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

    SciTech Connect (OSTI)

    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

    SciTech Connect (OSTI)

    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. 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.

  7. 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

  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

  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

    SciTech Connect (OSTI)

    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

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

    SciTech Connect (OSTI)

    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. Commentary on Inhaled 239PuO2 in Dogs — A Prophylaxis against Lung Cancer?

    SciTech Connect (OSTI)

    Cuttler, Jerry M.; Feinendegen, Ludwig E.

    2015-01-01

    Several studies on the effect of inhaled plutonium-dioxide particulates and the incidence of lung tumors in dogs reveal beneficial effects when the cumulative alpha-radiation dose is low. There is a threshold at an exposure level of about 100 cGy for excess tumor incidence and reduced lifespan. The observations conform to the expectations of the radiation hormesis dose-response model and contradict the predictions of the LNT hypothesis. These studies suggest investigating the possibility of employing low-dose alpha-radiation, such as from 239PuO2 inhalation, as a prophylaxis against lung cancer.

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

    SciTech Connect (OSTI)

    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.

  14. CUL4A overexpression enhances lung tumor growth and sensitizes lung cancer cells to Erlotinib via transcriptional regulation of EGFR

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

    Wang, Yunshan; Zhang, Pengju; Liu, Ziming; Wang, Qin; Wen, Mingxin; Wang, Yuli; Yuan, Hongtu; Mao, Jian-Hua; Wei, Guangwei

    2014-11-21

    CUL4A has been proposed as oncogene in several types of human cancer, but its clinical significance and functional role in human non-small cell lung cancer (NSCLC) remain unclear. Expression level of CUL4A was examined by RT-PCR and Western blot. Forced expression of CUL4A was mediated by retroviruses, and CUL4A silencing by shRNAs expressing lentiviruses. Growth capacity of lung cancer cells was measured by MTT in vitro and tumorigenesis in vivo, respectively. We found that CUL4A was highly expressed in human lung cancer tissues and lung cancer cell lines, and this elevated expression positively correlated with disease progression and prognosis. Overexpressionmore » of CUL4A in human lung cancer cell lines increased cell proliferation, inhibited apoptosis, and subsequently conferred resistance to chemotherapy. On other hand, silencing CUL4A expression in NSCLC cells reduced proliferation, promoted apoptosis and resulted in tumor growth inhibition in cancer xenograft model. Mechanistically, we revealed CUL4A regulated EGFR transcriptional expression and activation, and subsequently activated AKT. Targeted inhibition of EGFR activity blocked these CUL4A induced oncogenic activities. In conclusion, our results highlight the significance of CUL4A in NSCLC and suggest that CUL4A could be a promising therapy target and a potential biomarker for prognosis and EGFR target therapy in NSCLC patients.« less

  15. Chest wall invasion by lung cancer: limitations of CT evaluation

    SciTech Connect (OSTI)

    Pennes, D.R.; Glazer, G.M.; Wimbish, K.J.; Gross, B.H.; Long, R.W.; Orringer, M.B.

    1985-03-01

    Thirty-three patients with peripheral pulmonary malignancies contiguous with a pleural surface were evaluated for chest wall invasion by computed tomography (CT). CT criteria included pleural thickening adjacent to the tumor, encroachment on or increased density of the extrapleural fat, asymmetry of the extrapleural soft tissues adjacent to the tumor, apparent mass invading the chest wall, and rib destruction. The CT scans were classified as positive, negative, or equivocal for invasion, and a decision matrix was constructed comparing CT results with pathologic data. CT scanning has low accuracy in assessing chest wall invasion in patients with peripheral lung cancers.

  16. 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.

  17. 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

  18. Expression of hPNAS-4 Radiosensitizes Lewis Lung Cancer

    SciTech Connect (OSTI)

    Zeng Hui; Yuan Zhu; Zhu Hong; Li Lei; Shi Huashan; Wang Zi; Fan Yu; Deng Qian; Zeng Jianshuang; He Yinbo; Xiao Jianghong; Li Zhiping

    2012-11-15

    Purpose: This study aimed to transfer the hPNAS-4 gene, a novel apoptosis-related human gene, into Lewis lung cancer (LL2) and observe its radiosensitive effect on radiation therapy in vitro and in vivo. Methods and Materials: The hPNAS-4 gene was transfected into LL2 cells, and its expression was detected via western blot. Colony formation assay and flow cytometry were used to detect the growth and apoptosis of cells treated with irradiation/PNAS-4 in vitro. The hPNAS-4 gene was transferred into LL2-bearing mice through tail vein injection of the liposome/gene complex. The tumor volumes were recorded after radiation therapy. Proliferating cell nuclear antigen (PCNA) immunohistochemistry staining and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay were performed to detect the tumor cell growth and apoptosis in vivo. Results: The hPNAS-4 gene was successfully transferred into LL2 cells and tumor tissue, and its overexpressions were confirmed via western blot analysis. Compared with the control, empty plasmid, hPNAS-4, radiation, and empty plasmid plus radiation groups, the hPNAS-4 plus radiation group more significantly inhibited growth and enhanced apoptosis of LL2 cells in vitro and in vivo (P<.05). Conclusions: The hPNAS-4 gene was successfully transferred into LL2 cells and tumor tissue and was expressed in both LL2 cell and tumor tissue. The hPNAS-4 gene therapy significantly enhanced growth inhibition and apoptosis of LL2 tumor cells by radiation therapy in vitro and in vivo. Therefore, it may be a potential radiosensitive treatment of radiation therapy for lung cancer.

  19. Influence of Irradiated Lung Volumes on Perioperative Morbidity and Mortality in Patients After Neoadjuvant Radiochemotherapy for Esophageal Cancer

    SciTech Connect (OSTI)

    Daehn, Doreen; Martell, Joachim; Vorwerk, Hilke; Hess, Clemens F.; Becker, Heinz; Jung, Klaus; Hilgers, Reinhard; Wolff, Hendrik Andreas; Hermann, Robert Michael; Christiansen, Hans

    2010-05-01

    Purpose: In some randomized trials, the treatment outcome of locally advanced esophageal cancer has been significantly improved by neoadjuvant radiochemotherapy (RCT). However, increased perioperative pulmonary toxicity in terms of acute respiratory distress syndrome (ARDS) has been linked to radiation exposure of the lungs. In our study we evaluated perioperative morbidity and mortality in patients with cancer Stages IIA-IVA treated with curative intent either with surgery alone (S) or with neoadjuvant RCT followed by surgery (RCTS). Patients and Methods: Between 1996 and 2003, 55 patients received S, and 98 received RCTS. In the RCTS group, most patients received two cycles of 5-fluorouracil plus cisplatinum simultaneously with normofractionated radiotherapy (40Gy). Four weeks later they underwent surgery. Endpoints were the incidence of acute lung injury (ALI), ARDS, other postoperative complications, and mortality within 31 days. Results: Between both groups there were no significant differences between the incidence and severity of ALI and ARDS (RCTS: 42.9%, 42.9%; S: 45.5%, 38.2%). Furthermore, there were no significant differences in the incidences of pneumonia, pleural effusion, and pneumothorax (RCTS 29.6% vs. S 16.4%, p = 0.07). Perioperative complication rates and mortality did not vary significantly (mortality after RCTS 5.1% vs. S 3.6%). A detailed analysis of 54 RCTS patients according to lung dose-volume histograms did not show any correlation between ARDS and pulmonary exposure. In univariate analysis, only respiratory comorbidity correlated with ARDS. Conclusion: Neoadjuvant cisplatinum and 5-fluorouracil-based RCT apparently has no detrimental impact on the postoperative course.

  20. 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).

  1. 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.

  2. 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

  3. 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.

  4. Transcription factor FOXA2-centered transcriptional regulation network in non-small cell lung cancer

    SciTech Connect (OSTI)

    Jang, Sang-Min; An, Joo-Hee; Kim, Chul-Hong; Kim, Jung-Woong Choi, Kyung-Hee

    2015-08-07

    Lung cancer is the leading cause of cancer-mediated death. Although various therapeutic approaches are used for lung cancer treatment, these mainly target the tumor suppressor p53 transcription factor, which is involved in apoptosis and cell cycle arrest. However, p53-targeted therapies have limited application in lung cancer, since p53 is found to be mutated in more than half of lung cancers. In this study, we propose tumor suppressor FOXA2 as an alternative target protein for therapies against lung cancer and reveal a possible FOXA2-centered transcriptional regulation network by identifying new target genes and binding partners of FOXA2 by using various screening techniques. The genes encoding Glu/Asp-rich carboxy-terminal domain 2 (CITED2), nuclear receptor subfamily 0, group B, member 2 (NR0B2), cell adhesion molecule 1 (CADM1) and BCL2-associated X protein (BAX) were identified as putative target genes of FOXA2. Additionally, the proteins including highly similar to heat shock protein HSP 90-beta (HSP90A), heat shock 70 kDa protein 1A variant (HSPA1A), histone deacetylase 1 (HDAC1) and HDAC3 were identified as novel interacting partners of FOXA2. Moreover, we showed that FOXA2-dependent promoter activation of BAX and p21 genes is significantly reduced via physical interactions between the identified binding partners and FOXA2. These results provide opportunities to understand the FOXA2-centered transcriptional regulation network and novel therapeutic targets to modulate this network in p53-deficient lung cancer. - Highlights: • Identification of new target genes of FOXA2. • Identifications of novel interaction proteins of FOXA2. • Construction of FOXA2-centered transcriptional regulatory network in non-small cell lung cancer.

  5. Acute Esophagus Toxicity in Lung Cancer Patients After Intensity Modulated Radiation Therapy and Concurrent Chemotherapy

    SciTech Connect (OSTI)

    Kwint, Margriet; Uyterlinde, Wilma; Nijkamp, Jasper; Chen, Chun; Bois, Josien de; Sonke, Jan-Jakob; Heuvel, Michel van den; Knegjens, Joost; Herk, Marcel van; Belderbos, Jose

    2012-10-01

    Purpose: The purpose of this study was to investigate the dose-effect relation between acute esophageal toxicity (AET) and the dose-volume parameters of the esophagus after intensity modulated radiation therapy (IMRT) and concurrent chemotherapy for patients with non-small cell lung cancer (NSCLC). Patients and Methods: One hundred thirty-nine patients with inoperable NSCLC treated with IMRT and concurrent chemotherapy were prospectively analyzed. The fractionation scheme was 66 Gy in 24 fractions. All patients received concurrently a daily dose of cisplatin (6 mg/m Superscript-Two ). Maximum AET was scored according to Common Toxicity Criteria 3.0. Dose-volume parameters V5 to V70, D{sub mean} and D{sub max} of the esophagus were calculated. A logistic regression analysis was performed to analyze the dose-effect relation between these parameters and grade {>=}2 and grade {>=}3 AET. The outcome was compared with the clinically used esophagus V35 prediction model for grade {>=}2 after radical 3-dimensional conformal radiation therapy (3DCRT) treatment. Results: In our patient group, 9% did not experience AET, and 31% experienced grade 1 AET, 38% grade 2 AET, and 22% grade 3 AET. The incidence of grade 2 and grade 3 AET was not different from that in patients treated with CCRT using 3DCRT. The V50 turned out to be the most significant dosimetric predictor for grade {>=}3 AET (P=.012). The derived V50 model was shown to predict grade {>=}2 AET significantly better than the clinical V35 model (P<.001). Conclusions: For NSCLC patients treated with IMRT and concurrent chemotherapy, the V50 was identified as most accurate predictor of grade {>=}3 AET. There was no difference in the incidence of grade {>=}2 AET between 3DCRT and IMRT in patients treated with concurrent chemoradiation therapy.

  6. XCR1 promotes cell growth and migration and is correlated with bone metastasis in non-small cell lung cancer

    SciTech Connect (OSTI)

    Wang, Ting; Han, Shuai; Wu, Zhipeng; Han, Zhitao; Yan, Wangjun; Liu, Tielong; Wei, Haifeng; Song, Dianwen; Zhou, Wang Yang, Xinghai Xiao, Jianru

    2015-08-21

    Bone metastasis occurs in approximately 30–40% patients with advanced non-small cell lung cancer (NSCLC), but the mechanism underlying this bone metastasis remains poorly understood. The chemokine super family is believed to play an important role in tumor metastasis in lung cancer. The chemokine receptor XCR1 has been identified to promote cell proliferation and migration in oral cancer and ovarian carcinoma, but the role of XCR1 in lung cancer has not been reported. In this study, we demonstrated for the first time that XCR1 was overexpressed in lung cancer bone metastasis as compared with that in patients with primary lung cancer. In addition, the XCR1 ligand XCL1 promoted the proliferation and migration of lung cancer cells markedly, and knockdown of XCR1 by siRNA abolished the effect of XCL1 in cell proliferation and migration. Furthermore, we identified JAK2/STAT3 as a novel downstream pathway of XCR1, while XCL1/XCR1 increased the mRNA level of the downstream of JAK2/STAT3 including PIM1, JunB, TTP, MMP2 and MMP9. These results indicate that XCR1 is a new potential therapeutic target for the treatment of lung cancer bone metastasis. - Highlights: • XCR1 is overexpressed in bone metastasis compared with primary NSCLC. • XCR1 activation by XCL1 promotes lung cancer cell proliferation and migration. • JAK2/STAT3 is a novel potential downstream pathway of XCR1.

  7. The histone demethylase PHF8 is an oncogenic protein in human non-small cell lung cancer

    SciTech Connect (OSTI)

    Shen, Yuzhou; Pan, Xufeng; Zhao, Heng

    2014-08-15

    Highlights: • PHF8 overexpresses in human NSCLC and predicts poor survival. • PHF8 regulates lung cancer cell growth and transformation. • PHF8 regulates apoptosis in human lung cancer cells. • PHF8 promotes miR-21 expression in human lung cancer. • MiR-21 is critically essential for PHF8 function in human lung cancer cells. - Abstract: PHF8 is a JmjC domain-containing protein and erases repressive histone marks including H4K20me1 and H3K9me1/2. It binds to H3K4me3, an active histone mark usually located at transcription start sites (TSSs), through its plant homeo-domain, and is thus recruited and enriched in gene promoters. PHF8 is involved in the development of several types of cancer, including leukemia, prostate cancer, and esophageal squamous cell carcinoma. Herein we report that PHF8 is an oncogenic protein in human non-small cell lung cancer (NSCLC). PHF8 is up-regulated in human NSCLC tissues, and high PHF8 expression predicts poor survival. Our in vitro and in vivo evidence demonstrate that PHF8 regulates lung cancer cell proliferation and cellular transformation. We found that PHF8 knockdown induces DNA damage and apoptosis in lung cancer cells. PHF8 promotes miR-21 expression in human lung cancer, and miR-21 knockdown blocks the effects of PHF8 on proliferation and apoptosis of lung cancer cells. In summary, PHF8 promotes lung cancer cell growth and survival by regulating miR-21.

  8. Low-Dose Chest Computed Tomography for Lung Cancer Screening Among Hodgkin Lymphoma Survivors: A Cost-Effectiveness Analysis

    SciTech Connect (OSTI)

    Wattson, Daniel A.; Hunink, M.G. Myriam; DiPiro, Pamela J.; Das, Prajnan; Hodgson, David C.; Mauch, Peter M.; Ng, Andrea K.

