, J.

    1989-07-01

    As a result of clinical heart-lung transplantation, the lungs are denervated below the level of the tracheal anastomosis. It has been questioned whether afferent vagal reinnervation occurs after surgery. Here we report the cough frequency, during inhalation of ultrasonically nebulized distilled water, of 15 heart-lung transplant patients studied 6 wk to 36 months after surgery. They were compared with 15 normal subjects of a similar age and sex. The distribution of the aerosol was studied in five normal subjects using /sup 99m/technetium diethylene triamine pentaacetate (/sup 99m/Tc-DTPA) in saline. In seven patients, the sensitivity of the laryngeal mucosa to instilled distilled water (0.2 ml) was tested at the time of fiberoptic bronchoscopy by recording the cough response. Ten percent of the aerosol was deposited onto the larynx and trachea, 56% on the central airways, and 34% in the periphery of the lung. The cough response to the aerosol was strikingly diminished in the patients compared with normal subjects (p less than 0.001), but all seven patients coughed when distilled water was instilled onto the larynx. As expected, the laryngeal mucosa of heart-lung transplant patients remains sensitive to distilled water. However, the diminished coughing when the distilled water is distributed by aerosol to the central airways supports the view that vagal afferent nerves do not reinnervate the lungs after heart-lung transplantation, up to 36 months after surgery.

  20. Catastrophic Incident Recovery: Long-Term Recovery from an Anthrax Event Symposium

    SciTech Connect (OSTI)

    Lesperance, Ann M.

    2008-06-30

    On March 19, 2008, policy makers, emergency managers, and medical and Public Health officials convened in Seattle, Washington, for a workshop on Catastrophic Incident Recovery: Long-Term Recovery from an Anthrax Event. The day-long symposium was aimed at generating a dialogue about restoration and recovery through a discussion of the associated challenges that impact entire communities, including people, infrastructure, and critical systems.

  1. Handling Cyber Security Alerts and Advisories and Reporting Cyber Security Incidents

    Broader source: Directives, Delegations, and Requirements [Office of Management (MA)]

    2002-03-18

    To establish Department of Energy (DOE) requirements and responsibilities for reporting cyber security incidents involving classified and unclassified systems and responding to cyber security alerts and advisories; and to implement requirements of DOE N 205.1, Unclassified Cyber Security Program, and DOE M 471.2-2, Classified Information Systems Security Manual. DOE N 205.13, dated 7-6-04, extends this notice until 7-6-05. Cancels DOE M 471.2-2, Chapter III, section 8.

  2. A Planning Tool for Estimating Waste Generated by a Radiological Incident and Subsequent Decontamination Efforts - 13569

    SciTech Connect (OSTI)

    Boe, Timothy; Lemieux, Paul; Schultheisz, Daniel; Peake, Tom; Hayes, Colin

    2013-07-01

    Management of debris and waste from a wide-area radiological incident would probably constitute a significant percentage of the total remediation cost and effort. The U.S. Environmental Protection Agency's (EPA's) Waste Estimation Support Tool (WEST) is a unique planning tool for estimating the potential volume and radioactivity levels of waste generated by a radiological incident and subsequent decontamination efforts. The WEST was developed to support planners and decision makers by generating a first-order estimate of the quantity and characteristics of waste resulting from a radiological incident. The tool then allows the user to evaluate the impact of various decontamination/demolition strategies on the waste types and volumes generated. WEST consists of a suite of standalone applications and Esri{sup R} ArcGIS{sup R} scripts for rapidly estimating waste inventories and levels of radioactivity generated from a radiological contamination incident as a function of user-defined decontamination and demolition approaches. WEST accepts Geographic Information System (GIS) shape-files defining contaminated areas and extent of contamination. Building stock information, including square footage, building counts, and building composition estimates are then generated using the Federal Emergency Management Agency's (FEMA's) Hazus{sup R}-MH software. WEST then identifies outdoor surfaces based on the application of pattern recognition to overhead aerial imagery. The results from the GIS calculations are then fed into a Microsoft Excel{sup R} 2007 spreadsheet with a custom graphical user interface where the user can examine the impact of various decontamination/demolition scenarios on the quantity, characteristics, and residual radioactivity of the resulting waste streams. (authors)

  3. Analysis of incident-energy dependence of delayed neutron yields in actinides

    SciTech Connect (OSTI)

    Nasir, Mohamad Nasrun bin Mohd Metorima, Kouhei Ohsawa, Takaaki Hashimoto, Kengo

    2015-04-29

    The changes of delayed neutron yields (?{sub d}) of Actinides have been analyzed for incident energy up to 20MeV using realized data of precursor after prompt neutron emission, from semi-empirical model, and delayed neutron emission probability data (P{sub n}) to carry out a summation method. The evaluated nuclear data of the delayed neutron yields of actinide nuclides are still uncertain at the present and the cause of the energy dependence has not been fully understood. In this study, the fission yields of precursor were calculated considering the change of the fission fragment mass yield based on the superposition of fives Gaussian distribution; and the change of the prompt neutrons number associated with the incident energy dependence. Thus, the incident energy dependent behavior of delayed neutron was analyzed.The total number of delayed neutron is expressed as ?{sub d}=?Y{sub i} P{sub ni} in the summation method, where Y{sub i} is the mass yields of precursor i and P{sub ni} is the delayed neutron emission probability of precursor i. The value of Y{sub i} is derived from calculation of post neutron emission mass distribution using 5 Gaussian equations with the consideration of large distribution of the fission fragments. The prompt neutron emission ?{sub p} increases at higher incident-energy but there are two different models; one model says that the fission fragment mass dependence that prompt neutron emission increases uniformly regardless of the fission fragments mass; and the other says that the major increases occur at heavy fission fragments area. In this study, the changes of delayed neutron yields by the two models have been investigated.

  4. Iron supplementation at high altitudes induces inflammation and oxidative injury to lung tissues in rats

    SciTech Connect (OSTI)

    Salama, Samir A.; Omar, Hany A.; Maghrabi, Ibrahim A.; AlSaeed, Mohammed S.; EL-Tarras, Adel E.

    2014-01-01

    Exposure to high altitudes is associated with hypoxia and increased vulnerability to oxidative stress. Polycythemia (increased number of circulating erythrocytes) develops to compensate the high altitude associated hypoxia. Iron supplementation is, thus, recommended to meet the demand for the physiological polycythemia. Iron is a major player in redox reactions and may exacerbate the high altitudes-associated oxidative stress. The aim of this study was to explore the potential iron-induced oxidative lung tissue injury in rats at high altitudes (6000 ft above the sea level). Iron supplementation (2 mg elemental iron/kg, once daily for 15 days) induced histopathological changes to lung tissues that include severe congestion, dilatation of the blood vessels, emphysema in the air alveoli, and peribronchial inflammatory cell infiltration. The levels of pro-inflammatory cytokines (IL-1?, IL-6, and TNF-?), lipid peroxidation product and protein carbonyl content in lung tissues were significantly elevated. Moreover, the levels of reduced glutathione and total antioxidant capacity were significantly reduced. Co-administration of trolox, a water soluble vitamin E analog (25 mg/kg, once daily for the last 7 days of iron supplementation), alleviated the lung histological impairments, significantly decreased the pro-inflammatory cytokines, and restored the oxidative stress markers. Together, our findings indicate that iron supplementation at high altitudes induces lung tissue injury in rats. This injury could be mediated through excessive production of reactive oxygen species and induction of inflammatory responses. The study highlights the tissue injury induced by iron supplementation at high altitudes and suggests the co-administration of antioxidants such as trolox as protective measures. - Highlights: Iron supplementation at high altitudes induced lung histological changes in rats. Iron induced oxidative stress in lung tissues of rats at high altitudes. Iron increased the levels of IL-1?, IL-6 and TNF-? in lung tissues at high altitudes. Trolox alleviated the iron-induced histological and biochemical changes to the lungs.

  5. Advanced grazing-incidence techniques for modern soft-matter materials analysis

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Hexemer, Alexander; Müller-Buschbaum, Peter

    2015-01-01

    The complex nano-morphology of modern soft-matter materials is successfully probed with advanced grazing-incidence techniques. Based on grazing-incidence small- and wide-angle X-ray and neutron scattering (GISAXS, GIWAXS, GISANS and GIWANS), new possibilities arise which are discussed with selected examples. Due to instrumental progress, highly interesting possibilities for local structure analysis in this material class arise from the use of micro- and nanometer-sized X-ray beams in micro- or nanofocused GISAXS and GIWAXS experiments. The feasibility of very short data acquisition times down to milliseconds creates exciting possibilities forin situandin operandoGISAXS and GIWAXS studies. Tuning the energy of GISAXS and GIWAXS in themore » soft X-ray regime and in time-of flight GISANS allows the tailoring of contrast conditions and thereby the probing of more complex morphologies. In addition, recent progress in software packages, useful for data analysis for advanced grazing-incidence techniques, is discussed.« less

  6. Nucleation of diindenoperylene and pentacene at thermal and hyperthermal incident kinetic energies

    SciTech Connect (OSTI)

    Kish, Edward R.; Desai, Tushar V.; Greer, Douglas R.; Engstrom, James R.; Woll, Arthur R.

    2015-05-15

    The authors have examined the nucleation of diindenoperylene (DIP) on SiO{sub 2} employing primarily atomic force microscopy and focusing on the effect of incident kinetic energy employing both thermal and supersonic sources. For all incident kinetic energies examined (E{sub i}?=?0.0911.3?eV), the nucleation of DIP is homogeneous and the dependence of the maximum island density on the growth rate is described by a power law. A critical nucleus of approximately two molecules is implicated by our data. A re-examination of the nucleation of pentacene on SiO{sub 2} gives the same major result that the maximum island density is determined by the growth rate, and it is independent of the incident kinetic energy. These observations are readily understood by factoring in the size of the critical nucleus in each case, and the island density, which indicates that diffusive transport of molecules to the growing islands dominate the dynamics of growth in the submonolayer regime.

  7. Advanced grazing-incidence techniques for modern soft-matter materials analysis

    SciTech Connect (OSTI)

    Hexemer, Alexander; Mller-Buschbaum, Peter

    2015-01-01

    The complex nano-morphology of modern soft-matter materials is successfully probed with advanced grazing-incidence techniques. Based on grazing-incidence small- and wide-angle X-ray and neutron scattering (GISAXS, GIWAXS, GISANS and GIWANS), new possibilities arise which are discussed with selected examples. Due to instrumental progress, highly interesting possibilities for local structure analysis in this material class arise from the use of micro- and nanometer-sized X-ray beams in micro- or nanofocused GISAXS and GIWAXS experiments. The feasibility of very short data acquisition times down to milliseconds creates exciting possibilities forin situandin operandoGISAXS and GIWAXS studies. Tuning the energy of GISAXS and GIWAXS in the soft X-ray regime and in time-of flight GISANS allows the tailoring of contrast conditions and thereby the probing of more complex morphologies. In addition, recent progress in software packages, useful for data analysis for advanced grazing-incidence techniques, is discussed.

  8. Determination of In-Vitro Lung Solubility and Intake-To-Dose Conversion

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    Factors for Tritiated LaNi4.25Al0.75 Hydride | Department of Energy Determination of In-Vitro Lung Solubility and Intake-To-Dose Conversion Factors for Tritiated LaNi4.25Al0.75 Hydride Determination of In-Vitro Lung Solubility and Intake-To-Dose Conversion Factors for Tritiated LaNi4.25Al0.75 Hydride Presentation from the 34th Tritium Focus Group Meeting held in Idaho Falls, Idaho on September 23-25, 2014. PDF icon Determination of In-Vitro Lung Solubility and Intake-To-Dose Conversion

  9. Spatial Estimation of Populations at Risk from Radiological Dispersion Device Terrorism Incidents

    SciTech Connect (OSTI)

    Regens, J.L.; Gunter, J.T.

    2008-07-01

    Delineation of the location and size of the population potentially at risk of exposure to ionizing radiation is one of the key analytical challenges in estimating accurately the severity of the potential health effects associated with a radiological terrorism incident. Regardless of spatial scale, the geographical units for which population data commonly are collected rarely coincide with the geographical scale necessary for effective incident management and medical response. This paper identifies major government and commercial open sources of U.S. population data and presents a GIS-based approach for allocating publicly available population data, including age distributions, to geographical units appropriate for planning and implementing incident management and medical response strategies. In summary: The gravity model offers a straight-forward, empirical tool for estimating population flows, especially when geographical areas are relatively well-defined in terms of accessibility and spatial separation. This is particularly important for several reasons. First, the spatial scale for the area impacted by a RDD terrorism event is unlikely to match fully the spatial scale of available population data. That is, the plume spread typically will not uniformly overlay the impacted area. Second, the number of people within the impacted area varies as a function whether an attack occurs during the day or night. For example, the population of a central business district or industrial area typically is larger during the day while predominately residential areas have larger night time populations. As a result, interpolation techniques that link population data to geographical units and allocate those data based on time-frame at a spatial scale that is relevant to enhancing preparedness and response. The gravity model's main advantage is that it efficiently allocates readily available, open source population data to geographical units appropriate for planning and implementing incident management and medical monitoring strategies. The importance of being able to link population estimates to geographic areas during the course of an RDD incident can be understood intuitively: - The spatial distribution of actual total dose equivalents of ionizing radiation is likely to vary due to changes in meteorological parameters as an event evolves over time; - The size of the geographical area affected also is likely to vary as a function of the actual release scenario; - The ability to identify the location and size of the populations that may be exposed to doses of ionizing radiation is critical to carrying out appropriate treatment and post-event medical monitoring; - Once a spatial interaction model has been validated for a city or a region, it can then be used for simulation and prediction purposes to assess the possible human health consequences of different release scenarios. (authors)

  10. Search for: All records | SciTech Connect

    Office of Scientific and Technical Information (OSTI)

    ... composed of consultants of the International Atomic Energy Agency was held in ... of lung cancer, lung oligometastases, liver cancer, pancreas cancer, and kidney cancer. ...

  11. Assessment of uncertainties in radiation-induced cancer risk predictions at clinically relevant doses

    SciTech Connect (OSTI)

    Nguyen, J.; Moteabbed, M.; Paganetti, H.

    2015-01-15

    Purpose: Theoretical dose–response models offer the possibility to assess second cancer induction risks after external beam therapy. The parameters used in these models are determined with limited data from epidemiological studies. Risk estimations are thus associated with considerable uncertainties. This study aims at illustrating uncertainties when predicting the risk for organ-specific second cancers in the primary radiation field illustrated by choosing selected treatment plans for brain cancer patients. Methods: A widely used risk model was considered in this study. The uncertainties of the model parameters were estimated with reported data of second cancer incidences for various organs. Standard error propagation was then subsequently applied to assess the uncertainty in the risk model. Next, second cancer risks of five pediatric patients treated for cancer in the head and neck regions were calculated. For each case, treatment plans for proton and photon therapy were designed to estimate the uncertainties (a) in the lifetime attributable risk (LAR) for a given treatment modality and (b) when comparing risks of two different treatment modalities. Results: Uncertainties in excess of 100% of the risk were found for almost all organs considered. When applied to treatment plans, the calculated LAR values have uncertainties of the same magnitude. A comparison between cancer risks of different treatment modalities, however, does allow statistically significant conclusions. In the studied cases, the patient averaged LAR ratio of proton and photon treatments was 0.35, 0.56, and 0.59 for brain carcinoma, brain sarcoma, and bone sarcoma, respectively. Their corresponding uncertainties were estimated to be potentially below 5%, depending on uncertainties in dosimetry. Conclusions: The uncertainty in the dose–response curve in cancer risk models makes it currently impractical to predict the risk for an individual external beam treatment. On the other hand, the ratio of absolute risks between two modalities is less sensitive to the uncertainties in the risk model and can provide statistically significant estimates.

  12. Determination of In-Vitro Lung Solubility and Intake-To-Dose...

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    Presentation from the 34th Tritium Focus Group Meeting held in Idaho Falls, Idaho on September 23-25, 2014. PDF icon Determination of In-Vitro Lung Solubility and Intake-To-Dose ...

  13. Respiratory symptoms and lung function in oil mist-exposed workers

    SciTech Connect (OSTI)

    Jarvholm, B.; Bake, B.; Lavenius, B.; Thiringer, G.; Vokmann, R.

    1982-06-01

    The prevalence of respiratory symptoms was registered and ventilatory function was determined in 164 men exposed to oil mist. The average exposure time was 16.2 years. One hundred fifty-nine office workers served as controls. The exposed men reported more respiratory symptoms: 14% of the exposed nonsmokers v. 2% of the nonsmoking controls having cough at least three months a year. There were non significant differences between spirometric measurements and chest roentgenograms of the men exposed to oil mist and those of the office workers. The lung function of 25 nonsmoking exposed men was further examined with other lung function tests. The mean values for closing volume, slope of the alveolar plateau, total lung capacity, residual volume, elastic recoil at various lung volumes, and diffusion capacity did not differ significantly.

  14. Large scale validation of the M5L lung CAD on heterogeneous CT datasets

    SciTech Connect (OSTI)

    Lopez Torres, E. E-mail: cerello@to.infn.it; Fiorina, E.; Pennazio, F.; Peroni, C.; Saletta, M.; Cerello, P. E-mail: cerello@to.infn.it; Camarlinghi, N.; Fantacci, M. E.

    2015-04-15

    Purpose: M5L, a fully automated computer-aided detection (CAD) system for the detection and segmentation of lung nodules in thoracic computed tomography (CT), is presented and validated on several image datasets. Methods: M5L is the combination of two independent subsystems, based on the Channeler Ant Model as a segmentation tool [lung channeler ant model (lungCAM)] and on the voxel-based neural approach. The lungCAM was upgraded with a scan equalization module and a new procedure to recover the nodules connected to other lung structures; its classification module, which makes use of a feed-forward neural network, is based of a small number of features (13), so as to minimize the risk of lacking generalization, which could be possible given the large difference between the size of the training and testing datasets, which contain 94 and 1019 CTs, respectively. The lungCAM (standalone) and M5L (combined) performance was extensively tested on 1043 CT scans from three independent datasets, including a detailed analysis of the full Lung Image Database Consortium/Image Database Resource Initiative database, which is not yet found in literature. Results: The lungCAM and M5L performance is consistent across the databases, with a sensitivity of about 70% and 80%, respectively, at eight false positive findings per scan, despite the variable annotation criteria and acquisition and reconstruction conditions. A reduced sensitivity is found for subtle nodules and ground glass opacities (GGO) structures. A comparison with other CAD systems is also presented. Conclusions: The M5L performance on a large and heterogeneous dataset is stable and satisfactory, although the development of a dedicated module for GGOs detection could further improve it, as well as an iterative optimization of the training procedure. The main aim of the present study was accomplished: M5L results do not deteriorate when increasing the dataset size, making it a candidate for supporting radiologists on large scale screenings and clinical programs.

  15. Lung Toxicity and Mutagenicity of Emissions From Heavy-Duty Compressed

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    Natural Gas (CNG)-Powered Vehicles | Department of Energy Lung Toxicity and Mutagenicity of Emissions From Heavy-Duty Compressed Natural Gas (CNG)-Powered Vehicles Lung Toxicity and Mutagenicity of Emissions From Heavy-Duty Compressed Natural Gas (CNG)-Powered Vehicles 2005 Diesel Engine Emissions Reduction (DEER) Conference Presentations and Posters PDF icon 2005_deer_mauderly.pdf More Documents & Publications Relationship Between Composition and Toxicity of Engine Emission Samples

  16. Comments of the Southern Environmental Law Center and the American Lung

    Energy Savers [EERE]

    Association in response to the Department of Energy's Emergency Order to Resume Operations at the Potomac River Generating Station in Alexandria, VA | Department of Energy the Southern Environmental Law Center and the American Lung Association in response to the Department of Energy's Emergency Order to Resume Operations at the Potomac River Generating Station in Alexandria, VA Comments of the Southern Environmental Law Center and the American Lung Association in response to the Department

  17. Comparison of direct exposure of human lung cells to modern engine exhaust

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    partricles | Department of Energy direct exposure of human lung cells to modern engine exhaust partricles Comparison of direct exposure of human lung cells to modern engine exhaust partricles 2003 DEER Conference Presentation: Oak Ridge National Laboratory PDF icon 2003_deer_storey.pdf More Documents & Publications Pro-Inflammatory Cytokine Responses to Exposure to Diesel Soot Relationship Between Composition and Toxicity of Engine Emissions Comparative Toxicity of Combined Particle and

  18. Differential metabolism of 4-hydroxynonenal in liver, lung and brain of mice and rats

    SciTech Connect (OSTI)

    Zheng, Ruijin; Dragomir, Ana-Cristina; Mishin, Vladimir; Richardson, Jason R.; Heck, Diane E.; Laskin, Debra L.; Laskin, Jeffrey D.

    2014-08-15

    The lipid peroxidation end-product 4-hydroxynonenal (4-HNE) is generated in tissues during oxidative stress. As a reactive aldehyde, it forms Michael adducts with nucleophiles, a process that disrupts cellular functioning. Liver, lung and brain are highly sensitive to xenobiotic-induced oxidative stress and readily generate 4-HNE. In the present studies, we compared 4-HNE metabolism in these tissues, a process that protects against tissue injury. 4-HNE was degraded slowly in total homogenates and S9 fractions of mouse liver, lung and brain. In liver, but not lung or brain, NAD(P)+ and NAD(P)H markedly stimulated 4-HNE metabolism. Similar results were observed in rat S9 fractions from these tissues. In liver, lung and brain S9 fractions, 4-HNE formed protein adducts. When NADH was used to stimulate 4-HNE metabolism, the formation of protein adducts was suppressed in liver, but not lung or brain. In both mouse and rat tissues, 4-HNE was also metabolized by glutathione S-transferases. The greatest activity was noted in livers of mice and in lungs of rats; relatively low glutathione S-transferase activity was detected in brain. In mouse hepatocytes, 4-HNE was rapidly taken up and metabolized. Simultaneously, 4-HNE-protein adducts were formed, suggesting that 4-HNE metabolism in intact cells does not prevent protein modifications. These data demonstrate that, in contrast to liver, lung and brain have a limited capacity to metabolize 4-HNE. The persistence of 4-HNE in these tissues may increase the likelihood of tissue injury during oxidative stress. - Highlights: • Lipid peroxidation generates 4-hydroxynonenal, a highly reactive aldehyde. • Rodent liver, but not lung or brain, is efficient in degrading 4-hydroxynonenal. • 4-hydroxynonenal persists in tissues with low metabolism, causing tissue damage.

  19. Lung Irradiation Increases Mortality After Influenza A Virus Challenge Occurring Late After Exposure

    SciTech Connect (OSTI)

    Manning, Casey M.; Johnston, Carl J.; Department of Pediatrics, University of Rochester Medical Center, Rochester, New York ; Reed, Christina K.; Lawrence, B. Paige; Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, New York ; Williams, Jacqueline P.; Finkelstein, Jacob N.

    2013-05-01

    Purpose: To address whether irradiation-induced changes in the lung environment alter responses to a viral challenge delivered late after exposure but before the appearance of late lung radiation injury. Methods and Materials: C57BL/6J mice received either lung alone or combined lung and whole-body irradiation (0-15 Gy). At 10 weeks after irradiation, animals were infected with 120 HAU influenza virus strain A/HKx31. Innate and adaptive immune cell recruitment was determined using flow cytometry. Cytokine and chemokine production and protein leakage into the lung after infection were assessed. Results: Prior irradiation led to a dose-dependent failure to regain body weight after infection and exacerbated mortality, but it did not affect virus-specific immune responses or virus clearance. Surviving irradiated animals displayed a persistent increase in total protein in bronchoalveolar lavage fluid and edema. Conclusions: Lung irradiation increased susceptibility to death after infection with influenza virus and impaired the ability to complete recovery. This altered response does not seem to be due to a radiation effect on the immune response, but it may possibly be an effect on epithelial repair.

  20. Incidence, Risks, and Sequelae of Posterior Fossa Syndrome in Pediatric Medulloblastoma

    SciTech Connect (OSTI)

    Korah, Mariam P.; Esiashvili, Natia; Mazewski, Claire M.; Hudgins, Roger J.; Tighiouart, Mourad; Janss, Anna J.; Schwaibold, Frederick P.; Crocker, Ian R.; Curran, Walter J.; Marcus, Robert B.

    2010-05-01

    Purpose: To investigate the incidence, risks, severity, and sequelae of posterior fossa syndrome (PFS) in children with medulloblastoma. Methods and Materials: Between 1990 and 2007, 63 children with medulloblastoma at Emory University and Children's Healthcare of Atlanta were treated with craniectomy followed by radiation. Fifty-one patients were assigned to a standard-risk group, and 12 patients were assigned to a high-risk group. Five patients had <1.5-cm{sup 2} residual tumor, 4 had >=1.5-cm{sup 2} residual tumor, and the remainder had no residual tumor. Eleven patients had disseminated disease. Patients received craniospinal irradiation at a typical dose of 23.4 Gy or 36 Gy for standard- or high-risk disease, respectively. The posterior fossa was given a total dose of 54 or 55.8 Gy. Nearly all patients received chemotherapy following cooperative group protocols. Results: Median follow-up was 7 years. PFS developed in 18 patients (29%). On univariate analysis, brainstem invasion, midline tumor location, younger age, and the absence of radiographic residual tumor were found to be predictors of PFS; the last two variables remained significant on multivariate analysis. From 1990 to 2000 and from 2001 to 2007, the proportions of patients with no radiographic residual tumor were 77% and 94%, respectively. During the same eras, the proportions of patients with PFS were 17% and 39%. Only 4 patients had complete recovery at last follow-up. Conclusions: The incidence of PFS increased in the latter study period and is proportional to more aggressive surgery. Children with midline tumors exhibiting brainstem invasion are at increased risk. With the increased incidence of PFS and the permanent morbidity in many patients, the risks and benefits of complete tumor removal in all patients need to be reexamined.

  1. Incidence of Leukoencephalopathy After Whole-Brain Radiation Therapy for Brain Metastases

    SciTech Connect (OSTI)

    Ebi, Junko; Sato, Hisashi; Nakajima, Masaru; Shishido, Fumio

    2013-04-01

    Purpose: To evaluate the incidence of leukoencephalopathy after whole-brain radiation therapy (WBRT) in patients with brain metastases. Methods and Materials: We retrospectively reviewed 111 patients who underwent WBRT for brain metastases from April 2001 through March 2008 and had evaluable computed tomography (CT) and/or magnetic resonance imaging (MRI) at least 1 month after completion of WBRT. We evaluated the leukoencephalopathy according to the Common Terminology Criteria for Adverse Events, version 3.0. The patients who had brain tumor recurrence after WBRT were censored at the last follow-up CT or MRI without recurrence. To evaluate the risk factors for leukoencephalopathy, bivariate analysis was performed using a logistic regression analysis adjusted for follow-up time. Factors included in the analysis were age, gender, dose fractionation, 5-fluorouracil, methotrexate, cisplatin, and other chemotherapeutic agents. Results: The median age of the 111 patients was 60.0 years (range, 23-89 years). The median follow-up was 3.8 months (range, 1.0-38.1 months). Leukoencephalopathy developed in 23 of the 111 patients. Grades 1, 2, and 3 were observed in 8, 7, and 8 patients, respectively. The incidence was 34.4% (11 of 32), 42.9% (6 of 14), 66.7% (2 of 3), and 100% (2 of 2) of the patients who were followed up for ≥6, ≥12, ≥24, and ≥36 months, respectively. In the bivariate analysis, older age (≥65 years) was significantly correlated with higher risk of leukoencephalopathy (odds ratio 3.31; 95% confidence interval 1.15-9.50; P=.03). Conclusions: The incidence of leukoencephalopathy after WBRT was 34.4% with ≥6 months follow-up, and increased with longer follow-up. Older age was a significant risk factor. The schedule of WBRT for patients with brain metastases should be carefully determined, especially for favorable patients.

  2. Electron emission induced by resonant coherent ion-surface interaction at grazing incidence

    SciTech Connect (OSTI)

    Garcia de Abajo, F.J. ); Ponce, V.H. ); Echenique, P.M. )

    1992-10-19

    A new spectroscopy based on the resonant coherently induced electron loss to the continuum in ion-surface scattering under grazing incidence is proposed. A series of peaks, corresponding to the energy differences determined by the resonant interaction with the rows of atoms in the surface, is predicted to appear in the energy distribution of electrons emitted from electronic states bound to the probe. Calculations for MeV He{sup +} ions scattered at a W(001) surface along the {l angle}100{r angle} direction with a glancing angle of 0--2 mrad show a total yield close to 1.

  3. Physics of Cancer | Princeton Plasma Physics Lab

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    MBG Auditorium Physics of Cancer Professor Wolfgang Losert, Associate Professor, and ... PDF icon Wolfgang Losert Bio.pdf Physics of Cancer Contact Information ...

  4. Laser research shows promise for cancer treatment

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Cancer treatment Laser research shows promise for cancer treatment Scientists have observed for the first time how a laser penetrates dense, electron-rich plasma to generate ions....

  5. SQUID Instrumentation for Early Cancer Diagnostics: Combining...

    Office of Scientific and Technical Information (OSTI)

    Cancer Diagnostics: Combining SQUID-Based Ultra-Low Field MRI and Superparamagnetic Relaxometry Citation Details In-Document Search Title: SQUID Instrumentation for Early Cancer ...

  6. Electron emission induced by resonant coherent interaction in ion-surface scattering at grazing incidence

    SciTech Connect (OSTI)

    Garcia de Abajo, F.J. ); Ponce, V.H.; Echenique, P.M. )

    1994-01-15

    The resonant coherent interaction of an ion with an oriented crystal surface, under grazing-incidence conditions with respect to a special direction of the crystal, gives rise to electron loss to the continuum from electronic bound states of the ion. The calculations presented below predict large probabilities for electron emission due to this mechanism. The electrons are emitted with well defined energies, expressed in terms of the condition of resonance. Furthermore, the emission takes place around certain preferential directions, which are determined by both the latter condition and the symmetry of the surface lattice. Our calculations for MeV He[sup +] ions scattered at a W(001) surface along the [l angle]100[r angle] direction with glancing angle of 0--2 mrad indicate a yield of emission close to 1. Using heavier projectiles, one obtains smaller yields, but still large enough to be measurable in some cases (e.g., [approx]0.9 for 53 MeV B[sup 4+] and an angle of incidence of 1 mrad). Besides, the initial bound state is energy shifted due to the interaction with both the crystal potential and the velocity-dependent image potential. This results in a slight shift of the peaks of emission, which suggests a possible spectroscopy for analyzing the dynamical interaction of electronic bound states with solid surfaces.

  7. Electron-impact excitation of xenon at incident energies between 15 and 80 eV

    SciTech Connect (OSTI)

    Filipovic-acute-accent, D.; Marinkovic-acute-accent, B.; Pejcev, V.; Vuskovic-acute-accent, a.L.

    1988-01-15

    Normalized, absolute differential cross sections (DCS's) have been measured for the 20 lowest electronic states of xenon. Incident electron energies were 15, 20, 30, and 80 eV and the scattering angles ranged from 5/sup 0/ to 150/sup 0/. The energy resolution was 40 meV. Absolute elastic DCS's have been obtained by normalizing the relative values to the recently published absolute elastic DCS's by Register et al. (J. Phys. B 19, 1685 (1986)). Elastic-to-inelastic intensity ratios, at different incident energies for the 6s((3/2)/sub 1/ state were determined. These ratios were utilized as secondary standards to establish the absolute scale for the other inelastic processes in accordance with intensity ratios of lines in energy-loss spectra. The absolute inelastic DCS's were extrapolated to 0/sup 0/ and 180/sup 0/ and integrated to yield the integral cross sections (ICS's). A comparison of the present DCS's with the only available measurements at 20 eV impact energy shows satisfactory agreement in shape but considerable difference in absolute value.

  8. Predictors of Postoperative Complications After Trimodality Therapy for Esophageal Cancer

    SciTech Connect (OSTI)

    Wang, Jingya [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Wei, Caimiao [Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Tucker, Susan L. [Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Myles, Bevan; Palmer, Matthew [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Hofstetter, Wayne L.; Swisher, Stephen G. [Department of Thoracic and Cardiovascular Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Ajani, Jaffer A. [Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Cox, James D.; Komaki, Ritsuko; Liao, Zhongxing [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Lin, Steven H., E-mail: SHLin@mdanderson.org [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States)

    2013-08-01

    Purpose: While trimodality therapy for esophageal cancer has improved patient outcomes, surgical complication rates remain high. The goal of this study was to identify modifiable factors associated with postoperative complications after neoadjuvant chemoradiation. Methods and Materials: From 1998 to 2011, 444 patients were treated at our institution with surgical resection after chemoradiation. Postoperative (pulmonary, gastrointestinal [GI], cardiac, wound healing) complications were recorded up to 30 days postoperatively. Kruskal-Wallis tests and ?{sup 2} or Fisher exact tests were used to assess associations between continuous and categorical variables. Multivariate logistic regression tested the association between perioperative complications and patient or treatment factors that were significant on univariate analysis. Results: The most frequent postoperative complications after trimodality therapy were pulmonary (25%) and GI (23%). Lung capacity and the type of radiation modality used were independent predictors of pulmonary and GI complications. After adjusting for confounding factors, pulmonary and GI complications were increased in patients treated with 3-dimensional conformal radiation therapy (3D-CRT) versus intensity modulated radiation therapy (IMRT; odds ratio [OR], 2.018; 95% confidence interval [CI], 1.104-3.688; OR, 1.704; 95% CI, 1.03-2.82, respectively) and for patients treated with 3D-CRT versus proton beam therapy (PBT; OR, 3.154; 95% CI, 1.365-7.289; OR, 1.55; 95% CI, 0.78-3.08, respectively). Mean lung radiation dose (MLD) was strongly associated with pulmonary complications, and the differences in toxicities seen for the radiation modalities could be fully accounted for by the MLD delivered by each of the modalities. Conclusions: The radiation modality used can be a strong mitigating factor of postoperative complications after neoadjuvant chemoradiation.

  9. Technical Review of Law Enforcement Standards and Guides Relative to Incident Management

    SciTech Connect (OSTI)

    Stenner, Robert D.; Salter, R.; Stanton, J. R.; Fisher, D.

    2009-03-24

    In an effort to locate potential law enforcement-related standards that support incident management, a team from the Pacific Northwest National Laboratory (PNNL) contacted representatives from the National Institute of Standards-Office of Law Enforcement Standards (NIST-OLES), National Institute of Justice (NIJ), Federal Bureau of Investigation (FBI), Secret Service, ASTM International committees that have a law enforcement focus, and a variety of individuals from local and regional law enforcement organizations. Discussions were held with various state and local law enforcement organizations. The NIJ has published several specific equipment-related law enforcement standards that were included in the review, but it appears that law enforcement program and process-type standards are developed principally by organizations that operate at the state and local level. Input is provided from state regulations and codes and from external non-government organizations (NGOs) that provide national standards. The standards that are adopted from external organizations or developed independently by state authorities are available for use by local law enforcement agencies on a voluntary basis. The extent to which they are used depends on the respective jurisdictions involved. In some instances, use of state and local disseminated standards is mandatory, but in most cases, use is voluntary. Usually, the extent to which these standards are used appears to depend on whether or not jurisdictions receive certification from a governing entity due to their use and compliance with the standards. In some cases, these certification-based standards are used in principal but without certification or other compliance monitoring. In general, these standards appear to be routinely used for qualification, selection for employment, and training. In these standards, the term Peace Officer is frequently used to refer to law enforcement personnel. This technical review of national law enforcement standards and guides identified the following four guides as having content that supports incident management: TE-02-02 Guide to Radio Communications Interoperability Strategies and Products OSHA 335-10N Preparing and Protecting Security Personnel in Emergencies NIJ 181584 Fire and Arson Scene Evidence: A Guide for Public Safety Personnel NIJ 181869 A Guide for Explosion and Bombing Scene Investigation In conversations with various state and local law enforcement officials, it was determined that the following National Fire Protection Association (NPFA) standards are generally recognized and tend to be universally used by law enforcement organizations across the country: NFPA 1600 Standard on Disaster/Emergency Management and Business Continuity Programs NFPA 1561 Standard on Fire Department Incident Management Systems NFPA 472 Standard for Competence of Responders to Hazardous Materials/Weapons of Mass Destruction Incidents (2008 Edition) NFPA 473 Standard for Competencies for EMS Personnel Responding to Hazardous Materials/Weapons of Mass Destruction Incidents (2008 Edition)

  10. Breakthrough: Fighting Cancer with Nanoparticles

    SciTech Connect (OSTI)

    Rozhkova, Elena

    2012-01-01

    Argonne nanoscientist Elena Rozhkova is studying ways to enlist nanoparticles to treat brain cancer. This nano-bio technology may eventually provide an alternative form of therapy that targets only cancer cells and does not affect normal living tissue. Read more at http://1.usa.gov/JAXh7Q.