    2014-10-01

    Purpose: Hodgkin lymphoma (HL) survivors face an increased risk of treatment-related lung cancer. Screening with low-dose computed tomography (LDCT) may allow detection of early stage, resectable cancers. We developed a Markov decision-analytic and cost-effectiveness model to estimate the merits of annual LDCT screening among HL survivors. Methods and Materials: Population databases and HL-specific literature informed key model parameters, including lung cancer rates and stage distribution, cause-specific survival estimates, and utilities. Relative risks accounted for radiation therapy (RT) technique, smoking status (>10 pack-years or current smokers vs not), age at HL diagnosis, time from HL treatment, and excess radiation from LDCTs. LDCT assumptions, including expected stage-shift, false-positive rates, and likely additional workup were derived from the National Lung Screening Trial and preliminary results from an internal phase 2 protocol that performed annual LDCTs in 53 HL survivors. We assumed a 3% discount rate and a willingness-to-pay (WTP) threshold of $50,000 per quality-adjusted life year (QALY). Results: Annual LDCT screening was cost effective for all smokers. A male smoker treated with mantle RT at age 25 achieved maximum QALYs by initiating screening 12 years post-HL, with a life expectancy benefit of 2.1 months and an incremental cost of $34,841/QALY. Among nonsmokers, annual screening produced a QALY benefit in some cases, but the incremental cost was not below the WTP threshold for any patient subsets. As age at HL diagnosis increased, earlier initiation of screening improved outcomes. Sensitivity analyses revealed that the model was most sensitive to the lung cancer incidence and mortality rates and expected stage-shift from screening. Conclusions: HL survivors are an important high-risk population that may benefit from screening, especially those treated in the past with large radiation fields including mantle or involved-field RT. Screening

  9. 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; Pérez, Liliana; Cortés, 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 μg/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), 0.99–3.67), and 3.26 (1.76–6.04) (p-trend < 0.001). Corresponding odds ratios for bladder cancer were 1.00, 1.81 (1.06–3.11), and 2.02 (1.15–3.54) (p-trend < 0.001). In analyses confined to subjects only with arsenic water concentrations < 200 μg/L (median = 60 μg/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 (1.08–5.68) and 2.37 (1.01–5.57), 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 μg/L.

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

    SciTech Connect (OSTI)

    Kodama, Hiroshi Yamakado, Koichiro; Takaki, Haruyuki; Kashima, Masataka; Uraki, Junji; Nakatsuka, Atsuhiro; Takao, Motoshi; Taguchi, Osamu; Yamada, Tomomi; Takeda, Kan

    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.

  11. 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.

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

    SciTech Connect (OSTI)

    Matsuo, Yukinori; Shibuya, Keiko; Nagata, Yasushi; Takayama, Kenji; Norihisa, Yoshiki; Mizowaki, Takashi; Narabayashi, Masaru; Sakanaka, Katsuyuki; Hiraoka, Masahiro

    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.

  13. 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.

  14. 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.

  15. 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)

  16. Chronic inorganic arsenic exposure in vitro induces a cancer cell phenotype in human peripheral lung epithelial cells

    SciTech Connect (OSTI)

    Person, Rachel J.; Olive Ngalame, Ntube N.; Makia, Ngome L.; Bell, Matthew W.; Waalkes, Michael P.; Tokar, Erik J.

    2015-07-01

    Inorganic arsenic is a human lung carcinogen. We studied the ability of chronic inorganic arsenic (2 μM; as sodium arsenite) exposure to induce a cancer phenotype in the immortalized, non-tumorigenic human lung peripheral epithelial cell line, HPL-1D. After 38 weeks of continuous arsenic exposure, secreted matrix metalloproteinase-2 (MMP2) activity increased to over 200% of control, levels linked to arsenic-induced cancer phenotypes in other cell lines. The invasive capacity of these chronic arsenic-treated lung epithelial (CATLE) cells increased to 320% of control and colony formation increased to 280% of control. CATLE cells showed enhanced proliferation in serum-free media indicative of autonomous growth. Compared to control cells, CATLE cells showed reduced protein expression of the tumor suppressor gene PTEN (decreased to 26% of control) and the putative tumor suppressor gene SLC38A3 (14% of control). Morphological evidence of epithelial-to-mesenchymal transition (EMT) occurred in CATLE cells together with appropriate changes in expression of the EMT markers vimentin (VIM; increased to 300% of control) and e-cadherin (CDH1; decreased to 16% of control). EMT is common in carcinogenic transformation of epithelial cells. CATLE cells showed increased KRAS (291%), ERK1/2 (274%), phosphorylated ERK (p-ERK; 152%), and phosphorylated AKT1 (p-AKT1; 170%) protein expression. Increased transcript expression of metallothioneins, MT1A and MT2A and the stress response genes HMOX1 (690%) and HIF1A (247%) occurred in CATLE cells possibly in adaptation to chronic arsenic exposure. Thus, arsenic induced multiple cancer cell characteristics in human peripheral lung epithelial cells. This model may be useful to assess mechanisms of arsenic-induced lung cancer. - Highlights: • Chronic arsenic exposure transforms a human peripheral lung epithelia cell line. • Cells acquire characteristics in common with human lung adenocarcinoma cells. • These transformed cells provide a

  17. 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.

  18. 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.

  19. 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.

  20. Leisure time activities related to carcinogen exposure and lung cancer risk in never smokers. A case-control study

    SciTech Connect (OSTI)

    Ruano-Ravina, Alberto; García-Lavandeira, José Antonio; Torres-Durán, María; Prini-Guadalupe, Luciana; Parente-Lamelas, Isaura; Leiro-Fernández, Virginia; Montero-Martínez, Carmen; González-Barcala, Francisco Javier; Golpe-Gómez, Antonio; Martínez, Cristina; Castro-Añón, Olalla; Mejuto-Martí, María José; and others

    2014-07-15

    We aim to assess the relationship between leisure time activities related to exposure to carcinogenic substances and lung cancer risk in a hospital-based case-control study performed in never smokers. We included never smoking cases with anatomopathologically confirmed lung cancer and never smoking controls undergoing trivial surgery, at 8 Spanish hospitals. The study was conducted between January 2011 and June 2013. Participants were older than 30 and had no previous neoplasms. All were personally interviewed focusing on lifestyle, environmental tobacco smoke exposure, occupational history and leisure time activities (including duration of such activities). Results were analyzed through logistic regression and adjusted also by residential radon and education level. We included 513 never smokers, 191 cases and 322 controls. The OR for those performing the studied leisure time activities was 1.43 (95%CI 0.78–2.61). When we restricted the analysis to those performing do-it-yourself activities for more than 10 years the OR was 2.21 (95%CI 0.93–5.27). Environmental tobacco smoke exposure did not modify this association. The effect for the different lung cancer histological types was very close to significance for adenocarcinoma but only when these activities were performed for more than 10 years. We encourage health professionals to recommend protective measures for those individuals while performing these hobbies to reduce the risk of lung cancer. - Highlights: • Some leisure time activities are associated with the exposure to carcinogenic substances. • These activities are model-making, painting (artistic or not), furniture refinishing or wood working. • Few studies have assessed lung cancer risk due to these hobbies and none in never-smokers. • Leisure activities related to exposure to carcinogenic substances present higher lung cancer risk. • The risk is higher when these activities are performed for more than 10 years.

  1. Polycyclic aromatic hydrocarbons (PAHs): a possible cause of lung cancer mortality among nickel/copper smelter and refinery workers

    SciTech Connect (OSTI)

    Verma, D.K.; Julian, J.A.; Roberts, R.S.; Muir, D.C.; Jadon, N.; Shaw, D.S. )

    1992-05-01

    A retrospective industrial hygiene investigation was undertaken to explain the cause of a statistically significant excess lung cancer mortality observed in a subset of a large cohort of nickel workers involved in mining, smelting, and refining of nickel and copper in Ontario. The focus of this paper is to demonstrate how an industrial hygiene follow-up assessment of an epidemiologic finding can help to identify a likely cause. Polycyclic aromatic hydrocarbons (PAHs) alone or in association with particulate and gaseous contaminants (e.g., SO2) were likely the causative agents of the excess lung cancer observed among the lead welders, cranemen, and arc furnace workers of the copper refinery.

  2. 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

  3. 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.

  4. SU-E-T-500: Dose Escalation Strategy for Lung Cancer Patients Using a Biologically- Guided Target Definition

    SciTech Connect (OSTI)

    Shusharina, N; Khan, F; Choi, N; Sharp, G

    2014-06-01

    Purpose: Dose escalation strategy for lung cancer patients can lead to late symptoms such as pneumonitis and cardiac injury. We propose a strategy to increase radiation dose for improving local tumor control while simultaneously striving to minimize the injury of organs at risk (OAR). Our strategy is based on defining a small, biologically-guided target volume for receiving additional radiation dose. Methods: 106 patients with lung cancer treated with radiotherapy were selected for patients diagnosed with stage II and III disease. Previous research has shown that 50% of the maximum SUV threshold in FDG-PET imaging is appropriate for delineation of the most aggressive part of a tumor. After PET- and CT-derived targets were contoured, an IMRT treatment plan was designed to deliver 60 Gy to the GTV as delineated on a 4D CT (Plan 1). A second plan was designed with additional dose of 18 Gy to the PET-derived volume (Plan 2). A composite plan was generated by the addition of Plan 1 and Plan 2. Results: Plan 1 was compared to the composite plan and increases in OAR dose were assessed. For seven patients on average, lung V5 was increased by 1.4% and V20 by 4.2% for ipsilateral lung and by 13.5% and 7% for contralateral lung. For total lung, V5 and V20 were increased by 4.5% and 4.8% respectively. Mean lung dose was increased by 9.7% for the total lung. The maximum dose to the spinal cord increased by 16% on average. For the heart, V20 increased by 4.2% and V40 by 5.2%. Conclusion: It seems feasible that an additional 18 Gy of radiation dose can be delivered to FDG PET-derived subvolume of the CT-based GTV of the primary tumor without significant increase in total dose to the critical organs such as lungs, spinal cord and heart.

  5. Downregulated TIPE2 is associated with poor prognosis and promotes cell proliferation in non-small cell lung cancer

    SciTech Connect (OSTI)

    Li, Yuexia; Li, Xiaohui; Liu, Gang; Sun, Rongqing; Wang, Lirui; Wang, Jing; Wang, Hongmin

    2015-01-30

    Highlights: • TIPE2 is down-regulated in NSCLC tissues. • TIPE2 inhibits NSCLC cell proliferation, colony formation and invasion. • TIPE2 reduces the anti-apoptotic Bcl-XL protein and mesenchymal marker N-cadherin expression. - Abstract: The present study aims to investigate the expression pattern of TIPE2 protein and its clinical significance in human non-small cell lung cancer (NSCLC). We investigated the expression levels of TIPE2 in 96 NSCLC tumor samples by immunohistochemistry and then analyzed its clinical significance. Furthermore, the role of TIPE2 on the biological properties of the NSCLC cell line H1299 and A549 was experimentally tested in vitro and in vivo. We found that the expression level of TIPE2 was significantly higher in normal lung tissues compared with NSCLC tissues (P < 0.001), and TIPE2 downregulation was significantly correlated with advanced TNM stage (P = 0.006). TIPE2 expression was lower in lung cancer cell lines than normal bronchial cell line HBE. Transfection of TIPE2 plasmid was performed in H1299 and A549 cells. TIPE2 overexpression inhibited lung cancer cell proliferation, colony formation and cell invasive in vitro, and prevented lung tumor growth in vivo. In addition, TIPE2 transfection reduced the anti-apoptotic Bcl-XL protein and mesenchymal marker N-cadherin expression. Taken together, our results demonstrate that TIPE2 might serve as a tumor suppressor in NSCLC progression.

  6. 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.

  7. Differential Motion Between Mediastinal Lymph Nodes and Primary Tumor in Radically Irradiated Lung Cancer Patients

    SciTech Connect (OSTI)

    Schaake, Eva E.; Rossi, Maddalena M.G.; Buikhuisen, Wieneke A.; Burgers, Jacobus A.; Smit, Adrianus A.J.; Belderbos, José S.A.; Sonke, Jan-Jakob

    2014-11-15

    Purpose/Objective: In patients with locally advanced lung cancer, planning target volume margins for mediastinal lymph nodes and tumor after a correction protocol based on bony anatomy registration typically range from 1 to 1.5 cm. Detailed information about lymph node motion variability and differential motion with the primary tumor, however, is lacking from large series. In this study, lymph node and tumor position variability were analyzed in detail and correlated to the main carina to evaluate possible margin reduction. Methods and Materials: Small gold fiducial markers (0.35 × 5 mm) were placed in the mediastinal lymph nodes of 51 patients with non-small cell lung cancer during routine diagnostic esophageal or bronchial endoscopic ultrasonography. Four-dimensional (4D) planning computed tomographic (CT) and daily 4D cone beam (CB) CT scans were acquired before and during radical radiation therapy (66 Gy in 24 fractions). Each CBCT was registered in 3-dimensions (bony anatomy) and 4D (tumor, marker, and carina) to the planning CT scan. Subsequently, systematic and random residual misalignments of the time-averaged lymph node and tumor position relative to the bony anatomy and carina were determined. Additionally, tumor and lymph node respiratory amplitude variability was quantified. Finally, required margins were quantified by use of a recipe for dual targets. Results: Relative to the bony anatomy, systematic and random errors ranged from 0.16 to 0.32 cm for the markers and from 0.15 to 0.33 cm for the tumor, but despite similar ranges there was limited correlation (0.17-0.71) owing to differential motion. A large variability in lymph node amplitude between patients was observed, with an average motion of 0.56 cm in the cranial-caudal direction. Margins could be reduced by 10% (left-right), 27% (cranial-caudal), and 10% (anteroposterior) for the lymph nodes and −2%, 15%, and 7% for the tumor if an online carina registration protocol replaced a

  8. 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.

  9. 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

  10. 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).

  11. 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.

  12. Impact of Pretreatment Tumor Growth Rate on Outcome of Early-Stage Lung Cancer Treated With Stereotactic Body Radiation Therapy

    SciTech Connect (OSTI)

    Atallah, Soha; Cho, B.C. John; Allibhai, Zishan; Taremi, Mojgan; Giuliani, Meredith; Le, Lisa W.; Brade, Anthony; Sun, Alexander; Bezjak, Andrea; Hope, Andrew J.

    2014-07-01

    Purpose: To determine the influence of pretreatment tumor growth rate on outcomes in patients with early-stage non-small cell lung cancer (NSCLC) treated with stereotactic body radiation therapy (SBRT). Methods and Materials: A review was conducted on 160 patients with T1-T2N0M0 NSCLC treated with SBRT at single institution. The patient's demographic and clinical data, time interval (t) between diagnostic and planning computed tomography (CT), vital status, disease status, and cause of death were extracted from a prospectively kept database. Differences in gross tumor volume between diagnostic CT (GTV1) and planning CT (GTV2) were recorded, and growth rate was calculated by use of specific growth rate (SGR). Kaplan-Meier curves were constructed for overall survival (OS). Differences between groups were compared with a log-rank test. Multivariate analyses were performed by use of the Cox proportional hazard model with SGR and other relevant clinical factors. Cumulative incidence was calculated for local, regional, and distant failures by use of the competing risk approach and was compared with Gray's test. Results: The median time interval between diagnostic and planning CT was 82 days. The patients were divided into 2 groups, and the median SGR was used as a cut-off. The median survival times were 38.6 and 27.7 months for the low and high SGR groups, respectively (P=.03). Eastern Cooperative Oncology Group performance status (P=.01), sex (P=.04), SGR (P=.03), and GTV2 (P=.002) were predictive for OS in multivariable Cox regression analysis and, except sex, were similarly predictive for failure-free survival (FFS). The 3-year cumulative incidences of regional failure were 19.2% and 6.0% for the high and low SGR groups, respectively (P=.047). Conclusion: High SGR was correlated with both poorer OS and FFS in patients with early-stage NSCLC treated with SBRT. If validated, this measurement may be useful in identifying patients most likely to benefit from adjuvant

  13. Nodal Stage of Surgically Resected Non-Small Cell Lung Cancer and Its Effect on Recurrence Patterns and Overall Survival

    SciTech Connect (OSTI)

    Varlotto, John M.; Yao, Aaron N.; DeCamp, Malcolm M.; Ramakrishna, Satvik; Recht, Abe; Flickinger, John; Andrei, Adin; Reed, Michael F.; Toth, Jennifer W.; Fizgerald, Thomas J.; Higgins, Kristin; Zheng, Xiao; Shelkey, Julie; and others

    2015-03-15

    Purpose: Current National Comprehensive Cancer Network guidelines recommend postoperative radiation therapy (PORT) for patients with resected non-small cell lung cancer (NSCLC) with N2 involvement. We investigated the relationship between nodal stage and local-regional recurrence (LR), distant recurrence (DR) and overall survival (OS) for patients having an R0 resection. Methods and Materials: A multi-institutional database of consecutive patients undergoing R0 resection for stage I-IIIA NSCLC from 1995 to 2008 was used. Patients receiving any radiation therapy before relapse were excluded. A total of 1241, 202, and 125 patients were identified with N0, N1, and N2 involvement, respectively; 161 patients received chemotherapy. Cumulative incidence rates were calculated for LR and DR as first sites of failure, and Kaplan-Meier estimates were made for OS. Competing risk analysis and proportional hazards models were used to examine LR, DR, and OS. Independent variables included age, sex, surgical procedure, extent of lymph node sampling, histology, lymphatic or vascular invasion, tumor size, tumor grade, chemotherapy, nodal stage, and visceral pleural invasion. Results: The median follow-up time was 28.7 months. Patients with N1 or N2 nodal stage had rates of LR similar to those of patients with N0 disease, but were at significantly increased risk for both DR (N1, hazard ratio [HR] = 1.84, 95% confidence interval [CI]: 1.30-2.59; P=.001; N2, HR = 2.32, 95% CI: 1.55-3.48; P<.001) and death (N1, HR = 1.46, 95% CI: 1.18-1.81; P<.001; N2, HR = 2.33, 95% CI: 1.78-3.04; P<.001). LR was associated with squamous histology, visceral pleural involvement, tumor size, age, wedge resection, and segmentectomy. The most frequent site of LR was the mediastinum. Conclusions: Our investigation demonstrated that nodal stage is directly associated with DR and OS but not with LR. Thus, even some patients with, N0-N1 disease are at relatively high risk of local recurrence. Prospective

  14. 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.

  15. SU-E-J-266: A Pitfall of a Deformable Image Registration in Lung Cancer

    SciTech Connect (OSTI)

    Sugawara, Y; Tachibana, H; Moriya, S; Sawant, A

    2014-06-01

    Purpose: For four-dimensional (4D) planning and adaptive radiotherapy, deformable image registration (DIR) is needed and the accuracy is essential. We evaluated the accuracy of one free-downloadable DIR software library package (NiftyReg) and one commercial DIR software (MIM) in lung SBRT cancer patients. Methods: A rigid and non-rigid registrations were implemented to our in-house software. The non-rigid registration algorithm of the NiftyReg and MIM was based on the free-form deformation. The accuracy of the two software was evaluated when contoured structures to peak-inhale and peak-exhale 4DCT image data sets were measured using the dice similarity coefficient (DSC). The evaluation was performed in 20 lung SBRT patients. Results: In our visual evaluation, the eighteen cases show good agreement between the deformed structures for the peak-inhale phase and the peak-exhale phase structures (more than 0.8 DSC value). In the evaluation of the DSC in-house software, averaged DSC values of GTV and lung, heart, spinal cord, stomach and body were 0.862 and 0.979, 0.932, 0.974, 0.860, 0.998, respectively. As the Resultof the registration using the MIM program in the two cases which had less than 0.7 DSC value when analyzed using the in-house software, the DSC value were improved to 0.8. The CT images in a case with low DSC value shows the tumor was surrounded by the structure with the similar CT values, which were the chest wall or the diaphragm. Conclusion: Not only a free-downloadable DIR software but also a commercial software may provide unexpected results and there is a possibility that the results would make us misjudge the treatment planning. Therefore, we recommend that a commissioning test of any DIR software should be performed before clinical use and we should understand the characteristics of the software.

  16. 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.

  17. 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.

  18. 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

  19. A treatment planning approach to spatially fractionated megavoltage grid therapy for bulky lung cancer

    SciTech Connect (OSTI)

    Costlow, Heather N.; Zhang, Hualin; Das, Indra J.

    2014-10-01

    The purpose of this study was to explore the treatment planning methods of spatially fractionated megavoltage grid therapy for treating bulky lung tumors using multileaf collimator (MLC). A total of 5 patients with lung cancer who had gross tumor volumes ranging from 277 to 635 cm{sup 3} were retrospectively chosen for this study. The tumors were from 6.5 to 9.6 cm at shortest dimension. Several techniques using either electronic compensation or intensity-modulated radiation therapy (IMRT) were used to create a variety of grid therapy plans on the Eclipse treatment planning system. The dose prescription point was calculated to the volume, and a dose of 20 Gy with 6-MV/15-MV beams was used in each plan. The dose-volume histogram (DVH) curves were obtained to evaluate dosimetric characteristics. In addition, DVH curves from a commercially available cerrobend grid collimator were also used for comparison. The linear-quadratic radiobiological response model was used to assess therapeutic ratios (TRs) and equivalent uniform doses (EUD) for all generated plans. A total of 6 different grid therapy plans were created for each patient. Overall, 4 plans had different electronic compensation techniques: Ecomps-Tubes, Ecomps-Circles, Ecomps-Squares, and Ecomps-Weave; the other 2 plans used IMRT and IMRT-Weave techniques. The DVH curves and TRs demonstrated that these MLC-based grid therapy plans can achieve dosimetric properties very similar to those of the cerrobend grid collimator. However, the MLC-based plans have larger EUDs than those with the cerrobend grid collimator. In addition, the field shaping can be performed for targets of any shape in MLC-based plans. Thus, they can deliver a more conformal dose to the targets and spare normal structures better than the cerrobend grid collimator can. The plans generated by the MLC technique demonstrated the advantage over the standard cerrobend grid collimator on accommodating targets and sparing normal structures. Overall, 6

  20. 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.

  1. Evaluation of image guided motion management methods in lung cancer radiotherapy

    SciTech Connect (OSTI)

    Zhuang, Ling; Yan, Di; Liang, Jian; Ionascu, Dan; Mangona, Victor; Yang, Kai; Zhou, Jun

    2014-03-15

    Purpose: To evaluate the accuracy and reliability of three target localization methods for image guided motion management in lung cancer radiotherapy. Methods: Three online image localization methods, including (1) 2D method based on 2D cone beam (CB) projection images, (2) 3D method using 3D cone beam CT (CBCT) imaging, and (3) 4D method using 4D CBCT imaging, have been evaluated using a moving phantom controlled by (a) 1D theoretical breathing motion curves and (b) 3D target motion patterns obtained from daily treatment of 3 lung cancer patients. While all methods are able to provide target mean position (MP), the 2D and 4D methods can also provide target motion standard deviation (SD) and excursion (EX). For each method, the detected MP/SD/EX values are compared to the analytically calculated actual values to calculate the errors. The MP errors are compared among three methods and the SD/EX errors are compared between the 2D and 4D methods. In the theoretical motion study (a), the dependency of MP/SD/EX error on EX is investigated with EX varying from 2.0 cm to 3.0 cm with an increment step of 0.2 cm. In the patient motion study (b), the dependency of MP error on target sizes (2.0 cm and 3.0 cm), motion patterns (four motions per patient) and EX variations is investigated using multivariant linear regression analysis. Results: In the theoretical motion study (a), the MP detection errors are −0.2 ± 0.2, −1.5 ± 1.1, and −0.2 ± 0.2 mm for 2D, 3D, and 4D methods, respectively. Both the 2D and 4D methods could accurately detect motion pattern EX (error < 1.2 mm) and SD (error < 1.0 mm). In the patient motion study (b), MP detection error vector (mm) with the 2D method (0.7 ± 0.4) is found to be significantly less than with the 3D method (1.7 ± 0.8,p < 0.001) and the 4D method (1.4 ± 1.0, p < 0.001) using paired t-test. However, no significant difference is found between the 4D method and the 3D method. Based on multivariant linear regression analysis, the

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

    DOE Patents [OSTI]

    Cole, Dean A.; Moody, III, David C.; Ellinwood, L. Edward; Klein, M. Gerard

    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.

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

    DOE Patents [OSTI]

    Cole, Dean A.; Moody, III, David C.; Ellinwood, L. Edward; Klein, M. Gerard

    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.

  4. 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.

  5. 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.

  6. TU-F-17A-09: Four-Dimensional Cone Beam CT Ventilation Imaging Can Detect Interfraction Lung Function Variations for Locally Advanced Lung Cancer Patients

    SciTech Connect (OSTI)

    Kipritidis, J; Keall, P; Hugo, G; Weiss, E; Williamson, J

    2014-06-15

    Purpose: Four-dimensional cone beam CT ventilation imaging (4D-CBCT VI) is a novel functional lung imaging modality requiring validation. We hypothesize that 4D-CBCT VI satisfies a necessary condition for validity: that intrafraction variations (e.g. due to poor 4D-CBCT image quality) are substantially different to interfraction variations (e.g. due to changes in underlying function). We perform the first comparison of intrafraction (pre/post fraction) and interfraction (week-to-week) 4D-CBCT VIs for locally advanced non small cell lung cancer (LA NSCLC) patients undergoing radiation therapy. Methods: A total of 215 4D-CBCT scans were acquired for 19 LA NSCLC patients over 4-6 weeks of radiation therapy, including 75 pairs of pre-/post-fraction scans on the same day. 4D-CBCT VIs were obtained by applying state-of-the-art, B-spline deformable image registration to obtain the Jacobian determinant of deformation between the end-exhale and end-inhale phases. All VIs were deformably registered to the corresponding first day scan, normalized between the 10th and 90th percentile values and cropped to the ipsilateral lung only. Intrafraction variations were assessed by computing the mean and standard deviation of voxel-wise differences between all same-day pairs of pre-/post-fraction VIs. Interfraction differences were computed between first-day VIs and treatment weeks 2, 4 and 6 for all 19 patients. We tested the hypothesis by comparing cumulative distribution functions (CDFs) of intrafraction and interfraction ventilation differences using two-sided Kolmogorov-Smirnov goodness-of-fit tests. Results: The (mean ± std. dev.) of intrafraction differences was (−0.007 ± 0.079). Interfraction differences for weeks 2, 4 and 6 were (−0.035 ± 0.103), (−0.006 ± 0.094) and (−0.019 ± 0.127) respectively. For week 2, the changes in CDFs for intrafraction and interfraction differences approached statistical significance (p=0.099). Conclusion: We have shown that 4D-CBCT VI

  7. 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.

  8. Combination Effect of Regulatory T-Cell Depletion and Ionizing Radiation in Mouse Models of Lung and Colon Cancer

    SciTech Connect (OSTI)

    Son, Cheol-Hun; Bae, Jae-Ho; Shin, Dong-Yeok; Lee, Hong-Rae; Jo, Wol-Soon; Yang, Kwangmo; Park, You-Soo

    2015-06-01

    Purpose: To investigate the potential of low-dose cyclophosphamide (LD-CTX) and anti-CD25 antibody to prevent activation of regulatory T cells (Tregs) during radiation therapy. Methods and Materials: We used LD-CTX and anti-CD25 monoclonal antibody as a means to inhibit Tregs and improve the therapeutic effect of radiation in a mouse model of lung and colon cancer. Mice were irradiated on the tumor mass of the right leg and treated with LD-CTX and anti-CD25 antibody once per week for 3 weeks. Results: Combined treatment of LD-CTX or anti-CD25 antibody with radiation significantly decreased Tregs in the spleen and tumor compared with control and irradiation only in both lung and colon cancer. Combinatorial treatments resulted in a significant increase in the effector T cells, longer survival rate, and suppressed irradiated and distal nonirradiated tumor growth. Specifically, the combinatorial treatment of LD-CTX with radiation resulted in outstanding regression of local and distant tumors in colon cancer, and almost all mice in this group survived until the end of the study. Conclusions: Our results suggest that Treg depletion strategies may enhance radiation-mediated antitumor immunity and further improve outcomes after radiation therapy.

  9. 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.

  10. SU-E-T-538: Does Abdominal Compression Through Prone Patient Position Reduce Respiratory Motion in Lung Cancer Radiotherapy?

    SciTech Connect (OSTI)

    Catron, T; Rosu, M; Weiss, E

    2014-06-01

    Purpose: This study assesses the effect of physiological abdominal compression from prone positioning by comparing respiratory-induced tumor movements in supine and prone positions. Methods: 19 lung cancer patients underwent repeated supine and prone free-breathing 4DCT scans. The effect of patient position on motion magnitude was investigated for tumors, lymph nodes (9 cases), and subgroups of central (11 cases), peripheral (8 cases) and small peripheral tumors (5 cases), by evaluating the population average excursions, absolute and relative to a carina-point. Results: Absolute motion analysis: In prone, motion increased by ~20% for tumors and ~25% for lymph nodes. Central tumors moved more compared to peripheral tumors in both supine and prone (~22%, and ~4% respectively). Central tumors movement increased by ~12% in prone. For peripheral tumors the increase in prone position was ~25% (~40% and 29% changes on along RL and AP directions). Motion relative to carina-point analysis: Overall, tumor excursions relative to carina-point increased by ~17% in prone. Lymph node relative magnitudes were lower by ~4%. Likewise, the central tumors moved ~7% less in prone. The subgroup of peripheral tumors exhibited increased amplitudes by ~44%; the small peripheral tumors had even larger relative displacements in prone (~46%). Conclusion: Tumor and lymph node movement in the patient population from this study averaged to be higher in prone than in supine position. Results from carina analysis also suggest that peripheral tissues have more physiologic freedom of motility when placed in the prone position, regardless of size. From these observations we should continue to avoid prone positioning for all types of primary lung tumor, suggesting that patients should receive radiotherapy for primary lung cancer in supine position to minimize target tissue mobility during normal respiratory effort. Further investigation will include more patients with peripheral tumors to validate our

  11. 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.