  11. Breakthrough: Fighting Cancer with Nanoparticles

    ScienceCinema (OSTI)

    Rozhkova, Elena

    2013-04-19

    Argonne nanoscientist Elena Rozhkova is studying ways to enlist nanoparticles to treat brain cancer. This nano-bio technology may eventually provide an alternative form of therapy that targets only cancer cells and does not affect normal living tissue. Read more at http://1.usa.gov/JAXh7Q.

  12. Dissolution of metal tritides in a simulated lung fluid

    SciTech Connect (OSTI)

    Cheng, Yung-Sung; Dahl, A.R.; Jow, Hong Nian

    1997-10-01

    Metal tritides including titanium tritide (Ti {sup 3}H{sub x}) and erbium tritide (Er {sup 3}H{sub x}) have been used as components of neutron generators. The current understanding of metal tritides and their radiation dosimetry for internal exposure is very limited, and the ICRP Publication 30 does not provide for tritium dosimetry in metal tritide form. However, a few papers in the literature suggest that the solubility of metal tritides could be low. The current radiation protection guidelines for metal tritide particles are based on the assumption that their biological behavior is similar to tritiated water, which could be easily absorbed into body fluid. Therefore, these particles could have relatively short biological half-lives (10 d). If the solubility is low, the biological half-life of metal tritide particles and the dosimetry of an inhalation exposure to these particles could be quite different from tritiated water. This paper describes experiments on the dissolution rate of titanium tritide particles in a simulated lung fluid. Titanium tritide particles with mean sizes of 103 {mu}m (coarse) and 0.95 {mu}m (fine) were used. The results showed that the coarse particles dissolved much more slowly than the fine particles. The long-term dissolution half times were 361 and 33 d for the coarse and fine particles, respectively. Dissolution data of the fine particles were consistent with the diffusion theory. The dissolution half times were longer than the 10-d biological half time for tritiated water in the body. This finding has significant implications for the current health protection guidelines, including annual limits of intakes and derived air concentrations.

  13. Malfunctions of Implantable Cardiac Devices in Patients Receiving Proton Beam Therapy: Incidence and Predictors

    SciTech Connect (OSTI)

    Gomez, Daniel R., E-mail: dgomez@mdanderson.org [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Poenisch, Falk [Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Pinnix, Chelsea C. [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Sheu, Tommy [Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Chang, Joe Y. [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Memon, Nada [Department of Cardiology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Mohan, Radhe [Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Rozner, Marc A. [Department of Anesthesiology and Perioperative Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Dougherty, Anne H. [Department of Cardiology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States)

    2013-11-01

    Purpose: Photon therapy has been reported to induce resets of implanted cardiac devices, but the clinical sequelae of treating patients with such devices with proton beam therapy (PBT) are not well known. We reviewed the incidence of device malfunctions among patients undergoing PBT. Methods and Materials: From March 2009 through July 2012, 42 patients with implanted cardiac implantable electronic devices (CIED; 28 pacemakers and 14 cardioverter-defibrillators) underwent 42 courses of PBT for thoracic (23, 55%), prostate (15, 36%), liver (3, 7%), or base of skull (1, 2%) tumors at a single institution. The median prescribed dose was 74 Gy (relative biological effectiveness; range 46.8-87.5 Gy), and the median distance from the treatment field to the CIED was 10 cm (range 0.8-40 cm). Maximum proton and neutron doses were estimated for each treatment course. All CIEDs were checked before radiation delivery and monitored throughout treatment. Results: Median estimated peak proton and neutron doses to the CIED in all patients were 0.8 Gy (range 0.13-21 Gy) and 346 Sv (range 11-1100 mSv). Six CIED malfunctions occurred in 5 patients (2 pacemakers and 3 defibrillators). Five of these malfunctions were CIED resets, and 1 patient with a defibrillator (in a patient with a liver tumor) had an elective replacement indicator after therapy that was not influenced by radiation. The mean distance from the proton beam to the CIED among devices that reset was 7.0 cm (range 0.9-8 cm), and the mean maximum neutron dose was 655 mSv (range 330-1100 mSv). All resets occurred in patients receiving thoracic PBT and were corrected without clinical incident. The generator for the defibrillator with the elective replacement indicator message was replaced uneventfully after treatment. Conclusions: The incidence of CIED resets was about 20% among patients receiving PBT to the thorax. We recommend that PBT be avoided in pacing-dependent patients and that patients with any type of CIED receiving thoracic PBT be followed closely.

  14. Retrospective Evaluation Reveals That Long-term Androgen Deprivation Therapy Improves Cause-Specific and Overall Survival in the Setting of Dose-Escalated Radiation for High-Risk Prostate Cancer

    SciTech Connect (OSTI)

    Feng, Felix Y.; Blas, Kevin; Olson, Karin; Stenmark, Matthew; Sandler, Howard; Hamstra, Daniel A.

    2013-05-01

    Purpose: To evaluate the role of androgen deprivation therapy (ADT) and duration for high-risk prostate cancer patients treated with dose-escalated radiation therapy (RT). Methods and Materials: A retrospective analysis of high-risk prostate cancer patients treated with dose-escalated RT (minimum 75 Gy) with or without ADT was performed. The relationship between ADT use and duration with biochemical failure (BF), metastatic failure (MF), prostate cancer-specific mortality (PCSM), non-prostate cancer death (NPCD), and overall survival (OS) was assessed as a function of pretreatment characteristics, comorbid medical illness, and treatment using Fine and Gray's cumulative incidence methodology. Results: The median follow-up time was 64 months. In men with National Comprehensive Cancer Network defined high-risk prostate cancer treated with dose-escalated RT, on univariate analysis, both metastasis (P<.0001; hazard ratio 0.34; 95% confidence interval 0.18-0.67; cumulative incidence at 60 months 13% vs 35%) and PCSM (P=.015; hazard ratio 0.41; 95% confidence interval 0.2-1.0; cumulative incidence at 60 months 6% vs 11%) were improved with the use of ADT. On multivariate analysis for all high-risk patients, Gleason score was the strongest negative prognostic factor, and long-term ADT (LTAD) improved MF (P=.002), PCSM (P=.034), and OS (P=.001). In men with prostate cancer and Gleason scores 8 to 10, on multivariate analysis after adjustment for other risk features, there was a duration-dependent improvement in BF, metastasis, PCSM, and OS, all favoring LTAD in comparison with STAD or RT alone. Conclusion: For men with high-risk prostate cancer treated with dose-escalated EBRT, this retrospective study suggests that the combination of LTAD and RT provided a significant improvement in clinical outcome, which was especially true for those with Gleason scores of 8 to 10.

  15. A Phase II trial of subcutaneous amifostine and radiation therapy in patients with head-and-neck cancer

    SciTech Connect (OSTI)

    Anne, Pramila Rani . E-mail: rani.anne@mail.tju.edu; Machtay, Mitchell; Rosenthal, David I.; Brizel, David M.; Morrison, William H.; Irwin, David H.; Chougule, Prakash B.; Estopinal, Noel C.; Berson, Anthony; Curran, Walter J.

    2007-02-01

    Purpose: Intravenous amifostine 200 mg/m{sup 2} reduces xerostomia in head-and-neck cancer patients. This Phase II study evaluated subcutaneous (s.c.) amifostine in a similar patient population. Patients and Methods: Patients received amifostine 500 mg, administered as two 250-mg s.c. injections 60 min before once-daily radiation for head-and-neck cancer (50-70 Gy in 5-7 weeks). The primary endpoint was the incidence of {>=}Grade 2 acute xerostomia. Results: Fifty-four patients received s.c. amifostine and radiotherapy. The incidence of {>=}Grade 2 acute xerostomia was 56% (95% CI, 43-69%) and the incidence of {>=}Grade 2 late xerostomia at 1 year was 45% (95% CI, 29-61%). The incidence of acute xerostomia was lower than reported previously with no amifostine in a controlled study; rates of acute xerostomia were similar between s.c. and i.v. amifostine in the two studies. The rate of late xerostomia with s.c. amifostine was intermediate between rates for i.v. amifostine and no amifostine, and not statistically significantly different from either historical control. Grades 1-2 nausea and emesis were the most common amifostine-related adverse events. Grade 3 amifostine-related adverse events reported by >1 patient included: dehydration (11%); rash (6%); and weight decrease, mucositis, dyspnea, and allergic reaction (each 4%). Seven patients (13%) had serious cutaneous adverse events outside the injection site. One-year rates of locoregional control, progression-free survival, and overall survival were 78%, 75%, and 85%, respectively. Conclusions: Subcutaneous amifostine provides a well-tolerated yet simpler alternative to i.v. amifostine for reducing acute xerostomia in head-and-neck cancer patients.

  16. Metabolic kinetics and dosimetry of titanium tritide particles in the lung

    SciTech Connect (OSTI)

    Wang, Y.S.; Cheng, Y.S.; Snipes, M.B.; Jow, H.N.

    1996-06-01

    Internal radiation doses resulting from inhaled metal tritide aerosols are potentially a major radiation protection problem encountered by individuals handling tritium. Based on results of experiments with rats intratracheally instilled with titanium tritide particles and on a self-absorption factor of beta energy determined by a numerical method, a biokinetic model was developed for inhaled particles of titanium tritide. Results showed that lung burdens of the tritide are well represented by a 2-component exponential equation; biological half-lives observed for the retention of {sup 3}H in lung were 0.55 d and 64 d, respectively. The tritium clearance rate via urine or feces was described by a sum of three exponential components. At 121 d after instillation, 79.4% of the initial lung burden of {sup 3}H was eliminated of which 34% was excreted by urine, 35.8% via feces, and 9.6 % through exhaled air. After correction for 82% beta energy self-absorption by tritide particles, the cumulative 3H activity in the lungs of rats was 159 kBq d{sup -1} (4.3 {mu}Ci d{sup -1}) per 37 kBq (1 {mu}Ci) of instilled tritide. The cumulative radiation dose to the average lung mass of the rats was 0.28 mGy kBq{sup -1} of instilled tritide. This information will be useful in developing complete metabolic and dosimetric models for inhaled metal tritides for radiation protection purposes.

  17. Tensions in collaborative cyber security and how they affect incident detection and response

    SciTech Connect (OSTI)

    Fink, Glenn A.; McKinnon, Archibald D.; Clements, Samuel L.; Frincke, Deborah A.

    2009-12-01

    Security often requires collaboration, but when multiple stakeholders are involved, it is typical for their priorities to differ or even conflict with one another. In todays increasingly networked world, cyber security collaborations may span organizations and countries. In this chapter, we address collaboration tensions, their effects on incident detection and response, and how these tensions may potentially be resolved. We present three case studies of collaborative cyber security within the U.S. government and discuss technical, social, and regulatory challenges to collaborative cyber security. We suggest possible solutions, and present lessons learned from conflicts. Finally, we compare collaborative solutions from other domains and apply them to cyber security collaboration. Although we concentrate our analysis on collaborations whose purpose is to achieve cyber security, we believe that this work applies readily to security tensions found in collaborations of a general nature as well.

  18. Light trapping for emission from a photovoltaic cell under normally incident monochromatic illumination

    SciTech Connect (OSTI)

    Takeda, Yasuhiko Iizuka, Hideo; Mizuno, Shintaro; Hasegawa, Kazuo; Ichikawa, Tadashi; Ito, Hiroshi; Kajino, Tsutomu; Ichiki, Akihisa; Motohiro, Tomoyoshi

    2014-09-28

    We have theoretically demonstrated a new light-trapping mechanism to reduce emission from a photovoltaic (PV) cell used for a monochromatic light source, which improves limiting conversion efficiency determined by the detailed balance. A multilayered bandpass filter formed on the surface of a PV cell has been found to prevent the light generated inside by radiative recombination from escaping the cell, resulting in a remarkable decrease of the effective solid angle for the emission. We have clarified a guide to design a suitable configuration of the bandpass filter and achieved significant reduction of the emission. The resultant gain in monochromatic conversion efficiency in the radiative limit due to the optimally designed 18-layerd bandpass filters is as high as 6% under normally incident 1064 nm illumination of 10 mW/cm~ 1 kW/cm, compared with the efficiency for the perfect anti-reflection treatment to the surface of a conventional solar cell.

  19. Fractures of the Sacrum After Chemoradiation for Rectal Carcinoma: Incidence, Risk Factors, and Radiographic Evaluation

    SciTech Connect (OSTI)

    Kim, Han Jo; Boland, Patrick J.; Meredith, Dennis S.; Lis, Eric; Zhang Zhigang; Shi Weiji; Yamada, Yoshiya J.; Goodman, Karyn A.

    2012-11-01

    Purpose: Sacral insufficiency fractures after adjuvant radiation for rectal carcinoma can present similarly to recurrent disease. As a complication associated with pelvic radiation, it is important to be aware of the incidence and risk factors associated with sacral fractures in the clinical assessment of these patients. Methods and Materials: Between 1998 and 2007, a total of 582 patients with locally advanced rectal carcinoma received adjuvant chemoradiation and surgical excision. Of these, 492 patients had imaging studies available for review. Hospital records and imaging studies from all 492 patients were retrospectively evaluated to identify risk factors associated with developing a sacral insufficiency fracture. Results: With a median follow-up time of 3.5 years, the incidence of sacral fractures was 7.1% (35/492). The 4-year sacral fracture free rate was 0.91. Univariate analysis showed that increasing age ({>=}60 vs. <60 years), female sex, and history of osteoporosis were significantly associated with shorter time to sacral fracture (P=.01, P=.004, P=.001, respectively). There was no significant difference in the time to sacral fracture for patients based on stage, radiotherapy dose, or chemotherapy regimen. Multivariate analysis showed increasing age ({>=}60 vs. <60 years, hazard ratio [HR] = 2.50, 95% confidence interval [CI] = 1.22-5.13, P=.01), female sex (HR = 2.64, CI = 1.29-5.38, P=.008), and history of osteoporosis (HR = 3.23, CI = 1.23-8.50, P=.02) were independent risk factors associated with sacral fracture. Conclusions: Sacral insufficiency fractures after pelvic radiation for rectal carcinoma occur more commonly than previously described. Independent risk factors associated with fracture were osteoporosis, female sex, and age greater than 60 years.

  20. Decreased expression of RNA interference machinery, Dicer and Drosha, is associated with poor outcome in ovarian cancer patients

    SciTech Connect (OSTI)

    Merritt, William M.; Lin, Yvonne G.; Han, Liz Y.; Kamat, Aparna A.; Spannuth, Whitney A.; Schmandt, Rosemarie; Urbauer, Diana; Pennacchio, Len A.; Cheng, Jan-Fang; Zeidan, Alexandra; Wang, Hua; Mueller, Peter; Lenburg, Marc E.; Gray, Joe W.; Mok, Samuel; Birrer, Michael J.; Lopez-Berestein, Gabriel; Coleman, Robert L.; Bar-Eli, Menashe; Sood, Anil K.

    2008-05-06

    The clinical and functional significance of RNA interference (RNAi) machinery, Dicer and Drosha, in ovarian cancer is not known and was examined. Dicer and Drosha expression was measured in ovarian cancer cell lines (n=8) and invasive epithelial ovarian cancer specimens (n=111) and correlated with clinical outcome. Validation was performed with previously published cohorts of ovarian, breast, and lung cancer patients. Anti-Galectin-3 siRNA and shRNA transfections were used for in vitro functional studies. Dicer and Drosha mRNA and protein levels were decreased in 37% to 63% of ovarian cancer cell lines and in 60% and 51% of human ovarian cancer specimens, respectively. Low Dicer was significantly associated with advanced tumor stage (p=0.007), and low Drosha with suboptimal surgical cytoreduction (p=0.02). Tumors with both high Dicer and Drosha were associated with increased median patient survival (>11 years vs. 2.66 years for other groups; p<0.001). In multivariate analysis, high Dicer (HR=0.48; p=0.02), high-grade histology (HR=2.46; p=0.03), and poor chemoresponse (HR=3.95; p<0.001) were identified as independent predictors of disease-specific survival. Findings of poor clinical outcome with low Dicer expression were validated in separate cohorts of cancer patients. Galectin-3 silencing with siRNA transfection was superior to shRNA in cell lines with low Dicer (78-95% vs. 4-8% compared to non-targeting sequences), and similar in cell lines with high Dicer. Our findings demonstrate the clinical and functional impact of RNAi machinery alterations in ovarian carcinoma and support the use of siRNA constructs that do not require endogenous Dicer and Drosha for therapeutic applications.

  1. Accelerators for Cancer Therapy

    DOE R&D Accomplishments [OSTI]

    Lennox, Arlene J.

    2000-05-30

    The vast majority of radiation treatments for cancerous tumors are given using electron linacs that provide both electrons and photons at several energies. Design and construction of these linacs are based on mature technology that is rapidly becoming more and more standardized and sophisticated. The use of hadrons such as neutrons, protons, alphas, or carbon, oxygen and neon ions is relatively new. Accelerators for hadron therapy are far from standardized, but the use of hadron therapy as an alternative to conventional radiation has led to significant improvements and refinements in conventional treatment techniques. This paper presents the rationale for radiation therapy, describes the accelerators used in conventional and hadron therapy, and outlines the issues that must still be resolved in the emerging field of hadron therapy.

  2. Validated Competing Event Model for the Stage I-II Endometrial Cancer Population

    SciTech Connect (OSTI)

    Carmona, Ruben; Gulaya, Sachin; Murphy, James D.; Rose, Brent S.; Wu, John; Noticewala, Sonal; McHale, Michael T.; Yashar, Catheryn M.; Vaida, Florin; Mell, Loren K.

    2014-07-15

    Purpose/Objectives(s): Early-stage endometrial cancer patients are at higher risk of noncancer mortality than of cancer mortality. Competing event models incorporating comorbidity could help identify women most likely to benefit from treatment intensification. Methods and Materials: 67,397 women with stage I-II endometrioid adenocarcinoma after total hysterectomy diagnosed from 1988 to 2009 were identified in Surveillance, Epidemiology, and End Results (SEER) and linked SEER-Medicare databases. Using demographic and clinical information, including comorbidity, we sought to develop and validate a risk score to predict the incidence of competing mortality. Results: In the validation cohort, increasing competing mortality risk score was associated with increased risk of noncancer mortality (subdistribution hazard ratio [SDHR], 1.92; 95% confidence interval [CI], 1.60-2.30) and decreased risk of endometrial cancer mortality (SDHR, 0.61; 95% CI, 0.55-0.78). Controlling for other variables, Charlson Comorbidity Index (CCI)=1 (SDHR, 1.62; 95% CI, 1.45-1.82) and CCI >1 (SDHR, 3.31; 95% CI, 2.74-4.01) were associated with increased risk of noncancer mortality. The 10-year cumulative incidences of competing mortality within low-, medium-, and high-risk strata were 27.3% (95% CI, 25.2%-29.4%), 34.6% (95% CI, 32.5%-36.7%), and 50.3% (95% CI, 48.2%-52.6%), respectively. With increasing competing mortality risk score, we observed a significant decline in omega (?), indicating a diminishing likelihood of benefit from treatment intensification. Conclusion: Comorbidity and other factors influence the risk of competing mortality among patients with early-stage endometrial cancer. Competing event models could improve our ability to identify patients likely to benefit from treatment intensification.

  3. Outcomes After Intensity-Modulated Versus Conformal Radiotherapy in Older Men With Nonmetastatic Prostate Cancer

    SciTech Connect (OSTI)

    Bekelman, Justin E.; Mitra, Nandita; Efstathiou, Jason; Liao Kaijun; Sunderland, Robert; Yeboa, Deborah N.; Armstrong, Katrina

    2011-11-15

    Purpose: There is little evidence comparing complications after intensity-modulated (IMRT) vs. three-dimensional conformal radiotherapy (CRT) for prostate cancer. The study objective was to test the hypothesis that IMRT, compared with CRT, is associated with a reduction in bowel, urinary, and erectile complications in elderly men with nonmetastatic prostate cancer. Methods and Materials: We undertook an observational cohort study using registry and administrative claims data from the SEER-Medicare database. We identified men aged 65 years or older diagnosed with nonmetastatic prostate cancer in the United States between 2002 and 2004 who received IMRT (n = 5,845) or CRT (n = 6,753). The primary outcome was a composite measure of bowel complications. Secondary outcomes were composite measures of urinary and erectile complications. We also examined specific subsets of bowel (proctitis/hemorrhage) and urinary (cystitis/hematuria) events within the composite complication measures. Results: IMRT was associated with reductions in composite bowel complications (24-month cumulative incidence 18.8% vs. 22.5%; hazard ratio [HR] 0.86; 95% confidence interval [CI], 0.79-0.93) and proctitis/hemorrhage (HR 0.78; 95% CI, 0.64-0.95). IMRT was not associated with rates of composite urinary complications (HR 0.93; 95% CI, 0.83-1.04) or cystitis/hematuria (HR 0.94; 95% CI, 0.83-1.07). The incidence of erectile complications involving invasive procedures was low and did not differ significantly between groups, although IMRT was associated with an increase in new diagnoses of impotence (HR 1.27, 95% CI, 1.14-1.42). Conclusion: IMRT is associated with a small reduction in composite bowel complications and proctitis/hemorrhage compared with CRT in elderly men with nonmetastatic prostate cancer.

  4. Ancient Proteins Help Unravel a Modern Cancer Drug's Mechanism

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Ancient Proteins Help Unravel a Modern Cancer Drug's Mechanism Print The cancer drug Gleevec is extremely specific, binding and inhibiting only the cancer-causing tyrosine protein...

  5. MO-G-BRE-09: Validating FMEA Against Incident Learning Data: A Study in Stereotactic Body Radiation Therapy

    SciTech Connect (OSTI)

    Yang, F; Cao, N; Young, L; Howard, J; Sponseller, P; Logan, W; Arbuckle, T; Korssjoen, T; Meyer, J; Ford, E

    2014-06-15

    Purpose: Though FMEA (Failure Mode and Effects Analysis) is becoming more widely adopted for risk assessment in radiation therapy, to our knowledge it has never been validated against actual incident learning data. The objective of this study was to perform an FMEA analysis of an SBRT (Stereotactic Body Radiation Therapy) treatment planning process and validate this against data recorded within an incident learning system. Methods: FMEA on the SBRT treatment planning process was carried out by a multidisciplinary group including radiation oncologists, medical physicists, and dosimetrists. Potential failure modes were identified through a systematic review of the workflow process. Failure modes were rated for severity, occurrence, and detectability on a scale of 1 to 10 and RPN (Risk Priority Number) was computed. Failure modes were then compared with historical reports identified as relevant to SBRT planning within a departmental incident learning system that had been active for two years. Differences were identified. Results: FMEA identified 63 failure modes. RPN values for the top 25% of failure modes ranged from 60 to 336. Analysis of the incident learning database identified 33 reported near-miss events related to SBRT planning. FMEA failed to anticipate 13 of these events, among which 3 were registered with severity ratings of severe or critical in the incident learning system. Combining both methods yielded a total of 76 failure modes, and when scored for RPN the 13 events missed by FMEA ranked within the middle half of all failure modes. Conclusion: FMEA, though valuable, is subject to certain limitations, among them the limited ability to anticipate all potential errors for a given process. This FMEA exercise failed to identify a significant number of possible errors (17%). Integration of FMEA with retrospective incident data may be able to render an improved overview of risks within a process.

  6. Realizing thin electromagnetic absorbers for wide incidence angles from commercially available planar circuit materials

    SciTech Connect (OSTI)

    Glover, Brian B; Whites, Kieth W; Radway, Matthew J

    2009-01-01

    In this study, recent work on engineering R-card surface resistivity with printed metallic patterns is extended to the design of thin electromagnetic absorbers. Thin electromagnetic absorbers for wide incidence angles and both polarizations have recently been computationally verified by Luukkonen et al.. These absorbers are analytically modeled high-impedance surfaces with capacitive arrays of square patches implemented with relatively high dielectric constant and high loss substrate. However, the advantages provided by the accurate analytical model are largely negated by the need to obtain high dielectric constant material with accurately engineered loss. Fig. I(c) illustrates full-wave computational results for an absorber without vias engineered as proposed by Luukkonen et al.. Unique values for the dielectric loss are required for different center frequencies. Parameters for the capacitive grid are D=5.0 mm and w=O.l mm for a center frequency of 3.36 GHz. The relative permittivity and thickness is 9.20(1-j0.234) and 1=3.048 mm. Consider a center frequency of5.81 GHz and again 1=3.048 mm, the required parameters for the capacitive grid are D=2.0 mm and w=0.2 mm where the required relative permittivity is now 9.20(1-j0.371) Admittedly, engineered dielectrics are themselves a historically interesting and fruitful research area which benefits today from advances in monolithic fabrication using direct-write of dielectrics with nanometer scale inclusions. However, our objective in the present study is to realize the advantages of the absorber proposed by Luukkonen et al. without resort to engineered lossy dielectrics. Specifically we are restricted to commercially available planer circuit materials without use of in-house direct-write technology or materials engineering capability. The materials considered here are TMM 10 laminate with (35 {mu}lm copper cladding with a complex permittivity 9.20-j0.0022) and Ohmegaply resistor conductor material (maximum 250 {Omega}/sq.). A thin electromagnetic absorber for incidence angles greater than 30deg. but less than 60deg. and both polarizations is computationally demonstrated. This absorber utilizes high-permittivity, low-loss microwave substrate in conjunction with an engineered lossy sheet impedance. The lossy sheet impedance is easily engineered with simple analytical approximations and can be manufactured from commercially available laminate materials on microwave substrate.

  7. SU-E-T-272: Radiation Damage Comparison Between Intensity Modulated Radiotherapy and Field-In-Field Technique in Breast Cancer Treatments

    SciTech Connect (OSTI)

    Ai, H; Zhang, H

    2014-06-01

    Purpose: To compare normal tissue complications between IMRT and FIF treatment in breast cancer. Methods: 16 patients treated with IMRT plan and 20 patients treated with FIF plan were evaluated in this study. Both kinds of plans were generated using Eclipse treatment planning system by dosimetrist following clinical radiotherapy treatment guidelines. The plans were reviewed and approved by radiation oncologist. The average survival fraction (SF) for three different normal tissue cells of each concerned structure can be calculated from differential dose volume histogram (DVH) using linear quadratic model. The three types of normal tissues include radiosensitive, moderately radiosensitive and radio-resistant that represents 70%, 50% and 30% survival fractions, respectively, for a 2-Gy open field. Equivalent uniform doses (EUD) for corresponding normal tissues of each structure were calculated. Results: The EUDs of the lungs, heart, healthy breast and spinal cord with both IMRT and FIF treatments were calculated. Considering the average value of all IMRT plans, the lung of treated side absorbed 16.0% of dosage prescribed to the tumor if the radiosensitivity of the lung is similar to the radiosensitive cell line. For moderately radiosensitive and radio-resistant lung tissue, the average EUDs can be 18.9% and 22.4% of prescription. In contrast, patients treated with FIF plans were delivered 6.0%, 7.5% and 10.3% of prescribed dose for radiosensitive, moderately radiosensitive and radio-resistant lung tissue, respectively. Comparing heart EUDs between IMRT and FIF plans, average absorbed doses in IMRT treatment were 7.7%, 8.7% and 9.7% of prescription for three types of heart normal tissue cell lines while FIF treatments delivered only 1.3%, 1.5% and 1.6% of prescription dose. For the other organs, the results were similar. Conclusion: The results indicated that breast cancer treatment using IMRT technique had more normal tissue damage than FIF treatment. FIF demonstrated more effective normal tissue dose reduction in breast cancer treatment.

  8. Evaluation of internal contamination levels after a radiological dispersal device incident using portal monitors

    SciTech Connect (OSTI)

    Palmer, R.C.; Hertel, Nolan; Ansari, A.; Manger, Ryan P; Freibert, E.J.

    2012-01-01

    Following a radioactive dispersal device (RDD) incident, it may be necessary to evaluate the internal contamination levels of a large number of potentially affected individuals to determine if immediate medical follow-up is necessary. Since the current laboratory capacity to screen for internal contamination is limited, rapid field screening methods can be useful in prioritizing individuals. This study evaluated the suitability of a radiation portal monitor for such screening. A model of the portal monitor was created for use with models of six anthropomorphic phantoms in Monte Carlo N-Particle Transport Code Version 5 (MCNP) X-5 Monte Carlo Team (MCNP A General Monte Carlo N-Particle Transport Code Version 5. LA-CP-03-0245. Vol. 2. Los Alamos National Laboratory, 2004.). The count rates of the portal monitor were simulated for inhalation and ingestion of likely radionuclides from an RDD for each of the phantoms. The time-dependant organ concentrations of the radionuclides were determined using Dose and Risk Calculation Software Eckerman, Leggett, Cristy, Nelson, Ryman, Sjoreen and Ward (Dose and Risk Calculation Software Ver. 8.4. ORNL/TM-2001/190. Oak Ridge National Laboratory, 2006.). Portal monitor count rates corresponding to a committed effective dose E(50) of 10 mSv are reported.

  9. Microsoft PowerPoint - MBPCC CAMD Cancer Therapy Program, 12...

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Bird Perkins Cancer Center's CAMD Cancer Therapy Research Program CAMD Cancer Therapy Research Program Kenneth R Hogstrom, PhD, PI Chief of Physics Mary Bird Perkins Cancer Center...

  10. Cell-specific oxidative stress and cytotoxicity after wildfire coarse particulate matter instillation into mouse lung

    SciTech Connect (OSTI)

    Williams, Keisha M.; Franzi, Lisa M.; Last, Jerold A.

    2013-01-01

    Our previous work has shown that coarse particulate matter (PM{sub 10-2.5}) from wildfire smoke is more toxic to lung macrophages on an equal dose (by mass) basis than coarse PM isolated from normal ambient air, as evidenced by decreased numbers of macrophages in lung lavage fluid 6 and 24 hours after PM instillation into mouse lungs in vivo and by cytotoxicity to a macrophage cell line observed directly in vitro. We hypothesized that pulmonary macrophages from mice instilled with wildfire coarse PM would undergo more cytotoxicity than macrophages from controls, and that there would be an increase in oxidative stress in their lungs. Cytotoxicity was quantified as decreased viable macrophages and increased percentages of dead macrophages in the bronchoalveolar lavage fluid (BALF) of mice instilled with wildfire coarse PM. At 1 hour after PM instillation, we observed both decreased numbers of viable macrophages and increased dead macrophage percentages as compared to controls. An increase in free isoprostanes, an indicator of oxidative stress, from control values of 28.1 3.2 pg/mL to 83.9 12.2 pg/mL was observed a half-hour after PM instillation. By 1 hour after PM instillation, isoprostane values had returned to 30.4 7.6 pg/mL, not significantly different from control concentrations. Lung sections from mice instilled with wildfire coarse PM showed rapid Clara cell responses, with decreased intracellular staining for the Clara cell secretory protein CCSP 1 hour after wildfire PM instillation. In conclusion, very rapid cytotoxicity occurs in pulmonary macrophages and oxidative stress responses are seen 0.51 hour after wildfire coarse PM instillation. These results define early cellular and biochemical events occurring in vivo and support the hypothesis that oxidative stress-mediated macrophage toxicity plays a key role in the initial response of the mouse lung to wildfire PM exposure. -- Highlights: ? We studied very early events (0.51 hour) after giving wildfire PM{sub 10-2.5} to mice. ? Wildfire PM{sub 10-2.5} rapidly kills lung macrophages in mice. ? Wildfire PM{sub 10-2.5} rapidly elicits oxidative stress in mice. ? Wildfire PM{sub 10-2.5} rapidly elicits Clara cell CCSP secretion in mice. ? Wildfire PM{sub 10-2.5} rapidly elicits TNF-? secretion into BALF in mice.

  11. METEOROLOGICAL INFLUENCES ON VAPOR INCIDENTS IN THE 200 EAST & 200 WEST TANK FARMS FROM CY2001 THRU CY2004

    SciTech Connect (OSTI)

    FAUROTE, J.M.

    2004-09-30

    Investigation into the meteorological influences on vapor incidents in the tank farms to determine what, if any, meteorological influences contribute to the reporting of odors, smells, vapors, and other gases. Weather phenomena, specifically barometric pressure, and wind velocity and direction can potentially cause or exacerbate a vapor release within the farm systems.

  12. Inhibition of chlorine-induced lung injury by the type 4 phosphodiesterase inhibitor rolipram

    SciTech Connect (OSTI)

    Chang, Weiyuan; Chen, Jing; Schlueter, Connie F.; Rando, Roy J.; Pathak, Yashwant V.; Hoyle, Gary W.

    2012-09-01

    Chlorine is a highly toxic respiratory irritant that when inhaled causes epithelial cell injury, alveolar-capillary barrier disruption, airway hyperreactivity, inflammation, and pulmonary edema. Chlorine is considered a chemical threat agent, and its release through accidental or intentional means has the potential to result in mass casualties from acute lung injury. The type 4 phosphodiesterase inhibitor rolipram was investigated as a rescue treatment for chlorine-induced lung injury. Rolipram inhibits degradation of the intracellular signaling molecule cyclic AMP. Potential beneficial effects of increased cyclic AMP levels include inhibition of pulmonary edema, inflammation, and airway hyperreactivity. Mice were exposed to chlorine (whole body exposure, 228270 ppm for 1 h) and were treated with rolipram by intraperitoneal, intranasal, or intramuscular (either aqueous or nanoemulsion formulation) delivery starting 1 h after exposure. Rolipram administered intraperitoneally or intranasally inhibited chlorine-induced pulmonary edema. Minor or no effects were observed on lavage fluid IgM (indicative of plasma protein leakage), KC (Cxcl1, neutrophil chemoattractant), and neutrophils. All routes of administration inhibited chlorine-induced airway hyperreactivity assessed 1 day after exposure. The results of the study suggest that rolipram may be an effective rescue treatment for chlorine-induced lung injury and that both systemic and targeted administration to the respiratory tract were effective routes of delivery. -- Highlights: ? Chlorine causes lung injury when inhaled and is considered a chemical threat agent. ? Rolipram inhibited chlorine-induced pulmonary edema and airway hyperreactivity. ? Post-exposure rolipram treatments by both systemic and local delivery were effective. ? Rolipram shows promise as a rescue treatment for chlorine-induced lung injury.

  13. Diet-induced obesity reprograms the inflammatory response of the murine lung to inhaled endotoxin

    SciTech Connect (OSTI)

    Tilton, Susan C.; Waters, Katrina M.; Karin, Norman J.; Webb-Robertson, Bobbie-Jo M.; Zangar, Richard C.; Lee, K. Monica; Bigelow, Diana J.; Pounds, Joel G.; Corley, Richard A.