  12. SU-E-I-34: Evaluating Use of AEC to Lower Dose for Lung Cancer Screening CT Protocols

    SciTech Connect (OSTI)

    Arbique, G; Anderson, J; Guild, J; Duan, X; Malguria, N; Omar, H; Brewington, C; Zhang, D

    2015-06-15

    Purpose: The National Lung Screening Trial mandated manual low dose CT technique factors, where up to a doubling of radiation output could be used over a regular to large patient size range. Recent guidance from the AAPM and ACR for lung cancer CT screening recommends radiation output adjustment for patient size either through AEC or a manual technique chart. This study evaluated the use of AEC for output control and dose reduction. Methods: The study was performed on a multidetector helical CT scanner (Aquillion ONE, Toshiba Medical) equipped with iterative reconstruction (ADIR-3D), AEC was adjusted with a standard deviation (SD) image quality noise index. The protocol SD parameter was incrementally increased to reduce patient population dose while image quality was evaluated by radiologist readers scoring the clinical utility of images on a Likert scale. Results: Plots of effective dose vs. body size (water cylinder diameter reported by the scanner) demonstrate monotonic increase in patient dose with increasing patient size. At the initial SD setting of 19 the average CTDIvol for a standard size patient was ∼ 2.0 mGy (1.2 mSv effective dose). This was reduced to ∼1.0 mGy (0.5 mSv) at an SD of 25 with no noticeable reduction in clinical utility of images as demonstrated by Likert scoring. Plots of effective patient diameter and BMI vs body size indicate that these metrics could also be used for manual technique charts. Conclusion: AEC offered consistent and reliable control of radiation output in this study. Dose for a standard size patient was reduced to one-third of the 3 mGy CTDIvol limit required for ACR accreditation of lung cancer CT screening. Gary Arbique: Research Grant, Toshiba America Medical Systems; Cecelia Brewington: Research Grant, Toshiba America Medical Systems; Di Zhang: Employee, Toshiba America Medical Systems.

  13. 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.

  14. 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

  15. Preclinical and Pilot Clinical Studies of Docetaxel Chemoradiation for Stage III Non-Small-Cell Lung Cancer

    SciTech Connect (OSTI)

    Chen Yuhchyau; Pandya, Kishan J.; Hyrien, Ollivier; Keng, Peter C.; Smudzin, Therese; Anderson, Joy; Qazi, Raman; Smith, Brian; Watson, Thomas J.; Feins, Richard H.; Johnstone, David W.

    2011-08-01

    Purpose: Local and distant failure rates remain high despite aggressive chemoradiation (CRT) treatment for Stage III non-small-cell lung cancer. We conducted preclinical studies of docetaxel's cytotoxic and radiosensitizing effects on lung cancer cell lines and designed a pilot study to target distant micrometastasis upfront with one-cycle induction chemotherapy, followed by low-dose radiosensitizing docetaxel CRT. Methods and Materials: A preclinical study was conducted in human lung cancer cell lines NCI 520 and A549. Cells were treated with two concentrations of docetaxel for 3 h and then irradiated immediately or after a 24-h delay. A clonogenic survival assay was conducted and analyzed for cytotoxic effects vs. radiosensitizing effects of docetaxel. A pilot clinical study was designed based on preclinical study findings. Twenty-two patients were enrolled with a median follow-up of 4 years. Induction chemotherapy consisted of 75 mg/m{sup 2} of docetaxel and 75 mg/m{sup 2} of cisplatin on Day 1 and 150 mg/m{sup 2} of recombinant human granulocyte colony-stimulating factor on Days 2 through 10. Concurrent CRT was started 3 to 6 weeks later with twice-weekly docetaxel at 10 to 12 mg/m{sup 2} and daily delayed radiation in 1.8-Gy fractions to 64.5 Gy for gross disease. Results: The preclinical study showed potent cytotoxic effects of docetaxel and subadditive radiosensitizing effects. Delaying radiation resulted in more cancer cell death. The pilot clinical study resulted in a median survival of 32.6 months for the entire cohort, with 3- and 5-year survival rates of 50% and 19%, respectively, and a distant metastasis-free survival rate of 61% for both 3 and 5 years. A pattern-of-failure analysis showed 75% chest failures and 36% all-distant failures. Therapy was well tolerated with Grade 3 esophagitis observed in 23% of patients. Conclusions: One-cycle full-dose docetaxel/cisplatin induction chemotherapy with recombinant human granulocyte colony-stimulating factor

  16. 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.

  17. Percutaneous Lung Thermal Ablation of Non-surgical Clinical N0 Non-small Cell Lung Cancer: Results of Eight Years’ Experience in 87 Patients from Two Centers

    SciTech Connect (OSTI)

    Palussiere, Jean; Lagarde, Philippe; Aupérin, Anne; Deschamps, Frédéric; Chomy, François; Baere, Thierry de

    2015-02-15

    PurposeTo evaluate the survival outcomes of percutaneous thermal ablation (RFA + microwaves) for patients presenting N0 non-small-cell lung cancer (NSCLC) ineligible for surgery.Materials and MethodsEighty-seven patients from two comprehensive cancer centers were included. Eighty-two patients were treated with RFA electrodes and five with microwave antenna. Overall survival (OS) and disease-free survival (DFS) were estimated and predictive factors of local tumor progression, OS and DFS identified and compared by univariate and multivariate analysesResultsMedian follow-up was 30.5 months (interquartile range 16.7–51) and tumor size was 21 mm (range 10–54 mm). Treatment was incomplete for 14 patients with a local tumor progression of 11.5, 18.3, and 21.1 % at 1, 2, and 3 years, respectively. Two patients presented with neurological (grade III or IV) complications, and one died of respiratory and multivisceral failure as a result of the procedure at 29 days. In univariate analysis, increasing tumor size (P = 0.003) was the only predictive factor related to risk of local tumor progression. 5-year OS and DFS were 58.1 and 27.9 %, respectively. Sex (P = 0.044), pathology (P = 0.032), and tumor size >2 cm (P = 0.046) were prognostic factors for DFS. In multivariate analysis, pathology (P = 0.033) and tumor size >2 cm (P = 0.032) were independent prognostic factors for DFS.ConclusionsOversized and overlapping ablation of N0 NSCLC was well tolerated, effective, with few local tumor progressions, even over long-term follow-up. Increasing tumor size was the main prognostic factor linked to OS, DFS, and local tumor progression.

  18. MiR-153 inhibits migration and invasion of human non-small-cell lung cancer by targeting ADAM19

    SciTech Connect (OSTI)

    Shan, Nianxi; Shen, Liangfang; Wang, Jun; He, Dan; Duan, Chaojun

    2015-01-02

    Highlights: • Decreased miR-153 and up-regulated ADAM19 are correlated with NSCLC pathology. • MiR-153 inhibits the proliferation and migration and invasion of NSCLC cells in vitro. • ADAM19 is a direct target of miR-153. • ADAM19 is involved in miR-153-suppressed migration and invasion of NSCLC cells. - Abstract: MiR-153 was reported to be dysregulated in some human cancers. However, the function and mechanism of miR-153 in lung cancer cells remains unknown. In this study, we investigated the role of miR-153 in human non-small-cell lung cancer (NSCLC). Using qRT-PCR, we demonstrated that miR-153 was significantly decreased in clinical NSCLC tissues and cell lines, and downregulation of miR-153 was significantly correlated with lymph node status. We further found that ectopic expression of miR-153 significantly inhibited the proliferation and migration and invasion of NSCLC cells in vitro, suggesting that miR-153 may be a novel tumor suppressor in NSCLC. Further integrated analysis revealed that ADAM19 is as a direct and functional target of miR-153. Luciferase reporter assay demonstrated that miR-153 directly targeted 3′UTR of ADAM19, and correlation analysis revealed an inverse correlation between miR-153 and ADAM19 mRNA levels in clinical NSCLC tissues. Knockdown of ADAM19 inhibited migration and invasion of NSCLC cells which was similar with effects of overexpression of miR-153, while overexpression of ADAM19 attenuated the function of miR-153 in NSCLC cells. Taken together, our results highlight the significance of miR-153 and ADAM19 in the development and progression of NSCLC.

  19. 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.

  20. 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.

  1. 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.

  2. Knockdown of TWIST1 enhances arsenic trioxide- and ionizing radiation-induced cell death in lung cancer cells by promoting mitochondrial dysfunction

    SciTech Connect (OSTI)

    Seo, Sung-Keum; Kim, Jae-Hee; Choi, Ha-Na; Choe, Tae-Boo; Hong, Seok-Il; Yi, Jae-Youn; Hwang, Sang-Gu; Lee, Hyun-Gyu; Lee, Yun-Han; Park, In-Chul

    2014-07-11

    Highlights: • Knockdown of TWIST1 enhanced ATO- and IR-induced cell death in NSCLCs. • Intracellular ROS levels were increased in cells treated with TWIST1 siRNA. • TWIST1 siRNA induced MMP loss and mitochondrial fragmentation. • TWIST1 siRNA upregulated the fission-related proteins FIS1 and DRP1. - Abstract: TWIST1 is implicated in the process of epithelial mesenchymal transition, metastasis, stemness, and drug resistance in cancer cells, and therefore is a potential target for cancer therapy. In the present study, we found that knockdown of TWIST1 by small interfering RNA (siRNA) enhanced arsenic trioxide (ATO)- and ionizing radiation (IR)-induced cell death in non-small-cell lung cancer cells. Interestingly, intracellular reactive oxygen species levels were increased in cells treated with TWIST1 siRNA and further increased by co-treatment with ATO or IR. Pretreatment of lung cancer cells with the antioxidant N-acetyl-cysteine markedly suppressed the cell death induced by combined treatment with TWIST1 siRNA and ATO or IR. Moreover, treatment of cells with TWIST1 siRNA induced mitochondrial membrane depolarization and significantly increased mitochondrial fragmentation (fission) and upregulated the fission-related proteins FIS1 and DRP1. Collectively, our results demonstrate that siRNA-mediated TWIST1 knockdown induces mitochondrial dysfunction and enhances IR- and ATO-induced cell death in lung cancer cells.

  3. TH-A-19A-10: Fast Four Dimensional Monte Carlo Dose Computations for Proton Therapy of Lung Cancer

    SciTech Connect (OSTI)

    Mirkovic, D; Titt, U; Mohan, R; Yepes, P

    2014-06-15

    Purpose: To develop and validate a fast and accurate four dimensional (4D) Monte Carlo (MC) dose computation system for proton therapy of lung cancer and other thoracic and abdominal malignancies in which the delivered dose distributions can be affected by respiratory motion of the patient. Methods: A 4D computer tomography (CT) scan for a lung cancer patient treated with protons in our clinic was used to create a time dependent patient model using our in-house, MCNPX-based Monte Carlo system (“MC{sup 2}”). The beam line configurations for two passively scattered proton beams used in the actual treatment were extracted from the clinical treatment plan and a set of input files was created automatically using MC{sup 2}. A full MC simulation of the beam line was computed using MCNPX and a set of phase space files for each beam was collected at the distal surface of the range compensator. The particles from these phase space files were transported through the 10 voxelized patient models corresponding to the 10 phases of the breathing cycle in the 4DCT, using MCNPX and an accelerated (fast) MC code called “FDC”, developed by us and which is based on the track repeating algorithm. The accuracy of the fast algorithm was assessed by comparing the two time dependent dose distributions. Results: The error of less than 1% in 100% of the voxels in all phases of the breathing cycle was achieved using this method with a speedup of more than 1000 times. Conclusion: The proposed method, which uses full MC to simulate the beam line and the accelerated MC code FDC for the time consuming particle transport inside the complex, time dependent, geometry of the patient shows excellent accuracy together with an extraordinary speed.

  4. Tumor Antivascular Effects of Radiotherapy Combined with Combretastatin A4 Phosphate in Human Non-Small-Cell Lung Cancer

    SciTech Connect (OSTI)

    Ng, Q.-S.; Goh, Vicky; Carnell, Dawn; Meer, Khalda; Padhani, Anwar R.; Saunders, Michele I.; Hoskin, Peter J. . E-mail: peterhoskin@nhs.net

    2007-04-01

    Purpose: The tumor vascular effects of radiotherapy and subsequent administration of the vascular disrupting agent combretastatin A4 phosphate (CA4P) were studied in patients with advanced non-small-cell lung cancer using volumetric dynamic contrast-enhanced computed tomography (CT). Patients and Methods: Following ethical committee approval and informed consent, 8 patients receiving palliative radiotherapy (27 Gy in six fractions, twice weekly) also received CA4P (50 mg/m{sup 2}) after the second fraction of radiotherapy. Changes in dynamic CT parameters of tumor blood volume (BV) and permeability surface area product (PS) were measured for the whole tumor volume, tumor rim, and center after radiotherapy alone and after radiotherapy in combination with CA4P. Results: After the second fraction of radiotherapy, 6 of the 8 patients showed increases in tumor PS (23.6%, p = 0.011). Four hours after CA4P, a reduction in tumor BV (22.9%, p < 0.001) was demonstrated in the same 6 patients. Increase in PS after radiotherapy correlated with reduction in BV after CA4P (r = 0.77, p = 0.026). At 72 h after CA4P, there was a sustained reduction in tumor BV of 29.4% (p < 0.001). Both increase in PS after radiotherapy and reduction in BV after CA4P were greater at the rim of the tumor. The BV reduction at the rim was sustained to 72 h (51.4%, p 0.014). Conclusion: Radiotherapy enhances the tumor antivascular activity of CA4P in human non-small-cell lung cancer, resulting in sustained tumor vascular shutdown.

  5. 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.

  6. 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

  7. 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.

  8. 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.

  9. 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

  10. Inhibition of discoidin domain receptor 2-mediated lung cancer cells progression by gold nanoparticle-aptamer-assisted delivery of peptides containing transmembrane-juxtamembrane 1/2 domain

    SciTech Connect (OSTI)

    Kim, Daehwan; Yeom, Ji-Hyun; Lee, Boeun; Lee, Kangseok; Bae, Jeehyeon; Rhee, Sangmyung

    2015-08-21

    The delivery of biologically functional peptides into mammalian cells can be a direct and effective method for cancer therapy and treatment of other diseases. Discoidin domain receptor 2 (DDR2) is a collagen-induced receptor tyrosine kinase recently identified as a novel therapeutic target in lung cancer. In this study, we report that peptides containing the functional domain of DDR2 can be efficiently delivered into lung malignant cancer cells via a gold nanoparticle-DNA aptamer conjugate (AuNP-Apt)-based system. Peptide delivery resulted in the abrogation of DDR2 activation triggered by collagen. Moreover, the peptide delivered by the AuNP-Apt system inhibited cancer cell proliferation and invasion mediated by DDR2 activation. Thus, these results suggest that peptide loaded onto AuNP-Apt conjugates can be used for the development of peptide-based biomedical applications for the treatment of DDR2-positive cancer. - Highlights: • TM-JM1/2 peptides are efficiently delivered into cells by AuNP-Apt-conjugates. • TM-JM1/2 peptides loaded onto AuNP-Apt conjugates inhibit DDR2 activation. • Inhibition of DDR2 activation by TM-JM1/2 peptides decreases tumor progression.

  11. Total Gross Tumor Volume Is an Independent Prognostic Factor in Patients Treated With Selective Nodal Irradiation for Stage I to III Small Cell Lung Cancer

    SciTech Connect (OSTI)

    Reymen, Bart; Van Loon, Judith; Baardwijk, Angela van; Wanders, Rinus; Borger, Jacques; Dingemans, Anne-Marie C.; Bootsma, Gerben; Pitz, Cordula; Lunde, Ragnar; Geraedts, Wiel; Lambin, Philippe; De Ruysscher, Dirk; University Hospital Leuven/ KU Leuven, Leuven

    2013-04-01

    Purpose: In non-small cell lung cancer, gross tumor volume (GTV) influences survival more than other risk factors. This could also apply to small cell lung cancer. Methods and Materials: Analysis of our prospective database with stage I to III SCLC patients referred for concurrent chemo radiation therapy. Standard treatment was 45 Gy in 1.5-Gy fractions twice daily concurrently with carboplatin-etoposide, followed by prophylactic cranial irradiation (PCI) in case of non-progression. Only fluorodeoxyglucose (FDG)-positron emission tomography (PET)-positive or pathologically proven nodal sites were included in the target volume. Total GTV consisted of post chemotherapy tumor volume and pre chemotherapy nodal volume. Survival was calculated from diagnosis (Kaplan-Meier ). Results: A total of 119 patients were included between May 2004 and June 2009. Median total GTV was 93 ± 152 cc (7.5-895 cc). Isolated elective nodal failure occurred in 2 patients (1.7%). Median follow-up was 38 months, median overall survival 20 months (95% confidence interval = 17.8-22.1 months), and 2-year survival 38.4%. In multivariate analysis, only total GTV (P=.026) and performance status (P=.016) significantly influenced survival. Conclusions: In this series of stage I to III small cell lung cancer patients treated with FDG-PET-based selective nodal irradiation total GTV is an independent risk factor for survival.

  12. 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

  13. 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.

  14. 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

  15. Pulmonary Artery Invasion, High-Dose Radiation, and Overall Survival in Patients With Non-Small Cell Lung Cancer

    SciTech Connect (OSTI)

    Han, Cheng-Bo; Wang, Wei-Li; Quint, Leslie; Xue, Jian-Xin; Matuszak, Martha; Ten Haken, Randall; Kong, Feng-Ming

    2014-06-01

    Purpose: To investigate whether high-dose radiation to the pulmonary artery (PA) affects overall survival (OS) in patients with non-small cell lung cancer (NSCLC). Methods and Materials: Patients with medically inoperable/unresectable NSCLC treated with definitive radiation therapy in prospective studies were eligible for this study. Pulmonary artery involvement was defined on the basis of pretreatment chest CT and positron emission tomography/CT fusion. Pulmonary artery was contoured according to the Radiation Therapy Oncology Group protocol 1106 atlas, and dose-volume histograms were generated. Results: A total of 100 patients with a minimum follow-up of 1 year for surviving patients were enrolled: 82.0% underwent concurrent chemoradiation therapy. Radiation dose ranged from 60 to 85.5 Gy in 30-37 fractions. Patients with PA invasion of grade ≤2, 3, 4, and 5 had 1-year OS and median survival of 67% and 25.4 months (95% confidence interval [CI] 15.7-35.1), 62% and 22.2 months (95% CI 5.8-38.6), 90% and 35.8 months (95% CI 28.4-43.2), and 50% and 7.0 months, respectively (P=.601). Two of the 4 patients with grade 5 PA invasion died suddenly from massive hemorrhage at 3 and 4.5 months after completion of radiation therapy. Maximum and mean doses to PA were not significantly associated with OS. The V45, V50, V55, and V60 of PA were correlated significantly with a worse OS (P<.05). Patients with V45 >70% or V60 >37% had significantly worse OS (13.3 vs 37.9 months, P<.001, and 13.8 vs 37.9 months, P=.04, respectively). Conclusions: Grade 5 PA invasion and PA volume receiving more than 45-60 Gy may be associated with inferior OS in patients with advanced NSCLC treated with concurrent chemoradiation.

  16. 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.

  17. 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.

  18. SU-E-T-427: Cell Surviving Fractions Derived From Tumor-Volume Variation During Radiotherapy for Non-Small Cell Lung Cancer: Comparison with Predictive Assays

    SciTech Connect (OSTI)

    Chvetsov, A; Schwartz, J; Mayr, N; Yartsev, S

    2014-06-01

    Purpose: To show that a distribution of cell surviving fractions S{sub 2} in a heterogeneous group of patients can be derived from tumor-volume variation curves during radiotherapy for non-small cell lung cancer. 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 (MV) computed tomography (CT). Statistical distributions of cell surviving fractions S{sup 2} and cell clearance half-lives of lethally damaged cells T1/2 have been reconstructed in each patient group by using a version of the two-level cell population tumor response model 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: Non-small 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 fractions S{sub 2} for non-small 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{sup 2} reconstructed from tumor volume variation agree with the PDF measured in vitro. Comparison of the reconstructed cell surviving fractions with patient survival data shows that the patient survival time decreases as the cell surviving fraction increases. Conclusion: The data obtained in this work suggests that the cell surviving fractions S{sub 2} can be reconstructed from the tumor volume

  19. 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.

  20. 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.

  1. 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.

  2. 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

  3. Prognostic Value and Reproducibility of Pretreatment CT Texture Features in Stage III Non-Small Cell Lung Cancer

    SciTech Connect (OSTI)

    Fried, David V.; Tucker, Susan L.; Zhou, Shouhao; Liao, Zhongxing; Mawlawi, Osama; Ibbott, Geoffrey; Court, Laurence E.

    2014-11-15

    Purpose: To determine whether pretreatment CT texture features can improve patient risk stratification beyond conventional prognostic factors (CPFs) in stage III non-small cell lung cancer (NSCLC). Methods and Materials: We retrospectively reviewed 91 cases with stage III NSCLC treated with definitive chemoradiation therapy. All patients underwent pretreatment diagnostic contrast enhanced computed tomography (CE-CT) followed by 4-dimensional CT (4D-CT) for treatment simulation. We used the average-CT and expiratory (T50-CT) images from the 4D-CT along with the CE-CT for texture extraction. Histogram, gradient, co-occurrence, gray tone difference, and filtration-based techniques were used for texture feature extraction. Penalized Cox regression implementing cross-validation was used for covariate selection and modeling. Models incorporating texture features from the 33 image types and CPFs were compared to those with models incorporating CPFs alone for overall survival (OS), local-regional control (LRC), and freedom from distant metastases (FFDM). Predictive Kaplan-Meier curves were generated using leave-one-out cross-validation. Patients were stratified based on whether their predicted outcome was above or below the median. Reproducibility of texture features was evaluated using test-retest scans from independent patients and quantified using concordance correlation coefficients (CCC). We compared models incorporating the reproducibility seen on test-retest scans to our original models and determined the classification reproducibility. Results: Models incorporating both texture features and CPFs demonstrated a significant improvement in risk stratification compared to models using CPFs alone for OS (P=.046), LRC (P=.01), and FFDM (P=.005). The average CCCs were 0.89, 0.91, and 0.67 for texture features extracted from the average-CT, T50-CT, and CE-CT, respectively. Incorporating reproducibility within our models yielded 80.4% (±3.7% SD), 78.3% (±4.0% SD), and 78

  4. 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.; 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 2–5 month and 5–8 month follow-up time ranges. At 2–5 months post-treatment, first-order texture, energy, and entropy provided AUCs of 0.79–0.81 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

  5. MO-C-17A-06: Online Adaptive Re-Planning to Account for Independent Motions Between Multiple Targets During Radiotherapy of Lung Cancer

    SciTech Connect (OSTI)

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

    2014-06-15

    Purpose: To quantify interfractional independent motions between multiple targets in radiotherapy (RT) of lung cancer, and to study the dosimetric benefits of an online adaptive replanning method to account for these variations. Methods: Ninety five diagnostic-quality daily CTs acquired for 9 lung cancer patients treated with IGRT using an in-room CT (CTVision, Siemens) were analyzed. On each daily CT set, contours of the targets (GTV, CTV, or involved nodes) and organs at risk were generated by populating the planning contours using an auto-segmentation tool (ABAS, Elekta) with manual editing. For each patient, an IMRT plan was generated based on the planning CT with a prescription dose of 60 Gy in 2Gy fractions. Three plans were generated and compared for each daily CT set: an IGRT (repositioning) plan by copying the original plan with the required shifts, an online adaptive plan by rapidly modifying the aperture shapes and segment weights of the original plan to conform to the daily anatomy, and a new fully re-optimized plan based on the daily CT using a planning system (Panther, Prowess). Results: The daily deviations of the distance between centers of masses of the targets from the plans varied daily from -10 to 8 mm with an average −0.9±4.1 mm (one standard deviation). The average CTV V100 are 99.0±0.7%, 97.9±2.8%, 99.0±0.6%, and 99.1±0.6%, and the lung V20 Gy 928±332 cc, 944±315 cc, 917±300 cc, and 891±295 cc for the original, repositioning, adaptive, and re-optimized plans, respectively. Wilcoxon signed-rank tests show that the adaptive plans are statistically significantly better than the repositioning plans and comparable with the reoptimized plans. Conclusion: There exist unpredictable, interfractional, relative volume changes and independent motions between multiple targets during lung cancer RT which cannot be accounted for by the current IGRT repositioning but can be corrected by the online adaptive replanning method.

  6. Pretreatment Modified Glasgow Prognostic Score Predicts Clinical Outcomes After Stereotactic Body Radiation Therapy for Early-Stage Non-Small Cell Lung Cancer

    SciTech Connect (OSTI)

    Kishi, Takahiro; Matsuo, Yukinori Ueki, Nami; Iizuka, Yusuke; Nakamura, Akira; Sakanaka, Katsuyuki; Mizowaki, Takashi; Hiraoka, Masahiro

    2015-07-01

    Purpose: This study aimed to evaluate the prognostic significance of the modified Glasgow Prognostic Score (mGPS) in patients with non-small cell lung cancer (NSCLC) who received stereotactic body radiation therapy (SBRT). Methods and Materials: Data from 165 patients who underwent SBRT for stage I NSCLC with histologic confirmation from January 1999 to September 2010 were collected retrospectively. Factors, including age, performance status, histology, Charlson comorbidity index, mGPS, and recursive partitioning analysis (RPA) class based on sex and T stage, were evaluated with regard to overall survival (OS) using the Cox proportional hazards model. The impact of the mGPS on cause of death and failure patterns was also analyzed. Results: The 3-year OS was 57.9%, with a median follow-up time of 3.5 years. A higher mGPS correlated significantly with poor OS (P<.001). The 3-year OS of lower mGPS patients was 66.4%, whereas that of higher mGPS patients was 44.5%. On multivariate analysis, mGPS and RPA class were significant factors for OS. A higher mGPS correlated significantly with lung cancer death (P=.019) and distant metastasis (P=.013). Conclusions: The mGPS was a significant predictor of clinical outcomes for SBRT in NSCLC patients.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. Disturbance of DKK1 level is partly involved in survival of lung cancer cells via regulation of ROMO1 and γ-radiation sensitivity

    SciTech Connect (OSTI)

    Kim, In Gyu; Kim, Seo Yoen; Biomedical Translational Research Center, Korea Research Institute of Bioscience and Biotechnology, 125 Gwahak-ro, Yuseong-gu, Daejeon 305-806 ; Kim, Hyun A; Kim, Jeong Yul; Lee, Jae Ha; Choi, Soo Im; Department of Radiation Biotechnology and Applied Radioisotope, University of Science and Technology , 989-111 Daedeok-daero, Yuseong-gu, Daejeon 305-353 ; Han, Jeong Ran; Kim, Kug Chan; Cho, Eun Wie

    2014-01-03

    Highlights: •DKK1 was expressed differently among non-small-cell lung cancer cell lines. •DKK1 negatively regulated ROMO1 gene expression. •Disturbance of DKK1 level induced the imbalance of cellular ROS. •DKK1/ROMO1-induced ROS imbalance is involved in cell survival in NSCLC. -- Abstract: Dickkopf1 (DKK1), a secreted protein involved in embryonic development, is a potent inhibitor of the Wnt signaling pathway and has been postulated to be a tumor suppressor or tumor promoter depending on the tumor type. In this study, we showed that DKK1 was expressed differently among non-small-cell lung cancer cell lines. The DKK1 expression level was much higher in A549 cells than in H460 cells. We revealed that blockage of DKK1 expression by silencing RNA in A549 cells caused up-regulation of intracellular reactive oxygen species (ROS) modulator (ROMO1) protein, followed by partial cell death, cell growth inhibition, and loss of epithelial–mesenchymal transition property caused by ROS, and it also increased γ-radiation sensitivity. DKK1 overexpression in H460 significantly inhibited cell survival with the decrease of ROMO1 level, which induced the decrease of cellular ROS. Thereafter, exogenous N-acetylcysteine, an antioxidant, or hydrogen peroxide, a pro-oxidant, partially rescued cells from death and growth inhibition. In each cell line, both overexpression and blockage of DKK1 not only elevated p-RB activation, which led to cell growth arrest, but also inactivated AKT/NF-kB, which increased radiation sensitivity and inhibited cell growth. This study is the first to demonstrate that strict modulation of DKK1 expression in different cell types partially maintains cell survival via tight regulation of the ROS-producing ROMO1 and radiation resistance.

  15. Propensity Score–Matched Analysis of Comprehensive Local Therapy for Oligometastatic Non-Small Cell Lung Cancer That Did Not Progress After Front-Line Chemotherapy

    SciTech Connect (OSTI)

    Sheu, Tommy; Heymach, John V.; Swisher, Stephen G.; Rao, Ganesh; Weinberg, Jeffrey S.; Mehran, Reza; McAleer, Mary Frances; Liao, Zhongxing; Aloia, Thomas A.; Gomez, Daniel R.