    2013-03-01

    The co-occurrence of environmental factors is common in complex human diseases and, as such, understanding the molecular responses involved is essential to determine risk and susceptibility to disease. We have investigated the key biological pathways that define susceptibility for pulmonary infection during obesity in diet-induced obese (DIO) and regular weight (RW) C57BL/6 mice exposed to inhaled lipopolysaccharide (LPS). LPS induced a strong inflammatory response in all mice as indicated by elevated cell counts of macrophages and neutrophils and levels of proinflammatory cytokines (MDC, MIP-1?, IL-12, RANTES) in the bronchoalveolar lavage fluid. Additionally, DIO mice exhibited 50% greater macrophage cell counts, but decreased levels of the cytokines, IL-6, TARC, TNF-?, and VEGF relative to RW mice. Microarray analysis of lung tissue showed over half of the LPS-induced expression in DIO mice consisted of genes unique for obese mice, suggesting that obesity reprograms how the lung responds to subsequent insult. In particular, we found that obese animals exposed to LPS have gene signatures showing increased inflammatory and oxidative stress response and decreased antioxidant capacity compared with RW. Because signaling pathways for these responses can be common to various sources of environmentally induced lung damage, we further identified biomarkers that are indicative of specific toxicant exposure by comparing gene signatures after LPS exposure to those from a parallel study with cigarette smoke. These data show obesity may increase sensitivity to further insult and that co-occurrence of environmental stressors result in complex biosignatures that are not predicted from analysis of individual exposures. - Highlights: ? Obesity modulates inflammatory markers in BAL fluid after LPS exposure. ? Obese animals have a unique transcriptional signature in lung after LPS exposure. ? Obesity elevates inflammatory stress and reduces antioxidant capacity in the lung. ? Toxicant-specific biomarkers predict exposure independent of systemic inflammation.

  14. Real-time soft tissue motion estimation for lung tumors during radiotherapy delivery

    SciTech Connect (OSTI)

    Rottmann, Joerg; Berbeco, Ross; Keall, Paul

    2013-09-15

    Purpose: To provide real-time lung tumor motion estimation during radiotherapy treatment delivery without the need for implanted fiducial markers or additional imaging dose to the patient.Methods: 2D radiographs from the therapy beam's-eye-view (BEV) perspective are captured at a frame rate of 12.8 Hz with a frame grabber allowing direct RAM access to the image buffer. An in-house developed real-time soft tissue localization algorithm is utilized to calculate soft tissue displacement from these images in real-time. The system is tested with a Varian TX linear accelerator and an AS-1000 amorphous silicon electronic portal imaging device operating at a resolution of 512 × 384 pixels. The accuracy of the motion estimation is verified with a dynamic motion phantom. Clinical accuracy was tested on lung SBRT images acquired at 2 fps.Results: Real-time lung tumor motion estimation from BEV images without fiducial markers is successfully demonstrated. For the phantom study, a mean tracking error <1.0 mm [root mean square (rms) error of 0.3 mm] was observed. The tracking rms accuracy on BEV images from a lung SBRT patient (≈20 mm tumor motion range) is 1.0 mm.Conclusions: The authors demonstrate for the first time real-time markerless lung tumor motion estimation from BEV images alone. The described system can operate at a frame rate of 12.8 Hz and does not require prior knowledge to establish traceable landmarks for tracking on the fly. The authors show that the geometric accuracy is similar to (or better than) previously published markerless algorithms not operating in real-time.

  15. Cancer risk estimates from radiation therapy for heterotopic ossification prophylaxis after total hip arthroplasty

    SciTech Connect (OSTI)

    Mazonakis, Michalis; Berris, Theoharris; Damilakis, John; Lyraraki, Efrossyni

    2013-10-15

    Purpose: Heterotopic ossification (HO) is a frequent complication following total hip arthroplasty. This study was conducted to calculate the radiation dose to organs-at-risk and estimate the probability of cancer induction from radiotherapy for HO prophylaxis.Methods: Hip irradiation for HO with a 6 MV photon beam was simulated with the aid of a Monte Carlo model. A realistic humanoid phantom representing an average adult patient was implemented in Monte Carlo environment for dosimetric calculations. The average out-of-field radiation dose to stomach, liver, lung, prostate, bladder, thyroid, breast, uterus, and ovary was calculated. The organ-equivalent-dose to colon, that was partly included within the treatment field, was also determined. Organ dose calculations were carried out using three different field sizes. The dependence of organ doses upon the block insertion into primary beam for shielding colon and prosthesis was investigated. The lifetime attributable risk for cancer development was estimated using organ, age, and gender-specific risk coefficients.Results: For a typical target dose of 7 Gy, organ doses varied from 1.0 to 741.1 mGy by the field dimensions and organ location relative to the field edge. Blocked field irradiations resulted in a dose range of 1.4146.3 mGy. The most probable detriment from open field treatment of male patients was colon cancer with a high risk of 564.3 10{sup ?5} to 837.4 10{sup ?5} depending upon the organ dose magnitude and the patient's age. The corresponding colon cancer risk for female patients was (372.2541.0) 10{sup ?5}. The probability of bladder cancer development was more than 113.7 10{sup ?5} and 110.3 10{sup ?5} for males and females, respectively. The cancer risk range to other individual organs was reduced to (0.00368.5) 10{sup ?5}.Conclusions: The risk for cancer induction from radiation therapy for HO prophylaxis after total hip arthroplasty varies considerably by the treatment parameters, organ site in respect to treatment volume and patient's gender and age. The presented risk estimates may be useful in the follow-up studies of irradiated patients.

  16. SU-E-T-483: Treatment Planning Study of Volumetric Modulated Arc Therapy for Left-Sided Breast and Chestwall Cancers

    SciTech Connect (OSTI)

    Xu, H

    2014-06-01

    Purpose: To perform the comparison of dose distributions and dosevolume- histograms generated by VMAT and conventional field-in-field technique for left-sided breast and chestwall cancers; to determine whether VMAT offers more dosimetric benefits than does the field-in-field technique. Methods: All VMAT and field-in-filed plans were produced in Eclipse(version 10). Five plans were generated for left-sided breast and leftsided chestwall with supraclavicular nodes, respectively. A clockwise arc (CW) and a counter-clockwise arc (CCW) were used with start and stop angles being 310o10o and 140o10o. Collimator angles were 30o for CW and 330o for CCW. The conformity index (CI) is the ratio of V95% over PTV. The homogeneity index (HI) is the ratio of the difference between D2% and D98% over the prescribed dose. The V5, as an indicator of low dose bath to organs-at-risk, was used for ipsilateral lung, heart, contralateral lung, and contralateral breast. The V20, as an indicator of radiation pneumonitis, was used for ipsilateral lung. Results: Breast/chestwall VMAT delivers much higher low dose bath to ipsilateral lung, contralateral lung and contralateral breast/chestwall for both intact breast and chestwall with nodes. V5 for heart is increased in VMAT plans. V20 for ipsilateral lung is lower in VMAT plans. PTV coverage is similar for both techniques. For one particular chestwall patient with supraclavicular and internal mammary nodes, VMAT offers superior dose coverage of PTVs with slightly more low-dose-wash to heart, contralateral lung and contralateral breast. Conclusion: This study indicates that there is generally no benefit using VMAT for left-sided intact breast, due to large low-dose-bath (5Gy) to normal tissues with insignificant improvement in PTV coverage. Dosimetric benefits will be seen in VMAT plans for some chestwall patients with large size, and/or internal mammary nodes, etc. Whether a chestwall patient is treated with VMAT should be carefully analyzed on an individual basis.

  17. Genetics and molecular biology of breast cancer

    SciTech Connect (OSTI)

    King, M.C.; Lippman, M.

    1992-12-31

    This volume contains the abstracts of oral presentations and poster sessions presented at the Cold Springs Harbor Meeting on Cancer Cells, this meeting entitled Genetics and Molecular Biology of Breast Cancer.

  18. Novel targeted therapy for stomach cancer

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Novel targeted therapy for stomach cancer Novel targeted therapy for stomach cancer This finding has the potential to save thousand of lives a year by delivering a more effective,...

  19. Spectroscopic Imaging of Bladder Cancer

    SciTech Connect (OSTI)

    Demos, S G; Gandour-Edwards, R; Ramsamooj, R; deVere White, R

    2003-01-01

    The feasibility of developing bladder cancer detection methods using intrinsic tissue optical properties is the focus of this investigation. In vitro experiments have been performed using polarized elastic light scattering in combination with tissue autofluorescence in the NIR spectral region under laser excitation in the green and red spectral regions. The experimental results obtained from a set of tissue specimens from 25 patients reveal the presence of optical fingerprint characteristics suitable for cancer detection with high contrast and accuracy. These photonic methods are compatible with existing endoscopic imaging modalities which make them suitable for in-vivo application.

  20. Oblique-incidence sputtering of Ru intermediate layer for decoupling of intergranular exchange in perpendicular recording media

    SciTech Connect (OSTI)

    Saito, Shin; Inoue, Ken; Takahashi, Migaku

    2011-04-01

    During the Ru deposition process for granular type perpendicular magnetic recording media, both a reduction in the Ru intermediate layer thickness and lowering of sputtering gas pressure were successfully achieved by focusing on a self-shadowing effect. Oblique-incidence sputtering with a 60 deg. incident angle under an Ar gas pressure of 0.6 Pa yielded (1) columnar Ru grains with a growth direction of 30 deg. from the film normal, (2) c-plane sheet texture by epitaxial growth on the Pt underlayer, and (3) a flat envelope of the surface and a deep gap at grain boundaries. This change in the Ru structure significantly contributes to reducing exchange coupling among magnetic grains, especially in the initial growth region in an overlying granular medium.

  1. Grazing-incidence small-angle X-ray scattering: application to the study of quantum dot lattices

    SciTech Connect (OSTI)

    Buljan, Maja Radi?, Nikola; Bernstorff, Sigrid; Drai?, Goran; Bogdanovi?-Radovi?, Iva; Hol, Vclav

    2012-01-01

    The modelling of grazing-incidence small-angle X-ray scattering (GISAXS) from three-dimensional quantum dot lattices is described. The ordering of quantum dots in three-dimensional quantum dot lattices is investigated by grazing-incidence small-angle X-ray scattering (GISAXS). Theoretical models describing GISAXS intensity distributions for three general classes of lattices of quantum dots are proposed. The classes differ in the type of disorder of the positions of the quantum dots. The models enable full structure determination, including lattice type, lattice parameters, the type and degree of disorder in the quantum dot positions and the distributions of the quantum dot sizes. Applications of the developed models are demonstrated using experimentally measured data from several types of quantum dot lattices formed by a self-assembly process.

  2. SU-E-J-149: Establishing the Relationship Between Pre-Treatment Lung Ventilation, Dose, and Toxicity Outcome

    SciTech Connect (OSTI)

    Mistry, N; D'Souza, W; Sornsen de Koste, J; Senan, S

    2014-06-01

    Purpose: Recently, there has been an interest in incorporating functional information in treatment planning especially in thoracic tumors. The rationale is that healthy lung regions need to be spared from radiation if possible to help achieve better control on toxicity. However, it is still unclear whether high functioning regions need to be spared or have more capacity to deal with the excessive radiation as compared to the compromised regions of the lung. Our goal with this work is to establish the tools by which we can establish a relationship between pre-treatment lung function, dose, and radiographic outcomes of lung toxicity. Methods: Treatment planning was performed using a single phase of a 4DCT scan, and follow-up anatomical CT scans were performed every 3 months for most patients. In this study, we developed the pipeline of tools needed to analyze such a large dataset, while trying to establish a relationship between function, dose, and outcome. Pre-treatment lung function was evaluated using a recently published technique that evaluates Fractional Regional Ventilation (FRV). All images including the FRV map and the individual follow-up anatomical CT images were all spatially matched to the planning CT using a diffusion based Demons image registration algorithm. Change in HU value was used as a metric to capture the effects of lung toxicity. To validate the findings, a radiologist evaluated the follow-up anatomical CT images and scored lung toxicity. Results: Initial experience in 1 patient shows a relationship between the pre-treatment lung function, dose and toxicity outcome. The results are also correlated to the findings by the radiologist who was blinded to the analysis or dose. Conclusion: The pipeline we have established to study this enables future studies in large retrospective studies. However, the tools are dependent on the fidelity of 4DCT reconstruction for accurate evaluation of regional ventilation. Patent Pending for the technique presented in this work to evaluate FRV incorporating mass correction.

  3. Attenuation of acute nitrogen mustard-induced lung injury, inflammation and fibrogenesis by a nitric oxide synthase inhibitor

    SciTech Connect (OSTI)

    Malaviya, Rama; Venosa, Alessandro; Hall, LeRoy; Gow, Andrew J.; Sinko, Patrick J.; Laskin, Jeffrey D.; Laskin, Debra L.

    2012-12-15

    Nitrogen mustard (NM) is a toxic vesicant known to cause damage to the respiratory tract. Injury is associated with increased expression of inducible nitric oxide synthase (iNOS). In these studies we analyzed the effects of transient inhibition of iNOS using aminoguanidine (AG) on NM-induced pulmonary toxicity. Rats were treated intratracheally with 0.125 mg/kg NM or control. Bronchoalveolar lavage fluid (BAL) and lung tissue were collected 1 d28 d later and lung injury, oxidative stress and fibrosis assessed. NM exposure resulted in progressive histopathological changes in the lung including multifocal lesions, perivascular and peribronchial edema, inflammatory cell accumulation, alveolar fibrin deposition, bronchiolization of alveolar septal walls, and fibrosis. This was correlated with trichrome staining and expression of proliferating cell nuclear antigen (PCNA). Expression of heme oxygenase (HO)-1 and manganese superoxide dismutase (Mn-SOD) was also increased in the lung following NM exposure, along with levels of protein and inflammatory cells in BAL, consistent with oxidative stress and alveolar-epithelial injury. Both classically activated proinflammatory (iNOS{sup +} and cyclooxygenase-2{sup +}) and alternatively activated profibrotic (YM-1{sup +} and galectin-3{sup +}) macrophages appeared in the lung following NM administration; this was evident within 1 d, and persisted for 28 d. AG administration (50 mg/kg, 2 /day, 1 d3 d) abrogated NM-induced injury, oxidative stress and inflammation at 1 d and 3 d post exposure, with no effects at 7 d or 28 d. These findings indicate that nitric oxide generated via iNOS contributes to acute NM-induced lung toxicity, however, transient inhibition of iNOS is not sufficient to protect against pulmonary fibrosis. -- Highlights: ? Nitrogen mustard (NM) induces acute lung injury and fibrosis. ? Pulmonary toxicity is associated with increased expression of iNOS. ? Transient inhibition of iNOS attenuates acute lung injury induced by NM.

  4. Calculation of nuclear data for incident energies to 200 MeV with the FKK-GNASH code system

    SciTech Connect (OSTI)

    Chadwick, M.B.; Young, P.G.

    1993-02-01

    We describe how the FKK-GNASH code system has been extended to calculate nucleon-induced reactions up to 200 MeV, and used to predict (p,xn) and (p,xp) cross sections on {sup 208}Pb at incident energies of 25, 45, 80 and 160 MeV, for an intermediate energy code intercomparison. Details of the reaction mechanisms calculated by FKK-GNASH are given, and the calculational procedure is described.

  5. Upgrading RESRAD-RDD and Planning for Improvised Nuclear Device Incidents--The RESRAD-RDD&IND

    Broader source: Energy.gov [DOE]

    Upgrading RESRAD-RDD and Planning for Improvised Nuclear Device Incidents--The RESRAD-RDD&IND Abstract: The RESRAD-RDD code was developed through the interagency Operational Guidelines Task Group (OGT) to assist decision makers, emergency responders, and emergency preparedness planners for response to radiological dispersal device incidents (RDD). The RESRAD-RDD code was released as a companion software tool in 2009 to support the OGT Manual—Preliminary Report on Operational Guidelines Developed for Use in Emergency Preparedness and Response to a Radiological Dispersal Device Incident (DOE/HS-0001). The original RESRAD-RDD code was Microsoft Excel based software with the user interface written in Visual Basic. This version of RESRAD-RDD is being converted to a database driven software that runs on Windows 7 operating system in the .NET environment. The new RESRAD-RDD code is being tested to make sure it reproduces old code results. The new code runs faster than the old spreadsheets code by a factor of 10 or so, fewer clicks are required for the same calculations, operational guidelines can be easily located, and the reports can be written to PDFs instead of HTML. Additional radionuclides are also being added to the new RESRAD-RDD code. An Improvised Nuclear Device (IND) scenario is also being added to the code and about 44 - 60 radionuclides will be added to handle IND incident. A new OGT Task Group is in the process of updating the OGT Manual and providing guidance on the development of the IND scenario and methodology. The new code, RESRAD-RDD&IND is expected to be released in early 2015. Charley Yu*, Argonne National Laboratory ; Carlos Corredor, U.S. Department of Energy; Jing-Jy Cheng, Argonne National Laboratory; Sunita Kamboj, Argonne National Laboratory; David LePoire, Argonne National Laboratory; Paul Flood, Argonne National Laboratory

  6. AVTA: Battery Testing- Best Practices for Responding to Emergency Incidents in Plug-in Electric Vehicles (EV)

    Broader source: Energy.gov [DOE]

    The Vehicle Technologies Office's Advanced Vehicle Testing Activity carries out testing on a wide range of advanced vehicles and technologies on dynamometers, closed test tracks, and on-the-road. These results provide benchmark data that researchers can use to develop technology models and guide future research and development. The following report describes best practices for responding to emergency incidents involving plug-in electric vehicle batteries, based on the AVTA's testing of PEV batteries. This research was conducted by Idaho National Laboratory.

  7. New Mexico Governor Susana Martinez and U.S Energy Secretary Ernest Moniz Announce Settlement on Nuclear Waste Incidents

    Broader source: Energy.gov [DOE]

    WASHINGTON, D.C. —Today, New Mexico Governor Susana Martinez and Secretary of Energy Ernest Moniz released the terms of a $73 million settlement of the State’s claims against the U.S. Department of Energy and its contractors related to the February 2014 incidents at the Waste Isolation Pilot Plant in Carlsbad, New Mexico, including the associated activities at the Los Alamos National Laboratory.

  8. This National Response Framework (NRF) is a guide to how the Nation conducts all-hazards incident responseresponse

    National Nuclear Security Administration (NNSA)

    January 2008 National Response Fram ework Page i This National Response Framework (NRF) is a guide to how the Nation conducts all-hazards response. It is built upon scalable, flexible, and adaptable coordinating structures to align key roles and responsibilities across the Nation, linking all levels of government, nongovernmental organizations, and the private sector. It is intended to capture specific authorities and best practices for managing incidents that range from the serious but purely

  9. Pancreatic cancer: Pathogenesis, prevention and treatment

    SciTech Connect (OSTI)

    Sarkar, Fazlul H. Banerjee, Sanjeev; Li, Yiwei

    2007-11-01

    Pancreatic cancer is the fourth leading cause of cancer death in the United States with a very low survival rate of 5 years. To better design new preventive and/or therapeutic strategies for the fight against pancreatic cancer, the knowledge of the pathogenesis of pancreatic cancer at the molecular level is very important. It has been known that the development and the progression of pancreatic cancer are caused by the activation of oncogenes, the inactivation of tumor suppressor genes, and the deregulation of many signaling pathways among which the EGFR, Akt, and NF-{kappa}B pathways appear to be most relevant. Therefore, the strategies targeting EGFR, Akt, NF-{kappa}B, and their downstream signaling could be promising for the prevention and/or treatment of pancreatic cancer. In this brief review, we will summarize the current knowledge regarding the pathogenesis, prevention, and treatment of pancreatic cancer.

  10. Predictive and therapeutic markers in ovarian cancer

    DOE Patents [OSTI]

    Gray, Joe W.; Guan, Yinghui; Kuo, Wen-Lin; Fridlyand, Jane; Mills, Gordon B.

    2013-03-26

    Cancer markers may be developed to detect diseases characterized by increased expression of apoptosis-suppressing genes, such as aggressive cancers. Genes in the human chromosomal regions, 8q24, 11q13, 20q11-q13, were found to be amplified indicating in vivo drug resistance in diseases such as ovarian cancer. Diagnosis and assessment of amplification levels certain genes shown to be amplified, including PVT1, can be useful in prediction of poor outcome of patient's response and drug resistance in ovarian cancer patients with low survival rates. Certain genes were found to be high priority therapeutic targets by the identification of recurrent aberrations involving genome sequence, copy number and/or gene expression are associated with reduced survival duration in certain diseases and cancers, specifically ovarian cancer. Therapeutics to inhibit amplification and inhibitors of one of these genes, PVT1, target drug resistance in ovarian cancer patients with low survival rates is described.

  11. TRASH TO TREASURE: CONVERTING COLD WAR LEGACY WASTE INTO WEAPONS AGAINST CANCER

    SciTech Connect (OSTI)

    Nicholas, R.G.; Lacy, N.H.; Butz, T.R.; Brandon, N.E.

    2004-10-06

    As part of its commitment to clean up Cold War legacy sites, the U.S. Department of Energy (DOE) has initiated an exciting and unique project to dispose of its inventory of uranium-233 (233U) stored at Oak Ridge National Laboratory (ORNL), and extract isotopes that show great promise in the treatment of deadly cancers. In addition to increasing the supply of potentially useful medical isotopes, the project will rid DOE of a nuclear concern and cut surveillance and security costs. For more than 30 years, DOE's ORNL has stored over 1,200 containers of fissile 233U, originally produced for several defense-related projects, including a pilot study that looked at using 233U as a commercial reactor fuel. This uranium, designated as special nuclear material, requires expensive security, safety, and environmental controls. It has been stored at an ORNL facility, Building 3019A, that dates back to the Manhattan Project. Down-blending the material to a safer form, rather than continuing to store it, will eliminate a $15 million a year financial liability for the DOE and increase the supply of medical isotopes by 5,700 percent. During the down-blending process, thorium-229 (229Th) will be extracted. The thorium will then be used to extract actinium-225 (225Ac), which will ultimately supply its progeny, bismuth-213 (213Bi), for on-going cancer research. The research includes Phase II clinical trials for the treatment of acute myelogenous leukemia at Sloan-Kettering Memorial Cancer Center in New York, as well as other serious cancers of the lungs, pancreas, and kidneys using a technique known as alpha-particle radioimmunotherapy. Alpha-particle radioimmunotherapy is based on the emission of alpha particles by radionuclides. 213Bi is attached to a monoclonal antibody that targets specific cells. The bismuth then delivers a high-powered but short-range radiation dose, effectively killing the cancerous cells but sparing the surrounding tissue. Production of the actinium and bismuth would be a private venture at no cost to the government. Isotek Systems, LLC, was commissioned by the DOE to execute the project, known as the 233U Disposition, Medical Isotope Production, and Building 3019 Complex Shutdown Project. Isotek is a partnership between Duratek Federal Services, Burns and Roe Enterprises, and Nuclear Fuel Services. By pooling their pioneering experiences in nuclear engineering and design, nuclear recycling, and waste management, the partnership has developed a novel process to meet this clean-up milestone. The project is not only important for its cancer treatment potential, but also for setting the stage for reducing global threats through the down-blending of materials.

  12. Effects of effluents of coal combustion and gasification upon lung structure and function. Annual report

    SciTech Connect (OSTI)

    Hinton, D.E.

    1980-01-01

    The overall objective of the proposed research is to correlate both structural and functional alterations in cells and tissues of the lung brought about by exposure to fluidized bed combustion and fixed bed gasification effluents and reagent grade oxides of metals known to be associated with coal combustion gasification. Projected milestones are described. Progress during the first year in setting up aerosol exposure facilities, intratracheal instillations, pulmonary mechanics, and morphometric examinations is reported. (DMC)

  13. Classical and alternative macrophage activation in the lung following ozone-induced oxidative stress

    SciTech Connect (OSTI)

    Sunil, Vasanthi R.; Patel-Vayas, Kinal; Shen, Jianliang; Laskin, Jeffrey D.; Laskin, Debra L.

    2012-09-01

    Ozone is a pulmonary irritant known to cause oxidative stress, inflammation and tissue injury. Evidence suggests that macrophages play a role in the pathogenic response; however, their contribution depends on the mediators they encounter in the lung which dictate their function. In these studies we analyzed the effects of ozone-induced oxidative stress on the phenotype of alveolar macrophages (AM). Exposure of rats to ozone (2 ppm, 3 h) resulted in increased expression of 8-hydroxy-2?-deoxyguanosine (8-OHdG), as well as heme oxygenase-1 (HO-1) in AM. Whereas 8-OHdG was maximum at 24 h, expression of HO-1 was biphasic increasing after 3 h and 4872 h. Cleaved caspase-9 and beclin-1, markers of apoptosis and autophagy, were also induced in AM 24 h post-ozone. This was associated with increased bronchoalveolar lavage protein and cells, as well as matrix metalloproteinase (MMP)-2 and MMP-9, demonstrating alveolar epithelial injury. Ozone intoxication resulted in biphasic activation of the transcription factor, NF?B. This correlated with expression of monocyte chemotactic protein?1, inducible nitric oxide synthase and cyclooxygenase?2, markers of proinflammatory macrophages. Increases in arginase-1, Ym1 and galectin-3 positive anti-inflammatory/wound repair macrophages were also observed in the lung after ozone inhalation, beginning at 24 h (arginase-1, Ym1), and persisting for 72 h (galectin-3). This was associated with increased expression of pro-surfactant protein-C, a marker of Type II cell proliferation and activation, important steps in wound repair. These data suggest that both proinflammatory/cytotoxic and anti-inflammatory/wound repair macrophages are activated early in the response to ozone-induced oxidative stress and tissue injury. -- Highlights: ? Lung macrophages are highly sensitive to ozone induced oxidative stress. ? Ozone induces autophagy and apoptosis in lung macrophages. ? Proinflammatory and wound repair macrophages are activated early after ozone. ? Oxidative stress may contribute to regulating macrophage phenotype and function.

  14. In Vivo Evaluation of Lung Microwave Ablation in a Porcine Tumor Mimic Model

    SciTech Connect (OSTI)

    Planche, Olivier; Teriitehau, Christophe; Boudabous, Sana; Robinson, Joey Marie; Rao, Pramod; Deschamps, Frederic; Farouil, Geoffroy; Baere, Thierry de

    2013-02-15

    To evaluate the microwave ablation of created tumor mimics in the lung of a large animal model (pigs), with examination of the ablative synergy of multiple antennas. Fifty-six tumor-mimic models of various sizes were created in 15 pigs by using barium-enriched minced collected thigh muscle injected into the lung of the same animal. Tumors were ablated under fluoroscopic guidance by single-antenna and multiple-antenna microwaves. Thirty-five tumor models were treated in 11 pigs with a single antenna at 75 W for 15 min, with 15 measuring 20 mm in diameter, 10 measuring 30 mm, and 10 measuring 40 mm. Mean circularity of the single-antenna ablation zones measured 0.64 {+-} 0.12, with a diameter of 35.7 {+-} 8.7 mm along the axis of the antenna and 32.7 {+-} 12.8 mm perpendicular to the feeding point. Multiple-antenna delivery of 75 W for 15 min caused intraprocedural death of 2 animals; modified protocol to 60 W for 10 min resulted in an ablation zone with a diameter of 43.0 {+-} 7.7 along the axis of the antenna and 54.8 {+-} 8.5 mm perpendicular to the feeding point; circularity was 0.70 {+-} 0.10. A single microwave antenna can create ablation zones large enough to cover lung tumor mimic models of {<=}4 cm with no heat sink effect from vessels of {<=}6 mm. Synergic use of 3 antennas allows ablation of larger volumes than single-antenna or radiofrequency ablation, but great caution must be taken when 3 antennas are used simultaneously in the lung in clinical practice.

  15. A comparative analysis of 3D conformal deep inspiratorybreath hold and free-breathing intensity-modulated radiation therapy for left-sided breast cancer

    SciTech Connect (OSTI)

    Reardon, Kelli A.; Read, Paul W.; Morris, Monica M.; Reardon, Michael A.; Geesey, Constance; Wijesooriya, Krishni

    2013-07-01

    Patients undergoing radiation for left-sided breast cancer have increased rates of coronary artery disease. Free-breathing intensity-modulated radiation therapy (FB-IMRT) and 3-dimensional conformal deep inspiratorybreath hold (3D-DIBH) reduce cardiac irradiation. The purpose of this study is to compare the dose to organs at risk in FB-IMRT vs 3D-DIBH for patients with left-sided breast cancer. Ten patients with left-sided breast cancer had 2 computed tomography scans: free breathing and voluntary DIBH. Optimization of the IMRT plan was performed on the free-breathing scan using 6 noncoplanar tangential beams. The 3D-DIBH plan was optimized on the DIBH scan and used standard tangents. Mean volumes of the heart, the left anterior descending coronary artery (LAD), the total lung, and the right breast receiving 5% to 95% (5% increments) of the prescription dose were calculated. Mean volumes of the heart and the LAD were lower (p<0.05) in 3D-DIBH for volumes receiving 5% to 80% of the prescription dose for the heart and 5% for the LAD. Mean dose to the LAD and heart were lower in 3D-DIBH (p?0.01). Mean volumes of the total lung were lower in FB-IMRT for dose levels 20% to 75% (p<0.05), but mean dose was not different. Mean volumes of the right breast were not different for any dose; however, mean dose was lower for 3D-DIBH (p = 0.04). 3D-DIBH is an alternative approach to FB-IMRT that provides a clinically equivalent treatment for patients with left-sided breast cancer while sparing organs at risk with increased ease of implementation.

  16. Causes of Mortality After Dose-Escalated Radiation Therapy and Androgen Deprivation for High-Risk Prostate Cancer

    SciTech Connect (OSTI)

    Tendulkar, Rahul D.; Hunter, Grant K.; Reddy, Chandana A.; Stephans, Kevin L.; Ciezki, Jay P.; Abdel-Wahab, May; Stephenson, Andrew J.; Klein, Eric A.; Mahadevan, Arul; Kupelian, Patrick A.

    2013-09-01

    Purpose: Men with high-risk prostate cancer have other competing causes of mortality; however, current risk stratification schema do not account for comorbidities. We aim to identify the causes of death and factors predictive for mortality in this population. Methods and Materials: A total of 660 patients with high-risk prostate cancer were treated with definitive high-dose external beam radiation therapy (?74 Gy) and androgen deprivation (AD) between 1996 and 2009 at a single institution. Cox proportional hazards regression analysis was conducted to determine factors predictive of survival. Results: The median radiation dose was 78 Gy, median duration of AD was 6 months, and median follow-up was 74 months. The 10-year overall survival (OS) was 60.6%. Prostate cancer was the leading single cause of death, with 10-year mortality of 14.1% (95% CI 10.7-17.6), compared with other cancers (8.4%, 95% CI 5.7-11.1), cardiovascular disease (7.3%, 95% CI 4.7-9.9), and all other causes (10.4%, 95% CI 7.2-13.6). On multivariate analysis, older age (HR 1.55, P=.002) and Charlson comorbidity index score (CS) ?1 (HR 2.20, P<.0001) were significant factors predictive of OS, whereas Gleason score, T stage, prostate-specific antigen, duration of AD, radiation dose, smoking history, and body mass index were not. Men younger than 70 years of age with CS = 0 were more likely to die of prostate cancer than any other cause, whereas older men or those with CS ?1 more commonly suffered non-prostate cancer death. The cumulative incidences of prostate cancer-specific mortality were similar regardless of age or comorbidities (P=.60). Conclusions: Men with high-risk prostate cancer are more likely to die of causes other than prostate cancer, except for the subgroup of men younger than 70 years of age without comorbidities. Only older age and presence of comorbidities significantly predicted for OS, whereas prostate cancer- and treatment-related factors did not.

  17. The respiratory health and lung function of Anglo-American children in a smelter town

    SciTech Connect (OSTI)

    Dodge, R.

    1983-02-01

    Cooper smelters are large, usually isolated, sources of air pollution. Arizona has several such plants on the periphery of small communities. The smelters emit predominantly sulfur oxides and particulates, and the residents of these communities intermittently are exposed to high concentrations (24-h sulfur dioxide (SO2) . 250 to 500 micrograms/m3) of smelter smoke but little other pollution. This study compared the respiratory health of Anglo-American school children who lived in one smelter community with children living in another small community in Arizona that was free of smelter air pollution. The prevalence of cough, as determined by questionnaire, was 25.6% in the smelter town children and 14.3% in the nonsmelter town children (p less than 0.05). Pulmonary function at the study onset was equal in the two groups. Over the course of the 4 yr of study, lung function growth (measured as actual forced expiratory volume in one second (FEV1) after 4 yr of study minus predicted FEV1) was also equal in the smelter town and nonsmelter town children. These results suggest that children in smelter communities have slightly more cough when compared with children living in other communities, but no differences in initial lung function or lung function at yearly testing over the period of the study.

  18. High-Resolution Phase-Contrast Imaging of Submicron Particles in Unstained Lung Tissue

    SciTech Connect (OSTI)

    Schittny, J. C.; Barre, S. F.; Haberthuer, D.; Mokso, R.; Tsuda, A.; Stampanoni, M.

    2011-09-09

    To access the risks and chances of deposition of submicron particles in the gas-exchange area of the lung, a precise three-dimensional (3D)-localization of the sites of deposition is essential--especially because local peaks of deposition are expected in the acinar tree and in individual alveoli. In this study we developed the workflow for such an investigation. We administered 200-nm gold particles to young adult rats by intratracheal instillation. After fixation and paraffin embedding, their lungs were imaged unstained using synchrotron radiation x-ray tomographic microscopy (SRXTM) at the beamline TOMCAT (Swiss Light Source, Villigen, Switzerland) at sample detector distances of 2.5 mm (absorption contrast) and of 52.5 mm (phase contrast). A segmentation based on a global threshold of grey levels was successfully done on absorption-contrast images for the gold and on the phase-contrast images for the tissue. The smallest spots containing gold possessed a size of 1-2 voxels of 370-nm side length. We conclude that a combination of phase and absorption contrast SRXTM imaging is necessary to obtain the correct segmentation of both tissue and gold particles. This method will be used for the 3D localization of deposited particles in the gas-exchange area of the lung.

  19. TU-F-17A-08: The Relative Accuracy of 4D Dose Accumulation for Lung Radiotherapy Using Rigid Dose Projection Versus Dose Recalculation On Every Breathing Phase

    SciTech Connect (OSTI)

    Lamb, J; Lee, C; Tee, S; Lee, P; Iwamoto, K; Low, D; Valdes, G; Robinson, C

    2014-06-15

    Purpose: To investigate the accuracy of 4D dose accumulation using projection of dose calculated on the end-exhalation, mid-ventilation, or average intensity breathing phase CT scan, versus dose accumulation performed using full Monte Carlo dose recalculation on every breathing phase. Methods: Radiotherapy plans were analyzed for 10 patients with stage I-II lung cancer planned using 4D-CT. SBRT plans were optimized using the dose calculated by a commercially-available Monte Carlo algorithm on the end-exhalation 4D-CT phase. 4D dose accumulations using deformable registration were performed with a commercially available tool that projected the planned dose onto every breathing phase without recalculation, as well as with a Monte Carlo recalculation of the dose on all breathing phases. The 3D planned dose (3D-EX), the 3D dose calculated on the average intensity image (3D-AVE), and the 4D accumulations of the dose calculated on the end-exhalation phase CT (4D-PR-EX), the mid-ventilation phase CT (4D-PR-MID), and the average intensity image (4D-PR-AVE), respectively, were compared against the accumulation of the Monte Carlo dose recalculated on every phase. Plan evaluation metrics relating to target volumes and critical structures relevant for lung SBRT were analyzed. Results: Plan evaluation metrics tabulated using 4D-PR-EX, 4D-PR-MID, and 4D-PR-AVE differed from those tabulated using Monte Carlo recalculation on every phase by an average of 0.140.70 Gy, - 0.110.51 Gy, and 0.000.62 Gy, respectively. Deviations of between 8 and 13 Gy were observed between the 4D-MC calculations and both 3D methods for the proximal bronchial trees of 3 patients. Conclusions: 4D dose accumulation using projection without re-calculation may be sufficiently accurate compared to 4D dose accumulated from Monte Carlo recalculation on every phase, depending on institutional protocols. Use of 4D dose accumulation should be considered when evaluating normal tissue complication probabilities as well as in clinical situations where target volumes are directly inferior to mobile critical structures.