    2014-11-15

    Purpose: To retrospectively analyze factors influencing survival in patients with non-small cell lung cancer presenting with ≤3 synchronous metastatic lesions. Methods and Materials: We identified 90 patients presenting between 1998 and 2012 with non-small cell lung cancer and ≤3 metastatic lesions who had received at least 2 cycles of chemotherapy followed by surgery or radiation therapy before disease progression. The median number of chemotherapy cycles before comprehensive local therapy (CLT) (including concurrent chemoradiation as first-line therapy) was 6. Factors potentially affecting overall (OS) or progression-free survival (PFS) were evaluated with Cox proportional hazards regression. Propensity score matching was used to assess the efficacy of CLT. Results: Median follow-up time was 46.6 months. Benefits in OS (27.1 vs 13.1 months) and PFS (11.3 months vs 8.0 months) were found with CLT, and the differences were statistically significant when propensity score matching was used (P ≤ .01). On adjusted analysis, CLT had a statistically significant benefit in terms of OS (hazard ratio, 0.37; 95% confidence interval, 0.20-0.70; P ≤ .01) but not PFS (P=.10). In an adjusted subgroup analysis of patients receiving CLT, favorable performance status (hazard ratio, 0.43; 95% confidence interval, 0.22-0.84; P=.01) was found to predict improved OS. Conclusions: Comprehensive local therapy was associated with improved OS in an adjusted analysis and seemed to favorably influence OS and PFS when factors such as N status, number of metastatic lesions, and disease sites were controlled for with propensity score–matched analysis. Patients with favorable performance status had improved outcomes with CLT. Ultimately, prospective, randomized trials are needed to provide definitive evidence as to the optimal treatment approach for this patient population.

  16. SU-E-T-40: Analysis of Composite MVCT Planning Dosimetry with SBRT of Upper Peripheral Lung Cancer

    SciTech Connect (OSTI)

    Yang, C; Doxsee, K; Chen, Y

    2014-06-01

    Purpose: Quantitatively evaluate and compare the final adaptive planning doses of upper peripherally located lung SBRT treated with Tomotherapy using 3rd party software tool. Methods: With tumor located in the upper quadrant of lung, a 3rd party software tool was implemented to evaluate the Tomotherapy composite dosimetry created by adaptive fan beam MVCT images described by RTOG 0915 dose criteria (48 Gy / 4 fractions). The composite doses was then summarized with deformable registration in this package with corresponding target and critical structures. The final dosimetry variation, both for target and critical structures, were evaluated in a tabular format and isodose distribution comparisons. Results: Composite SBRT treatment doses were evaluated with adaptive planning. The PTV and several critical structures were mapped/deformed into the package via DICOM from Tomotherapy after the final composite doses were created. Initial plan versus the final composite plan calculated from verification images were compared. The ITV defined by 4D CT and contoured on MVCT images were correlated in patient repositioning. Final composite dose calculated for PTV coverage has shown 0.1–0.17 cGy coverage (0.2–0.4% of prescription dose) variation. Total lung and cord were both less than 0.17 Gy which represented <0.4% difference. All other critical structure were within statistical significance. The adaptive plans justified/included the breathing and motion during the treatment process. Final 95% isotope line coverage from prescription has been met without issues. Conclusions: With lung tumor location in the upper peripheral area, breathing control was not necessary required during SBRT treatment using Tomotherapy technique. Slow fan beam CT provides definitive ITV information and the adaptive composite plan for all fractions were suitable for final dose delivery. The final composite dose calculated with Tomotherapy adaptive tool indicated that the composite dosimetry

  17. SU-E-J-94: Geometric and Dosimetric Evaluation of Deformation Image Registration Algorithms Using Virtual Phantoms Generated From Patients with Lung Cancer

    SciTech Connect (OSTI)

    Shen, Z; Greskovich, J; Xia, P; Bzdusek, K

    2015-06-15

    Purpose: To generate virtual phantoms with clinically relevant deformation and use them to objectively evaluate geometric and dosimetric uncertainties of deformable image registration (DIR) algorithms. Methods: Ten lung cancer patients undergoing adaptive 3DCRT planning were selected. For each patient, a pair of planning CT (pCT) and replanning CT (rCT) were used as the basis for virtual phantom generation. Manually adjusted meshes were created for selected ROIs (e.g. PTV, lungs, spinal cord, esophagus, and heart) on pCT and rCT. The mesh vertices were input into a thin-plate spline algorithm to generate a reference displacement vector field (DVF). The reference DVF was used to deform pCT to generate a simulated replanning CT (srCT) that was closely matched to rCT. Three DIR algorithms (Demons, B-Spline, and intensity-based) were applied to these ten virtual phantoms. The images, ROIs, and doses were mapped from pCT to srCT using the DVFs computed by these three DIRs and compared to those mapped using the reference DVF. Results: The average Dice coefficients for selected ROIs were from 0.85 to 0.96 for Demons, from 0.86 to 0.97 for intensity-based, and from 0.76 to 0.95 for B-Spline. The average Hausdorff distances for selected ROIs were from 2.2 to 5.4 mm for Demons, from 2.3 to 6.8 mm for intensity-based, and from 2.4 to 11.4 mm for B-Spline. The average absolute dose errors for selected ROIs were from 0.2 to 0.6 Gy for Demons, from 0.1 to 0.5 Gy for intensity-based, and from 0.5 to 1.5 Gy for B-Spline. Conclusion: Virtual phantoms were modeled after patients with lung cancer and were clinically relevant for adaptive radiotherapy treatment replanning. Virtual phantoms with known DVFs serve as references and can provide a fair comparison when evaluating different DIRs. Demons and intensity-based DIRs were shown to have smaller geometric and dosimetric uncertainties than B-Spline. Z Shen: None; K Bzdusek: an employee of Philips Healthcare; J Greskovich: None; P Xia

  18. 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

  19. Combined photon-electron beams in the treatment of the supraclavicular lymph nodes in breast cancer: A novel technique that achieves adequate coverage while reducing lung dose

    SciTech Connect (OSTI)

    Salem, Ahmed; Mohamad, Issa; Dayyat, Abdulmajeed; Kanaa’n, Haitham; Sarhan, Nasim; Roujob, Ibrahim; Salem, Abdel-Fattah; Afifi, Shatha; Jaradat, Imad; Mubiden, Rasmi; Almousa, Abdelateif

    2015-10-01

    Radiation pneumonitis is a well-documented side effect of radiation therapy for breast cancer. The purpose of this study was to compare combined photon-electron, photon-only, and electron-only plans in the radiation treatment of the supraclavicular lymph nodes. In total, 13 patients requiring chest wall and supraclavicular nodal irradiation were planned retrospectively using combined photon-electron, photon-only, and electron-only supraclavicular beams. A dose of 50 Gy over 25 fractions was prescribed. Chest wall irradiation parameters were fixed for all plans. The goal of this planning effort was to cover 95% of the supraclavicular clinical target volume (CTV) with 95% of the prescribed dose and to minimize the volume receiving ≥ 105% of the dose. Comparative end points were supraclavicular CTV coverage (volume covered by the 95% isodose line), hotspot volume, maximum radiation dose, contralateral breast dose, mean total lung dose, total lung volume percentage receiving at least 20 Gy (V{sub 20} {sub Gy}), heart volume percentage receiving at least 25 Gy (V{sub 25} {sub Gy}). Electron and photon energies ranged from 8 to 18 MeV and 4 to 6 MV, respectively. The ratio of photon-to-electron fractions in combined beams ranged from 5:20 to 15:10. Supraclavicular nodal coverage was highest in photon-only (mean = 96.2 ± 3.5%) followed closely by combined photon-electron (mean = 94.2 ± 2.5%) and lowest in electron-only plans (mean = 81.7 ± 14.8%, p < 0.001). The volume of tissue receiving ≥ 105% of the prescription dose was higher in the electron-only (mean = 69.7 ± 56.1 cm{sup 3}) as opposed to combined photon-electron (mean = 50.8 ± 40.9 cm{sup 3}) and photon-only beams (mean = 32.2 ± 28.1 cm{sup 3}, p = 0.114). Heart V{sub 25} {sub Gy} was not statistically different among the plans (p = 0.999). Total lung V{sub 20} {sub Gy} was lowest in electron-only (mean = 10.9 ± 2.3%) followed by combined photon-electron (mean = 13.8 ± 2.3%) and highest in photon

  20. Distribution Atlas of Proliferating Bone Marrow in Non-Small Cell Lung Cancer Patients Measured by FLT-PET/CT Imaging, With Potential Applicability in Radiation Therapy Planning

    SciTech Connect (OSTI)

    Campbell, Belinda A.; Callahan, Jason; Bressel, Mathias; Simoens, Nathalie; Everitt, Sarah; Hofman, Michael S.; Hicks, Rodney J.; Burbury, Kate; MacManus, Michael

    2015-08-01

    Purpose: Proliferating bone marrow is exquisitely sensitive to ionizing radiation. Knowledge of its distribution could improve radiation therapy planning to minimize unnecessary marrow exposure and avoid consequential prolonged myelosuppression. [18F]-Fluoro-3-deoxy-3-L-fluorothymidine (FLT)–positron emission tomography (PET) is a novel imaging modality that provides detailed quantitative images of proliferating tissues, including bone marrow. We used FLT-PET imaging in cancer patients to produce an atlas of marrow distribution with potential clinical utility. Methods and Materials: The FLT-PET and fused CT scans of eligible patients with non-small cell lung cancer (no distant metastases, no prior cytotoxic exposure, no hematologic disorders) were reviewed. The proportions of skeletal FLT activity in 10 predefined bony regions were determined and compared according to age, sex, and recent smoking status. Results: Fifty-one patients were studied: 67% male; median age 68 (range, 31-87) years; 8% never smokers; 70% no smoking in the preceding 3 months. Significant differences in marrow distribution occurred between sex and age groups. No effect was detected from smoking in the preceding 3 months. Using the mean percentages of FLT uptake per body region, we created an atlas of the distribution of functional bone marrow in 4 subgroups defined by sex and age. Conclusions: This atlas has potential utility for estimating the distribution of active marrow in adult cancer patients to guide radiation therapy planning. However, because of interindividual variation it should be used with caution when radiation therapy risks ablating large proportions of active marrow; in such cases, individual FLT-PET scans may be required.

  1. 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.

  2. 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.

  3. 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.

  4. SU-E-T-539: Maximum Energy of Helium and Carbon Ions Clinically Needed for Spine, Lung, Prostate and Pancreas Cancer

    SciTech Connect (OSTI)

    Pompos, A; Choy, H; Jia, X; Jiang, S; Timmerman, R

    2015-06-15

    Purpose: Maximum available kinetic energy of accelerated heavy ions is a critical parameter to consider during the establishment of a heavy ion therapy center. It dictates the maximum range in tissue and determines the size and cost of ion gantry. We have started planning our heavy ion therapy center and we report on the needed ion range. Methods: We analyzed 50 of random SBRT-spine, SBRT- lung, prostate and pancreatic cancer patients from our photon clinic. In the isocentric axial CT cut we recorded the maximum water equivalent depth (WED4Field) of PTV’s most distal edge in four cardinal directions and also in a beam direction that required the largest penetration, WEDGantry. These depths were then used to calculate the percentage of our patients we would be able to treat as a function of available maximum carbon and helium beam energy. Based on the Anterior-Posterior WED for lung patients and the maximum available ion energy we estimated the largest possible non-coplanar beam entry angle φ (deviation from vertical) in the isocentric vertical sagittal plane. Results: We found that if 430MeV/u C-12, equivalently 220MeV/u He-4, beams are available, more than 96% (98%) of all patients can be treated without any gantry restrictions (in cardinals angles only) respectively. If the energy is reduced to 400MeV/u C-12, equivalently 205MeV/u He-4, the above fractions reduce to 80% (87%) for prostate and 88% (97%) for other sites. This 7% energy decrease translates to almost 5% gantry size and cost decrease for both ions. These energy limits in combination with the WED in the AP direction for lung patients resulted in average non-coplanar angles of φ430MeV/u = 68°±8° and φ400MeV/u = 65°±10° if nozzle clearance permits them. Conclusion: We found that the two worldwide most common maximum carbon beam energies will treat above 80% of all our patients.

  5. MicroRNA-134 regulates lung cancer cell H69 growth and apoptosis by targeting WWOX gene and suppressing the ERK1/2 signaling pathway

    SciTech Connect (OSTI)

    Chen, Tianjun; Gao, Fei; Feng, Sifang; Yang, Tian; Chen, Mingwei

    2015-08-28

    MicroRNAs have been shown to act as crucial modulators during carcinogenesis. Recent studies have implied that miR-134 expression associated with epithelial-to-mesenchymal transition phenotype and invasive potential of NSCLC cells. Our study investigated the pathogenic implications of miR-134 in small cell lung cancer (SCLC). Overexpression or inhibition MiR-134 expression by miR-134 mimics or miR-134 inhibitors (anti-miR-134) in SCLC cell lines was detected using qRT-PCR. Lactate dehydrogenase (LDH) assay, MTT assays and flow cytometry were performed in order to clarify the growth and apoptosis of SCLC cells which had been transfected with miR-134 mimics or anti-miR-134. WWOX expression in H69 cells was detected by qRT-PCR and western blot, respectively. The results showed that overexpression miR-134 was significantly promoting SCLC cells growth and inhibit its apoptosis. In addition, reduced miR-134 expression was significantly correlated with cell growth inhibition and apoptosis promotion. Furthermore, transfection of miR-134 mimics into the SCLC cells markedly down-regulated the level of WWOX, whereas, anti-miR-134 up-regulated WWOX expression. We also found that overexpression WWOX attenuate miR-134 induced H69 cells growth, and promote cell apoptosis. Moreover, miR-134 promoted cell proliferation and inhibit apoptosis via the activation of ERK1/2 pathway. These findings suggest that miR-134 may be an ideal diagnostic and prognostic marker, and may be attributed to the molecular therapy of SCLC. - Highlights: • MiR-134 play roles in small cell lung cancer cell growth and apoptosis. • MiR-134 negative regulated the level of WWOX in H69 cells. • WWOX overexpression attenuate miR-134 induced H69 cells growth. • MiR-134 promotes cell growth via the activation of ERK1/2 pathway.

  6. 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.

  7. Adding Erlotinib to Chemoradiation Improves Overall Survival but Not Progression-Free Survival in Stage III Non-Small Cell Lung Cancer

    SciTech Connect (OSTI)

    Komaki, Ritsuko; Allen, Pamela K.; Wei, Xiong; Blumenschein, George R.; Tang, Ximing; Lee, J. Jack; Welsh, James W.; Wistuba, Ignacio I.; Liu, Diane D.; Hong, Waun Ki

    2015-06-01

    Purpose: To test, in a single-arm, prospective, phase 2 trial, whether adding the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor erlotinib to concurrent chemoradiotherapy for previously untreated, locally advanced, inoperable non-small cell lung cancer would improve survival and disease control without increasing toxicity. Methods and Materials: Forty-eight patients with previously untreated non-small cell lung cancer received intensity modulated radiation therapy (63 Gy/35 fractions) on Monday through Friday, with chemotherapy (paclitaxel 45 mg/m², carboplatin area under the curve [AUC] = 2) on Mondays, for 7 weeks. All patients also received the EGFR tyrosine kinase inhibitor erlotinib (150 mg orally 1/d) on Tuesday-Sunday for 7 weeks, followed by consolidation paclitaxel–carboplatin. The primary endpoint was time to progression; secondary endpoints were overall survival (OS), toxicity, response, and disease control and whether any endpoint differed by EGFR mutation status. Results: Of 46 patients evaluable for response, 40 were former or never-smokers, and 41 were evaluable for EGFR mutations (37 wild-type [WT] and 4 mutated [all adenocarcinoma]). Median time to progression was 14.0 months and did not differ by EGFR status. Toxicity was acceptable (no grade 5, 1 grade 4, 11 grade 3). Twelve patients (26%) had complete responses (10 WT, 2 mutated), 27 (59%) partial (21 WT, 2 mutated, 4 unknown), and 7 (15%) none (6 WT, 2 mutated, 1 unknown) (P=.610). At 37.0 months' follow-up (range, 3.6-76.5 months) for all patients, median OS time was 36.5 months, and 1-, 2-, and 5-year OS rates were 82.6%, 67.4%, and 35.9%, respectively; none differed by mutation status. Twelve patients had no progression, and 34 had local and/or distant failure. Eleven of 27 distant failures were in the brain (7 WT, 3 mutated, 1 unknown). Conclusions: Toxicity and OS were promising, but time to progression did not meet expectations. The prevalence of distant

  8. 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

  9. Cancer incidence and community exposure to air emissions from petroleum and chemical plants in Contra Costa County, California: A critical epidemiological assessment

    SciTech Connect (OSTI)

    Otto Wong ); Bailey, W.J.