  20. Strain-dependent Damage in Mouse Lung After Carbon Ion Irradiation

    SciTech Connect (OSTI)

    Moritake, Takashi; Proton Medical Research Center, University of Tsukuba, Tsukuba ; Fujita, Hidetoshi; Yanagisawa, Mitsuru; Nakawatari, Miyako; Imadome, Kaori; Nakamura, Etsuko; Iwakawa, Mayumi; Imai, Takashi

    2012-09-01

    Purpose: To examine whether inherent factors produce differences in lung morbidity in response to carbon ion (C-ion) irradiation, and to identify the molecules that have a key role in strain-dependent adverse effects in the lung. Methods and Materials: Three strains of female mice (C3H/He Slc, C57BL/6J Jms Slc, and A/J Jms Slc) were locally irradiated in the thorax with either C-ion beams (290 MeV/n, in 6 cm spread-out Bragg peak) or with {sup 137}Cs {gamma}-rays as a reference beam. We performed survival assays and histologic examination of the lung with hematoxylin-eosin and Masson's trichrome staining. In addition, we performed immunohistochemical staining for hyaluronic acid (HA), CD44, and Mac3 and assayed for gene expression. Results: The survival data in mice showed a between-strain variance after C-ion irradiation with 10 Gy. The median survival time of C3H/He was significantly shortened after C-ion irradiation at the higher dose of 12.5 Gy. Histologic examination revealed early-phase hemorrhagic pneumonitis in C3H/He and late-phase focal fibrotic lesions in C57BL/6J after C-ion irradiation with 10 Gy. Pleural effusion was apparent in C57BL/6J and A/J mice, 168 days after C-ion irradiation with 10 Gy. Microarray analysis of irradiated lung tissue in the three mouse strains identified differential expression changes in growth differentiation factor 15 (Gdf15), which regulates macrophage function, and hyaluronan synthase 1 (Has1), which plays a role in HA metabolism. Immunohistochemistry showed that the number of CD44-positive cells, a surrogate marker for HA accumulation, and Mac3-positive cells, a marker for macrophage infiltration in irradiated lung, varied significantly among the three mouse strains during the early phase. Conclusions: This study demonstrated a strain-dependent differential response in mice to C-ion thoracic irradiation. Our findings identified candidate molecules that could be implicated in the between-strain variance to early hemorrhagic pneumonitis after C-ion irradiation.

  1. Field-in-field plan does not improve the dosimetric outcome compared with the wedged beams plan for breast cancer radiotherapy

    SciTech Connect (OSTI)

    Sun, Li-Min; Meng, Fan-Yun; Yang, Tsung-Han; Tsao, Min-Jen

    2014-04-01

    To evaluate and compare the dosimetry of field-in-field (FIF) and wedged beams (WB) techniques for patients with breast cancer receiving adjuvant radiotherapy after conservative surgery. A total of 89 patients with breast cancer participated in this study. Each patient received a computed tomographybased treatment plan with opposed tangential fields. Two planning techniques (FIF and WB) were generated for each patient by using the Pinnacle treatment-planning system. Three indices, the homogeneity index (HI), conformity index (CI), and uniformity index (UI), as well as maximum dose (D{sub max}), median dose (D{sub 50}), number of portals, monitor unit (MU), and lung volume at 20 Gy (lung{sub 20}) were used for comparison. The mean values tested using a t-test indicated that the WB technique had a significantly lower HI (p < 0.0001), a significantly higher CI (p < 0.0001), and a significantly higher D{sub 50} (p = 0.0002) than did the FIF technique. The FIF technique had a significantly higher D{sub max} compared with the WB technique, but lung{sub 20} did not exhibit a significant difference. By contrast, the FIF technique had a significantly higher UI and a significantly lower MU compared with the WB technique, but a significantly higher number of portals were found in the FIF technique. The FIF technique did not demonstrate superior dosimetric results. The WB technique had a significantly lower HI, higher CI, lower D{sub max}, and lower number of portals; but the FIF technique had a significantly higher UI and lower MU.

  2. Genome Science and Personalized Cancer Treatment

    SciTech Connect (OSTI)

    Gray, Joe

    2009-08-07

    August 4, 2009 Berkeley Lab lecture: Results from the Human Genome Project are enabling scientists to understand how individual cancers form and progress. This information, when combined with newly developed drugs, can optimize the treatment of individual cancers. Joe Gray, director of Berkeley Labs Life Sciences Division and Associate Laboratory Director for Life and Environmental Sciences, will focus on this approach, its promise, and its current roadblocks particularly with regard to breast cancer.

  3. Genome Science and Personalized Cancer Treatment

    SciTech Connect (OSTI)

    Gray, Joe

    2009-08-04

    Summer Lecture Series 2009: Results from the Human Genome Project are enabling scientists to understand how individual cancers form and progress. This information, when combined with newly developed drugs, can optimize the treatment of individual cancers. Joe Gray, director of Berkeley Labs Life Sciences Division and Associate Laboratory Director for Life and Environmental Sciences, will focus on this approach, its promise, and its current roadblocks particularly with regard to breast cancer.

  4. Isotopes for cancer and cardiac care

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Isotopes for cancer Isotopes for cancer and cardiac care Eva Birnbaum is interviewed on KSFR radio on the Lab's Isotope Program February 4, 2016 hot cell facility A worker uses remote manipulator arms to handle a highly radioactive target inside the Lab's radiochemistry hot cell facility. Isotopes from Los Alamos are used for the diagnosis of cardiac disease, for the calibration of PET scanners which in turn diagnose cancer, neurological disease, inflammatory diseases, trauma, and other

  5. Genome Science and Personalized Cancer Treatment

    ScienceCinema (OSTI)

    Gray, Joe

    2010-01-08

    August 4, 2009 Berkeley Lab lecture: Results from the Human Genome Project are enabling scientists to understand how individual cancers form and progress. This information, when combined with newly developed drugs, can optimize the treatment of individual cancers. Joe Gray, director of Berkeley Labs Life Sciences Division and Associate Laboratory Director for Life and Environmental Sciences, will focus on this approach, its promise, and its current roadblocks ? particularly with regard to breast cancer.

  6. Responding to Terrorist Incidents in Your Community: Flammable-Liquid Fire Fighting Techniques for Municipal and Rural Firefighters

    SciTech Connect (OSTI)

    Denise Baclawski

    2010-03-08

    The University of Nevada, Reno Fire Science Academy (FSA) applied for grant funding to develop and deliver programs for municipal, rural, and volunteer firefighters. The FSA specializes in preparing responders for a variety of emergency events, including flammable liquid fires resulting from accidents, intentional acts, or natural disasters. Live fire training on full scale burnable props is the hallmark of FSA training, allowing responders to practice critical skills in a realistic, yet safe environment. Unfortunately, flammable liquid live fire training is often not accessible to municipal, rural, or volunteer firefighters due to limited department training budgets, even though most department personnel will be exposed to flammable liquid fire incidents during the course of their careers. In response to this training need, the FSA developed a course during the first year of the grant (Year One), Responding to Terrorist Incidents in Your Community: Flammable-Liquid Fire Fighting Techniques for Municipal and Rural Firefighters. During the three years of the grant, a total of 2,029 emergency responders received this training. In Year Three, two new courses, a train-the-trainer for Responding to Terrorist Incidents in Your Community and Management of Large-Scale Disasters for Public Officials were developed and pilot tested during the Real-World Disaster Management Conference held at the FSA in June of 2007. Two research projects were conducted during Years Two and Three. The first, conducted over a two year period, evaluated student surveys regarding the value of the flammable liquids training received. The second was a needs assessment conducted for rural Nevada. Both projects provided important feedback and a basis for curricula development and improvements.

  7. SQUID Instrumentation for Early Cancer Diagnostics: Combining...

    Office of Scientific and Technical Information (OSTI)

    Conference: SQUID Instrumentation for Early Cancer Diagnostics: Combining SQUID-Based Ultra-Low Field MRI and Superparamagnetic Relaxometry Citation Details In-Document Search...

  8. Breast Density and Cancer | GE Global Research

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Home > Innovation > Breast Cancer Awareness Series: Understanding Breast Density Click to email this to a friend (Opens in new window) Share on Facebook (Opens in new window) Click...

  9. HIV/Cancer DB Match Document

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    COLLECTION AND VERIFICATION OF DATA FOR MATCHED RECORDS FROM US CANCER AND HIVAIDS REGISTRIES Janice Watkins, Oak Ridge Associated Universities, T. Borges, Robert Stafford, Oak...

  10. Endoscopic Radiation Revolutionizes Cancer Treatment - Energy...

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Endoscopic Radiation Revolutionizes Cancer Treatment Argonne National Laboratory Contact ANL About This Technology

    Conventional X-ray radiation and electron beam therapy: a...

  11. Wide-angle point-to-point x-ray imaging with almost arbitrarily large angles of incidence

    SciTech Connect (OSTI)

    Bitter, M.; Hill, K. W.; Scott, S.; Feder, R.; Ko, Jinseok; Ince-Cushman, A.; Rice, J. E.

    2008-10-15

    The paper describes a new scheme for wide-angle point-to-point x-ray imaging with almost arbitrarily large angles of incidence by a matched pair of spherically bent crystals to eliminate the astigmatism, which is a well-known imaging error of spherical mirrors. In addition to x rays, the scheme should be applicable to a very broad spectrum of the electromagnetic radiation, including microwaves, infrared and visible light, as well as UV and extreme UV radiation, if the crystals are replaced with appropriate spherical reflectors. The scheme may also be applicable to the imaging with ultrasound.

  12. Best Practices for Emergency Response to Incidents Involving Electric Vehicles Battery Hazards: A Report on Full-Scale Testing Results

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    Best Practices for Emergency Response to Incidents Involving Electric Vehicles Battery Hazards: A Report on Full-Scale Testing Results Final Report Prepared by: R. Thomas Long Jr., P.E., CFEI Andrew F. Blum, P.E., CFEI Thomas J. Bress, Ph.D., P.E., CRE Benjamin R.T. Cotts, Ph.D. Exponent, Inc. 17000 Science Drive, Suite 200 Bowie, MD 20715 © June 2013 Fire Protection Research Foundation THE FIRE PROTECTION RESEARCH FOUNDATION ONE BATTERYMARCH PARK QUINCY, MASSACHUSETTS, U.S.A. 02169-7471

  13. Ancient Proteins Help Unravel a Modern Cancer Drug's Mechanism

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Ancient Proteins Help Unravel a Modern Cancer Drug's Mechanism Ancient Proteins Help Unravel a Modern Cancer Drug's Mechanism Print Tuesday, 23 June 2015 13:00 The cancer drug...

  14. Dynamic MRI of Grid-Tagged Hyperpolarized Helium-3 for the Assessment of Lung Motion During Breathing

    SciTech Connect (OSTI)

    Cai Jing; Sheng Ke; Benedict, Stanley H.; Read, Paul W.; Larner, James M.; Mugler, John P.; Lange, Eduard E. de; Cates, Gordon D.; Miller, G. Wilson

    2009-09-01

    Purpose: To develop a dynamic magnetic resonance imaging (MRI) tagging technique using hyperpolarized helium-3 (HP He-3) to track lung motion. Methods and Materials: An accelerated non-Cartesian k-space trajectory was used to gain acquisition speed, at the cost of introducing image artifacts, providing a viable strategy for obtaining whole-lung coverage with adequate temporal resolution. Multiple-slice two-dimensional dynamic images of the lung were obtained in three healthy subjects after inhaling He-3 gas polarized to 35%-40%. Displacement, strain, and ventilation maps were computed from the observed motion of the grid peaks. Results: Both temporal and spatial variations of pulmonary mechanics were observed in normal subjects, including shear motion between different lobes of the same lung. Conclusion: These initial results suggest that dynamic imaging of grid-tagged hyperpolarized magnetization may potentially be a powerful tool for observing and quantifying pulmonary biomechanics on a regional basis and for assessing, validating, and improving lung deformable image registration algorithms.

  15. Diet-Induced Obesity Reprograms the Inflammatory Response of the Murine Lung to Inhaled Endotoxin

    SciTech Connect (OSTI)

    Tilton, Susan C.; Waters, Katrina M.; Karin, Norman J.; Webb-Robertson, Bobbie-Jo M.; Zangar, Richard C.; Lee, Monika K.; Bigelow, Diana J.; Pounds, Joel G.; Corley, Richard A.

    2013-03-01

    The co-occurrence of environmental factors is common in complex human diseases and, as such, understanding the molecular responses involved is essential to determine risk and susceptibility to disease. We have investigated the key biological pathways that define susceptibility for pulmonary infection during obesity in diet-induced obese (DIO) and regular weight (RW) C57BL/6 mice exposed to inhaled lipopolysaccharide (LPS). LPS induced a strong inflammatory response in all mice as indicated by elevated cell counts of macrophages and neutrophils and levels of proinflammatory cytokines (MDC, MIP-1?, IL-12, RANTES) in the bronchoalveolar lavage fluid. Additionally, DIO mice exhibited 50% greater macrophage cell counts, but decreased levels of the cytokines, IL-6, TARC, TNF-?, and VEGF relative to RW mice. Microarray analysis of lung tissue showed over half of the LPS-induced expression in DIO mice consisted of genes unique for obese mice, suggesting that obesity reprograms how the lung responds to subsequent insult. In particular, we found that obese animals exposed to LPS have gene signatures showing increased inflammatory and oxidative stress response and decreased antioxidant capacity compared with RW. Because signaling pathways for these responses can be common to various sources of environmentally induced lung damage, we further identified biomarkers that are indicative of specific toxicant exposure by comparing gene signatures after LPS exposure to those from a parallel study with cigarette smoke. These data show obesity may increase sensitivity to further insult and that co-occurrence of environmental stressors result in complex biosignatures that are not predicted from analysis of individual exposures.

  16. Ancient Proteins Help Unravel a Modern Cancer Drug's Mechanism

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Print The cancer drug Gleevec is extremely specific, binding and inhibiting only the cancer-causing tyrosine protein kinase Blc-Abl, while not targeting homologous protein...

  17. Isotope production facility produces cancer-fighting actinium

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Cancer therapy gets a boost from new isotope Isotope production facility produces cancer-fighting actinium A new medical isotope project shows promise for rapidly producing major...

  18. Endoscopic Electron-Beam Cancer Therapy | Argonne National Laboratory

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Endoscopic Electron-Beam Cancer Therapy Technology available for licensing: A successful and cost-effective means of treating cancer in previously inoperable or radiation-sensitive...

  19. Designer Proteins Target Epstein-Barr-Virus-Associated Cancer

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Designer Proteins Target Epstein-Barr-Virus-Associated Cancer Designer Proteins Target Epstein-Barr-Virus-Associated Cancer Print Wednesday, 03 December 2014 00:00 Immortality is...

  20. Los Alamos researcher pens prizewinning essay on cancer

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Researcher pens prizewinning essay on cancer Los Alamos researcher pens prizewinning essay on cancer Ludmil Alexandrov made strong points this week in the journal Science winning a...

  1. Cancer-fighting treatment gets boost from Isotope Production...

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Cancer-fighting treatment gets boost from Isotope Production Facility Cancer-fighting treatment gets boost from Isotope Production Facility New capability expands existing program,...

  2. Harnessing Light in the Fight against Cancer | Argonne National...

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Harnessing Light in the Fight against Cancer A new semiconductor bioluminescent nanoparticle can be injected, then activated via the excessive ATP molecules emitted by cancer cells...

  3. Locally Advanced Prostate Cancer: Three-Dimensional Magnetic...

    Office of Scientific and Technical Information (OSTI)

    Cancer: Three-Dimensional Magnetic Resonance Spectroscopy to Monitor Prostate Response to Therapy Citation Details In-Document Search Title: Locally Advanced Prostate Cancer: ...

  4. Magnetic relaxometry as applied to sensitive cancer detection...

    Office of Scientific and Technical Information (OSTI)

    relaxometry as applied to sensitive cancer detection and localization Title: Magnetic relaxometry as applied to sensitive cancer detection and localization Here we describe ...

  5. DOE Laboratories Help Develop Promising New Cancer Fighting Drug...

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    Laboratories Help Develop Promising New Cancer Fighting Drug, Vemurafenib DOE Laboratories Help Develop Promising New Cancer Fighting Drug, Vemurafenib August 18, 2011 - 1:03pm ...

  6. DOE Research Contributions to Radiation and Cancer Therapy

    Office of Scientific and Technical Information (OSTI)

    DOE Research Contributions to Radiation and Cancer Therapy Resources with Additional ... made many contributions to radiation and cancer therapy, including PEREGRINE and Boron ...

  7. Preoperative chemoradiation of locally advanced T3 rectal cancer...

    Office of Scientific and Technical Information (OSTI)

    T3 rectal cancer combined with an endorectal boost Citation Details In-Document Search Title: Preoperative chemoradiation of locally advanced T3 rectal cancer combined with ...

  8. Cornell dots research collaboration leads to $10M cancer center...

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    at MSKCC in New York City - will focus on melanoma (skin) and malignant brain cancers. ... Assessment of particles in brain tumors for cancer therapy. C dots successfully have ...

  9. Lung autophagic response following exposure of mice to whole body irradiation, with and without amifostine

    SciTech Connect (OSTI)

    Zois, Christos E.; Giatromanolaki, Alexandra; Kainulainen, Heikki; Botaitis, Sotirios; Torvinen, Sira; Simopoulos, Constantinos; Kortsaris, Alexandros; Sivridis, Efthimios; Koukourakis, Michael I.

    2011-01-07

    Research highlights: {yields} We investigated the effect 6 Gy of WBI on the autophagic machinery of normal mouse lung. {yields} Irradiation induces dysfunction of the autophagic machinery in normal lung, characterized by decreased transcription of the LC3A/Beclin-1 mRNA and accumulation of the LC3A, and p62 proteins. {yields} The membrane bound LC3A-II protein levels increased in the cytosolic fraction (not in the pellet), contrasting the patterns noted after starvation-induced autophagy. {yields} Administration of amifostine, reversed all the LC3A and p62 findings, suggesting protection of the normal autophagic function. -- Abstract: Purpose: The effect of ionizing irradiation on the autophagic response of normal tissues is largely unexplored. Abnormal autophagic function may interfere the protein quality control leading to cell degeneration and dysfunction. This study investigates its effect on the autophagic machinery of normal mouse lung. Methods and materials: Mice were exposed to 6 Gy of whole body {gamma}-radiation and sacrificed at various time points. The expression of MAP1LC3A/LC3A/Atg8, beclin-1, p62/sequestosome-1 and of the Bnip3 proteins was analyzed. Results: Following irradiation, the LC3A-I and LC3A-II protein levels increased significantly at 72 h and 7 days. Strikingly, LC3A-II protein was increased (5.6-fold at 7 days; p < 0.001) only in the cytosolic fraction, but remained unchanged in the membrane fraction. The p62 protein, was significantly increased in both supernatant and pellet fraction (p < 0.001), suggesting an autophagosome turnover deregulation. These findings contrast the patterns of starvation-induced autophagy up-regulation. Beclin-1 levels remained unchanged. The Bnip3 protein was significantly increased at 8 h, but it sharply decreased at 72 h (p < 0.05). Administration of amifostine (200 mg/kg), 30 min before irradiation, reversed all the LC3A and p62 findings on blots, suggesting restoration of the normal autophagic function. The LC3A and Beclin1 mRNA levels significantly declined following irradiation (p < 0.01), whereas Bnip3 levels increased. Conclusions: It is suggested that irradiation induces dysfunction of the autophagic machinery in normal lung, characterized by decreased transcription of the LC3A/Beclin-1 mRNA and accumulation of the LC3A, and p62 proteins. Whether this is due to defective maturation or to aberrant degradation of the autophagosomes requires further investigation.

  10. AZD5438, an Inhibitor of Cdk1, 2, and 9, Enhances the Radiosensitivity of Non-Small Cell Lung Carcinoma Cells

    SciTech Connect (OSTI)

    Raghavan, Pavithra; Tumati, Vasu; Yu Lan; Chan, Norman; Tomimatsu, Nozomi; Burma, Sandeep; Simmons Comprehensive Cancer Center, Dallas, Texas ; Bristow, Robert G.; Saha, Debabrata; Simmons Comprehensive Cancer Center, Dallas, Texas

    2012-11-15

    Purpose: Radiation therapy (RT) is one of the primary modalities for treatment of non-small cell lung cancer (NSCLC). However, due to the intrinsic radiation resistance of these tumors, many patients experience RT failure, which leads to considerable tumor progression including regional lymph node and distant metastasis. This preclinical study evaluated the efficacy of a new-generation cyclin-dependent kinase (Cdk) inhibitor, AZD5438, as a radiosensitizer in several NSCLC models that are specifically resistant to conventional fractionated RT. Methods and Materials: The combined effect of ionizing radiation and AZD5438, a highly specific inhibitor of Cdk1, 2, and 9, was determined in vitro by surviving fraction, cell cycle distribution, apoptosis, DNA double-strand break (DSB) repair, and homologous recombination (HR) assays in 3 NSCLC cell lines (A549, H1299, and H460). For in vivo studies, human xenograft animal models in athymic nude mice were used. Results: Treatment of NSCLC cells with AZD5438 significantly augmented cellular radiosensitivity (dose enhancement ratio rangeing from 1.4 to 1.75). The degree of radiosensitization by AZD5438 was greater in radioresistant cell lines (A549 and H1299). Radiosensitivity was enhanced specifically through inhibition of Cdk1, prolonged G{sub 2}-M arrest, inhibition of HR, delayed DNA DSB repair, and increased apoptosis. Combined treatment with AZD5438 and irradiation also enhanced tumor growth delay, with an enhancement factor ranging from 1.2-1.7. Conclusions: This study supports the evaluation of newer generation Cdk inhibitors, such as AZD5438, as potent radiosensitizers in NSCLC models, especially in tumors that demonstrate variable intrinsic radiation responses.

  11. Restoration of normal phenotype in cancer cells

    DOE Patents [OSTI]

    Bissell, M.J.; Weaver, V.M.

    1998-12-08

    A method for reversing expression of malignant phenotype in cancer cells is described. The method comprises applying {beta}{sub 1} integrin function-blocking antibody to the cells. The method can be used to assess the progress of cancer therapy. Human breast epithelial cells were shown to be particularly responsive. 14 figs.

  12. Restoration of normal phenotype in cancer cells

    DOE Patents [OSTI]

    Bissell, Mina J.; Weaver, Valerie M.

    1998-01-01

    A method for reversing expression of malignant phenotype in cancer cells is described. The method comprises applying .beta..sub.1 integrin function-blocking antibody to the cells. The method can be used to assess the progress of cancer therapy. Human breast epithelial cells were shown to be particularly responsive.

  13. Diet and Cancer Are Cooked Meats Involved

    ScienceCinema (OSTI)

    LLNL - University of California Television

    2009-09-01

    Diet has been associated with differences in cancer rates in human populations for many years. Mark Knize presents the latest research on cancer causes including work performed at Lawrence Livermore National Laboratory investigating some interesting chemical products created when meat is cooked and how to reduce them. Series: Science on Saturday [10/2006] [Health and Medicine] [Science] [Show ID: 11542

  14. TU-A-12A-01: Consistency of Lung Expansion and Contraction During Respiration: Implications for Quantitative Imaging

    SciTech Connect (OSTI)

    Patton, T; Du, K; Bayouth, J; Christensen, G; Reinhardt, J

    2014-06-15

    Purpose: Four-dimensional computed tomography (4DCT) can be used to evaluate longitudinal changes in pulmonary function. The sensitivity of such measurements to identify function change may be improved with reproducible breathing patterns. The purpose of this study was to determine if inhale was more consistent than exhale, i.e., lung expansion during inhalation compared to lung contraction during exhalation. Methods: Repeat 4DCT image data acquired within a short time interval from 8 patients. Using a tissue volume preserving deformable image registration algorithm, Jacobian ventilation maps in two scanning sessions were computed and compared on the same coordinate for reproducibility analysis. Equivalent lung volumes (ELV) were used for 5 subjects and equivalent title volumes (ETV) for the 3 subjects who experienced a baseline shift between scans. In addition, gamma pass rate was calculated from a modified gamma index evaluation between two ventilation maps, using acceptance criterions of 2mm distance-to-agreement and 5% ventilation difference. The gamma pass rates were then compared using paired t-test to determine if there was a significant difference. Results: Inhalation was more reproducible than exhalation. In the 5 ELV subjects 78.5% of the lung voxels met the gamma criteria for expansion during inhalation when comparing the two scans, while significantly fewer (70.9% of the lung voxels) met the gamma criteria for contraction during exhalation (p = .027). In the 8 total subjects analyzed the average gamma pass rate for expansion during inhalation was 75.2% while for contraction during exhalation it was 70.3%; which trended towards significant (p = .064). Conclusion: This work implies inhalation is more reproducible than exhalation, when equivalent respiratory volumes are considered. The reason for this difference is unknown. Longitudinal investigation of pulmonary function change based on inhalation images appears appropriate for Jacobian-based measure of lung tissue expansion. NIH Grant: R01 CA166703.

  15. SU-E-J-87: Lung Deformable Image Registration Using Surface Mesh Deformation for Dose Distribution Combination

    SciTech Connect (OSTI)

    Labine, A; Carrier, J; Bedwani, S; Chav, R; DeGuise, J

    2014-06-01

    Purpose: To allow a reliable deformable image registration (DIR) method for dose calculation in radiation therapy. This work proposes a performance assessment of a morphological segmentation algorithm that generates a deformation field from lung surface displacements with 4DCT datasets. Methods: From the 4DCT scans of 15 selected patients, the deep exhale phase of the breathing cycle is identified as the reference scan. Varian TPS EclipseTM is used to draw lung contours, which are given as input to the morphological segmentation algorithm. Voxelized contours are smoothed by a Gaussian filter and then transformed into a surface mesh representation. Such mesh is adapted by rigid and elastic deformations to match each subsequent lung volumes. The segmentation efficiency is assessed by comparing the segmented lung contour and the TPS contour considering two volume metrics, defined as Volumetric Overlap Error (VOE) [%] and Relative Volume Difference (RVD) [%] and three surface metrics, defined as Average Symmetric Surface Distance (ASSD) [mm], Root Mean Square Symmetric Surface Distance (RMSSD) [mm] and Maximum Symmetric Surface Distance (MSSD) [mm]. Then, the surface deformation between two breathing phases is determined by the displacement of corresponding vertices in each deformed surface. The lung surface deformation is linearly propagated in the lung volume to generate 3D deformation fields for each breathing phase. Results: The metrics were averaged over the 15 patients and calculated with the same segmentation parameters. The volume metrics obtained are a VOE of 5.2% and a RVD of 2.6%. The surface metrics computed are an ASSD of 0.5 mm, a RMSSD of 0.8 mm and a MSSD of 6.9 mm. Conclusion: This study shows that the morphological segmentation algorithm can provide an automatic method to capture an organ motion from 4DCT scans and translate it into a volume deformation grid needed by DIR method for dose distribution combination.

  16. Dissolution and clearance of titanium tritide particles in the lungs of F344/Crl rats

    SciTech Connect (OSTI)

    Cheng, Yung-Sung; Snipes, M.B.; Wang, Yansheng

    1995-12-01

    Metal tritides are compounds in which the radioactive isotope tritium, following adsorption onto the metal, forms a stable chemical compound with the metal. When particles of tritiated metals become airborne, they can be inhaled by workers. Because the particles may be retained in the lung for extended periods, the resulting dose will be greater than doses following exposure to tritium gas or tritium oxide (HTO). Particles of triated metals may be dispersed into the air during routine handling, disruption of contaminated metals, or as a result of spontaneous radioactive decay processes. Unlike metal hydrides and deuterides, tritides are radioactive, and the decay of the tritium atoms affects the metal. Because helium is a product of the decay, helium bubbles form within the metal tritide matrix. The pressure from these bubbles leads to respirable particles breaking off from the tritide surface. Our results show that a substantial amount of titanium tritide remains in the rat lung 10 d after intratracheal instillation, confirming results previously obtain in an in vitro dissolution study.

  17. Chlorobenzene induces oxidative stress in human lung epithelial cells in vitro

    SciTech Connect (OSTI)

    Feltens, Ralph; Moegel, Iljana; Roeder-Stolinski, Carmen; Simon, Jan-Christoph; Herberth, Gunda; Lehmann, Irina

    2010-01-01

    Chlorobenzene is a volatile organic compound (VOC) that is widely used as a solvent, degreasing agent and chemical intermediate in many industrial settings. Occupational studies have shown that acute and chronic exposure to chlorobenzene can cause irritation of the mucosa of the upper respiratory tract and eyes. Using in vitro assays, we have shown in a previous study that human bronchial epithelial cells release inflammatory mediators such as the cytokine monocyte chemoattractant protein-1 (MCP-1) in response to chlorobenzene. This response is mediated through the NF-kappaB signaling pathway. Here, we investigated the effects of monochlorobenzene on human lung cells, with emphasis on potential alterations of the redox equilibrium to clarify whether the chlorobenzene-induced inflammatory response in lung epithelial cells is caused via an oxidative stress-dependent mechanism. We found that expression of cellular markers for oxidative stress, such as heme oxygenase 1 (HO-1), glutathione S-transferase pi1 (GSTP1), superoxide dismutase 1 (SOD1), prostaglandin-endoperoxide synthase 2 (PTGS2) and dual specificity phosphatase 1 (DUSP1), were elevated in the presence of monochlorobenzene. Likewise, intracellular reactive oxygen species (ROS) were increased in response to exposure. However, in the presence of the antioxidants N-(2-mercaptopropionyl)-glycine (MPG) or bucillamine, chlorobenzene-induced upregulation of marker proteins and release of the inflammatory mediator MCP-1 are suppressed. These results complement our previous findings and point to an oxidative stress-mediated inflammatory response following chlorobenzene exposure.

  18. Continuum-kinetic-microscopic model of lung clearance due to core-annular fluid entrainment

    SciTech Connect (OSTI)

    Mitran, Sorin

    2013-07-01

    The human lung is protected against aspirated infectious and toxic agents by a thin liquid layer lining the interior of the airways. This airway surface liquid is a bilayer composed of a viscoelastic mucus layer supported by a fluid film known as the periciliary liquid. The viscoelastic behavior of the mucus layer is principally due to long-chain polymers known as mucins. The airway surface liquid is cleared from the lung by ciliary transport, surface tension gradients, and airflow shear forces. This work presents a multiscale model of the effect of airflow shear forces, as exerted by tidal breathing and cough, upon clearance. The composition of the mucus layer is complex and variable in time. To avoid the restrictions imposed by adopting a viscoelastic flow model of limited validity, a multiscale computational model is introduced in which the continuum-level properties of the airway surface liquid are determined by microscopic simulation of long-chain polymers. A bridge between microscopic and continuum levels is constructed through a kinetic-level probability density function describing polymer chain configurations. The overall multiscale framework is especially suited to biological problems due to the flexibility afforded in specifying microscopic constituents, and examining the effects of various constituents upon overall mucus transport at the continuum scale.

  19. Van Andel Research Institute, Los Alamos National Laboratory...

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Computational model to study lung cancer Van Andel Research Institute, Los Alamos National Laboratory to develop detailed computational model to study lung cancer Scientists are...

  20. Search for: All records | SciTech Connect

    Office of Scientific and Technical Information (OSTI)

    Mechanism for activation of mutated epidermal growth factor receptors in lung cancer ... Exon 20 Insertion Mutations in Lung Cancer Yasuda, Hiroyuki ; Park, Eunyoung ; Yun, ...

  1. Workers' Spotlight Newsletters | Department of Energy

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    ... May 2013 issue covers BTMed takes aim at COPD, Lung Cancer and Pantex Former Worker ... Remembrance, Secure Electronic Records Transfer (SERT), and Early Lung Cancer Detection.

  2. Anterior Myocardial Territory May Replace the Heart as Organ at Risk in Intensity-Modulated Radiotherapy for Left-Sided Breast Cancer

    SciTech Connect (OSTI)

    Tan Wenyong; Liu Dong; Xue Chenbin; Xu Jiaozhen; Li Beihui; Chen Zhengwang; Hu Desheng; Wang Xionghong

    2012-04-01

    Purpose: We investigated whether the heart could be replaced by the anterior myocardial territory (AMT) as the organ at risk (OAR) in intensity-modulated radiotherapy (IMRT) of the breast for patients with left-sided breast cancer. Methods and Materials: Twenty-three patients with left-sided breast cancer who received postoperative radiation after breast-conserving surgery were studied. For each patient, we generated five IMRT plans including heart (H), left ventricle (LV), AMT, LV+AMT, and H+LV as the primary OARs, respectively, except both lungs and right breast, which corresponded to IMRT(H), IMRT(LV), IMRT(AMT), IMRT(LV+AMT), and IMRT(H+LV). For the planning target volumes and OARs, the parameters of dose-volume histograms were compared. Results: The homogeneity index, conformity index, and coverage index were not compromised significantly in IMRT(AMT), IMRT(LV) and IMRT(LV+ AMT), respectively, when compared with IMRT(H). The mean dose to the heart, LV, and AMT decreased 5.3-21.5% (p < 0.05), 19.9-29.5% (p < 0.05), and 13.3-24.5% (p < 0.05), respectively. Similarly, the low (e.g., V5%), middle (e.g., V20%), and high (e.g., V30%) dose-volume of the heart, LV, and AMT decreased with different levels. The mean dose and V10% of the right lung increased by 9.2% (p < 0.05) and 27.6% (p < 0.05), respectively, in IMRT(LV), and the mean dose and V5% of the right breast decreased significantly in IMRT(AMT) and IMRT(LV+AMT). IMRT(AMT) was the preferred plan and was then compared with IMRT(H+LV); the majority of dose-volume histogram parameters of OARs including the heart, LV, AMT, both lungs, and the right breast were not statistically different. However, the low dose-volume of LV increased and the middle dose-volume decreased significantly (p < 0.05) in IMRT(AMT). Also, those of the right lung (V10%, V15%) and right breast (V5%, V10%) decreased significantly (p < 0.05). Conclusions: The AMT may replace the heart as the OAR in left-sided breast IMRT after breast-conserving surgery to decrease the radiation dose to the heart.

  3. Realizing in-plane surface diffraction by x-ray multiple-beam diffraction with large incidence angle

    SciTech Connect (OSTI)

    Huang, Xian-Rong Gog, Thomas; Assoufid, Lahsen; Peng, Ru-Wen; Siddons, D. P.

    2014-11-03

    Based on rigorous dynamical-theory calculations, we demonstrate the principle of an x-ray multiple-beam diffraction (MBD) scheme that overcomes the long-lasting difficulties of high-resolution in-plane diffraction from crystal surfaces. This scheme only utilizes symmetric reflection geometry with large incident angles but activates the out-of-plane and in-plane diffraction processes simultaneously and separately in the continuous MBD planes. The in-plane diffraction is realized by detoured MBD, where the intermediate diffracted waves propagate parallel to the surface, which corresponds to an absolute Bragg surface diffraction configuration that is extremely sensitive to surface structures. A series of MBD diffraction and imaging techniques may be developed from this principle to study surface/interface (misfit) strains, lateral nanostructures, and phase transitions of a wide range of (pseudo)cubic crystal structures, including ultrathin epitaxial films and multilayers, quantum dots, strain-engineered semiconductor or (multi)ferroic materials, etc.

  4. Adapting the U.S. Domestic Radiological Emergency Response Process to an Overseas Incident: FRMAC Without the F

    SciTech Connect (OSTI)

    Blumenthal, Daniel J.; Bowman, David R.; Remick, Alan

    2012-05-01

    The earthquake and resulting tsunami in Japan led to a radiological release from the Fukushima Daiichi Nuclear Power Plan, which in turn resulted in the rapid activation and deployment by the U.S. Department of Energy National Nuclear Security Administration (DOE/NNSA) emergency response teams. These teams and those from other federal agencies are typically coordinated through the Federal Radiological Monitoring and Assessment Center (FRMAC) when responding to radiological incidents in the U.S. FRMAC is the body through which the collection, analysis, and assessment of environmental radiological data are coordinated and products released to decision makers. This article discusses DOE/NNSAs role in the U.S. response to the Fukushima accident as it implemented its components of FRMAC in a foreign country, coordinated its assets, integrated with its federal partners, and collaborated with the Government of Japan. The technical details of the various data collections and analyses are covered in other articles of this issue.