    1993-12-01

    The northern part of Contra Costa County, California is heavily industrialized with a number of petroleum refineries, chemical facilities and other small industrial plants. Several epidemiological studies have been conducted in the country to assess cancer risk in relation to estimated air pollution levels. In this paper, the air monitoring data, air pollution modeling and the epidemiologic studies are critically reviewed. The association between cancer risk and estimated emissions is critically evaluated. The role of occupational and lifestyle (such as cigarette smoking and diet) confounding exposures is also assessed. The importance of validating exposure data generated by air pollution models in epidemiologic studies is emphasized. Pollutants of major concern are sulfur dioxide, nitrogen oxides, and hydrocarbons.

  10. Posttraumatic Stress Disorder After High-Dose-Rate Brachytherapy for Cervical Cancer With 2 Fractions in 1 Application Under Spinal/Epidural Anesthesia: Incidence and Risk Factors

    SciTech Connect (OSTI)

    Kirchheiner, Kathrin; Czajka-Pepl, Agnieszka; Scharbert, Gisela; Wetzel, Léonore; Sturdza, Alina; Dörr, Wolfgang; Pötter, Richard

    2014-06-01

    Purpose: To investigate the psychological consequences of high-dose-rate brachytherapy with 2 fractions in 1 application under spinal/epidural anesthesia in the treatment of locally advanced cervical cancer. Methods and Materials: In 50 patients with locally advanced cervical cancer, validated questionnaires were used for prospective assessment of acute and posttraumatic stress disorder (ASD/PTSD) (Impact of Event Scale–Revision), anxiety/depression (Hospital Anxiety and Depression Scale), quality of life (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30/Cervical Cancer 24), physical functioning (World Health Organization performance status), and pain (visual analogue scale), before and during treatment and 1 week and 3 months after treatment. Qualitative interviews were recorded in open format for content analysis. Results: Symptoms of ASD occurred in 30% of patients 1 week after treatment; and of PTSD in 41% 3 months after treatment in association with this specific brachytherapy procedure. Pretreatment predictive variables explain 82% of the variance of PTSD symptoms. Helpful experiences were the support of the treatment team, psychological support, and a positive attitude. Stressful factors were pain, organizational problems during treatment, and immobility between brachytherapy fractions. Conclusions: The specific brachytherapy procedure, as performed in the investigated mono-institutional setting with 2 fractions in 1 application under spinal/epidural anesthesia, bears a considerable risk of traumatization. The source of stress seems to be not the brachytherapy application itself but the maintenance of the applicator under epidural anesthesia in the time between fractions. Patients at risk may be identified before treatment, to offer targeted psycho-social support. The patients' open reports regarding helpful experiences are an encouraging feedback for the treatment team; the reported stressful factors

  11. 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.

  12. 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.

  13. Incidence and Treatment Patterns in Hospitalizations for Malignant Spinal Cord Compression in the United States, 1998-2006

    SciTech Connect (OSTI)

    Mak, Kimberley S.; Lee, Leslie K.; Mak, Raymond H.; Wang, Shuang; Pile-Spellman, John; Abrahm, Janet L.; Prigerson, Holly G.; Balboni, Tracy A.

    2011-07-01

    Purpose: To characterize patterns in incidence, management, and costs of malignant spinal cord compression (MSCC) hospitalizations in the United States, using population-based data. Methods and Materials: Using the Nationwide Inpatient Sample, an all-payer healthcare database representative of all U.S. hospitalizations, MSCC-related hospitalizations were identified for the period 1998-2006. Cases were combined with age-adjusted Surveillance, Epidemiology and End Results cancer death data to estimate annual incidence. Linear regression characterized trends in patient, treatment, and hospital characteristics, costs, and outcomes. Logistic regression was used to examine inpatient treatment (radiotherapy [RT], surgery, or neither) by hospital characteristics and year, adjusting for confounding. Results: We identified 15,367 MSCC-related cases, representing 75,876 hospitalizations. Lung cancer (24.9%), prostate cancer (16.2%), and multiple myeloma (11.1%) were the most prevalent underlying cancer diagnoses. The annual incidence of MSCC hospitalization among patients dying of cancer was 3.4%; multiple myeloma (15.0%), Hodgkin and non-Hodgkin lymphomas (13.9%), and prostate cancer (5.5%) exhibited the highest cancer-specific incidence. Over the study period, inpatient RT for MSCC decreased (odds ratio [OR] 0.68, 95% confidence interval [CI] 0.61-0.81), whereas surgery increased (OR 1.48, 95% CI 1.17-1.84). Hospitalization costs for MSCC increased (5.3% per year, p < 0.001). Odds of inpatient RT were greater at teaching hospitals (OR 1.41, 95% CI 1.19-1.67), whereas odds of surgery were greater at urban institutions (OR 1.82, 95% CI 1.29-2.58). Conclusions: In the United States, patients dying of cancer have an estimated 3.4% annual incidence of MSCC requiring hospitalization. Inpatient management of MSCC varied over time and by hospital characteristics, with hospitalization costs increasing. Future studies are required to determine the impact of treatment patterns on MSCC

  14. Is Intermediate Radiation Dose Escalation With Concurrent Chemotherapy for Stage III Non–Small-Cell Lung Cancer Beneficial? A Multi-Institutional Propensity Score Matched Analysis

    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, Núria 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 non–small-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 74 Gy. 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 ≤ 76.8 Gy (eg 60-64 Gy/30-32 fractions [fr]), and those receiving intermediate dose (ID; n=497), consisting of 76.8Gy < BED 10 < 100.8 Gy (eg >64 Gy/32 fr and <74 Gy/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 89 months; ID were 40 months). Median dose fractionation was 60 Gy/30 fr in SD (BED 10 IQR: 72.0-75.5 Gy) and 66 Gy/33 fr (BED 10 IQR: 78.6-79.2 Gy) 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 15 months (median survival SD: 19.3 months; ID: 21.0

  15. A Multicenter Retrospective Analysis of Survival Outcome Following Postoperative Chemoradiotherapy in Non-Small-Cell Lung Cancer Patients With N2 Nodal Disease

    SciTech Connect (OSTI)

    Zou Bingwen; Xu Yong; Li Tao; Li Wenhui; Tang Bangxian; Zhou Lin; Li Lu; Liu Yongmei; Zhu Jiang; Huang Meijuan; Wang Jin; Ren Li; Gong Youlin; Che Guowei; Liu Lunxu; Hou Mei; Lu You

    2010-06-01

    Purpose: To retrospectively evaluate the role of postoperative chemoradiotherapy (POCRT) in patients with completely resected non-small-cell lung cancer (NSCLC) with N2 lymph node involvement. Methods and Materials: This study included 183 patients from four centers in southwest China who underwent radical section of Stage III-N2 NSCLC without any preoperative therapy. One hundred and four were treated with POCRT and 79 with postoperative chemotherapy (POCT) alone. The median radiation dose to clinical target volume (CTV) was 50 Gy (varying between 48 and 54 Gy), whereas the cycles of platinum-based chemotherapy ranged from two to six with a median of four. Results: The median duration of follow-up was 72 months. The 5-year overall survival rate (OS) was 30.5% in the POCRT group, and 14.4% in the POCT group (p = 0.007). The 5-year disease-free survival rate (DFS) was 22.2% in POCRT group and 9.3% in POCT group (p = 0.003). In a multivariate analysis, N1 nodal involvement (N1+/N2+) was associated with significantly worse OS (HR = 1.454, 95% CI, 1.012-2.087, p = 0.043) and DFS (HR = 1.685, 95% CI, 1.196-2.372, p = 0.003). Absence of radiotherapy and treatment with fewer than three cycles of chemotherapy both were poor prognostic factors for both OS and DFS. Conclusions: As compared with chemotherapy alone, adjuvant treatment with both radiotherapy and chemotherapy improves survival in patients with completely resected Stage III-N2 nodal disease in NSCLC. Future study of treatment modality with radiotherapy and chemotherapy is warranted, especially focusing on both N1 and N2 nodal status.

  16. Predicting Overall Survival After Stereotactic Ablative Radiation Therapy in Early-Stage Lung Cancer: Development and External Validation of the Amsterdam Prognostic Model

    SciTech Connect (OSTI)

    Louie, Alexander V.; Haasbeek, Cornelis J.A.; Mokhles, Sahar; Rodrigues, George B.; Stephans, Kevin L.; Lagerwaard, Frank J.; Palma, David A.; Videtic, Gregory M.M.; Warner, Andrew; Takkenberg, Johanna J.M.; Reddy, Chandana A.; Maat, Alex P.W.M.; Woody, Neil M.; Slotman, Ben J.; Senan, Suresh

    2015-09-01

    Purpose: A prognostic model for 5-year overall survival (OS), consisting of recursive partitioning analysis (RPA) and a nomogram, was developed for patients with early-stage non-small cell lung cancer (ES-NSCLC) treated with stereotactic ablative radiation therapy (SABR). Methods and Materials: A primary dataset of 703 ES-NSCLC SABR patients was randomly divided into a training (67%) and an internal validation (33%) dataset. In the former group, 21 unique parameters consisting of patient, treatment, and tumor factors were entered into an RPA model to predict OS. Univariate and multivariate models were constructed for RPA-selected factors to evaluate their relationship with OS. A nomogram for OS was constructed based on factors significant in multivariate modeling and validated with calibration plots. Both the RPA and the nomogram were externally validated in independent surgical (n=193) and SABR (n=543) datasets. Results: RPA identified 2 distinct risk classes based on tumor diameter, age, World Health Organization performance status (PS) and Charlson comorbidity index. This RPA had moderate discrimination in SABR datasets (c-index range: 0.52-0.60) but was of limited value in the surgical validation cohort. The nomogram predicting OS included smoking history in addition to RPA-identified factors. In contrast to RPA, validation of the nomogram performed well in internal validation (r{sup 2}=0.97) and external SABR (r{sup 2}=0.79) and surgical cohorts (r{sup 2}=0.91). Conclusions: The Amsterdam prognostic model is the first externally validated prognostication tool for OS in ES-NSCLC treated with SABR available to individualize patient decision making. The nomogram retained strong performance across surgical and SABR external validation datasets. RPA performance was poor in surgical patients, suggesting that 2 different distinct patient populations are being treated with these 2 effective modalities.

  17. A Validated Prediction Model for Overall Survival From Stage III Non-Small Cell Lung Cancer: Toward Survival Prediction for Individual Patients

    SciTech Connect (OSTI)

    Oberije, Cary; De Ruysscher, Dirk; Houben, Ruud; Heuvel, Michel van de; Uyterlinde, Wilma; Deasy, Joseph O.; Belderbos, Jose; Dingemans, Anne-Marie C.; Rimner, Andreas; Din, Shaun; Lambin, Philippe

    2015-07-15

    Purpose: Although patients with stage III non-small cell lung cancer (NSCLC) are homogeneous according to the TNM staging system, they form a heterogeneous group, which is reflected in the survival outcome. The increasing amount of information for an individual patient and the growing number of treatment options facilitate personalized treatment, but they also complicate treatment decision making. Decision support systems (DSS), which provide individualized prognostic information, can overcome this but are currently lacking. A DSS for stage III NSCLC requires the development and integration of multiple models. The current study takes the first step in this process by developing and validating a model that can provide physicians with a survival probability for an individual NSCLC patient. Methods and Materials: Data from 548 patients with stage III NSCLC were available to enable the development of a prediction model, using stratified Cox regression. Variables were selected by using a bootstrap procedure. Performance of the model was expressed as the c statistic, assessed internally and on 2 external data sets (n=174 and n=130). Results: The final multivariate model, stratified for treatment, consisted of age, gender, World Health Organization performance status, overall treatment time, equivalent radiation dose, number of positive lymph node stations, and gross tumor volume. The bootstrapped c statistic was 0.62. The model could identify risk groups in external data sets. Nomograms were constructed to predict an individual patient's survival probability ( (www.predictcancer.org)). The data set can be downloaded at (https://www.cancerdata.org/10.1016/j.ijrobp.2015.02.048). Conclusions: The prediction model for overall survival of patients with stage III NSCLC highlights the importance of combining patient, clinical, and treatment variables. Nomograms were developed and validated. This tool could be used as a first building block for a decision support system.

  18. 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.

  19. 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.

  20. 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

  1. 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.