  5. Energetic deposition of metal ions: Observation of self-sputtering and limited sticking for off-normal angles of incidence

    SciTech Connect (OSTI)

    Wu, Hongchen; Anders, Andre

    2009-09-15

    The deposition of films under normal and off-normal angle of incidence has been investigated to show the relevance of non-sticking of and self-sputtering by energetic ions, leading to the formation of neutral atoms. The flow of energetic ions was obtained using a filtered cathodic arc system in high vacuum and therefore the ion flux had a broad energy distribution of typically 50-100 eV per ion. The range of materials included Cu, Ag, Au, Ti, and Ni. Consistent with molecular dynamics simulations published in the literature, the experiments show, for all materials, that the combined effects of non-sticking and self-sputtering are very significant, especially for large off-normal angles. Modest heating and intentional introduction of oxygen background affect the results.

  6. Marginal Misses After Postoperative Intensity-Modulated Radiotherapy for Head and Neck Cancer

    SciTech Connect (OSTI)

    Chen, Allen M.; Farwell, D. Gregory; Luu, Quang; Chen, Leon M.; Vijayakumar, Srinivasan; Purdy, James A.

    2011-08-01

    Purpose: To describe the spatial distribution of local-regional recurrence (LRR) among patients treated postoperatively with intensity-modulated radiotherapy (IMRT) for head and neck cancer. Methods and Materials: The medical records of 90 consecutive patients treated by gross total resection and postoperative IMRT for squamous cell carcinoma of the head and neck from January 2003 to July 2009 were reviewed. Sites of disease were the oral cavity (43 patients), oropharynx (20 patients), larynx (15 patients), and hypopharynx (12 patients). Fifty patients (56%) received concurrent chemotherapy. Results: Seventeen of 90 patients treated with postoperative IMRT experienced LRR, yielding a 2-year estimate of local regional control of 80%. Among the LRR patients, 11 patients were classified as in-field recurrences, occurring within the physician-designated clinical target volume, and 6 patients were categorized as marginal recurrences. There were no out-of-field geographical misses. Sites of marginal LRRs included the contralateral neck adjacent to the spared parotid gland (3 patients), the dermal/subcutaneous surface (2 patients), and the retropharyngeal/retrostyloid lymph node region (1 patient). Conclusions: Although the incidence of geographical misses was relatively low, the possibility of this phenomenon should be considered in the design of target volumes among patients treated by postoperative IMRT for head and neck cancer.

  7. Oblique incidence effects in direct x-ray detectors: A first-order approximation using a physics-based analytical model

    SciTech Connect (OSTI)

    Badano, Aldo; Freed, Melanie; Fang Yuan

    2011-04-15

    Purpose: The authors describe the modifications to a previously developed analytical model of indirect CsI:Tl-based detector response required for studying oblique x-ray incidence effects in direct semiconductor-based detectors. This first-order approximation analysis allows the authors to describe the associated degradation in resolution in direct detectors and compare the predictions to the published data for indirect detectors. Methods: The proposed model is based on a physics-based analytical description developed by Freed et al. [''A fast, angle-dependent, analytical model of CsI detector response for optimization of 3D x-ray breast imaging systems,'' Med. Phys. 37(6), 2593-2605 (2010)] that describes detector response functions for indirect detectors and oblique incident x rays. The model, modified in this work to address direct detector response, describes the dependence of the response with x-ray energy, thickness of the transducer layer, and the depth-dependent blur and collection efficiency. Results: The authors report the detector response functions for indirect and direct detector models for typical thicknesses utilized in clinical systems for full-field digital mammography (150 {mu}m for indirect CsI:Tl and 200 {mu}m for a-Se direct detectors). The results suggest that the oblique incidence effect in a semiconductor detector differs from that in indirect detectors in two ways: The direct detector model produces a sharper overall PRF compared to the response corresponding to the indirect detector model for normal x-ray incidence and a larger relative increase in blur along the x-ray incidence direction compared to that found in indirect detectors with respect to the response at normal incidence angles. Conclusions: Compared to the effect seen in indirect detectors, the direct detector model exhibits a sharper response at normal x-ray incidence and a larger relative increase in blur along the x-ray incidence direction with respect to the blur in the orthogonal direction. The results suggest that the oblique incidence effect in direct detectors can be considered to be caused mostly by the geometry of the path where the x-ray beam and its secondary particles deposit energy in the semiconductor layer.

  8. Biodiesel versus diesel exposure: Enhanced pulmonary inflammation, oxidative stress, and differential morphological changes in the mouse lung

    SciTech Connect (OSTI)

    Yanamala, Naveena; Birch, M. Eileen; Kisin, Elena; Bugarski, Aleksandar D.

    2013-10-15

    The use of biodiesel (BD) or its blends with petroleum diesel (D) is considered to be a viable approach to reduce occupational and environmental exposures to particulate matter (PM). Due to its lower particulate mass emissions compared to D, use of BD is thought to alleviate adverse health effects. Considering BD fuel is mainly composed of unsaturated fatty acids, we hypothesize that BD exhaust particles could induce pronounced adverse outcomes, due to their ability to readily oxidize. The main objective of this study was to compare the effects of particles generated by engine fueled with neat BD and neat petroleum-based D. Biomarkers of tissue damage and inflammation were significantly elevated in lungs of mice exposed to BD particulates. Additionally, BD particulates caused a significant accumulation of oxidatively modified proteins and an increase in 4-hydroxynonenal. The up-regulation of inflammatory cytokines/chemokines/growth factors was higher in lungs upon BD particulate exposure. Histological evaluation of lung sections indicated presence of lymphocytic infiltrate and impaired clearance with prolonged retention of BD particulate in pigment laden macrophages. Taken together, these results clearly indicate that BD exhaust particles could exert more toxic effects compared to D. - Highlights: Exposure of mice to BDPM caused higher pulmonary toxicity compared to DPM. Oxidative stress and inflammation were higher in BD vs to D exposed mice. Inflammatory lymphocyte infiltrates were seen only in lungs of mice exposed to BD. Ineffective clearance, prolonged PM retention was present only after BD exposure.

  9. siRNA-mediated knockdown against CDCA1 and KNTC2, both frequently overexpressed in colorectal and gastric cancers, suppresses cell proliferation and induces apoptosis

    SciTech Connect (OSTI)

    Kaneko, Naoyuki; Department of Surgery, Tohoku University School of Medicine, Sendai, Miyagi 980-8575 ; Miura, Koh; Gu, Zhaodi; Karasawa, Hideaki; Ohnuma, Shinobu; Sasaki, Hiroyuki; Tsukamoto, Nobukazu; Yokoyama, Satoru; Yamamura, Akihiro; Department of Surgery, Tohoku University School of Medicine, Sendai, Miyagi 980-8575 ; Nagase, Hiroki; Shibata, Chikashi; Sasaki, Iwao; Horii, Akira

    2009-12-25

    Ndc80 has been shown to play an important role in stable microtubule-kinetochore attachment, chromosome alignment, and spindle checkpoint activation in mitosis. It is composed of two heterodimers, CDCA1-KNTC2 and SPC24-SPC25. Overexpression of CDCA1 and KNTC2 is reported to be associated with poor prognosis in non-small cell lung cancers (NSCLC), and siRNA-mediated knockdown against CDCA1 or KNTC2 has been found to inhibit cell proliferation and induction of apoptosis in NSCLC, ovarian cancer, cervical cancer and glioma. Therefore, CDCA1 and KNTC2 can be considered good candidates for molecular target therapy as well as diagnosis in some cancers. However, the role of the Ndc80 complex in colorectal and gastric cancers (CRC and GC) still remains unclear. In the present study, we used qRT-PCR to evaluate the expression levels of CDCA1, KNTC2, SPC24 and SPC25 in CRC and GC and employed siRNA-mediated knockdown to examine cell proliferation and apoptosis. mRNA overexpression of these four genes was observed in CRCs and GCs when compared with the corresponding normal mucosae. Additionally, the expression levels of tumor/normal ratios of CDCA1, KNTC2, SPC24 and SPC25 correlated with each other in CRCs. MTT assays revealed that cell growths after the siRNA-mediated knockdown of either CDCA1 or KNTC2 were significantly suppressed, and flow cytometry analyses revealed significant increases of the subG1 fractions after knockdown against both genes. Our present results suggest that expressional control of component molecules of Ndc80 can be utilized for molecular target therapy of patients with CRC and GC.

  10. Ancient Proteins Help Unravel a Modern Cancer Drug's Mechanism

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Ancient Proteins Help Unravel a Modern Cancer Drug's Mechanism Print The cancer drug Gleevec is extremely specific, binding and inhibiting only the cancer-causing tyrosine protein kinase Blc-Abl, while not targeting homologous protein kinases found in normal, healthy cells. It has been widely used to fight colon cancers and chronic myeloid leukemia. The protein kinase Abl is involved in regulating cell growth. Protein kinases have in general been the target of many cancer drug designs, since

  11. Ancient Proteins Help Unravel a Modern Cancer Drug's Mechanism

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Ancient Proteins Help Unravel a Modern Cancer Drug's Mechanism Print The cancer drug Gleevec is extremely specific, binding and inhibiting only the cancer-causing tyrosine protein kinase Blc-Abl, while not targeting homologous protein kinases found in normal, healthy cells. It has been widely used to fight colon cancers and chronic myeloid leukemia. The protein kinase Abl is involved in regulating cell growth. Protein kinases have in general been the target of many cancer drug designs, since

  12. Ancient Proteins Help Unravel a Modern Cancer Drug's Mechanism

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Ancient Proteins Help Unravel a Modern Cancer Drug's Mechanism Print The cancer drug Gleevec is extremely specific, binding and inhibiting only the cancer-causing tyrosine protein kinase Blc-Abl, while not targeting homologous protein kinases found in normal, healthy cells. It has been widely used to fight colon cancers and chronic myeloid leukemia. The protein kinase Abl is involved in regulating cell growth. Protein kinases have in general been the target of many cancer drug designs, since

  13. Ancient Proteins Help Unravel a Modern Cancer Drug's Mechanism

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Ancient Proteins Help Unravel a Modern Cancer Drug's Mechanism Print The cancer drug Gleevec is extremely specific, binding and inhibiting only the cancer-causing tyrosine protein kinase Blc-Abl, while not targeting homologous protein kinases found in normal, healthy cells. It has been widely used to fight colon cancers and chronic myeloid leukemia. The protein kinase Abl is involved in regulating cell growth. Protein kinases have in general been the target of many cancer drug designs, since

  14. Ancient Proteins Help Unravel a Modern Cancer Drug's Mechanism

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Ancient Proteins Help Unravel a Modern Cancer Drug's Mechanism Ancient Proteins Help Unravel a Modern Cancer Drug's Mechanism Print Tuesday, 23 June 2015 13:00 The cancer drug Gleevec is extremely specific, binding and inhibiting only the cancer-causing tyrosine protein kinase Blc-Abl, while not targeting homologous protein kinases found in normal, healthy cells. It has been widely used to fight colon cancers and chronic myeloid leukemia. The protein kinase Abl is involved in regulating cell

  15. Genetic heterogeneity of breast-ovarian cancer revisited

    SciTech Connect (OSTI)

    Narod, S.; Ford, D.; Easton, D.

    1995-10-01

    We have recently reported the results of a linkage analysis of 145 breast-ovarian cancer families. Each family has three or more cases of early-onset breast cancer (age {le}60) or of ovarian cancer, and all families have at least one case of ovarian cancer (there were nine site-specific ovarian cancer families). Overall, we estimated that 76% of the families were linked to the BRCA1 locus. 5 refs., 1 tab.

  16. WE-E-BRE-10: Level of Breast Cancer Stem Cell Correlated with...

    Office of Scientific and Technical Information (OSTI)

    WE-E-BRE-10: Level of Breast Cancer Stem Cell Correlated with Tumor Radioresistence: An Indication for Individualized Breast Cancer Therapy Adapted to Cancer Stem Cell Fractions ...

  17. Tobacco Smoking During Radiation Therapy for Head-and-Neck Cancer Is Associated With Unfavorable Outcome

    SciTech Connect (OSTI)

    Chen, Allen M.; Chen, Leon M.; Vaughan, Andrew; Sreeraman, Radhika; Farwell, D. Gregory; Luu, Quang; Lau, Derick H.; Stuart, Kerri; Purdy, James A.; Vijayakumar, Srinivasan

    2011-02-01

    Purpose: To evaluate the effect of continued cigarette smoking among patients undergoing radiation therapy for head-and-neck cancer by comparing the clinical outcomes among active smokers and quitters. Methods and Materials: A review of medical records identified 101 patients with newly diagnosed squamous cell carcinoma of the head and neck who continued to smoke during radiation therapy. Each active smoker was matched to a control patient who had quit smoking before initiation of radiation therapy. Matching was based on tobacco history (pack-years), primary site, age, sex, Karnofsky Performance Status, disease stage, radiation dose, chemotherapy use, year of treatment, and whether surgical resection was performed. Outcomes were compared by use of Kaplan-Meier analysis. Normal tissue effects were graded according to the Radiation Therapy Oncology Group/European Organization for the Treatment of Cancer toxicity criteria. Results: With a median follow-up of 49 months, active smokers had significantly inferior 5-year overall survival (23% vs. 55%), locoregional control (58% vs. 69%), and disease-free survival (42% vs. 65%) compared with the former smokers who had quit before radiation therapy (p < 0.05 for all). These differences remained statistically significant when patients treated by postoperative or definitive radiation therapy were analyzed separately. The incidence of Grade 3 or greater late complications was also significantly increased among active smokers compared with former smokers (49% vs. 31%, p = 0.01). Conclusions: Tobacco smoking during radiation therapy for head-and-neck cancer is associated with unfavorable outcomes. Further studies analyzing the biologic and molecular reasons underlying these differences are planned.

  18. TH-E-17A-10: Markerless Lung Tumor Tracking Based On Beams Eye View EPID Images

    SciTech Connect (OSTI)

    Chiu, T; Kearney, V; Liu, H; Jiang, L; Foster, R; Mao, W; Rozario, T; Bereg, S; Klash, S

    2014-06-15

    Purpose: Dynamic tumor tracking or motion compensation techniques have proposed to modify beam delivery following lung tumor motion on the flight. Conventional treatment plan QA could be performed in advance since every delivery may be different. Markerless lung tumor tracking using beams eye view EPID images provides a best treatment evaluation mechanism. The purpose of this study is to improve the accuracy of the online markerless lung tumor motion tracking method. Methods: The lung tumor could be located on every frame of MV images during radiation therapy treatment by comparing with corresponding digitally reconstructed radiograph (DRR). A kV-MV CT corresponding curve is applied on planning kV CT to generate MV CT images for patients in order to enhance the similarity between DRRs and MV treatment images. This kV-MV CT corresponding curve was obtained by scanning a same CT electron density phantom by a kV CT scanner and MV scanner (Tomotherapy) or MV CBCT. Two sets of MV DRRs were then generated for tumor and anatomy without tumor as the references to tracking the tumor on beams eye view EPID images. Results: Phantom studies were performed on a Varian TrueBeam linac. MV treatment images were acquired continuously during each treatment beam delivery at 12 gantry angles by iTools. Markerless tumor tracking was applied with DRRs generated from simulated MVCT. Tumors were tracked on every frame of images and compared with expected positions based on programed phantom motion. It was found that the average tracking error were 2.3 mm. Conclusion: This algorithm is capable of detecting lung tumors at complicated environment without implanting markers. It should be noted that the CT data has a slice thickness of 3 mm. This shows the statistical accuracy is better than the spatial accuracy. This project has been supported by a Varian Research Grant.

  19. GE Cancer Research | GE Global Research

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Technology "Relay Race" Against Cancer Click to email this to a friend (Opens in new window) Share on Facebook (Opens in new window) Click to share (Opens in new window) Click to...

  20. Colon Cancer Mapping | GE Global Research

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Vanderbilt, GE Team Seek Deeper Understanding of Colon Cancer Click to email this to a friend (Opens in new window) Share on Facebook (Opens in new window) Click to share (Opens in...

  1. SU-E-P-03: Implementing a Low Dose Lung Screening CT Program Meeting Regulatory Requirements

    SciTech Connect (OSTI)

    LaFrance, M; Marsh, S; O'Donnell, G

    2014-06-01

    Purpose: To provide information pertaining to IROC Houston QA Center's (RPC) credentialing process for institutions participating in NCI-sponsored clinical trials. Purpose: Provide guidance to the Radiology Departments with the intent of implementing a Low Dose CT Screening Program using different CT Scanners with multiple techniques within the framework of the required state regulations. Method: State Requirements for the purpose of implementing a Low Dose CT Lung Protocol required working with the Radiology and Pulmonary Department in setting up a Low Dose Screening Protocol designed to reduce the radiation burden to the patients enrolled. Radiation dose measurements (CTDIvol) for various CT manufacturers (Siemens16, Siemens 64, Philips 64, and Neusoft128) for three different weight based protocols. All scans were reviewed by the Radiologist. Prior to starting a low dose lung screening protocol, information had to be submitted to the state for approval. Performing a Healing Arts protocol requires extensive information. This not only includes name and address of the applicant but a detailed description of the disease, the x-ray examination and the population to be examined. The unit had to be tested by a qualified expert using the technique charts. The credentials of all the operators, the supervisors and the Radiologists had to be submitted to the state. Results: All the appropriate documentation was sent to the state for review. The measured results between the Low Dose Protocol versus the default Adult Chest Protocol showed that there was a dose reduction of 65% for small (100-150 lb.) patient, 75% for the Medium patient (151-250 lbs.), and a 55% reduction for the Large patient ( over 250 lbs.). Conclusion: Measured results indicated that the Low Dose Protocol indeed lowered the screening patient's radiation dose and the institution was able to submit the protocol to the State's regulators.

  2. Source apportionment of particulate matter in the US and associations with lung inflammatory markers

    SciTech Connect (OSTI)

    Duvall, R.M.; Norris, G.A.; Dailey, L.A.; Burke, J.M.; McGee, J.K.; Gilmour, M.I.; Gordon, T.; Devlin, R.B.

    2008-07-01

    Size-fractionated particulate matter (PM) samples were collected from six U.S. cities and chemically analyzed as part of the Multiple Air Pollutant Study. Particles were administered to cultured lung cells and the production of three different proinflammatory markers was measured to explore the association between the health effect markers and PM. Ultrafine, fine, and coarse PM samples were collected between December 2003 and May 2004 over a 4-wk period in each city. Filters were pooled for each city and the PM samples were extracted then analyzed for trace metals, ions, and elemental carbon. Particle extracts were applied to cultured human primary airway epithelial cells, and the secreted levels of interleukin-8 (IL-8), heme oxygenase-1, and cyclooxygenase-2 were measured 1 and 24 h following exposure. Fine PM sources were quantified by the chemical mass balance (CMB) model. The relationship between toxicological measures, PM sources, and individual species were evaluated using linear regression. Ultrafine and fine PM mass were associated with increases in IL-8 (r{sup 2} = .80 for ultrafine and r{sup 2} = .52 for fine). Sources of fine PM and their relative contributions varied across the sampling sites and a strong linear association was observed between IL-8 and secondary sulfate from coal combustion (r{sup 2} = .79). Ultrafine vanadium, lead, copper, and sulfate were also associated with increases in IL-8. Increases in inflammatory markers were not observed for coarse PM mass and source markers. These findings suggest that certain PM size fractions and sources are associated with markers of lung injury or inflammation.

  3. Erlotinib Versus Radiation Therapy for Brain Metastases in Patients With EGFR-Mutant Lung Adenocarcinoma

    SciTech Connect (OSTI)

    Gerber, Naamit K.; Yamada, Yoshiya; Rimner, Andreas; Shi, Weiji; Riely, Gregory J.; Beal, Kathryn; Yu, Helena A.; Chan, Timothy A.; Zhang, Zhigang; Wu, Abraham J.

    2014-06-01

    Purpose/Objectives: Radiation therapy (RT) is the principal modality in the treatment of patients with brain metastases (BM). However, given the activity of EGFR tyrosine kinase inhibitors in the central nervous system, it is uncertain whether upfront brain RT is necessary for patients with EGFR-mutant lung adenocarcinoma with BM. Methods and Materials: Patients with EGFR-mutant lung adenocarcinoma and newly diagnosed BM were identified. Results: 222 patients were identified. Exclusion criteria included prior erlotinib use, presence of a de novo erlotinib resistance mutation, or incomplete data. Of the remaining 110 patients, 63 were treated with erlotinib, 32 with whole brain RT (WBRT), and 15 with stereotactic radiosurgery (SRS). The median overall survival (OS) for the whole cohort was 33 months. There was no significant difference in OS between the WBRT and erlotinib groups (median, 35 vs 26 months; P=.62), whereas patients treated with SRS had a longer OS than did those in the erlotinib group (median, 64 months; P=.004). The median time to intracranial progression was 17 months. There was a longer time to intracranial progression in patients who received WBRT than in those who received erlotinib upfront (median, 24 vs 16 months, P=.04). Patients in the erlotinib or SRS group were more likely to experience intracranial failure as a component of first failure, whereas WBRT patients were more likely to experience failure outside the brain (P=.004). Conclusions: The survival of patients with EGFR-mutant adenocarcinoma with BM is notably long, whether they receive upfront erlotinib or brain RT. We observed longer intracranial control with WBRT, even though the WBRT patients had a higher burden of intracranial disease. Despite the equivalent survival between the WBRT and erlotinib group, this study underscores the role of WBRT in producing durable intracranial control in comparison with a targeted biologic agent with known central nervous system activity.

  4. Breast Density and Cancer | GE Global Research

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Breast Cancer Awareness Series: Understanding Breast Density Click to email this to a friend (Opens in new window) Share on Facebook (Opens in new window) Click to share (Opens in new window) Click to share on LinkedIn (Opens in new window) Click to share on Tumblr (Opens in new window) Breast Cancer Awareness Series: Understanding Breast Density Researcher Andrea Schmitz describes what breast density is and discusses important health and diagnostics points related to breast density. You Might

  5. The Impact of Hypofractionated Whole Breast Radiotherapy on Local Relapse in Patients With Grade 3 Early Breast Cancer: A Population-Based Cohort Study

    SciTech Connect (OSTI)

    Herbert, Christopher; Nichol, Alan; Olivotto, Ivo; Weir, Lorna; Woods, Ryan; Speers, Caroline; Truong, Pauline; Tyldesley, Scott

    2012-04-01

    Purpose: To determine whether patients with Grade 3 early breast cancer have an inferior rate of local disease control at 10 years with hypofractionated radiotherapy compared with more conventionally fractionated schedules. Methods and Materials: Local relapse rates were compared between patients receiving hypofractionated radiotherapy or conventionally fractionated radiotherapy to the whole breast in a population-based cohort of women with early-stage (T1-T2, N0, M0) Grade 3 breast cancers diagnosed between 1990 and 2000 and referred to the British Columbia Cancer Agency. Cumulative rates of local relapse were estimated using a competing risk method, and factors significant on univariate analysis were included with fractionation group in a multivariate model. The primary end point was local control at 10 years. Results: A total of 1,335 patients with Grade 3 tumors were treated with adjuvant radiotherapy, 252 with conventional fractionation, and 1,083 with a hypofractionated schedule. The 10-year cumulative incidence of local relapse was 6.9% in the hypofractionated group and 6.2% in the conventionally fractionated group (p = 0.99). Conclusions: There is no evidence that hypofractionation is inferior to conventional fractionation for breast conserving therapy in patients with Grade 3 breast cancer in this large population-based series after 10 years of follow-up.

  6. Radiation Dose and Subsequent Risk for Stomach Cancer in Long-term Survivors of Cervical Cancer

    SciTech Connect (OSTI)

    Kleinerman, Ruth A.; Smith, Susan A.; Holowaty, Eric; Hall, Per; Pukkala, Eero; Vaalavirta, Leila; Stovall, Marilyn; Weathers, Rita; Gilbert, Ethel; Aleman, Berthe M.P.; Kaijser, Magnus; Andersson, Michael; Storm, Hans; Joensuu, Heikki; Lynch, Charles F.; and others

    2013-08-01

    Purpose: To assess the doseresponse relationship for stomach cancer after radiation therapy for cervical cancer. Methods and Materials: We conducted a nested, matched casecontrol study of 201 cases and 378 controls among 53,547 5-year survivors of cervical cancer diagnosed from 1943 to 1995, from 5 international, population-based cancer registries. We estimated individual radiation doses to the site of the stomach cancer for all cases and to corresponding sites for the matched controls (overall mean stomach tumor dose, 2.56 Gy, range 0.03-46.1 and after parallel opposed pelvic fields, 1.63 Gy, range 0.12-6.3). Results: More than 90% of women received radiation therapy, mostly with external beam therapy in combination with brachytherapy. Stomach cancer risk was nonsignificantly increased (odds ratio 1.27-2.28) for women receiving between 0.5 and 4.9 Gy to the stomach cancer site and significantly increased at doses ?5 Gy (odds ratio 4.20, 95% confidence interval 1.41-13.4, P{sub trend}=.047) compared with nonirradiated women. A highly significant radiation doseresponse relationship was evident when analyses were restricted to the 131 cases (251 controls) whose stomach cancer was located in the middle and lower portions of the stomach (P{sub trend}=.003), whereas there was no indication of increasing risk with increasing dose for 30 cases (57 controls) whose cancer was located in the upper stomach (P{sub trend}=.23). Conclusions: Our findings show for the first time a significant linear doseresponse relationship for risk of stomach cancer in long-term survivors of cervical cancer.

  7. A Local Incident Flux Response Expansion Transport Method for Coupling to the Diffusion Method in Cylindrical Geometry

    SciTech Connect (OSTI)

    Dingkang Zhang; Farzad Rahnema; Abderrafi M. Ougouag

    2013-09-01

    A local incident flux response expansion transport method is developed to generate transport solutions for coupling to diffusion theory codes regardless of their solution method (e.g., fine mesh, nodal, response based, finite element, etc.) for reactor core calculations in both two-dimensional (2-D) and three-dimensional (3-D) cylindrical geometries. In this approach, a Monte Carlo method is first used to precompute the local transport solution (i.e., response function library) for each unique transport coarse node, in which diffusion theory is not valid due to strong transport effects. The response function library is then used to iteratively determine the albedo coefficients on the diffusion-transport interfaces, which are then used as the coupling parameters within the diffusion code. This interface coupling technique allows a seamless integration of the transport and diffusion methods. The new method retains the detailed heterogeneity of the transport nodes and naturally constructs any local solution within them by a simple superposition of local responses to all incoming fluxes from the contiguous coarse nodes. A new technique is also developed for coupling to fine-mesh diffusion methods/codes. The local transport method/module is tested in 2-D and 3-D pebble-bed reactor benchmark problems consisting of an inner reflector, an annular fuel region, and a controlled outer reflector. It is found that the results predicted by the transport module agree very well with the reference fluxes calculated directly by MCNP in both benchmark problems.

  8. Preliminary report on operational guidelines developed for use in emergency preparedness and response to a radiological dispersal device incident.

    SciTech Connect (OSTI)

    Yu, C.; Cheng, J.-J.; Kamboj, S.; Domotor, S.; Wallo, A.; Environmental Science Division; DOE

    2006-12-15

    This report presents preliminary operational guidelines and supporting work products developed through the interagency Operational Guidelines Task Group (OGT). The report consolidates preliminary operational guidelines, all ancillary work products, and a companion software tool that facilitates their implementation into one reference source document. The report is intended for interim use and comment and provides the foundation for fostering future reviews of the operational guidelines and their implementation within emergency preparedness and response initiatives in the event of a radiological dispersal device (RDD) incident. The report principally focuses on the technical derivation and presentation of the operational guidelines. End-user guidance providing more details on how to apply these operational guidelines within planning and response settings is being considered and developed elsewhere. The preliminary operational guidelines are categorized into seven groups on the basis of their intended application within early, intermediate, and long-term recovery phases of emergency response. We anticipate that these operational guidelines will be updated and refined by interested government agencies in response to comments and lessons learned from their review, consideration, and trial application. This review, comment, and trial application process will facilitate the selection of a final set of operational guidelines that may be more or less inclusive of the preliminary operational guidelines presented in this report. These and updated versions of the operational guidelines will be made available through the OGT public Web site (http://ogcms.energy.gov) as they become finalized for public distribution and comment.

  9. Decision Support Tool for the Management of Debris from Radiological Dispersal Devices and Other Incidents of National Significance

    SciTech Connect (OSTI)

    Lemieux, P.; Thorneloe, S.; Hayes, C.; Rodgers, M.; Christman, R.

    2008-07-01

    Unique challenges exist for the handling, transport, and disposal of debris resulting from homeland security incidents, disasters or other national emergencies. Access to guidance to facilitate decision making to ensure the safe and timely disposal of debris is critical to helping restore a community or region and prevent further contamination or spread of disease. For a radiological dispersal device (RDD), proper characterization of the quantity, properties, and level of contamination of debris can have a significant impact on cleanup costs and timelines. A suite of decision support tools (DSTs) is being developed by the U.S. EPA's Office of Research and Development to assist individuals responsible for making decisions associated with handling, transport, and disposal of such debris. The DSTs are location-specific to help identify specific facilities and contacts for making final disposal decisions. The DSTs provide quick reference to technical information, regulations, and other information to provide decision makers with assistance in guiding disposal decisions that are important for the protection of public health, first responders, and the environment. These tools are being developed in partnership with other U.S. government agencies, EPA program offices, industry, and state and local emergency response programs. (authors)

  10. Reference computations of public dose and cancer risk from airborne releases of plutonium. Nuclear safety technical report

    SciTech Connect (OSTI)

    Peterson, V.L.

    1993-12-23

    This report presents results of computations of doses and the associated health risks of postulated accidental atmospheric releases from the Rocky Flats Plant (RFP) of one gram of weapons-grade plutonium in a form that is respirable. These computations are intended to be reference computations that can be used to evaluate a variety of accident scenarios by scaling the dose and health risk results presented here according to the amount of plutonium postulated to be released, instead of repeating the computations for each scenario. The MACCS2 code has been used as the basis of these computations. The basis and capabilities of MACCS2 are summarized, the parameters used in the evaluations are discussed, and results are presented for the doses and health risks to the public, both the Maximum Offsite Individual (a maximally exposed individual at or beyond the plant boundaries) and the population within 50 miles of RFP. A number of different weather scenarios are evaluated, including constant weather conditions and observed weather for 1990, 1991, and 1992. The isotopic mix of weapons-grade plutonium will change as it ages, the {sup 241}Pu decaying into {sup 241}Am. The {sup 241}Am reaches a peak concentration after about 72 years. The doses to the bone surface, liver, and whole body will increase slightly but the dose to the lungs will decrease slightly. The overall cancer risk will show almost no change over this period. This change in cancer risk is much smaller than the year-to-year variations in cancer risk due to weather. Finally, x/Q values are also presented for other applications, such as for hazardous chemical releases. These include the x/Q values for the MOI, for a collocated worker at 100 meters downwind of an accident site, and the x/Q value integrated over the population out to 50 miles.

  11. Quality of Life and Toxicity From Passively Scattered and Spot-Scanning Proton Beam Therapy for Localized Prostate Cancer

    SciTech Connect (OSTI)

    Pugh, Thomas J. [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Munsell, Mark F. [Department of Biostatistics, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Choi, Seungtaek; Nguyen, Quyhn Nhu; Mathai, Benson [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Zhu, X. Ron; Sahoo, Narayan; Gillin, Michael; Johnson, Jennifer L.; Amos, Richard A. [Department of Radiation Physics, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Dong, Lei [Scripps Proton Therapy Center, San Diego, California (United States); Mahmood, Usama; Kuban, Deborah A.; Frank, Steven J.; Hoffman, Karen E.; McGuire, Sean E. [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Lee, Andrew K., E-mail: aklee@mdanderson.org [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States)

    2013-12-01

    Purpose: To report quality of life (QOL)/toxicity in men treated with proton beam therapy for localized prostate cancer and to compare outcomes between passively scattered proton therapy (PSPT) and spot-scanning proton therapy (SSPT). Methods and Materials: Men with localized prostate cancer enrolled on a prospective QOL protocol with a minimum of 2 years' follow-up were reviewed. Comparative groups were defined by technique (PSPT vs SSPT). Patients completed Expanded Prostate Cancer Index Composite questionnaires at baseline and every 3-6 months after proton beam therapy. Clinically meaningful differences in QOL were defined as ?0.5 baseline standard deviation. The cumulative incidence of modified Radiation Therapy Oncology Group grade ?2 gastrointestinal (GI) or genitourinary (GU) toxicity and argon plasma coagulation were determined by the Kaplan-Meier method. Results: A total of 226 men received PSPT, and 65 received SSPT. Both PSPT and SSPT resulted in statistically significant changes in sexual, urinary, and bowel Expanded Prostate Cancer Index Composite summary scores. Only bowel summary, function, and bother resulted in clinically meaningful decrements beyond treatment completion. The decrement in bowel QOL persisted through 24-month follow-up. Cumulative grade ?2 GU and GI toxicity at 24 months were 13.4% and 9.6%, respectively. There was 1 grade 3 GI toxicity (PSPT group) and no other grade ?3 GI or GU toxicity. Argon plasma coagulation application was infrequent (PSPT 4.4% vs SSPT 1.5%; P=.21). No statistically significant differences were appreciated between PSPT and SSPT regarding toxicity or QOL. Conclusion: Both PSPT and SSPT confer low rates of grade ?2 GI or GU toxicity, with preservation of meaningful sexual and urinary QOL at 24 months. A modest, yet clinically meaningful, decrement in bowel QOL was seen throughout follow-up. No toxicity or QOL differences between PSPT and SSPT were identified. Long-term comparative results in a larger patient cohort are warranted.

  12. Benefit of Adjuvant Brachytherapy Versus External Beam Radiation for Early Breast Cancer: Impact of Patient Stratification on Breast Preservation

    SciTech Connect (OSTI)

    Smith, Grace L.; Jiang, Jing; Buchholz, Thomas A.; Xu, Ying; Hoffman, Karen E.; Giordano, Sharon H.; Hunt, Kelly K.; Smith, Benjamin D.

    2014-02-01

    Purpose: Brachytherapy after lumpectomy is an increasingly popular breast cancer treatment, but data concerning its effectiveness are conflicting. Recently proposed suitability criteria guiding patient selection for brachytherapy have never been empirically validated. Methods: Using the Surveillance, Epidemiology, and End ResultsMedicare linked database, we compared women aged 66 years or older with invasive breast cancer (n=28,718) or ductal carcinoma in situ (n=7229) diagnosed from 2002 to 2007, treated with lumpectomy alone, brachytherapy, or external beam radiation therapy (EBRT). The likelihood of breast preservation, measured by subsequent mastectomy risk, was compared by use of multivariate proportional hazards, further stratified by American Society for Radiation Oncology (ASTRO) brachytherapy suitability groups. We compared 1-year postoperative complications using the ?{sup 2} test and 5-year local toxicities using the log-rank test. Results: For patients with invasive cancer, the 5-year subsequent mastectomy risk was 4.7% after lumpectomy alone (95% confidence interval [CI], 4.1%-5.4%), 2.8% after brachytherapy (95% CI, 1.8%-4.3%), and 1.3% after EBRT (95% CI, 1.1%-1.5%) (P<.001). Compared with lumpectomy alone, brachytherapy achieved a more modest reduction in adjusted risk (hazard ratio [HR], 0.61; 95% CI, 0.40-0.94) than achieved with EBRT (HR, 0.22; 95% CI, 0.18-0.28). Relative risks did not differ when stratified by ASTRO suitability group (P=.84 for interaction), although ASTRO suitable patients did show a low absolute subsequent mastectomy risk, with a minimal absolute difference in risk after brachytherapy (1.6%; 95% CI, 0.7%-3.5%) versus EBRT (0.8%; 95% CI, 0.6%-1.1%). For patients with ductal carcinoma in situ, EBRT maintained a reduced risk of subsequent mastectomy (HR, 0.40; 95% CI, 0.28-0.55; P<.001), whereas the small number of patients treated with brachytherapy (n=179) precluded definitive comparison with lumpectomy alone. In all patients, brachytherapy showed a higher postoperative infection risk (16.5% vs 9.9% after lumpectomy alone vs 11.4% after EBRT, P<.001); higher incidence of breast pain (22.9% vs 11.2% vs 16.7%, P<.001); and higher incidence of fat necrosis (15.3% vs 5.3% vs 7.7%, P<.001). Conclusions: In this study era, brachytherapy showed lesser breast preservation benefit compared with EBRT. Suitability criteria predicted differential absolute, but not relative, benefit in patients with invasive cancer.

  13. Status Update on the NCRP Scientific Committee SC 5-1 Report: Decision Making for Late-Phase Recovery from Nuclear or Radiological Incidents - 13450

    SciTech Connect (OSTI)

    Chen, S.Y.

    2013-07-01

    In August 2008, the U.S. Department of Homeland Security (DHS) issued its final Protective Action Guide (PAG) for radiological dispersal device (RDD) and improvised nuclear device (IND) incidents. This document specifies protective actions for public health during the early and intermediate phases and cleanup guidance for the late phase of RDD or IND incidents, and it discusses approaches to implementing the necessary actions. However, while the PAG provides specific guidance for the early and intermediate phases, it prescribes no equivalent guidance for the late-phase cleanup actions. Instead, the PAG offers a general description of a complex process using a site-specific optimization approach. This approach does not predetermine cleanup levels but approaches the problem from the factors that would bear on the final agreed-on cleanup levels. Based on this approach, the decision-making process involves multifaceted considerations including public health, the environment, and the economy, as well as socio-political factors. In an effort to fully define the process and approach to be used in optimizing late-phase recovery and site restoration following an RDD or IND incident, DHS has tasked the NCRP with preparing a comprehensive report addressing all aspects of the optimization process. Preparation of the NCRP report is a three-year (2010-2013) project assigned to a scientific committee, the Scientific Committee (SC) 5-1; the report was initially titled, Approach to Optimizing Decision Making for Late- Phase Recovery from Nuclear or Radiological Terrorism Incidents. Members of SC 5-1 represent a broad range of expertise, including homeland security, health physics, risk and decision analysis, economics, environmental remediation and radioactive waste management, and communication. In the wake of the Fukushima nuclear accident of 2011, and guided by a recent process led by the White House through a Principal Level Exercise (PLE), the optimization approach has since been expanded to include off-site contamination from major nuclear power plant accidents as well as other nuclear or radiological incidents. The expanded application under the current guidance has thus led to a broadened scope of the report, which is reflected in its new title, Decision Making for Late-Phase Recovery from Nuclear or Radiological Incidents. The NCRP report, which is due for publication in 2013, will substantiate the current DHS guidance by clarifying and elaborating on the processes required for the development and implementation of procedures for optimizing decision making for late-phase recovery, enabling the establishment of cleanup goals on a site-specific basis. The report will contain a series of topics addressing important issues related to the long-term recovery from nuclear or radiological incidents. Special topics relevant to supporting the optimization of the decision-making process will include cost-benefit analysis, radioactive waste management, risk communication, stakeholder interaction, risk assessment, and decontamination approaches and techniques. The committee also evaluated past nuclear and radiological incidents for their relevance to the report, including the emerging issues associated with the Fukushima nuclear accident. Thus, due to the commonality of the late-phase issues (such as the potential widespread contamination following an event), the majority of the information pertaining to the response in the late-phase decision-making period, including site-specific optimization framework and approach, could be used or adapted for use in case of similar situations that are not due to terrorism, such as those that would be caused by major nuclear facility accidents or radiological incidents. To ensure that the report and the NCRP recommendations are current and relevant to the effective implementation of federal guidance, SC 5-1 has actively coordinated with the agencies of interest and other relevant stakeholders throughout the duration of the project. The resulting report will be an important resource to guide those involved in late-phase recovery efforts following a nuclear or radiological incident. (authors)

  14. Experimental validation of the van Herk margin formula for lung radiation therapy

    SciTech Connect (OSTI)

    Ecclestone, Gillian; Heath, Emily; Bissonnette, Jean-Pierre

    2013-11-15

    Purpose: To validate the van Herk margin formula for lung radiation therapy using realistic dose calculation algorithms and respiratory motion modeling. The robustness of the margin formula against variations in lesion size, peak-to-peak motion amplitude, tissue density, treatment technique, and plan conformity was assessed, along with the margin formula assumption of a homogeneous dose distribution with perfect plan conformity.Methods: 3DCRT and IMRT lung treatment plans were generated within the ORBIT treatment planning platform (RaySearch Laboratories, Sweden) on 4DCT datasets of virtual phantoms. Random and systematic respiratory motion induced errors were simulated using deformable registration and dose accumulation tools available within ORBIT for simulated cases of varying lesion sizes, peak-to-peak motion amplitudes, tissue densities, and plan conformities. A detailed comparison between the margin formula dose profile model, the planned dose profiles, and penumbra widths was also conducted to test the assumptions of the margin formula. Finally, a correction to account for imperfect plan conformity was tested as well as a novel application of the margin formula that accounts for the patient-specific motion trajectory.Results: The van Herk margin formula ensured full clinical target volume coverage for all 3DCRT and IMRT plans of all conformities with the exception of small lesions in soft tissue. No dosimetric trends with respect to plan technique or lesion size were observed for the systematic and random error simulations. However, accumulated plans showed that plan conformity decreased with increasing tumor motion amplitude. When comparing dose profiles assumed in the margin formula model to the treatment plans, discrepancies in the low dose regions were observed for the random and systematic error simulations. However, the margin formula respected, in all experiments, the 95% dose coverage required for planning target volume (PTV) margin derivation, as defined by the ICRU; thus, suitable PTV margins were estimated. The penumbra widths calculated in lung tissue for each plan were found to be very similar to the 6.4 mm value assumed by the margin formula model. The plan conformity correction yielded inconsistent results which were largely affected by image and dose grid resolution while the trajectory modified PTV plans yielded a dosimetric benefit over the standard internal target volumes approach with up to a 5% decrease in the V20 value.Conclusions: The margin formula showed to be robust against variations in tumor size and motion, treatment technique, plan conformity, as well as low tissue density. This was validated by maintaining coverage of all of the derived PTVs by 95% dose level, as required by the formal definition of the PTV. However, the assumption of perfect plan conformity in the margin formula derivation yields conservative margin estimation. Future modifications to the margin formula will require a correction for plan conformity. Plan conformity can also be improved by using the proposed trajectory modified PTV planning approach. This proves especially beneficial for tumors with a large anteriorposterior component of respiratory motion.

  15. Cold atmospheric plasma in cancer therapy

    SciTech Connect (OSTI)

    Keidar, Michael; Shashurin, Alex; Volotskova, Olga; Ann Stepp, Mary; Srinivasan, Priya; Sandler, Anthony; Trink, Barry

    2013-05-15

    Recent progress in atmospheric plasmas has led to the creation of cold plasmas with ion temperature close to room temperature. This paper outlines recent progress in understanding of cold plasma physics as well as application of cold atmospheric plasma (CAP) in cancer therapy. Varieties of novel plasma diagnostic techniques were developed recently in a quest to understand physics of CAP. It was established that the streamer head charge is about 10{sup 8} electrons, the electrical field in the head vicinity is about 10{sup 7} V/m, and the electron density of the streamer column is about 10{sup 19} m{sup ?3}. Both in-vitro and in-vivo studies of CAP action on cancer were performed. It was shown that the cold plasma application selectively eradicates cancer cells in-vitro without damaging normal cells and significantly reduces tumor size in-vivo. Studies indicate that the mechanism of action of cold plasma on cancer cells is related to generation of reactive oxygen species with possible induction of the apoptosis pathway. It is also shown that the cancer cells are more susceptible to the effects of CAP because a greater percentage of cells are in the S phase of the cell cycle.

  16. Enzyme Structure Provides Insights into Cancer and Aging

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Enzyme Structure Provides Insights into Cancer and Aging Enzyme Structure Provides Insights into Cancer and Aging Print Wednesday, 25 February 2009 00:00 XPD helicase is an enzyme...

  17. Breaking a Pocket of Resistance in the Fight Against Cancer

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Breaking a Pocket of Resistance in the Fight Against Cancer Breaking a Pocket of Resistance in the Fight Against Cancer Print Thursday, 12 December 2013 11:55 ras protein The new...

  18. Lab Breakthrough: Nanomaterials Discoveries Lead to Possible Cancer

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    Treatment | Department of Energy Nanomaterials Discoveries Lead to Possible Cancer Treatment Lab Breakthrough: Nanomaterials Discoveries Lead to Possible Cancer Treatment June 4, 2012 - 3:05pm Addthis Argonne nanoscientist Elena Rozhkova is studying ways to enlist nanoparticles to treat brain cancer. This nano-bio technology may eventually provide an alternative form of therapy that targets only cancer cells and does not affect normal living tissue. View the entire Lab Breakthrough playlist.

  19. Zinc chromate induces chromosome instability and DNA double strand breaks in human lung cells

    SciTech Connect (OSTI)

    Xie Hong; Holmes, Amie L.; Young, Jamie L.; Qin Qin; Joyce, Kellie; Pelsue, Stephen C.; Peng Cheng; Wise, Sandra S.; Jeevarajan, Antony S.; Wallace, William T.; Hammond, Dianne; Wise, John Pierce E-mail: John.Wise@usm.maine.edu

    2009-02-01

    Hexavalent chromium Cr(VI) is a respiratory toxicant and carcinogen, with solubility playing an important role in its carcinogenic potential. Zinc chromate, a water insoluble or 'particulate' Cr(VI) compound, has been shown to be carcinogenic in epidemiology studies and to induce tumors in experimental animals, but its genotoxicity is poorly understood. Our study shows that zinc chromate induced concentration-dependent increases in cytotoxicity, chromosome damage and DNA double strand breaks in human lung cells. In response to zinc chromate-induced breaks, MRE11 expression was increased and ATM and ATR were phosphorylated, indicating that the DNA double strand break repair system was initiated in the cells. In addition, our data show that zinc chromate-induced double strand breaks were only observed in the G2/M phase population, with no significant amount of double strand breaks observed in G1 and S phase cells. These data will aid in understanding the mechanisms of zinc chromate toxicity and carcinogenesis.

  20. Magnetic relaxometry as applied to sensitive cancer detection and

    Office of Scientific and Technical Information (OSTI)

    localization (Journal Article) | SciTech Connect Magnetic relaxometry as applied to sensitive cancer detection and localization Citation Details In-Document Search Title: Magnetic relaxometry as applied to sensitive cancer detection and localization Here we describe superparamagnetic relaxometry (SPMR), a technology that utilizes highly sensitive magnetic sensors and superparamagnetic nanoparticles for cancer detection. Using SPMR, we sensitively and specifically detect nanoparticles

  1. Genomic Prostate Cancer Classifier Predicts Biochemical Failure and Metastases in Patients After Postoperative Radiation Therapy

    SciTech Connect (OSTI)

    Den, Robert B.; Feng, Felix Y.; Showalter, Timothy N.; Mishra, Mark V.; Trabulsi, Edouard J.; Lallas, Costas D.; Gomella, Leonard G.; Kelly, W. Kevin; Birbe, Ruth C.; McCue, Peter A.; Ghadessi, Mercedeh; Yousefi, Kasra; Davicioni, Elai; Knudsen, Karen E.; Dicker, Adam P.

    2014-08-01

    Purpose: Totest the hypothesis that a genomic classifier (GC) would predict biochemical failure (BF) and distant metastasis (DM) in men receiving radiation therapy (RT) after radical prostatectomy (RP). Methods and Materials: Among patients who underwent post-RP RT, 139 were identified for pT3 or positive margin, who did not receive neoadjuvant hormones and had paraffin-embedded specimens. Ribonucleic acid was extracted from the highest Gleason grade focus and applied to a high-density-oligonucleotide microarray. Receiver operating characteristic, calibration, cumulative incidence, and Cox regression analyses were performed to assess GC performance for predicting BF and DM after post-RP RT in comparison with clinical nomograms. Results: Thearea under the receiver operating characteristic curve of the Stephenson model was 0.70 for both BF and DM, with addition of GC significantly improving area under the receiver operating characteristic curve to 0.78 and 0.80, respectively. Stratified by GC risk groups, 8-year cumulative incidence was 21%, 48%, and 81% for BF (P<.0001) and for DM was 0, 12%, and 17% (P=.032) for low, intermediate, and high GC, respectively. In multivariable analysis, patients with high GC had a hazard ratio of 8.1 and 14.3 for BF and DM. In patients with intermediate or high GC, those irradiated with undetectable prostate-specific antigen (PSA ?0.2ng/mL) had median BF survival of >8years, compared with <4years for patients with detectable PSA (>0.2ng/mL) before initiation of RT. At 8years, the DM cumulative incidence for patients with high GC and RT with undetectable PSA was 3%, compared with 23% with detectable PSA (P=.03). No outcome differences were observed for low GC between the treatment groups. Conclusion: The GC predicted BF and metastasis after post-RP irradiation. Patients withlower GC risk may benefit from delayed RT, as opposed to those with higher GC; however, this needs prospective validation. Genomic-based models may be useful forimproved decision-making for treatment of high-risk prostate cancer.

  2. Blood Vessel Normalization in the Hamster Oral Cancer Model for Experimental Cancer Therapy Studies

    SciTech Connect (OSTI)

    Ana J. Molinari; Romina F. Aromando; Maria E. Itoiz; Marcela A. Garabalino; Andrea Monti Hughes; Elisa M. Heber; Emiliano C. C. Pozzi; David W. Nigg; Veronica A. Trivillin; Amanda E. Schwint

    2012-07-01

    Normalization of tumor blood vessels improves drug and oxygen delivery to cancer cells. The aim of this study was to develop a technique to normalize blood vessels in the hamster cheek pouch model of oral cancer. Materials and Methods: Tumor-bearing hamsters were treated with thalidomide and were compared with controls. Results: Twenty eight hours after treatment with thalidomide, the blood vessels of premalignant tissue observable in vivo became narrower and less tortuous than those of controls; Evans Blue Dye extravasation in tumor was significantly reduced (indicating a reduction in aberrant tumor vascular hyperpermeability that compromises blood flow), and tumor blood vessel morphology in histological sections, labeled for Factor VIII, revealed a significant reduction in compressive forces. These findings indicated blood vessel normalization with a window of 48 h. Conclusion: The technique developed herein has rendered the hamster oral cancer model amenable to research, with the potential benefit of vascular normalization in head and neck cancer therapy.

  3. New opportunities for quasielastic and inelastic neutron scattering at steady-state sources using mechanical selection of the incident and final neutron energy

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Mamantov, Eugene

    2015-06-12

    We propose a modification of the neutron wide-angle velocity selector (WAVES) device that enables inelastic (in particular, quasielastic) scattering measurements not relying on the neutron time-of-flight. The proposed device is highly suitable for a steady-state neutron source, somewhat similar to a triple-axis spectrometer, but with simultaneous selection of the incident and final neutron energy over a broad range of scattering momentum transfer. Both the incident and final neutron velocities are defined by the WAVES geometry and rotation frequency. The variable energy transfer is achieved through the natural variation of the velocity of the transmitted neutrons as a function of themore » scattering angle component out of the equatorial plane.« less

  4. Isotope Cancer Treatment Research at LANL

    ScienceCinema (OSTI)

    Weidner, John; Nortier, Meiring

    2014-06-02

    Los Alamos National Laboratory has produced medical isotopes for diagnostic and imaging purposes for more than 30 years. Now LANL researchers have branched out into isotope cancer treatment studies. New results show that an accelerator-based approach can produce clinical trial quantities of actinium-225, an isotope that has promise as a way to kill tumors without damaging surrounding healthy cells.

  5. Downregulation of tumor suppressor QKI in gastric cancer and its implication in cancer prognosis

    SciTech Connect (OSTI)

    Bian, Yongqian [The State Key Laboratory of Cancer Biology, Xijing Hospital of Digestive Diseases, The Fourth Military Medical University, Xi'an 710032 (China)] [The State Key Laboratory of Cancer Biology, Xijing Hospital of Digestive Diseases, The Fourth Military Medical University, Xi'an 710032 (China); Wang, Li; Lu, Huanyu; Yang, Guodong [The State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, The Fourth Military Medical University, Xi'an 710032 (China)] [The State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, The Fourth Military Medical University, Xi'an 710032 (China); Zhang, Zhang [The State Key Laboratory of Cancer Biology, Xijing Hospital of Digestive Diseases, The Fourth Military Medical University, Xi'an 710032 (China)] [The State Key Laboratory of Cancer Biology, Xijing Hospital of Digestive Diseases, The Fourth Military Medical University, Xi'an 710032 (China); Fu, Haiyan; Lu, Xiaozhao; Wei, Mengying [The State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, The Fourth Military Medical University, Xi'an 710032 (China)] [The State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, The Fourth Military Medical University, Xi'an 710032 (China); Sun, Jianyong; Zhao, Qingchuan [The State Key Laboratory of Cancer Biology, Xijing Hospital of Digestive Diseases, The Fourth Military Medical University, Xi'an 710032 (China)] [The State Key Laboratory of Cancer Biology, Xijing Hospital of Digestive Diseases, The Fourth Military Medical University, Xi'an 710032 (China); Dong, Guanglong, E-mail: gldong301@gmail.com [The State Key Laboratory of Cancer Biology, Xijing Hospital of Digestive Diseases, The Fourth Military Medical University, Xi'an 710032 (China) [The State Key Laboratory of Cancer Biology, Xijing Hospital of Digestive Diseases, The Fourth Military Medical University, Xi'an 710032 (China); Department of General Surgery, The General Hospital of the PLA, Beijing 100853 (China); Lu, Zifan, E-mail: luzfliuq@fmmu.edu.cn [The State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, The Fourth Military Medical University, Xi'an 710032 (China)] [The State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, The Fourth Military Medical University, Xi'an 710032 (China)

    2012-05-25

    Highlights: Black-Right-Pointing-Pointer QKI expression is decreased in gastric cancer samples. Black-Right-Pointing-Pointer Promoter hyper methylation contributes to the downregulation of QKI. Black-Right-Pointing-Pointer QKI inhibits the growth of gastric cancer cells. Black-Right-Pointing-Pointer Decreased QKI expression predicts poor survival. -- Abstract: Gastric cancer (GC) is the fourth most common cancer and second leading cause of cancer-related death worldwide. RNA-binding protein Quaking (QKI) is a newly identified tumor suppressor in multiple cancers, while its role in GC is largely unknown. Our study here aimed to clarify the relationship between QKI expression with the clinicopathologic characteristics and the prognosis of GC. In the 222 GC patients' specimens, QKI expression was found to be significantly decreased in most of the GC tissues, which was largely due to promoter hypermethylation. QKI overexpression reduced the proliferation ability of GC cell line in vitro study. In addition, the reduced QKI expression correlated well with poor differentiation status, depth of invasion, gastric lymph node metastasis, distant metastasis, advanced TNM stage, and poor survival. Multivariate analysis showed QKI expression was an independent prognostic factor for patient survival.

  6. Kinase Expression and Chromosomal Rearrangements in Papillary Thyroid Cancer Tissues: Investigations at the Molecular and Microscopic Levels

    SciTech Connect (OSTI)

    Weier, Heinz-Ulrich; Kwan, Johnson; Lu, Chun-Mei; Ito, Yuko; Wang, Mei; Baumgartner, Adolf; Hayward, Simon W.; Weier, Jingly F.; Zitzelsberger, Horst F.

    2009-07-07

    Structural chromosome aberrations are known hallmarks of many solid tumors. In the papillary form of thyroid cancer (PTC), for example, activation of the receptor tyrosine kinase (RTK) genes, ret or the neurotrophic tyrosine kinase receptor type I (NTRK1) by intra- or interchromosomal rearrangements have been suggested as a cause of the disease. The 1986 accident at the nuclear power plant in Chernobyl, USSR, led to the uncontrolled release of high levels of radioisotopes. Ten years later, the incidence of childhood papillary thyroid cancer (chPTC) near Chernobyl had risen by two orders of magnitude. Tumors removed from some of these patients showed aberrant expression of the ret RTK gene due to a ret/PTC1 or ret/PTC3 rearrangement involving chromosome 10. However, many cultured chPTC cells show a normal G-banded karyotype and no ret rearrangement. We hypothesize that the 'ret-negative' tumors inappropriately express a different oncogene or have lost function of a tumor suppressor as a result of chromosomal rearrangements, and decided to apply molecular and cytogenetic methods to search for potentially oncogenic chromosomal rearrangements in Chernobyl chPTC cases. Knowledge of the kind of genetic alterations may facilitate the early detection and staging of chPTC as well as provide guidance for therapeutic intervention.

  7. Ethanol metabolism, oxidative stress, and endoplasmic reticulum stress responses in the lungs of hepatic alcohol dehydrogenase deficient deer mice after chronic ethanol feeding

    SciTech Connect (OSTI)

    Kaphalia, Lata; Boroumand, Nahal; Hyunsu, Ju; Kaphalia, Bhupendra S.; Calhoun, William J.

    2014-06-01

    Consumption and over-consumption of alcoholic beverages are well-recognized contributors to a variety of pulmonary disorders, even in the absence of intoxication. The mechanisms by which alcohol (ethanol) may produce disease include oxidative stress and prolonged endoplasmic reticulum (ER) stress. Many aspects of these processes remain incompletely understood due to a lack of a suitable animal model. Chronic alcohol over-consumption reduces hepatic alcohol dehydrogenase (ADH), the principal canonical metabolic pathway of ethanol oxidation. We therefore modeled this situation using hepatic ADH-deficient deer mice fed 3.5% ethanol daily for 3 months. Blood ethanol concentration was 180 mg% in ethanol fed mice, compared to < 1.0% in the controls. Acetaldehyde (oxidative metabolite of ethanol) was minimally, but significantly increased in ethanol-fed vs. pair-fed control mice. Total fatty acid ethyl esters (FAEEs, nonoxidative metabolites of ethanol) were 47.6 ?g/g in the lungs of ethanol-fed mice as compared to 1.5 ?g/g in pair-fed controls. Histological and immunohistological evaluation showed perivascular and peribronchiolar lymphocytic infiltration, and significant oxidative injury, in the lungs of ethanol-fed mice compared to pair-fed controls. Several fold increases for cytochrome P450 2E1, caspase 8 and caspase 3 found in the lungs of ethanol-fed mice as compared to pair-fed controls suggest role of oxidative stress in ethanol-induced lung injury. ER stress and unfolded protein response signaling were also significantly increased in the lungs of ethanol-fed mice. Surprisingly, no significant activation of inositol-requiring enzyme-1? and spliced XBP1 was observed indicating a lack of activation of corrective mechanisms to reinstate ER homeostasis. The data suggest that oxidative stress and prolonged ER stress, coupled with formation and accumulation of cytotoxic FAEEs may contribute to the pathogenesis of alcoholic lung disease. - Highlights: Chronic ethanol feeding causes oxidative stress, ER stress and inflammation in lungs of ADH deer mice. Chronic ethanol feeding generates FAEEs (nonoxidative metabolites of ethanol) in lungs of ADH deer mice. Chronic ethanol feeding induces CYP2E1 in the lungs of ADH deer mice. Lack of ER homeostasis due to a prolonged ethanol feeding could trigger inflammation.

  8. Brachial Plexus-Associated Neuropathy After High-Dose Radiation Therapy for Head-and-Neck Cancer

    SciTech Connect (OSTI)

    Chen, Allen M.; Hall, William H.; Li, Judy; Beckett, Laurel; Farwell, D. Gregory; Lau, Derick H.; Purdy, James A.

    2012-09-01

    Purpose: To identify clinical and treatment-related predictors of brachial plexus-associated neuropathies after radiation therapy for head-and-neck cancer. Methods and Materials: Three hundred thirty patients who had previously completed radiation therapy for head-and-neck cancer were prospectively screened using a standardized instrument for symptoms of neuropathy thought to be related to brachial plexus injury. All patients were disease-free at the time of screening. The median time from completion of radiation therapy was 56 months (range, 6-135 months). One-hundred fifty-five patients (47%) were treated by definitive radiation therapy, and 175 (53%) were treated postoperatively. Radiation doses ranged from 50 to 74 Gy (median, 66 Gy). Intensity-modulated radiation therapy was used in 62% of cases, and 133 patients (40%) received concurrent chemotherapy. Results: Forty patients (12%) reported neuropathic symptoms, with the most common being ipsilateral pain (50%), numbness/tingling (40%), motor weakness, and/or muscle atrophy (25%). When patients with <5 years of follow-up were excluded, the rate of positive symptoms increased to 22%. On univariate analysis, the following factors were significantly associated with brachial plexus symptoms: prior neck dissection (p = 0.01), concurrent chemotherapy (p = 0.01), and radiation maximum dose (p < 0.001). Cox regression analysis confirmed that both neck dissection (p < 0.001) and radiation maximum dose (p < 0.001) were independently predictive of symptoms. Conclusion: The incidence of brachial plexus-associated neuropathies after radiation therapy for head-and-neck cancer may be underreported. In view of the dose-response relationship identified, limiting radiation dose to the brachial plexus should be considered when possible.

  9. SU-E-J-23: An Accurate Algorithm to Match Imperfectly Matched Images for Lung Tumor Detection Without Markers

    SciTech Connect (OSTI)

    Rozario, T; Bereg, S; Chiu, T; Liu, H; Kearney, V; Jiang, L; Mao, W

    2014-06-01

    Purpose: In order to locate lung tumors on projection images without internal markers, digitally reconstructed radiograph (DRR) is created and compared with projection images. Since lung tumors always move and their locations change on projection images while they are static on DRRs, a special DRR (background DRR) is generated based on modified anatomy from which lung tumors are removed. In addition, global discrepancies exist between DRRs and projections due to their different image originations, scattering, and noises. This adversely affects comparison accuracy. A simple but efficient comparison algorithm is reported. Methods: This method divides global images into a matrix of small tiles and similarities will be evaluated by calculating normalized cross correlation (NCC) between corresponding tiles on projections and DRRs. The tile configuration (tile locations) will be automatically optimized to keep the tumor within a single tile which has bad matching with the corresponding DRR tile. A pixel based linear transformation will be determined by linear interpolations of tile transformation results obtained during tile matching. The DRR will be transformed to the projection image level and subtracted from it. The resulting subtracted image now contains only the tumor. A DRR of the tumor is registered to the subtracted image to locate the tumor. Results: This method has been successfully applied to kV fluoro images (about 1000 images) acquired on a Vero (Brainlab) for dynamic tumor tracking on phantom studies. Radiation opaque markers are implanted and used as ground truth for tumor positions. Although, other organs and bony structures introduce strong signals superimposed on tumors at some angles, this method accurately locates tumors on every projection over 12 gantry angles. The maximum error is less than 2.6 mm while the total average error is 1.0 mm. Conclusion: This algorithm is capable of detecting tumor without markers despite strong background signals.

  10. SU-E-I-25: Determining Tube Current, Tube Voltage and Pitch Suitable for Low- Dose Lung Screening CT

    SciTech Connect (OSTI)

    Williams, K; Matthews, K

    2014-06-01

    Purpose: The quality of a computed tomography (CT) image and the dose delivered during its acquisition depend upon the acquisition parameters used. Tube current, tube voltage, and pitch are acquisition parameters that potentially affect image quality and dose. This study investigated physicians' abilities to characterize small, solid nodules in low-dose CT images for combinations of current, voltage and pitch, for three CT scanner models. Methods: Lung CT images was acquired of a Data Spectrum anthropomorphic torso phantom with various combinations of pitch, tube current, and tube voltage; this phantom was used because acrylic beads of various sizes could be placed within the lung compartments to simulate nodules. The phantom was imaged on two 16-slice scanners and a 64-slice scanner. The acquisition parameters spanned a range of estimated CTDI levels; the CTDI estimates from the acquisition software were verified by measurement. Several experienced radiologists viewed the phantom lung CT images and noted nodule location, size and shape, as well as the acceptability of overall image quality. Results: Image quality for assessment of nodules was deemed unsatisfactory for all scanners at 80 kV (any tube current) and at 35 mA (any tube voltage). Tube current of 50 mA or more at 120 kV resulted in similar assessments from all three scanners. Physician-measured sphere diameters were closer to actual diameters for larger spheres, higher tube current, and higher kV. Pitch influenced size measurements less for larger spheres than for smaller spheres. CTDI was typically overestimated by the scanner software compared to measurement. Conclusion: Based on this survey of acquisition parameters, a low-dose CT protocol of 120 kV, 50 mA, and pitch of 1.4 is recommended to balance patient dose and acceptable image quality. For three models of scanners, this protocol resulted in estimated CTDIs from 2.93.6 mGy.

  11. Search for: All records | SciTech Connect

    Office of Scientific and Technical Information (OSTI)

    ... Methods: Sixteen lung cancer patients scheduled for stereotactic body radiotherapy ... 116 were analyzable (43 had oropharyngeal cancer, 54 had hypopharyngeal cancer, and 19 had ...

  12. Viscoelastic Model for Lung Parenchyma for Multi-Scale Modeling of Respiratory System Phase I: Hypo-Elastic Model for CFD Implementation

    SciTech Connect (OSTI)

    Freed, Alan D.; Einstein, Daniel R.

    2011-04-14

    An isotropic constitutive model for the parenchyma of lung has been derived from the theory of hypo-elasticity. The intent is to use it to represent the mechanical response of this soft tissue in sophisticated, computational, fluid-dynamic models of the lung. This demands that the continuum model be accurate, yet simple and effcient. An objective algorithm for its numeric integration is provided. The response of the model is determined for several boundary-value problems whose experiments are used for material characterization. The effective elastic, bulk, and shear moduli, and Poissons ratio, as tangent functions, are also derived. The model is characterized against published experimental data for lung. A bridge between this continuum model and a dodecahedral model of alveolar geometry is investigated, with preliminary findings being reported.

  13. Garcinol, a Histone Acetyltransferase Inhibitor, Radiosensitizes Cancer Cells by Inhibiting Non-Homologous End Joining

    SciTech Connect (OSTI)

    Oike, Takahiro; Division of Genome Biology, National Cancer Center Research Institute, Chuo-ku, Tokyo; Department of Radiation Oncology, Gunma University Graduate School of Medicine, Maebashi, Gunma ; Ogiwara, Hideaki; Torikai, Kohta; Nakano, Takashi; Yokota, Jun; Kohno, Takashi

    2012-11-01

    Purpose: Non-homologous end joining (NHEJ), a major pathway used to repair DNA double-strand breaks (DSBs) generated by ionizing radiation (IR), requires chromatin remodeling at DSB sites through the acetylation of histones by histone acetyltransferases (HATs). However, the effect of compounds with HAT inhibitory activities on the DNA damage response (DDR), including the NHEJ and cell cycle checkpoint, as well as on the radiosensitivity of cancer cells, remains largely unclear. Here, we investigated whether garcinol, a HAT inhibitor found in the rinds of Garcinia indica fruit (called mangosteens), has effects on DDR, and whether it can be used for radiosensitization. Methods and Materials: The following assays were used to examine the effect of garcinol on the inhibition of DSB repair, including the following: a conventional neutral comet assay; a cell-based assay recently developed by us, in which NHEJ repair of DSBs on chromosomal DNA was evaluated; the micrococcal nuclease sensitivity assay; and immunoblotting for autophosphorylation of DNA-dependent protein kinase catalytic subunit (DNA-PKcs). We assessed the effect of garcinol on the cell cycle checkpoint after IR treatment by analyzing the phosphorylation levels of checkpoint kinases CHK1 and CHK2 and histone H3, and by cell cycle profile analysis using flow cytometry. The radiosensitizing effect of garcinol was assessed by a clonogenic survival assay, whereas its effects on apoptosis and senescence were examined by annexin V and senescence-associated {beta}-galactosidase (SA-{beta}-Gal) staining, respectively. Results: We found that garcinol inhibits DSB repair, including NHEJ, without affecting cell cycle checkpoint. Garcinol radiosensitized A549 lung and HeLa cervical carcinoma cells with dose enhancement ratios (at 10% surviving fraction) of 1.6 and 1.5, respectively. Cellular senescence induced by IR was enhanced by garcinol. Conclusion: These results suggest that garcinol is a radiosensitizer that inhibits NHEJ and facilitates senescence without impairing activation of the cell cycle checkpoint.

  14. Compositions and methods for cancer treatment using targeted carbon nanotubes

    DOE Patents [OSTI]

    Harrison, Jr., Roger G; Resasco, Daniel E; Neves, Luis Filipe Ferreira

    2013-08-27

    The present invention is a method for detecting and destroying cancer tumors. The method is based on the concept of associating a linking protein or linking peptide such as, but not limited to, annexin V or other annexins to carbon nanotubes such as single-walled carbon nanotubes (SWNTs) to form a protein-CNT complex. Said linking protein or peptide can selectively bind to cancerous cells, especially tumor vasculature endothelial cells, rather than to healthy ones by binding to cancer-specific external receptors such as anionic phospholipids including phosphatidylserine expressed on the outer surfaces of cancer cells only. Irradiation of bound CNTs with one or more specific electromagnetic wavelengths is then used to detect and destroy those cells to which the CNTs are bound via the linking protein or peptide thereby destroying the tumor or cancer cells and preferably an immunostimulant is provided to the patient to enhance the immune response against antigens released from the tumor or cancer cells.

  15. Translating the cancer genome: Going beyond p values

    SciTech Connect (OSTI)

    Chin, Lynda; Chin, Lynda; Gray, Joe W.

    2008-04-03

    Cancer cells are endowed with diverse biological capabilities driven by myriad inherited and somatic genetic and epigenetic aberrations that commandeer key cancer-relevant pathways. Efforts to elucidate these aberrations began with Boveri's hypothesis of aberrant mitoses causing cancer and continue today with a suite of powerful high-resolution technologies that enable detailed catalogues of genomic aberrations and epigenomic modifications. Tomorrow will likely bring the complete atlas of reversible and irreversible alteration in individual cancers. The challenge now is to discern causal molecular abnormalities from genomic and epigenomic 'noise', to understand how the ensemble of these aberrations collaborate to drive cancer pathophysiology. Here, we highlight lessons learned from now classical examples of successful translation of genomic discoveries into clinical practice, lessons that may be used to guide and accelerate translation of emerging genomic insights into practical clinical endpoints that can impact on practice of cancer medicine.

  16. Genome Science and Personalized Cancer Treatment (LBNL Summer Lecture Series)

    SciTech Connect (OSTI)

    Gray, Joe

    2009-08-04

    Summer Lecture Series 2009: Results from the Human Genome Project are enabling scientists to understand how individual cancers form and progress. This information, when combined with newly developed drugs, can optimize the treatment of individual cancers. Joe Gray, director of Berkeley Labs Life Sciences Division and Associate Laboratory Director for Life and Environmental Sciences, will focus on this approach, its promise, and its current roadblocks particularly with regard to breast cancer.

  17. Receipt of Guideline-Concordant Treatment in Elderly Prostate Cancer

    Office of Scientific and Technical Information (OSTI)

    Patients (Journal Article) | SciTech Connect Receipt of Guideline-Concordant Treatment in Elderly Prostate Cancer Patients Citation Details In-Document Search Title: Receipt of Guideline-Concordant Treatment in Elderly Prostate Cancer Patients Purpose: To examine the proportion of elderly prostate cancer patients receiving guideline-concordant treatment, using the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database. Methods and Materials: A total of 29,001 men

  18. Los Alamos researcher pens prizewinning essay on cancer

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Researcher pens prizewinning essay on cancer Los Alamos researcher pens prizewinning essay on cancer Ludmil Alexandrov made strong points this week in the journal Science winning a 2015 Science & SciLifeLab Prize, on "Understanding the Origins of Human Cancer." December 6, 2015 The international prize is awarded annually to four young scientists for outstanding life science research for which he or she earned a doctoral degree in the previous two years. The international prize is

  19. Isotope production facility produces cancer-fighting actinium

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Cancer therapy gets a boost from new isotope Isotope production facility produces cancer-fighting actinium A new medical isotope project shows promise for rapidly producing major quantities of a new cancer-treatment agent, actinium 225 (Ac-225). April 11, 2012 Los Alamos scientist Meiring Nortier holds a thorium foil test target for the proof-of-concept production experiments. Los Alamos scientist Meiring Nortier holds a thorium foil test target for the proof-of-concept production experiments.

  20. Genome Science and Personalized Cancer Treatment (LBNL Summer Lecture Series)

    ScienceCinema (OSTI)

    Gray, Joe

    2011-04-28

    Summer Lecture Series 2009: Results from the Human Genome Project are enabling scientists to understand how individual cancers form and progress. This information, when combined with newly developed drugs, can optimize the treatment of individual cancers. Joe Gray, director of Berkeley Labs Life Sciences Division and Associate Laboratory Director for Life and Environmental Sciences, will focus on this approach, its promise, and its current roadblocks ? particularly with regard to breast cancer.

  1. eFRMAC Overview: Data Management and Enabling Technologies for Characterization of a Radiological Release A Case Study: The Fukushima Nuclear Power Plant Incident

    SciTech Connect (OSTI)

    Blumenthal, Daniel J.; Clark, Harvey W.; Essex, James J.; Wagner, Eric C.

    2013-07-01

    The eFRMAC enterprise is a suite of technologies and software developed by the United States Department of Energy, National Nuclear Security Administration’s Office of Emergency Response to coordinate the rapid data collection, management, and analysis required during a radiological emergency. This enables the Federal Radiological Monitoring and Assessment Center assets to evaluate a radiological or nuclear incident efficiently to facilitate protective actions to protect public health and the environment. This document identifies and describes eFRMAC methods including (1) data acquisition, (2) data management, (3) data analysis, (4) product creation, (5) quality control, and (6) dissemination.

  2. Expression of transforming growth factor alpha in plutonium-239-induced lung neoplasms in dogs: investigations of autocrine mechanisms of growth

    SciTech Connect (OSTI)

    Gillett, N.A.; Stegelmeier, B.L.; Chang, I.Y.; Kelly, G. )

    1991-06-01

    We have previously shown that 47% of radiation-induced lung neoplasms in dogs exhibit increased expression of epidermal growth factor receptor (EGFR). In this study, we investigated the expression of transforming growth factor alpha (TGF-alpha), a ligand for EGFR, to determine if an autocrine mechanism for growth stimulation was present in these tumors. As determined by immunohistochemistry, 59% (26/44) of the lung neoplasms examined had increased expression of TGF-alpha. Expression of TGF-alpha was not related to the etiology of the tumor, e.g., spontaneous or plutonium-induced; however, it was related to the phenotype of the tumor. Statistical analysis of the correlation of EGFR and TGF-alpha expression within the same tumor did not show a positive association; however, specific phenotypes did have statistically significant expression of EGFR or TGF-alpha, suggesting that overexpression of either the ligand or its receptor conferred a growth advantage to the neoplasm. Twenty-seven percent (32/117) of radiation-induced proliferative epithelial foci expressed TGF-alpha, and a portion of those foci (8/32) expressed both EGFR and TGF-alpha. This supports the hypothesis that these foci represent preneoplastic lesions, and suggests that those foci exhibiting increased expression of the growth factor or its receptor are at greater risk for progressing to neoplasia.

  3. Understanding the chemical properties of macerals and minerals in coal and its potential application for occupational lung disease prevention

    SciTech Connect (OSTI)

    Huang, X.; Finkelman, R.B.

    2008-07-01

    The objective of this review was to assess whether some chemical parameters in coal play a role in producing environmental health problems. Basic properties of coal - such as chemical forms of the organic materials, structure, compositions of minerals - vary from one coal mine region to another as well as from coals of different ranks. Most importantly, changes in chemical properties of coals due to exposure to air and humidity after mining - a dynamic process - significantly affect toxicity attributed to coal and environmental fate. Although coal is an extremely complex and heterogeneous material, the fundamental properties of coal responsible for environmental and adverse health problems are probably related to the same inducing components of coal. For instance, oxidation of pyrite (FeS{sub 2}) in the coal forms iron sulfate and sulfuric acid, which produces occupational lung diseases (e.g., pneumoconiosis) and other environmental problems (e.g., acid mine drainage and acid rain). Calcite (CaCO{sub 3}) contained in certain coals alters the end products of pyrite oxidation, which may make these coals less toxic to human inhalation and less hazardous to environmental pollution. Finally, knowledge gained on understanding of the chemical properties of coals is illustrated to apply for prediction of toxicity due to coal possibly before large-scale mining and prevention of occupational lung disease during mining.

  4. Development of a Rhesus Monkey Lung Geometry Model and Application to Particle Deposition in Comparison to Humans

    SciTech Connect (OSTI)

    Asgharian, Bahman; Price, Owen; McClellan, Gene; Corley, Richard A.; Einstein, Daniel R.; Jacob, Rick E.; Harkema, Jack R.; Carey, Stephen A.; Schelegle, Edward; Hyde, D.; Kimbell, Julia; Miller, Frederick J.

    2012-11-01

    The exposure-dose-response characterization of an inhalation hazard established in an animal species needs to be translated to an equivalent characterization in humans relative to comparable doses or exposure scenarios. Here, the first geometry model of the conducting airways for rhesus monkeys is developed based upon CT images of the conducting airways of a 6-month-old male, rhesus monkey. An algorithm was developed for adding the alveolar region airways using published rhesus morphometric data. The resultant lung geometry model can be used in mechanistic particle or gaseous dosimetry models. Such dosimetry models require estimates of the upper respiratory tract volume of the animal and the functional residual capacity, as well as of the tidal volume and breathing frequency of the animal. The relationship of these variables to rhesus monkeys of differing body weights was established by synthesizing and modeling published data as well as modeling pulmonary function measurements on 121 rhesus control animals. Deposition patterns of particles up to 10 ?m in size were examined for endotracheal and and up to 5 ?m for spontaneous breathing in infant and young adult monkeys and compared to those for humans. Deposition fraction of respirable size particles was found to be higher in the conducting airways of infant and young adult rhesus monkeys compared to humans. Due to the filtering effect of the conducting airways, pulmonary deposition in rhesus monkeys was lower than that in humans. Future research areas are identified that would either allow replacing assumptions or improving the newly developed lung model.

  5. Enzyme Structure Provides Insights into Cancer and Aging

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    protein are responsible for three different human diseases: in xeroderma pigmentosum (XP), extreme sensitivity to sunlight promotes cancer; Cockayne syndrome (CS) involves...

  6. Is Primary Prostate Cancer Treatment Influenced by Likelihood...

    Office of Scientific and Technical Information (OSTI)

    ... Authors: Holmes, Jordan A. 1 ; Wang, Andrew Z. 1 ; University of North Carolina-Lineberger Comprehensive Cancer Center, Chapel Hill, NC 2 ; Hoffman, Karen E. 3 ; Hendrix, ...

  7. Radioisotopes for Medical Diagnostics and Cancer Therapy at BNL...

    Office of Science (SC) Website

    Radioisotopes for Medical Diagnostics and Cancer Therapy at BNL Nuclear Physics (NP) NP Home About Research Facilities Science Highlights Benefits of NP Applications of Nuclear ...

  8. Protocadherin-7 induces bone metastasis of breast cancer

    SciTech Connect (OSTI)

    Li, Ai-Min; Tian, Ai-Xian; Zhang, Rui-Xue; Ge, Jie; Key Laboratory of Breast Cancer Prevention and Treatment of the Ministry of Education, Tianjin Medical University Cancer Institute and Hospital, Tianjin ; Sun, Xuan; Cao, Xu-Chen; Key Laboratory of Breast Cancer Prevention and Treatment of the Ministry of Education, Tianjin Medical University Cancer Institute and Hospital, Tianjin

    2013-07-05

    Highlights: PCDH7 is overexpression in high bone metastatic MDA-MB-231 cells. PCDH7 is up-regulation in bone metastatic breast cancer tissues. Suppression of PCDH7 inhibits cell proliferation, migration, and invasion in vitro. PCDH7 induces breast cancer bone metastasis in vivo. -- Abstract: Breast cancer had a propensity to metastasize to bone, resulting in serious skeletal complications associated with poor outcome. Previous study showed that Protocadherin-7 (PCDH7) play an important role in brain metastatic breast cancer, however, the role of PCDH7 in bone metastatic breast cancer has never been explored. In the present study, we found that PCDH7 expression was up-regulation in bone metastatic breast cancer tissues by real-time PCR and immunohistochemistry assays. Furthermore, suppression of PCDH7 inhibits breast cancer cell proliferation, migration, and invasion in vitro by MTT, scratch, and transwell assays. Most importantly, overexpression of PCDH7 promotes breast cancer cell proliferation and invasion in vitro, and formation of bone metastasis in vivo. These data provide an important insight into the role of PCDH7 in bone metastasis of breast cancer.

  9. Software speeds detection of diseases and cancer-treatment targets

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Software speeds detection of diseases and cancer-treatment targets Alumni Link: Opportunities, News and Resources for Former Employees Latest Issue:September 2015 all issues All...

  10. Insight into Alzheimer's, cancer, anemia gleaned from ribosome...

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Insights from ribosome research Insight into Alzheimer's, cancer, anemia gleaned from ribosome research Groundbreaking study of the human ribosome reveals tiny molecular machine is...

  11. Three-Dimensional Thermal Tomography Advances Cancer Treatment...

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Three-Dimensional Thermal Tomography Advances Cancer Treatment Technology available for licensing: A 3D technique to detect early skin changes due to radiation treatment in breast...

  12. Identification of cancer protein biomarkers using proteomic techniques

    DOE Patents [OSTI]

    Mor, Gil G.; Ward, David C.; Bray-Ward, Patricia

    2010-02-23

    The claimed invention describes methods to diagnose or aid in the diagnosis of cancer. The claimed methods are based on the identification of biomarkers which are particularly well suited to discriminate between cancer subjects and healthy subjects. These biomarkers were identified using a unique and novel screening method described herein. The biomarkers identified herein can also be used in the prognosis and monitoring of cancer. The invention comprises the use of leptin, prolactin, OPN and IGF-II for diagnosing, prognosis and monitoring of ovarian cancer.

  13. Identification of cancer protein biomarkers using proteomic techniques

    DOE Patents [OSTI]

    Mor, Gil G; Ward, David C; Bray-Ward, Patricia

    2015-03-10

    The claimed invention describes methods to diagnose or aid in the diagnosis of cancer. The claimed methods are based on the identification of biomarkers which are particularly well suited to discriminate between cancer subjects and healthy subjects. These biomarkers were identified using a unique and novel screening method described herein. The biomarkers identified herein can also be used in the prognosis and monitoring of cancer. The invention comprises the use of leptin, prolactin, OPN and IGF-II for diagnosing, prognosis and monitoring of ovarian cancer.

  14. From Bombs to Breast Cancer Imaging: Los Alamos National Laboratory

    SciTech Connect (OSTI)

    Martineau, Rebecca M

    2012-07-26

    In the United States, one in eight women will be affected by breast cancer. According to the American Cancer Society, breast cancer is the most commonly diagnosed - as well as the second most fatal - cancer in American women. It is estimated that there will be nearly 200,000 diagnoses of breast cancer this year; more than 40,000 of these will be fatal. Although advances in medical technologies have greatly increased the odds of surviving the disease, the increase in screenings has not resulted in a significant reduction in the breast cancer mortality rate. Moreover, recent studies have even suggested that an increase in these methods might, in itself, cause cancer. A new tool for early detection and diagnosis of breast cancer, supported by an award from the Breast Cancer Research Program (BCRP) of the Congressionally Directed Medical Research Programs of Department of Defense, could give women a new advantage in the fight against breast cancer. This LANL-led project will integrate ultrasound tomography (UST) with recent discoveries in the field of cell and tissue biomechanics to improve breast cancer detection and characterization. UST uses ultrasound waves instead of X-rays to identify and characterize breast tumors. This technology reveals small mechanical-property changes within the breast. These changes are often the earliest signs of breast cancer. Additionally, UST is effective for women with dense breast tissue, who have a higher risk of developing breast cancer. Because the technology does not use radiation, UST can also be used as frequently as needed for women with a high risk of developing breast cancer. In contrast, mammography, the only routine breast-cancer screening tool currently available, is not effective for women with dense breast tissue and may come with unwanted side-effects caused by ionizing radiation. UST has great potential to become an alternative breast-cancer screening tool because of UST's advantages and benefits over mammography. Currently, there is fierce debate surrounding the age at which breast cancer screening should begin, and once begun, how often it should occur. The American Cancer Society recommends yearly mammograms starting at age 40. On the other hand, the U.S. Preventive Services Task Force recommends against routine so early. Rather, the Task Force recommends biennial mammography screening for women aged 50 to 74 years. The ten-year discrepancy in the onset of screening results from recent data suggesting that the frequent use of X-ray radiation during screenings could potentially increase the likelihood of developing cancer. This danger is increased by the low sensitivity and accuracy of mammograms, which sometimes require multiple screenings to yield results. Furthermore, mammograms are often not only inaccurate, but average appalling misdiagnoses rates: about 80% false positives and 15% false negatives. These misdiagnoses lead to unwarranted biopsies at an estimated health care cost of $2 billion per year, while at the same time, resulting in excessive cases of undetected cancer. As such, the National Cancer Institute recommends more studies on the advantages of types and frequency of screenings, as well as alternative screening options. The UST technology developed at LANL could be an alternative option to greatly improve the specificity and sensitivity of breast cancer screening without using ionizing radiation. LANL is developing high-resolution ultrasound tomography algorithms and a clinical ultrasound tomography scanner to conduct patient studies at the UNM Hospital. During UST scanning, the patient lies face-down while her breast, immersed in a tank of warm water, is scanned by phased-transducer arrays. UST uses recorded ultrasound signals to reconstruct a high-resolution three-dimensional image of the breast, showing the spatial distribution of mechanical properties within the breast. Breast cancers are detected by higher values of mechanical properties compared to surrounding tissues. Thus, high-resolution breast images obtained using LANL's novel UST algorithms ha

  15. WE-E-BRE-10: Level of Breast Cancer Stem Cell Correlated with Tumor

    Office of Scientific and Technical Information (OSTI)

    Radioresistence: An Indication for Individualized Breast Cancer Therapy Adapted to Cancer Stem Cell Fractions (Journal Article) | SciTech Connect WE-E-BRE-10: Level of Breast Cancer Stem Cell Correlated with Tumor Radioresistence: An Indication for Individualized Breast Cancer Therapy Adapted to Cancer Stem Cell Fractions Citation Details In-Document Search Title: WE-E-BRE-10: Level of Breast Cancer Stem Cell Correlated with Tumor Radioresistence: An Indication for Individualized Breast

  16. CT reconstruction techniques for improved accuracy of lung CT airway measurement

    SciTech Connect (OSTI)

    Rodriguez, A.; Ranallo, F. N.; Judy, P. F.; Gierada, D. S.; Fain, S. B.

    2014-11-01

    Purpose: To determine the impact of constrained reconstruction techniques on quantitative CT (qCT) of the lung parenchyma and airways for low x-ray radiation dose. Methods: Measurement of small airways with qCT remains a challenge, especially for low x-ray dose protocols. Images of the COPDGene quality assurance phantom (CTP698, The Phantom Laboratory, Salem, NY) were obtained using a GE discovery CT750 HD scanner for helical scans at x-ray radiation dose-equivalents ranging from 1 to 4.12 mSv (12100 mA s currenttime product). Other parameters were 40 mm collimation, 0.984 pitch, 0.5 s rotation, and 0.625 mm thickness. The phantom was sandwiched between 7.5 cm thick water attenuating phantoms for a total length of 20 cm to better simulate the scatter conditions of patient scans. Image data sets were reconstructed using STANDARD (STD), DETAIL, BONE, and EDGE algorithms for filtered back projection (FBP), 100% adaptive statistical iterative reconstruction (ASIR), and Veo reconstructions. Reduced (half) display field of view (DFOV) was used to increase sampling across airway phantom structures. Inner diameter (ID), wall area percent (WA%), and wall thickness (WT) measurements of eight airway mimicking tubes in the phantom, including a 2.5 mm ID (42.6 WA%, 0.4 mm WT), 3 mm ID (49.0 WA%, 0.6 mm WT), and 6 mm ID (49.0 WA%, 1.2 mm WT) were performed with Airway Inspector (Surgical Planning Laboratory, Brigham and Womens Hospital, Boston, MA) using the phase congruency edge detection method. The average of individual measures at five central slices of the phantom was taken to reduce measurement error. Results: WA% measures were greatly overestimated while IDs were underestimated for the smaller airways, especially for reconstructions at full DFOV (36 cm) using the STD kernel, due to poor sampling and spatial resolution (0.7 mm pixel size). Despite low radiation dose, the ID of the 6 mm ID airway was consistently measured accurately for all methods other than STD FBP. Veo reconstructions showed slight improvement over STD FBP reconstructions (4%9% increase in accuracy). The most improved ID and WA% measures were for the smaller airways, especially for low dose scans reconstructed at half DFOV (18 cm) with the EDGE algorithm in combination with 100% ASIR to mitigate noise. Using the BONE + ASIR at half BONE technique, measures improved by a factor of 2 over STD FBP even at a quarter of the x-ray dose. Conclusions: The flexibility of ASIR in combination with higher frequency algorithms, such as BONE, provided the greatest accuracy for conventional and low x-ray dose relative to FBP. Veo provided more modest improvement in qCT measures, likely due to its compatibility only with the smoother STD kernel.

  17. Prevention of Gynecomastia and Breast Pain Caused by Androgen Deprivation Therapy in Prostate Cancer: Tamoxifen or Radiotherapy?

    SciTech Connect (OSTI)

    Arruda Viani, Gustavo; Bernardes da Silva, Lucas Godoi; Stefano, Eduardo Jose

    2012-07-15

    Purpose: To determine, in a meta-analysis, whether gynecomastia and breast pain rates in men with prostate cancer treated with androgen deprivation therapy (ADT) are reduced if treated with prophylactic radiotherapy (RT) or tamoxifen (TMX). Methods and Materials: The MEDLINE, EMBASE, CANCERLIT, and Cochrane Library databases, as well as proceedings of annual meetings, were systematically searched to identify randomized, controlled studies comparing RT or TMX with observation for men with prostate cancer using ADT. Results: Six RCTs (three RT trials and three TMX trials, N = 777 patients total) were identified that met the study criteria. Pooled results from these RCTs comparing RT vs. observation showed a significant reduction in the incidence of gynecomastia and breast pain rates in patients treated with RT (odds ratio [OR] = 0.21, 95% confidence interval [CI] = 0.12-0.37, p < 0.0001, and OR = 0.34, 95% CI 0.20-0.57, p < 0.0001, respectively). Use of RT resulted in an absolute risk reduction (ARR) of 29.4% and 19.9%, with a number needed to treat (NNT) of 3.4 and 5 to avoid one case of gynecomastia and breast pain, respectively. Pooled results from trials comparing TMX vs. observation showed a statistical benefit for breast pain and gynecomastia in favor of TMX arms (OR = 0.04, 95% CI = 0.02-0.08, p < 0.0001 and OR = 0.07, 95% CI = 0.0-0.14, p < 0.00001). TMX resulted in an ARR = 64.1% and 47.6%, with an NNT of 1.56 and 2.1 to avoid one case of gynecomastia and breast pain, respectively. Considering adverse effects, TMX was 6 times more adverse effects than RT. Conclusions: Our data have shown that both TMX and RT prevented gynecomastia and breast pain in patients with prostate cancer receiving ADT for prostate cancer. Although TMX was two times more effective in preventing gynecomastia, RT should represent an effective and safe treatment option, to take into account mainly in patients with cardiovascular risk factors or thrombotic diathesis.

  18. Targeting NRF2 signaling for cancer chemoprevention

    SciTech Connect (OSTI)

    Kwak, Mi-Kyoung; Kensler, Thomas W.

    2010-04-01

    Modulation of the metabolism and disposition of carcinogens through induction of cytoprotective enzymes is one of several promising strategies to prevent cancer. Chemopreventive efficacies of inducers such as dithiolethiones and sulforaphane have been extensively studied in animals as well as in humans. The KEAP1-NRF2 system is a key, but not unilateral, molecular target for these chemopreventive agents. The transcription factor NRF2 (NF-E2-related factor 2) is a master regulator of the expression of a subset of genes, which produce proteins responsible for the detoxication of electrophiles and reactive oxygen species as well as the removal or repair of some of their damage products. It is believed that chemopreventive enzyme inducers affect the interaction between KEAP1 and NRF2 through either mediating conformational changes of the KEAP1 protein or activating phosphorylation cascades targeting the KEAP1-NRF2 complex. These events in turn affect NRF2 stability and trafficking. Recent advances elucidating the underlying structural biology of KEAP1-NRF2 signaling and identification of the gene clusters under the transcriptional control of NRF2 are facilitating understanding of the potential pleiotropic effects of NRF2 activators and discovery of novel classes of potent chemopreventive agents such as the triterpenoids. Although there is appropriately a concern regarding a deleterious role of the KEAP1-NRF2 system in cancer cell biology, especially as the pathway affects cell survival and drug resistance, the development and the use of NRF2 activators as chemopreventive agents still holds a great promise for protection of normal cells from a diversity of environmental stresses that contribute to the burden of cancer and other chronic, degenerative diseases.

  19. Using HEP Technology to Fight Cancer

    SciTech Connect (OSTI)

    Le Du, Patrick

    2004-06-30

    Many engineering and physics HEP groups are now collaborating with medical doctors and biomedical scientists to develop new modern and 'state of the art' radiation instruments for cancer diagnostics and treatment. This presentation will review some of these studies, oriented towards the imaging fields for diagnostic (Positron Emission Tomography and Computed Tomography) and particle therapy for tumor treatment (from proton to light ions). I will try, using appropriate examples, to show what are the challenges and where the development of HEP concepts, tools and techniques can be used.

  20. Liposome-encapsulated actinomycin for cancer chemotherapy

    DOE Patents [OSTI]

    Rahman, Yueh-Erh; Cerny, Elizabeth A.

    1976-01-01

    An improved method is provided for chemotherapy of malignant tumors by injection of antitumor drugs. The antitumor drug is encapsulated within liposomes and the liposomes containing the encapsulated drug are injected into the body. The encapsulated drug penetrates into the tumor cells where the drug is slowly released and induces degeneration and death of the tumor cells, while any toxicity to the host body is reduced. Liposome encapsulation of actinomycin D has been found to be particularly effective in treating cancerous abdominal tumors, while drastically reducing the toxicity of actinomycin D to the host.

  1. A mutational signature in gastric cancer suggests therapeutic strategies

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Alexandrov, Ludmil B.; Nik-Zainal, Serena; Siu, Hoi Cheong; Leung, Suet Yi; Stratton, Michael R.

    2015-10-29

    Targeting defects in the DNA repair machinery of neoplastic cells, for example, those due to inactivating BRCA1 and/or BRCA2 mutations, has been used for developing new therapies in certain types of breast, ovarian and pancreatic cancers. Recently, a mutational signature was associated with failure of double-strand DNA break repair by homologous recombination based on its high mutational burden in samples harbouring BRCA1 or BRCA2 mutations. In pancreatic cancer, all responders to platinum therapy exhibit this mutational signature including a sample that lacked any defects in BRCA1 or BRCA2. Here, we examine 10,250 cancer genomes across 36 types of cancer andmore » demonstrate that, in addition to breast, ovarian and pancreatic cancers, gastric cancer is another cancer type that exhibits this mutational signature. Furthermore, our results suggest that 7–12% of gastric cancers have defective double-strand DNA break repair by homologous recombination and may benefit from either platinum therapy or PARP inhibitors.« less

  2. Three-Dimensional Thermal Tomography Advances Cancer Treatment | Argonne

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    National Laboratory Three-Dimensional Thermal Tomography Advances Cancer Treatment Technology available for licensing: A 3D technique to detect early skin changes due to radiation treatment in breast cancer patients. Lowers medical costs due to lessened side effects Noninvasive, enhances healing and detects other conditions PDF icon thermal_tomography

  3. Harnessing Light in the Fight Against Cancer | Argonne National Laboratory

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Against Cancer Medical researchers are looking to target diseases such as cancer at increasingly precise levels, down to the nanoscale. Recent advances in this effort have revealed that molecules triggered by the diseases themselves may well provide the signals necessary to achieve this refinement. PDF icon Nano Sheet_harnessing light

  4. Berkeley Lab Scientist Co-Leads Breast Cancer Dream Team

    ScienceCinema (OSTI)

    Gray, Joe

    2013-05-29

    An $16.5 million, three-year grant to develop new and more effective therapies to fight breast cancer was awarded today to a multi-institutional Dream Team of scientists and clinicians that is co-led by Joe Gray, a renowned cancer researcher with the U.S. Department of Energys Lawrence Berkeley National Laboratory. http://newscenter.lbl.gov/

  5. Method for detecting the presence of prostate cancer

    DOE Patents [OSTI]

    Karin, Michael; Luo, Jun-Li; Tan, Wei

    2010-04-13

    The present invention relates to compositions and methods for cancer diagnosis, treatment and drug screening. In particular, the present invention provides compositions and methods for targeting the nuclear translocation of IkB kinase-.alpha. (IKK.alpha.) and the IKK.alpha.-mediated suppression of Maspin expression observed in metastatic prostate cancer cells.

  6. Method for restoration of normal phenotype in cancer cells

    DOE Patents [OSTI]

    Bissell, Mina J.; Weaver, Valerie M.

    2000-01-01

    A method for reversing expression of malignant phenotype in cancer cells is described. The method comprises applying .beta..sub.1 integrin function-blocking antibody to the cells. The method can be used to assess the progress of cancer therapy. Human breast epithelial cells were shown to be particularly responsive.

  7. Berkeley Lab Scientist Co-Leads Breast Cancer Dream Team

    SciTech Connect (OSTI)

    Gray, Joe

    2009-01-01

    An $16.5 million, three-year grant to develop new and more effective therapies to fight breast cancer was awarded today to a multi-institutional Dream Team of scientists and clinicians that is co-led by Joe Gray, a renowned cancer researcher with the U.S. Department of Energys Lawrence Berkeley National Laboratory. http://newscenter.lbl.gov/

  8. Effects of two Asian sand dusts transported from the dust source regions of Inner Mongolia and northeast China on murine lung eosinophilia

    SciTech Connect (OSTI)

    He, Miao; Ichinose, Takamichi; Song, Yuan; Yoshida, Yasuhiro; Arashidani, Keiichi; Yoshida, Seiichi; Liu, Boying; Nishikawa, Masataka; Takano, Hirohisa; and others

    2013-11-01

    The quality and quantity of toxic materials adsorbed onto Asian sand dust (ASD) are different based on dust source regions and passage routes. The aggravating effects of two ASDs (ASD1 and ASD2) transported from the source regions of Inner Mongolia and northeast China on lung eosinophilia were compared to clarify the role of toxic materials in ASD. The ASDs contained different amounts of lipopolysaccharides (LPS) and ?-glucan (ASD1 < ASD2) and SiO{sub 2} (ASD1 > ASD2). CD-1 mice were instilled intratracheally with ASD1, ASD2 and/or ovalbumin (OVA) four times at 2-week intervals. ASD1 and ASD2 enhanced eosinophil recruitment induced by OVA in the submucosa of the airway, with goblet cell proliferation in the bronchial epithelium. ASD1 and ASD2 synergistically increased OVA-induced eosinophil-relevant cytokines interleukin-5 (IL-5), IL-13 (ASD1 < ASD2) and chemokine eotaxin (ASD1 > ASD2) in bronchoalveolar lavage fluid. ASD2 aggravating effects on lung eosinophilia were greater than ASD1. The role of LPS and ?-glucan in ASD2 on the production of pro-inflammatory mediators was assessed using in vitro bone marrow-derived macrophages (BMDMs) from wild type, Toll-like receptor 2-deficient (TLR2 ?/?), TLR4 ?/?, and MyD88 ?/? mice (on Balb/c background). ASD2-stimulated TLR2 ?/? BMDMs enhanced IL-6, IL-12, TNF-?, MCP-1 and MIP-1? secretion compared with ASD2-stimulated TLR4 ?/? BMDMs. Protein expression from ASD2-stimulated MyD88 ?/? BMDM were very low or undetectable. The in vitro results indicate that lung eosinophilia caused by ASD is TLR4 dependent. Therefore, the aggravation of OVA-related lung eosinophilia by ASD may be dependent on toxic substances derived from microbes, such as LPS, rather than SiO{sub 2}. - Highlights: Asian sand dust (ASD) from the deserts of China causes serious respiratory problems. The aggravating effects of two ASDs on lung eosinophilia were compared. The ASDs contained different LPS and ?-glucan (ASD1 < ASD2) and SiO{sub 2} (ASD1 > ASD2). The ASD2 aggravating effects on lung eosinophilia were greater than ASD1. The aggravation of lung eosinophilia may be dependent on LPS in ASD, rather than SiO{sub 2}.

  9. BRCA1-linked marker in postmenopausal breast cancer families

    SciTech Connect (OSTI)

    Folsom, A.R.; Chen, P.L.; Sellers, T.A.

    1994-09-01

    A majority of breast and ovarian cancer families and half of the early-onset breast cancer families are linked to markers on 17q (BRCA1). While linkage has been demonstrated in families with premenopausal disease, few studies have tested these markers in families with postmenopausal breast cancer. In the Iowa Women`s Health Study, a population-based study of over 42,000 women, an association of waist-to-hip ratio (WHR) with the risk of postmenopausal breast cancer was found predominantly in women with a positive family history -- this interaction was associated with a 3.2-fold elevated risk. This effect was even more pronounced when the definition of family history included breast and ovarian cancer, known to be linked to 17q markers. We evaluated evidence for linkage with D17S579, a BRCA-1-linked marker, in 13 families in which the index case had postmenopausal breast cancer. Genotyping for alleles at D17S579 was performed on 84 blood samples. Linkage analysis assumed that the breast cancer trait had an autosomal dominant mode of inheritance with a penetrance of 80%. For the 13 families studied, the maximum lod score was 0.29 at a theta of 0.27. There was significant evidence against tight linkage of breast cancer with D17S579 (theta<0.4). Heterogeneity analysis suggested evidence for the presence of both linked and unlinked families. Partitioning informative families on WHR of the index case suggested heterogeneity. These data suggest that, in a subset of families identified by a postmenopausal breast cancer proband, risk of breast cancer may be mediated by BRCA1, with heterogeneity defined by WHR.

  10. Discrimination and quantification of contamination and implanted solar wind in Genesis collector shards using grazing incidence synchrotron x-ray techniqies: Initial results

    SciTech Connect (OSTI)

    Kitts, K.; Sutton, S.; Eng, P.; Ghose, S.; Burnett, D.

    2006-12-13

    Grazing incidence X-ray fluorescence is a non-destructive technique that can differentiate the embedded solar wind component from surface contamination and collector background in the Genesis shards. Initial solar Fe abundance in D30554 is 8 x 10{sup 12}/cm{sup 2}. Accurate knowledge of the composition of the Sun provides a baseline, which allows an understanding of how the solar system has evolved over time and how solar processes and solar wind mechanics behave. Unfortunately, the errors in photospheric abundances are too large for many planetary science problems and this hampers our understanding of these different processes. Analyses of solar wind implanted in meteorites or lunar soils have provided more precise data but alteration processes on these bodies may complicate such information. In response to this need for pristine solar wind samples, NASA developed and launched the Genesis Probe. Unfortunately, the probe smashed into the Utah desert shattering the 300 collector plates into 15,000+ pieces all of which are now coated in a both a fine terrestrial dust and Si and Ge powder from the disrupted collectors themselves. The solar wind penetration depth is 100-200 nm and the superposed contamination layers are typically 40-50 nm. Stringent cleaning regimes have the potential of removing the solar wind itself. The best solution is to have sufficient spatial resolution to separately analyze the surface contamination and penetrated solar wind. To that end, three Genesis collector array shards and their appropriate flight spares were characterized via grazing incidence x-ray fluorescence and x-ray reflectivity. The goals were (1) to evaluate the various cleaning methods used to eliminate contamination, (2) to identify the collector substrates most suited for this technique, (3) to determine whether the solar wind signature could be deconvolved from the collector background signature, and (4) to measure the relative abundances of Ca to Ge in the embedded solar wind.

  11. TU-F-17A-06: Motion Stability and Dosimetric Impact of Spirometer-Based DIBH-RT of Left-Sided Breast Cancer

    SciTech Connect (OSTI)

    McKenzie, E; Yang, W; Burnison, M; Mirhadi, A; Hakimian, B; Stephen, S; Robert, R; Yue, Y; Sandler, H; Fraass, B

    2014-06-15

    Purpose: Patients undergoing radiotherapy (RT) for left-sided breast cancer have increased risk of coronary artery disease. Deep Inhalation Breath Hold assisted RT (DIBH-RT) is shown to increase the geometric separation of the target area and heart, reducing cardiac radiation dose. The purposes of this study are to use Cine MV portal images to determine the stability of spirometer-guided DIBH-RT and examine the dosimetric cardiopulmonary impact of this technique. Methods: Twenty consecutive patients with left-sided breast cancer were recruited to the IRB-approved study. Free-breathing (FB) and DIBH-CT's were acquired at simulation. Rigid registration of the FB-CT and DIBH-CT was performed using primarily breast tissue. Treatment plans were created for each FB-CT and DIBH-CT using identical paired tangent fields with field-in-field or electronic compensation techniques. Dosimetric evaluation included mean and maximum (Dmax) doses for the left anterior descending artery (LAD), mean heart dose, and left lung V20. Cine MV portal images were acquired for medial and lateral fields during treatment. Analysis of Cine images involved chest wall segmentation using an algorithm developed in-house. Intra- and inter-fractional chest wall motion were determined through affine registration to the first frame of each Cine. Results: Dose to each cardiac structure evaluated was significantly (p<0.001) reduced with the DIBH plans. Mean heart dose decreased from 2.9(0.96.6) to 1.6(0.65.3) Gy; mean LAD dose from 16.6(343.6) to 7.4(1.732.7) Gy; and LAD Dmax from 35.4 (6.153) to 18.4(2.551.2) Gy. No statistically significant reduction was found for the left lung V20. Average AP and SI median chest wall motion (intrafractional) was 0.1 (SD=0.9) and 0.5 (SD=1.1) mm, respectively. Average AP inter-fractional chest wall motion was 2.0 (SD=1.4) mm. Conclusion: Spirometer-based DIBH treatments of the left breast are reproducible both inter- and intra-fractionally, and provide a statistically and potentially clinically useful dosimetric advantage to cardiac structures.

  12. Geranylgeranylacetone inhibits ovarian cancer progression in vitro and in vivo

    SciTech Connect (OSTI)

    Hashimoto, Kae; Morishige, Ken-ichirou . E-mail: mken@gyne.med.osaka-u.ac.jp; Sawada, Kenjiro; Ogata, Seiji; Tahara, Masahiro; Shimizu, Shoko; Sakata, Masahiro; Tasaka, Keiichi; Kimura, Tadashi

    2007-04-27

    Geranylgeranylacetone (GGA), an isoprenoid compound, is an anti-ulcer drug developed in Japan. In our previous study, GGA was shown to inhibit ovarian cancer invasion by attenuating Rho activation [K. Hashimoto, K. Morishige, K. Sawada, M. Tahara, S. Shimizu, M. Sakata, K. Tasaka, Y. Murata, Geranylgeranylacetone inhibits lysophosphatidic acid-induced invasion of human ovarian carcinoma cells in vitro. Cancer 103 (2005) 1529-1536.]. In the present study, GGA treatment inhibited ovarian cancer progression in vitro and suppressed the tumor growth and ascites in the in vivo ovarian cancer model. In vitro analysis, treatment of cancer cells by GGA resulted in the inhibition of cancer cell proliferation, the inactivation of Ras, and the suppression of tyrosine phosphorylation of mitogen-activated protein kinase (MAPK). In conclusion, this is the first report that GGA inhibited ovarian cancer progression and the anti-tumor effect by GGA is, at least in part, derived not only from the suppression of Rho activation but also Ras-MAPK activation.

  13. Evaluating the Role of Prophylactic Gastrostomy Tube Placement Prior to Definitive Chemoradiotherapy for Head and Neck Cancer

    SciTech Connect (OSTI)

    Chen, Allen M.; Li Baoqing; Lau, Derick H.; Farwell, D. Gregory; Luu, Quang; Stuart, Kerri; Newman, Kathleen; Purdy, James A.; Vijayakumar, Srinivasan M.D.

    2010-11-15

    Purpose: To determine the effect of prophylactic gastrostomy tube (GT) placement on acute and long-term outcome for patients treated with definitive chemoradiotherapy for locally advanced head and neck cancer. Methods and Materials: One hundred twenty consecutive patients were treated with chemoradiotherapy for Stage III/IV head and neck cancer to a median dose of 70 Gy (range, 64-74 Gy). The most common primary site was the oropharynx (66 patients). Sixty-seven patients (56%) were treated using intensity-modulated radiotherapy (IMRT). Seventy patients (58%) received prophylactic GT placement at the discretion of the physician before initiation of chemoradiotherapy. Results: Prophylactic GT placement significantly reduced weight loss during radiation therapy from 43 pounds (range, 0 to 76 pounds) to 19 pounds (range, 0 to 51 pounds), which corresponded to a net change of -14% (range, 0% to -30%) and -8% (range, +1% to -22%) from baseline, respectively (p < 0.001). However, the proportion of patients who were GT-dependent at 6- and 12-months after treatment was 41% and 21%, respectively, compared with 8% and 0%, respectively, for those with and without prophylactic GT (p < 0.001). Additionally, prophylactic GT was associated with a significantly higher incidence of late esophageal stricture compared with those who did not have prophylactic GT (30% vs. 6%, p < 0.001). Conclusions: Although prophylactic GT placement was effective at preventing acute weight loss and the need for intravenous hydration, it was also associated with significantly higher rates of late esophageal toxicity. The benefits of this strategy must be balanced with the risks.

  14. Improved Dosimetric and Clinical Outcomes With Intensity-Modulated Radiotherapy for Head-and-Neck Cancer of Unknown Primary Origin

    SciTech Connect (OSTI)

    Chen, Allen M.; Li Baoqing; Farwell, D. Gregory; Marsano, Joseph; Vijayakumar, Srinivasan; Purdy, James A.

    2011-03-01

    Purpose: To compare differences in dosimetric, clinical, and quality-of-life endpoints among a cohort of patients treated by intensity-modulated radiotherapy (IMRT) and conventional radiotherapy (CRT) for head-and-neck cancer of unknown primary origin. Methods and Materials: The medical records of 51 patients treated by radiation therapy for squamous cell carcinoma of the head and neck presenting as cervical lymph node metastasis of occult primary origin were reviewed. Twenty-four patients (47%) were treated using CRT, and 27 (53%) were treated using IMRT. The proportions of patients receiving concurrent chemotherapy were 54% and 63%, respectively. Results: The 2-year estimates of overall survival, local-regional control, and disease-specific survival for the entire patient population were 86%, 89%, and84%, respectively. There were no significant differences in any of these endpoints with respect to radiation therapy technique (p > 0.05 for all). Dosimetric analysis revealed that the use of IMRT resulted in significant improvements with respect to mean dose and V30 to the contralateral (spared) parotid gland. In addition, mean doses to the ipsilateral inner and middle ear structures were significantly reduced with IMRT (p < 0.05 for all). The incidence of severe xerostomia in the late setting was 58% and 11% among patients treated by CRT and IMRT, respectively (p < 0.001). The percentages of patients who were G-tube dependent at 6 months after treatment were 42% and 11%, respectively (p < 0.001). Conclusions: IMRT results in significant improvements in the therapeutic ratio among patients treated by radiation therapy for head-and-neck cancer of unknown primary origin.

  15. Practice Patterns of Radiotherapy in Cervical Cancer Among Member Groups of the Gynecologic Cancer Intergroup (GCIG)

    SciTech Connect (OSTI)

    Gaffney, David K. . E-mail: david.gaffney@hci.utah.edu; Du Bois, Andreas; Narayan, Kailash; Reed, Nick; Toita, Takafumi; Pignata, Sandro; Blake, Peter; Portelance, Lorraine; Sadoyze, Azmat; Poetter, Richard; Colombo, Alessandro; Randall, Marcus; Mirza, Mansoor R.; Trimble, Edward L.

    2007-06-01

    Purpose: The aim of this study was to describe radiotherapeutic practice of the treatment of cervical cancer in member groups of the Gynecologic Cancer Intergroup (GCIG). Methods and Materials: A survey was developed and distributed to the members of the GCIG focusing on details of radiotherapy practice. Different scenarios were queried including advanced cervical cancer, postoperative patients, and para-aortic-positive lymph node cases. Items focused on indications for radiation therapy, radiation fields, dose, use of chemotherapy, brachytherapy and others. The cooperative groups from North America were compared with the other groups to evaluate potential differences in radiotherapy doses. Results: A total of 39 surveys were returned from 13 different cooperative groups. For the treatment of advanced cervical cancer, external beam pelvic doses and total doses to point A were 47 + 3.5 Gy (mean + SD) and 79.1 + 7.9 Gy, respectively. Point A doses were not different between the North American cooperative groups compared with the others (p = 0.103). All groups used concomitant chemotherapy, with 30 of 36 respondents using weekly cisplatin. Of 33 respondents, 31 intervened for a low hemoglobin level. For a para-aortic field, the upper border was most commonly (15 of 24) at the T12-L1 interspace. Maintenance chemotherapy (after radiotherapy) was not performed by 68% of respondents. For vaginal brachytherapy after hysterectomy, 23 groups performed HDR brachytherapy and four groups used LDR brachytherapy. In the use of brachytherapy, there was no uniformity in dose prescription. Conclusions: Radiotherapy practices among member groups of the GCIG are similar in terms of both doses and use of chemotherapy.

  16. Radiotherapy in the management of early breast cancer

    SciTech Connect (OSTI)

    Wang, Wei

    2013-03-15

    Radiotherapy is an indispensible part of the management of all stages of breast cancer. In this article, the common indications for radiotherapy in the management of early breast cancer (stages 0, I, and II) are reviewed, including whole-breast radiotherapy as part of breast-conserving treatment for early invasive breast cancer and pre-invasive disease of ductal carcinoma in situ, post-mastectomy radiotherapy, locoregional radiotherapy, and partial breast irradiation. Key clinical studies that underpin our current practice are discussed briefly.

  17. Protein Modifications as Potential Biomarkers in Breast Cancer

    SciTech Connect (OSTI)

    Jin, Hongjun; Zangar, Richard C.

    2009-11-30

    A variety of post-translational protein modifications (PTMs) are known to be altered as a result of cancer development. Thus, these PTMs are potentially useful biomarkers for breast cancer. Mass spectrometry, antibody microarrays and immunohistochemistry techniques have shown promise for identifying changes in PTMs. In this review, we summarize the current literature on PTMs identified in the plasma and tumor tissue of breast-cancer patients or in breast cell lines. We also discuss some of the analytical techniques currently being used to evaluate PTMs.

  18. SU-F-BRD-05: Dosimetric Comparison of Protocol-Based SBRT Lung Treatment Modalities: Statistically Significant VMAT Advantages Over Fixed- Beam IMRT

    SciTech Connect (OSTI)

    Best, R; Harrell, A; Geesey, C; Libby, B; Wijesooriya, K

    2014-06-15

    Purpose: The purpose of this study is to inter-compare and find statistically significant differences between flattened field fixed-beam (FB) IMRT with flattening-filter free (FFF) volumetric modulated arc therapy (VMAT) for stereotactic body radiation therapy SBRT. Methods: SBRT plans using FB IMRT and FFF VMAT were generated for fifteen SBRT lung patients using 6 MV beams. For each patient, both IMRT and VMAT plans were created for comparison. Plans were generated utilizing RTOG 0915 (peripheral, 10 patients) and RTOG 0813 (medial, 5 patients) lung protocols. Target dose, critical structure dose, and treatment time were compared and tested for statistical significance. Parameters of interest included prescription isodose surface coverage, target dose heterogeneity, high dose spillage (location and volume), low dose spillage (location and volume), lung dose spillage, and critical structure maximum- and volumetric-dose limits. Results: For all criteria, we found equivalent or higher conformality with VMAT plans as well as reduced critical structure doses. Several differences passed a Student's t-test of significance: VMAT reduced the high dose spillage, evaluated with conformality index (CI), by an average of 9.4%15.1% (p=0.030) compared to IMRT. VMAT plans reduced the lung volume receiving 20 Gy by 16.2%15.0% (p=0.016) compared with IMRT. For the RTOG 0915 peripheral lesions, the volumes of lung receiving 12.4 Gy and 11.6 Gy were reduced by 27.0%13.8% and 27.5%12.6% (for both, p<0.001) in VMAT plans. Of the 26 protocol pass/fail criteria, VMAT plans were able to achieve an average of 0.20.7 (p=0.026) more constraints than the IMRT plans. Conclusions: FFF VMAT has dosimetric advantages over fixed beam IMRT for lung SBRT. Significant advantages included increased dose conformity, and reduced organs-at-risk doses. The overall improvements in terms of protocol pass/fail criteria were more modest and will require more patient data to establish difference trends of more statistical significance.

  19. Gene expression profiles in irradiated cancer cells

    SciTech Connect (OSTI)

    Minafra, L.; Bravat, V.; Russo, G.; Ripamonti, M.; Gilardi, M. C.

    2013-07-26

    Knowledge of the molecular and genetic mechanisms underlying cellular response to radiation may provide new avenues to develop innovative predictive tests of radiosensitivity of tumours and normal tissues and to improve individual therapy. Nowadays very few studies describe molecular changes induced by hadrontherapy treatments, therefore this field has to be explored and clarified. High-throughput methodologies, such as DNA microarray, allow us to analyse mRNA expression of thousands of genes simultaneously in order to discover new genes and pathways as targets of response to hadrontherapy. Our aim is to elucidate the molecular networks involved in the sensitivity/resistance of cancer cell lines subjected to hadrontherapy treatments with a genomewide approach by using cDNA microarray technology to identify gene expression profiles and candidate genes responsible of differential cellular responses.

  20. Detection of eight BRCA1 mutations in 10 breast/ovarian cancer families, including 1 family with male breast cancer

    SciTech Connect (OSTI)

    Sruewing, J.P.; Brody, L.C.; Erdos, M.R.

    1995-07-01

    Genetic epidemiological evidence suggests that mutations in BRCA1 may be responsible for approximately one half of early onset familial breast cancer and the majority of familial breast/ovarian cancer. The recent cloning of BRCA1 allows for the direct detection of mutations, but the feasibility of presymptomatic screening for cancer susceptibility is unknown. We analyzed genomic DNA from one affected individual from each of 24 families with at least three cases of ovarian or breast cancer, using SSCP assays. Variant SSCP bands were subcloned and sequenced. Allele-specific oligonucleotide hybridization was used to verify sequence changes and to screen DNA from control individuals. Six frameshift and two missense mutations were detected in 10 different families. A frameshift mutation was detected in a male proband affected with both breast and prostate cancer. A 40-bp deletion was detected in a patient who developed intra-abdominal carcinomatosis 1 year after prophylactic oophorectomy. Mutations were detected throughout the gene, and only one was detected in more than a single family. These results provide further evidence that inherited breast and ovarian cancer can occur as a consequence of a wide array of BRCA1 mutations. These results suggests that development of a screening test for BRCA1 mutations will be technically challenging. The finding of a mutation in a family with male breast cancer, not previously thought to be related to BRCA1, also illustrates the potential difficulties of genetic counseling for individuals known to carry mutations. 37 refs., 1 fig., 1 tab.

  1. Intraoperative radiation therapy in recurrent ovarian cancer

    SciTech Connect (OSTI)

    Yap, O.W. Stephanie . E-mail: stbeast@stanford.edu; Kapp, Daniel S.; Teng, Nelson N.H.; Husain, Amreen

    2005-11-15

    Purpose: To evaluate disease outcomes and complications in patients with recurrent ovarian cancer treated with cytoreductive surgery and intraoperative radiation therapy (IORT). Methods and Materials: A retrospective study of 24 consecutive patients with ovarian carcinoma who underwent secondary cytoreduction and intraoperative radiation therapy at our institution between 1994 and 2002 was conducted. After optimal cytoreductive surgery, IORT was delivered with orthovoltage X-rays (200 kVp) using individually sized and beveled cone applications. Outcomes measures were local control of disease, progression-free interval, overall survival, and treatment-related complications. Results: Of these 24 patients, 22 were available for follow-up analysis. Additional treatment at the time of and after IORT included whole abdominopelvic radiation, 9; pelvic or locoregional radiation, 5; chemotherapy, 6; and no adjuvant treatment, 2. IORT doses ranged from 9-14 Gy (median, 12 Gy). The anatomic sites treated were pelvis (sidewalls, vaginal cuff, presacral area, anterior pubis), para-aortic and paracaval lymph node beds, inguinal region, or porta hepatitis. At a median follow-up of 24 months, 5 patients remain free of disease, whereas 17 patients have recurred, of whom 4 are alive with disease and 13 died from disease. Five patients recurred within the radiation fields for a locoregional relapse rate of 32% and 12 patients recurred at distant sites with a median time to recurrence of 13.7 months. Five-year overall survival was 22% with a median survival of 26 months from time of IORT. Nine patients (41%) experienced Grade 3 toxicities from their treatments. Conclusion: In carefully selected patients with locally recurrent ovarian cancer, combined IORT and tumor reductive surgery is reasonably tolerated and may contribute to achieving local control and disease palliation.

  2. Propensity Score-based Comparison of Long-term Outcomes With 3-Dimensional Conformal Radiotherapy vs Intensity-Modulated Radiotherapy for Esophageal Cancer

    SciTech Connect (OSTI)

    Lin, Steven H., E-mail: SHLin@mdanderson.org [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Wang Lu [Department of Biostatistics, University of Michigan, Ann Arbor, Michigan (United States)] [Department of Biostatistics, University of Michigan, Ann Arbor, Michigan (United States); Myles, Bevan [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States)] [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Thall, Peter F. [Department of Biostatistics, University of Texas MD Anderson Cancer Center, Houston, Texas (United States)] [Department of Biostatistics, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Hofstetter, Wayne L.; Swisher, Stephen G. [Department of Thoracic Surgery, University of Texas MD Anderson Cancer Center, Houston, Texas (United States)] [Department of Thoracic Surgery, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Ajani, Jaffer A. [Department of Gastrointestinal Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States)] [Department of Gastrointestinal Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Cox, James D.; Komaki, Ritsuko; Liao Zhongxing [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States)] [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States)

    2012-12-01

    Purpose: Although 3-dimensional conformal radiotherapy (3D-CRT) is the worldwide standard for the treatment of esophageal cancer, intensity modulated radiotherapy (IMRT) improves dose conformality and reduces the radiation exposure to normal tissues. We hypothesized that the dosimetric advantages of IMRT should translate to substantive benefits in clinical outcomes compared with 3D-CRT. Methods and Materials: An analysis was performed of 676 nonrandomized patients (3D-CRT, n=413; IMRT, n=263) with stage Ib-IVa (American Joint Committee on Cancer 2002) esophageal cancers treated with chemoradiotherapy at a single institution from 1998-2008. An inverse probability of treatment weighting and inclusion of propensity score (treatment probability) as a covariate were used to compare overall survival time, interval to local failure, and interval to distant metastasis, while accounting for the effects of other clinically relevant covariates. The propensity scores were estimated using logistic regression analysis. Results: A fitted multivariate inverse probability weighted-adjusted Cox model showed that the overall survival time was significantly associated with several well-known prognostic factors, along with the treatment modality (IMRT vs 3D-CRT, hazard ratio 0.72, P<.001). Compared with IMRT, 3D-CRT patients had a significantly greater risk of dying (72.6% vs 52.9%, inverse probability of treatment weighting, log-rank test, P<.0001) and of locoregional recurrence (P=.0038). No difference was seen in cancer-specific mortality (Gray's test, P=.86) or distant metastasis (P=.99) between the 2 groups. An increased cumulative incidence of cardiac death was seen in the 3D-CRT group (P=.049), but most deaths were undocumented (5-year estimate, 11.7% in 3D-CRT vs 5.4% in IMRT group, Gray's test, P=.0029). Conclusions: Overall survival, locoregional control, and noncancer-related death were significantly better after IMRT than after 3D-CRT. Although these results need confirmation, IMRT should be considered for the treatment of esophageal cancer.

  3. Intensity-Modulated Radiotherapy as Primary Therapy for Prostate Cancer: Report on Acute Toxicity After Dose Escalation With Simultaneous Integrated Boost to Intraprostatic Lesion

    SciTech Connect (OSTI)

    Fonteyne, Valerie Villeirs, Geert; Speleers, Bruno; Neve, Wilfried de; Wagter, Carlos de; Lumen, Nicolas; Meerleer, Gert de

    2008-11-01

    Purpose: To report on the acute toxicity of a third escalation level using intensity-modulated radiotherapy for prostate cancer (PCa) and the acute toxicity resulting from delivery of a simultaneous integrated boost (SIB) to an intraprostatic lesion (IPL) detected on magnetic resonance imaging (MRI), with or without spectroscopy. Methods and Materials: Between January 2002 and March 2007, we treated 230 patients with intensity-modulated radiotherapy to a third escalation level as primary therapy for prostate cancer. If an IPL (defined by MRI or MRI plus spectroscopy) was present, a SIB was delivered to the IPL. To report on acute toxicity, patients were seen weekly during treatment and 1 and 3 months after treatment. Toxicity was scored using the Radiation Therapy Oncology Group toxicity scale, supplemented by an in-house-developed scoring system. Results: The median dose to the planning target volume was 78 Gy. An IPL was found in 118 patients. The median dose to the MRI-detected IPL and MRI plus spectroscopy-detected IPL was 81 Gy and 82 Gy, respectively. No Grade 3 or 4 acute gastrointestinal toxicity developed. Grade 2 acute gastrointestinal toxicity was present in 26 patients (11%). Grade 3 genitourinary toxicity was present in 15 patients (7%), and 95 patients developed Grade 2 acute genitourinary toxicity (41%). No statistically significant increase was found in Grade 2-3 acute gastrointestinal or genitourinary toxicity after a SIB to an IPL. Conclusion: The results of our study have shown that treatment-induced acute toxicity remains low when intensity-modulated radiotherapy to 80 Gy as primary therapy for prostate cancer is used. In addition, a SIB to an IPL did not increase the severity or incidence of acute toxicity.

  4. Boron-Nitride Nanotubes Show Potential in Cancer Treatment |...

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Although this research is in the very early stages, it could one day lead to better therapies for cancer. The study was carried out by researchers in Italy at the Institute of Life ...

  5. Cancer mortality and residence near petrochemical industries in Taiwan

    SciTech Connect (OSTI)

    Yang, Chun-Yuh; Chiu, Hui-Fen; Chiu, Jeng-Fen

    1997-02-21

    An ecologic study design was used to investigate the relationship between cancer risks and residence in communities adjacent to petrochemical industrial counties (PICs). Directly age-adjusted mortality rates for cancer during 1982-1991 among 16 counties characterized by a heavy concentration of petrochemical industries were compared to rates among 16 matched counties with similar concentration of nonpetrochemical manufacturing industries, urbanization level, and demographic characteristics. An excess rate for liver cancer among males was found in the so-called PICs. The correlation could not be explained by confounding variables such as urbanization, socioeconomic class, or employment in nonpetrochemical industries. No other increased cancer risks were found to be associated with residence near petrochemical industries. 30 refs., 3 tabs.

  6. Topo II: An Enzyme Target for Antibacterial and Cancer Drugs

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    a cell's DNA is fatal to the cell, which is why drugs that target topo II serve as agents against bacterial infections and some forms of cancer. This first ever structural...

  7. Our Role in the War on Cancer | GE Global Research

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Our Role in the War on Cancer Click to email this to a friend (Opens in new window) Share on Facebook (Opens in new window) Click to share (Opens in new window) Click to share on...

  8. Genomics at the Ontario Institute for Cancer Research

    SciTech Connect (OSTI)

    Ali, Johar

    2010-06-02

    Johar Ali of the Ontario Institute for Cancer Research discusses genomics and next-gen applications at the OICR on June 2, 2010 at the "Sequencing, Finishing, Analysis in the Future" meeting in Santa Fe, NM

  9. Doctor Patient Conversation Around Breast Cancer | GE Global...

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Doctor Patient Conversation Around Breast Cancer Click to email this to a friend (Opens in new window) Share on Facebook (Opens in new window) Click to share (Opens in new window)...

  10. Technology Relay Race in Cancer Prevention Research | GE Global...

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Technology Relay Race in Cancer Prevention Research Click to email this to a friend (Opens in new window) Share on Facebook (Opens in new window) Click to share (Opens in new...

  11. Enzyme Structure Provides Insights into Cancer and Aging

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Provides Insights into Cancer and Aging Print XPD helicase is an enzyme that unwinds the DNA double helix; it is one component of an essential repair mechanism that maintains the...

  12. Topo II: An Enzyme Target for Antibacterial and Cancer Drugs

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Topo II: An Enzyme Target for Antibacterial and Cancer Drugs Print The veil has finally been lifted on an enzyme that is critical to the process of DNA transcription and...

  13. Iran Thomas Auditorium, 8600 Fighting Cancer with Nanoparticle...

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    October 13, 2011 4:00 pm Iran Thomas Auditorium, 8600 Fighting Cancer with Nanoparticle Medicines Mark E. Davis Chemical Engineering California Institute of Technology CNMS D D I I...

  14. 6.21 Improving Neutron Beams for Cancer Treatment

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    1 612011 6.21 Improving Neutron Beams for Cancer Treatment Beams of neutrons long have been used in scientific experiments, but recently, for the first time, a novel type of...

  15. Enzyme Structure Provides Insights into Cancer and Aging

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Enzyme Structure Provides Insights into Cancer and Aging Print XPD helicase is an enzyme that unwinds the DNA double helix; it is one component of an essential repair mechanism...

  16. Designer Proteins Target Epstein-Barr-Virus-Associated Cancer

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Designer Proteins Target Epstein-Barr-Virus-Associated Cancer Print Immortality is not a good thing for cells, and in fact, cells will destroy themselves in a process called...

  17. Proton Therapy for Cancer: Current Status, Promise and Challenges...

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    March 9, 2016, 4:15pm to 5:30pm Colloquia MBG Auditorium Proton Therapy for Cancer: Current Status, Promise and Challenges Dr. Dennis Mah ProCure Proton Therapy Center Colloquium...

  18. World Cancer Day 2015: Not Beyond Us | GE Global Research

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    World Cancer Day 2015: Not Beyond Us Click to email this to a friend (Opens in new window) Share on Facebook (Opens in new window) Click to share (Opens in new window) Click to...

  19. Software speeds detection of diseases and cancer-treatment targets

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Software speeds detection of diseases Software speeds detection of diseases and cancer-treatment targets The Lab has released an updated version of software that is now capable of...

  20. Scanxiety: Waiting anxiously for childhood cancer test results...

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    results that could change your life Mark Frontera 2015.09.18 September is Childhood Cancer Awareness Month and we are publishing a series of blog posts to share stories about...

  1. Structures and Activities Shed Light into Cancer and Aging Phenotypes...

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    8 Structures and Activities Shed Light into Cancer and Aging Phenotypes of Helicase XPD Mutations figure 1 Figure 1. Ribbon diagram of crystal structures of SaXPD (A) and apo SaXPD...

  2. Bacillus anthracis spores germinate extracellularly at air-liquid interface in an in vitro lung model under serum-free conditions

    SciTech Connect (OSTI)

    Powell, Joshua D.; Hutchison, Janine R.; Hess, Becky M.; Straub, Tim M.

    2015-07-30

    Aims: To better understand the parameters that govern spore dissemination after lung exposure using in vitro cell systems. Methods and Results: We evaluated the kinetics of uptake, germination and proliferation of B. anthracis Sterne spores in association with human primary lung epithelial cells, Calu-3, and A549 cell lines. We also analyzed the influence of various cell culture media formulations related to spore germination. Conclusions: We found negligible spore uptake by epithelial cells, but germination and proliferation of spores in the extracellular environment was evident, and was appreciably higher in A549 and Calu-3 cultures than in primary epithelial cells. Additionally, our results revealed spores in association with primary cells submerged in cell culture media germinated 1 h

  3. Bacillus anthracis spores germinate extracellularly at air-liquid interface in an in vitro lung model under serum-free conditions

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Powell, Joshua D.; Hutchison, Janine R.; Hess, Becky M.; Straub, Tim M.

    2015-07-30

    Aims: To better understand the parameters that govern spore dissemination after lung exposure using in vitro cell systems. Methods and Results: We evaluated the kinetics of uptake, germination and proliferation of B. anthracis Sterne spores in association with human primary lung epithelial cells, Calu-3, and A549 cell lines. We also analyzed the influence of various cell culture media formulations related to spore germination. Conclusions: We found negligible spore uptake by epithelial cells, but germination and proliferation of spores in the extracellular environment was evident, and was appreciably higher in A549 and Calu-3 cultures than in primary epithelial cells. Additionally, ourmore » results revealed spores in association with primary cells submerged in cell culture media germinated 1 h« less

  4. SU-E-J-30: Benchmark Image-Based TCP Calculation for Evaluation of PTV Margins for Lung SBRT Patients

    SciTech Connect (OSTI)

    Li, M; Chetty, I; Zhong, H

    2014-06-01

    Purpose: Tumor control probability (TCP) calculated with accumulated radiation doses may help design appropriate treatment margins. Image registration errors, however, may compromise the calculated TCP. The purpose of this study is to develop benchmark CT images to quantify registration-induced errors in the accumulated doses and their corresponding TCP. Methods: 4DCT images were registered from end-inhale (EI) to end-exhale (EE) using a demons algorithm. The demons DVFs were corrected by an FEM model to get realistic deformation fields. The FEM DVFs were used to warp the EI images to create the FEM-simulated images. The two images combined with the FEM DVF formed a benchmark model. Maximum intensity projection (MIP) images, created from the EI and simulated images, were used to develop IMRT plans. Two plans with 3 and 5 mm margins were developed for each patient. With these plans, radiation doses were recalculated on the simulated images and warped back to the EI images using the FEM DVFs to get the accumulated doses. The Elastix software was used to register the FEM-simulated images to the EI images. TCPs calculated with the Elastix-accumulated doses were compared with those generated by the FEM to get the TCP error of the Elastix registrations. Results: For six lung patients, the mean Elastix registration error ranged from 0.93 to 1.98 mm. Their relative dose errors in PTV were between 0.28% and 6.8% for 3mm margin plans, and between 0.29% and 6.3% for 5mm-margin plans. As the PTV margin reduced from 5 to 3 mm, the mean TCP error of the Elastix-reconstructed doses increased from 2.0% to 2.9%, and the mean NTCP errors decreased from 1.2% to 1.1%. Conclusion: Patient-specific benchmark images can be used to evaluate the impact of registration errors on the computed TCPs, and may help select appropriate PTV margins for lung SBRT patients.

  5. LANL responds to radiological incident

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Center(LANSCE). Aerial view of the Los Alamos Neutron Science Center (LANSCE). The contamination poses no danger to the public. The Laboratory is investigating the inadvertent...

  6. Hazardous Materials Incident Response Procedure

    Broader source: Energy.gov [DOE]

    The purpose of this procedure is to provide guidance for developing an emergency response plan, as outlined in OSHA’s 29 CFR 1910.120(q), for facility response.  This model has been adopted and...

  7. A Phase II Study of Radiotherapy and Concurrent Paclitaxel Chemotherapy in Breast-Conserving Treatment for Node-Positive Breast Cancer

    SciTech Connect (OSTI)

    Chen, William C.; Kim, Janice; Kim, Edward; Silverman, Paula; Overmoyer, Beth; Cooper, Brenda W.; Anthony, Sue; Shenk, Robert; Leeming, Rosemary; Hanks, Shelli H.; Lyons, Janice A.

    2012-01-01

    Purpose: Administering adjuvant chemotherapy before breast radiotherapy decreases the risk of systemic recurrence, but delays in radiotherapy could yield higher local failure. We assessed the feasibility and efficacy of placing radiotherapy earlier in the breast-conserving treatment course for lymph node-positive breast cancer. Methods and Materials: Between June 2000 and December 2004, 44 women with node-positive Stage II and III breast cancer were entered into this trial. Breast-conserving surgery and 4 cycles of doxorubicin (60 mg/m{sup 2})/cyclophosphamide (600 mg/m{sup 2}) were followed by 4 cycles of paclitaxel (175 mg/m{sup 2}) delivered every 3 weeks. Radiotherapy was concurrent with the first 2 cycles of paclitaxel. The breast received 39.6 Gy in 22 fractions with a tumor bed boost of 14 Gy in 7 fractions. Regional lymphatics were included when indicated. Functional lung volume was assessed by use of the diffusing capacity for carbon monoxide as a proxy. Breast cosmesis was evaluated with the Harvard criteria. Results: The 5-year actuarial rate of disease-free survival is 88%, and overall survival is 93%. There have been no local failures. Median follow-up is 75 months. No cases of radiation pneumonitis developed. There was no significant change in the diffusing capacity for carbon monoxide either immediately after radiotherapy (p = 0.51) or with extended follow-up (p = 0.63). Volume of irradiated breast tissue correlated with acute cosmesis, and acute Grade 3 skin toxicity developed in 2 patients. Late cosmesis was not adversely affected. Conclusions: Concurrent paclitaxel chemotherapy and radiotherapy after breast-conserving surgery shortened total treatment time, provided excellent local control, and was well tolerated.

  8. Is Primary Prostate Cancer Treatment Influenced by Likelihood of

    Office of Scientific and Technical Information (OSTI)

    Extraprostatic Disease? A Surveillance, Epidemiology and End Results Patterns of Care Study (Journal Article) | SciTech Connect Is Primary Prostate Cancer Treatment Influenced by Likelihood of Extraprostatic Disease? A Surveillance, Epidemiology and End Results Patterns of Care Study Citation Details In-Document Search Title: Is Primary Prostate Cancer Treatment Influenced by Likelihood of Extraprostatic Disease? A Surveillance, Epidemiology and End Results Patterns of Care Study Purpose: To

  9. Locally Advanced Prostate Cancer: Three-Dimensional Magnetic Resonance

    Office of Scientific and Technical Information (OSTI)

    Spectroscopy to Monitor Prostate Response to Therapy (Journal Article) | SciTech Connect Locally Advanced Prostate Cancer: Three-Dimensional Magnetic Resonance Spectroscopy to Monitor Prostate Response to Therapy Citation Details In-Document Search Title: Locally Advanced Prostate Cancer: Three-Dimensional Magnetic Resonance Spectroscopy to Monitor Prostate Response to Therapy Purpose: To correlate results of three-dimensional magnetic resonance spectroscopic imaging (MRSI) with

  10. Preoperative chemoradiation of locally advanced T3 rectal cancer combined

    Office of Scientific and Technical Information (OSTI)

    with an endorectal boost (Journal Article) | SciTech Connect SciTech Connect Search Results Journal Article: Preoperative chemoradiation of locally advanced T3 rectal cancer combined with an endorectal boost Citation Details In-Document Search Title: Preoperative chemoradiation of locally advanced T3 rectal cancer combined with an endorectal boost Purpose: To investigate the effect and feasibility of concurrent radiation and chemotherapy combined with endorectal brachytherapy in T3 rectal

  11. Magnetic relaxometry as applied to sensitive cancer detection and

    Office of Scientific and Technical Information (OSTI)

    localization (Journal Article) | SciTech Connect Journal Article: Magnetic relaxometry as applied to sensitive cancer detection and localization Citation Details In-Document Search Title: Magnetic relaxometry as applied to sensitive cancer detection and localization × You are accessing a document from the Department of Energy's (DOE) SciTech Connect. This site is a product of DOE's Office of Scientific and Technical Information (OSTI) and is provided as a public service. Visit OSTI to

  12. DOE Laboratories Help Develop Promising New Cancer Fighting Drug,

    Energy Savers [EERE]

    Vemurafenib | Department of Energy Laboratories Help Develop Promising New Cancer Fighting Drug, Vemurafenib DOE Laboratories Help Develop Promising New Cancer Fighting Drug, Vemurafenib August 18, 2011 - 1:03pm Addthis Powerful X-Rays Enable Development of Successful Treatment for Melanoma and Other Life-Threatening Diseases WASHINGTON, DC - Powerful X-ray technology developed at the U.S. Department of Energy's (DOE's) national laboratories is revealing new insights into diseases ranging

  13. Enzyme Structure Provides Insights into Cancer and Aging

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Enzyme Structure Provides Insights into Cancer and Aging Print XPD helicase is an enzyme that unwinds the DNA double helix; it is one component of an essential repair mechanism that maintains the integrity of DNA. XPD is unique, however, in that pinpoint mutations of this single protein are responsible for three different human diseases: in xeroderma pigmentosum (XP), extreme sensitivity to sunlight promotes cancer; Cockayne syndrome (CS) involves stunted growth and premature aging;

  14. Enzyme Structure Provides Insights into Cancer and Aging

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Enzyme Structure Provides Insights into Cancer and Aging Print XPD helicase is an enzyme that unwinds the DNA double helix; it is one component of an essential repair mechanism that maintains the integrity of DNA. XPD is unique, however, in that pinpoint mutations of this single protein are responsible for three different human diseases: in xeroderma pigmentosum (XP), extreme sensitivity to sunlight promotes cancer; Cockayne syndrome (CS) involves stunted growth and premature aging;

  15. Mathematical Models Shed New Light on Cancer Mutations

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Mathematical Models Shed New Light on Cancer Mutations Mathematical Models Shed New Light on Cancer Mutations Calculations Run at NERSC Pinpoint Rare Mutants More Quickly November 3, 2014 Contact: David Cameron, 617.432.0441, david_cameron@hms.harvard.edu cancermutations3 Heat map of the average magnitude of interaction energies projected onto a structural representation of SH2 domains (white) in complex with phosphopeptide (green). SH2 (Src Homology 2) is a protein domain found in many

  16. Jefferson Lab Medical Imager Spots Breast Cancer | Jefferson Lab

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    PEM This PEM image shows two cancerous lesions. The one on the right was depicted by conventional mammography, but the one on the left was only identified by the PEM unit. Image courtesy: Eric Rosen, Duke University Medical Center Jefferson Lab Medical Imager Spots Breast Cancer March 3, 2005 Newport News, VA - A study published in the February issue of the journal Radiology shows that a positron emission mammography (PEM) device designed and built by Jefferson Lab scientists is capable of

  17. Enzyme Structure Provides Insights into Cancer and Aging

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Enzyme Structure Provides Insights into Cancer and Aging Print XPD helicase is an enzyme that unwinds the DNA double helix; it is one component of an essential repair mechanism that maintains the integrity of DNA. XPD is unique, however, in that pinpoint mutations of this single protein are responsible for three different human diseases: in xeroderma pigmentosum (XP), extreme sensitivity to sunlight promotes cancer; Cockayne syndrome (CS) involves stunted growth and premature aging;

  18. Enzyme Structure Provides Insights into Cancer and Aging

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Enzyme Structure Provides Insights into Cancer and Aging Print XPD helicase is an enzyme that unwinds the DNA double helix; it is one component of an essential repair mechanism that maintains the integrity of DNA. XPD is unique, however, in that pinpoint mutations of this single protein are responsible for three different human diseases: in xeroderma pigmentosum (XP), extreme sensitivity to sunlight promotes cancer; Cockayne syndrome (CS) involves stunted growth and premature aging;

  19. Enzyme Structure Provides Insights into Cancer and Aging

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Enzyme Structure Provides Insights into Cancer and Aging Print XPD helicase is an enzyme that unwinds the DNA double helix; it is one component of an essential repair mechanism that maintains the integrity of DNA. XPD is unique, however, in that pinpoint mutations of this single protein are responsible for three different human diseases: in xeroderma pigmentosum (XP), extreme sensitivity to sunlight promotes cancer; Cockayne syndrome (CS) involves stunted growth and premature aging;

  20. Enzyme Structure Provides Insights into Cancer and Aging

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Enzyme Structure Provides Insights into Cancer and Aging Print XPD helicase is an enzyme that unwinds the DNA double helix; it is one component of an essential repair mechanism that maintains the integrity of DNA. XPD is unique, however, in that pinpoint mutations of this single protein are responsible for three different human diseases: in xeroderma pigmentosum (XP), extreme sensitivity to sunlight promotes cancer; Cockayne syndrome (CS) involves stunted growth and premature aging;