  2. WE-G-18C-02: Estimation of Optimal B-Value Set for Obtaining Apparent Diffusion Coefficient Free From Perfusion in Non-Small Cell Lung Cancer

    SciTech Connect (OSTI)

    Karki, K; Hugo, G; Ford, J; Saraiya, S; Weiss, E; Olsen, K; Groves, R

    2014-06-15

    Purpose: Diffusion-weighted MRI (DW-MRI) is increasingly being investigated for radiotherapy planning and response assessment. Selection of a limited number of b-values in DW-MRI is important to keep geometrical variations low and imaging time short. We investigated various b-value sets to determine an optimal set for obtaining monoexponential apparent diffusion coefficient (ADC) close to perfusion-insensitive intravoxel incoherent motion (IVIM) model ADC (ADCIVIM) in nonsmall cell lung cancer. Methods: Seven patients had 27 DW-MRI scans before and during radiotherapy in a 1.5T scanner. Respiratory triggering was applied to the echo-planar DW-MRI with TR=4500ms approximately, TE=74ms, pixel size=1.98X1.98mm{sub 2}, slice thickness=4–6mm and 7 axial slices. Diffusion gradients were applied to all three axes producing traceweighted images with eight b-values of 0–1000μs/μm{sup 2}. Monoexponential model ADC values using various b-value sets were compared to ADCIVIM using all b-values. To compare the relative noise in ADC maps, intra-scan coefficient of variation (CV) of active tumor volumes was computed. Results: ADCIVIM, perfusion coefficient and perfusion fraction for tumor volumes were in the range of 880-1622 μm{sup 2}/s, 8119-33834 μm{sup 2}/s and 0.104–0.349, respectively. ADC values using sets of 250, 800 and 1000; 250, 650 and 1000; and 250–1000μs/μm{sup 2} only were not significantly different from ADCIVIM(p>0.05, paired t-test). Error in ADC values for 0–1000, 50–1000, 100–1000, 250–1000, 500–1000, and three b-value sets- 250, 500 and 1000; 250, 650 and 1000; and 250, 800 and 1000μs/μm{sup 2} were 15.0, 9.4, 5.6, 1.4, 11.7, 3.7, 2.0 and 0.2% relative to the reference-standard ADCIVIM, respectively. Mean intrascan CV was 20.2, 20.9, 21.9, 24.9, 32.6, 25.8, 25.4 and 24.8%, respectively, whereas that for ADCIVIM was 23.3%. Conclusion: ADC values of two 3 b-value sets

  3. Targeting glucosylceramide synthase induction of cell surface globotriaosylceramide (Gb3) in acquired cisplatin-resistance of lung cancer and malignant pleural mesothelioma cells

    SciTech Connect (OSTI)

    Tyler, Andreas; Johansson, Anders; Karlsson, Terese; Gudey, Shyam Kumar; Brännström, Thomas; Grankvist, Kjell; Behnam-Motlagh, Parviz

    2015-08-01

    Background: Acquired resistance to cisplatin treatment is a caveat when treating patients with non-small cell lung cancer (NSCLC) and malignant pleural mesothelioma (MPM). Ceramide increases in response to chemotherapy, leading to proliferation arrest and apoptosis. However, a tumour stress activation of glucosylceramide synthase (GCS) follows to eliminate ceramide by formation of glycosphingolipids (GSLs) such as globotriaosylceramide (Gb3), the functional receptor of verotoxin-1. Ceramide elimination enhances cell proliferation and apoptosis blockade, thus stimulating tumor progression. GSLs transactivate multidrug resistance 1/P-glycoprotein (MDR1) and multidrug resistance-associated protein 1 (MRP1) expression which further prevents ceramide accumulation and stimulates drug efflux. We investigated the expression of Gb3, MDR1 and MRP1 in NSCLC and MPM cells with acquired cisplatin resistance, and if GCS activity or MDR1 pump inhibitors would reduce their expression and reverse cisplatin-resistance. Methods: Cell surface expression of Gb3, MDR1 and MRP1 and intracellular expression of MDR1 and MRP1 was analyzed by flow cytometry and confocal microscopy on P31 MPM and H1299 NSCLC cells and subline cells with acquired cisplatin resistance. The effect of GCS inhibitor PPMP and MDR1 pump inhibitor cyclosporin A for 72 h on expression and cisplatin cytotoxicity was tested. Results: The cisplatin-resistant cells expressed increased cell surface Gb3. Cell surface Gb3 expression of resistant cells was annihilated by PPMP whereas cyclosporin A decreased Gb3 and MDR1 expression in H1299 cells. No decrease of MDR1 by PPMP was noted in using flow cytometry, whereas a decrease of MDR1 in H1299 and H1299res was indicated with confocal microscopy. No certain co-localization of Gb3 and MDR1 was noted. PPMP, but not cyclosporin A, potentiated cisplatin cytotoxicity in all cells. Conclusions: Cell surface Gb3 expression is a likely tumour biomarker for acquired cisplatin

  4. 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; Hope, Andrew J.; Lindsay, Patricia E.; Bosch, Walter R.; Matthews, John W.; Sause, William T.; Graham, Mary V.; Deasy, Joseph O.

    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

  5. 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

  6. 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

  7. 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

  8. Reduction in Tumor Volume by Cone Beam Computed Tomography Predicts Overall Survival in Non-Small Cell Lung Cancer Treated With Chemoradiation Therapy

    SciTech Connect (OSTI)

    Jabbour, Salma K.; Kim, Sinae; Haider, Syed A.; Xu, Xiaoting; Wu, Alson; Surakanti, Sujani; Aisner, Joseph; Langenfeld, John; Yue, Ning J.; Haffty, Bruce G.; Zou, Wei

    2015-07-01

    Purpose: We sought to evaluate whether tumor response using cone beam computed tomography (CBCT) performed as part of the routine care during chemoradiation therapy (CRT) could forecast the outcome of unresectable, locally advanced, non-small cell lung cancer (NSCLC). Methods and Materials: We manually delineated primary tumor volumes (TV) of patients with NSCLC who were treated with radical CRT on days 1, 8, 15, 22, 29, 36, and 43 on CBCTs obtained as part of the standard radiation treatment course. Percentage reductions in TV were calculated and then correlated to survival and pattern of recurrence using Cox proportional hazard models. Clinical information including histologic subtype was also considered in the study of such associations. Results: We evaluated 38 patients with a median follow-up time of 23.4 months. The median TV reduction was 39.3% (range, 7.3%-69.3%) from day 1 (D1) to day 43 (D43) CBCTs. Overall survival was associated with TV reduction from D1 to D43 (hazard ratio [HR] 0.557, 95% CI 0.39-0.79, P=.0009). For every 10% decrease in TV from D1 to D43, the risk of death decreased by 44.3%. For patients whose TV decreased ≥39.3 or <39.3%, log-rank test demonstrated a separation in survival (P=.02), with median survivals of 31 months versus 10 months, respectively. Neither local recurrence (HR 0.791, 95% CI 0.51-1.23, P=.29), nor distant recurrence (HR 0.78, 95% CI 0.57-1.08, P=.137) correlated with TV decrease from D1 to D43. Histologic subtype showed no impact on our findings. Conclusions: TV reduction as determined by CBCT during CRT as part of routine care predicts post-CRT survival. Such knowledge may justify intensification of RT or application of additional therapies. Assessment of genomic characteristics of these tumors may permit a better understanding of behavior or prediction of therapeutic outcomes.

  9. 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

  10. 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 ...

  11. 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...

  12. 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').

  13. 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.

  14. Anatomy of an incident

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

    Cournoyer, Michael E.; Trujillo, Stanley; Lawton, Cindy M.; Land, Whitney M.; Schreiber, Stephen B.

    2016-03-23

    A traditional view of incidents is that they are caused by shortcomings in human competence, attention, or attitude. It may be under the label of “loss of situational awareness,” procedure “violation,” or “poor” management. A different view is that human error is not the cause of failure, but a symptom of failure – trouble deeper inside the system. In this perspective, human error is not the conclusion, but rather the starting point of investigations. During an investigation, three types of information are gathered: physical, documentary, and human (recall/experience). Through the causal analysis process, apparent cause or apparent causes are identifiedmore » as the most probable cause or causes of an incident or condition that management has the control to fix and for which effective recommendations for corrective actions can be generated. A causal analysis identifies relevant human performance factors. In the following presentation, the anatomy of a radiological incident is discussed, and one case study is presented. We analyzed the contributing factors that caused a radiological incident. When underlying conditions, decisions, actions, and inactions that contribute to the incident are identified. This includes weaknesses that may warrant improvements that tolerate error. Measures that reduce consequences or likelihood of recurrence are discussed.« less

  15. Colorectal Histology Is Associated With an Increased Risk of Local Failure in Lung Metastases Treated With Stereotactic Ablative Radiation Therapy

    SciTech Connect (OSTI)

    Binkley, Michael S.; Trakul, Nicholas; Jacobs, Lisa Rose; Eyben, Rie von; Le, Quynh-Thu; Maxim, Peter G.; Loo, Billy W.; Shultz, David Benjamin; Diehn, Maximilian

    2015-08-01

    Purpose: Stereotactic ablative radiation therapy (SABR) is increasingly used to treat lung oligometastases. We set out to determine the safety and efficacy of this approach and to identify factors associated with outcomes. Methods and Materials: We conducted a retrospective study of patients treated with SABR for metastatic lung tumors at our institution from 2003 to 2014. We assessed the association between various patient and treatment factors with local failure (LF), progression, subsequent treatment, systemic treatment, and overall survival (OS), using univariate and multivariate analyses. Results: We identified 122 tumors in 77 patients meeting inclusion criteria for this study. Median follow-up was 22 months. The 12- and 24-month cumulative incidence rates of LF were 8.7% and 16.2%, respectively; the 24-month cumulative incidence rates of progression, subsequent treatment, and subsequent systemic treatment were 75.2%, 64.5%, and 35.1%, respectively. Twenty-four-month OS was 74.6%, and median OS was 36 months. Colorectal metastases had a significantly higher cumulative incidence of LF at 12 and 24 months (25.5% and 42.2%, respectively), than all other histologies (4.4% and 9.9%, respectively; P<.0004). The 24-month cumulative incidences of LF for colorectal metastases treated with a biologically effective dose at α/β = 10 (BED{sub 10}) of <100 Gy versus BED{sub 10} of ≥100 Gy were 62.5% and 16.7%, respectively (P=.08). Toxicity was minimal, with only a single grade 3 or higher event observed. Conclusions: SABR for metastatic lung tumors appears to be safe and effective with excellent local control, treatment-free intervals, and OS. An exception is metastases from colorectal cancer, which have a high LF rate consistent with a radioresistant phenotype, suggesting a potential role for dose escalation.

  16. Time-Adjusted Internal Target Volume: A Novel Approach Focusing on Heterogeneity of Tumor Motion Based on 4-Dimensional Computed Tomography Imaging for Radiation Therapy Planning of Lung Cancer

    SciTech Connect (OSTI)

    Nishibuchi, Ikuno; Kimura, Tomoki; Nakashima, Takeo; Ochi, Yusuke; Takahashi, Ippei; Doi, Yoshiko; Kenjo, Masahiro; Kaneyasu, Yuko; Ozawa, Syuichi; Murakami, Yuji; Wadasaki, Koichi; Nagata, Yasushi

    2014-08-01

    Purpose: To consider nonuniform tumor motion within the internal target volume (ITV) by defining time-adjusted ITV (TTV), a volume designed to include heterogeneity of tumor existence on the basis of 4-dimensional computed tomography (4D-CT). Methods and Materials: We evaluated 30 lung cancer patients. Breath-hold CT (BH-CT) and free-breathing 4D-CT scans were acquired for each patient. The tumors were manually delineated using a lung CT window setting (window, 1600 HU; level, −300 HU). Tumor in BH-CT images was defined as gross tumor volume (GTV), and the sum of tumors in 4D-CT images was defined as ITV-4D. The TTV images were generated from the 4D-CT datasets, and the tumor existence probability within ITV-4D was calculated. We calculated the TTV{sub 80} value, which is the percentage of the volume with a tumor existence probability that exceeded 80% on ITV-4D. Several factors that affected the TTV{sub 80} value, such as the ITV-4D/GTV ratio or tumor centroid deviation, were evaluated. Results: Time-adjusted ITV images were acquired for all patients, and tumor respiratory motion heterogeneity was visualized. The median (range) ITV-4D/GTV ratio and median tumor centroid deviation were 1.6 (1.0-4.1) and 6.3 mm (0.1-30.3 mm), respectively. The median TTV{sub 80} value was 43.3% (2.9-98.7%). Strong correlations were observed between the TTV{sub 80} value and the ITV-4D/GTV ratio (R=−0.71) and tumor centroid deviation (R=−0.72). The TTV images revealed the tumor motion pattern features within ITV. Conclusions: The TTV images reflected nonuniform tumor motion, and they revealed the tumor motion pattern features, suggesting that the TTV concept may facilitate various aspects of radiation therapy planning of lung cancer while incorporating respiratory motion in the future.

  17. 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.

  18. Second Malignancies After Adjuvant Radiation Therapy for Early Stage Breast Cancer: Is There Increased Risk With Addition of Regional Radiation to Local Radiation?

    SciTech Connect (OSTI)

    Hamilton, Sarah Nicole; Tyldesley, Scott; Li, Dongdong; Olson, Robert; McBride, Mary

    2015-04-01

    Purpose: This study was undertaken to determine whether there was an increased risk of second malignancies (SM), particularly lung cancer, in early stage breast cancer patients treated with the addition of nodal fields to breast and/or chest wall radiation therapy (RT). Materials and Methods: Subjects were stage I/II female breast cancer patients 20 to 79 years of age, diagnosed between 1989 and 2005 and treated with adjuvant RT at our institution. Patients were included if they survived and did not have SM within 3 years of diagnosis. Standardized incidence ratios (SIR) with 95% confidence intervals (CI) were calculated to compare SM incidence to cancer incidence in the general sex- and age-matched populations. Secondary malignancy risks in patients treated with local RT (LRT) to the breast/chest wall were compared to those in patients treated with locoregional RT (LRRT) to the breast/chest wall and regional nodes, using multivariate regression analysis (MVA) to account for covariates. Results: The cohort included 12,836 patients with a median follow-up of 8.4 years. LRRT was used in 18% of patients. The SIR comparing patients treated with LRT to the general population was 1.29 (CI: 1.21-1.38). No statistically significant increased incidence of in-field malignancies (SIR, 1.04; CI: 0.87-1.23) and lung cancers (SIR, 1.06; CI: 0.88-1.26) was detected. The SIR comparing patients treated with LRRT to the general population was 1.39 (CI: 1.17-1.64). No statistically significant increased incidence of in-field malignancies (SIR, 1.26; CI: 0.77-1.94) and lung cancers (SIR, 1.27; CI: 0.76-1.98) was detected. On MVA comparing LRRT to LRT, the adjusted hazard ratio was 1.20 for in-field malignancies (CI: 0.68-2.16) and 1.26 for lung cancer (CI: 0.67-2.36). The excess attributable risk (EAR) to regional RT was 3.1 per 10,000 person years (CI: −8.7 to 9.9). Conclusions: No statistically significant increased risk of second malignancy was detected after LRRT relative to

  19. 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

  20. Computed Tomography–Guided Interstitial High-Dose-Rate Brachytherapy in Combination With Regional Positive Lymph Node Intensity-Modulated Radiation Therapy in Locally Advanced Peripheral Non–Small Cell Lung Cancer: A Phase 1 Clinical Trial

    SciTech Connect (OSTI)

    Xiang, Li; Zhang, Jian-wen; Lin, Sheng; Luo, Hui-Qun; Wen, Qing-Lian; He, Li-Jia; Shang, Chang-Ling; Ren, Pei-Rong; Yang, Hong-Ru; Pang, Hao-Wen; Yang, Bo; He, Huai-Lin; Chen, Yue; Wu, Jing-Bo

    2015-08-01

    Purpose: To assess the technical safety, adverse events, and efficacy of computed tomography (CT)-guided interstitial high-dose-rate (HDR) brachytherapy in combination with regional positive lymph node intensity modulated radiation therapy in patients with locally advanced peripheral non–small cell lung cancer (NSCLC). Methods and Materials: Twenty-six patients with histologically confirmed NSCLC were enrolled in a prospective, officially approved phase 1 trial. Primary tumors were treated with HDR brachytherapy. A single 30-Gy dose was delivered to the 90% isodose line of the gross lung tumor volume. A total dose of at least 70 Gy was administered to the 95% isodose line of the planning target volume of malignant lymph nodes using 6-MV X-rays. The patients received concurrent or sequential chemotherapy. We assessed treatment efficacy, adverse events, and radiation toxicity. Results: The median follow-up time was 28 months (range, 7-44 months). There were 3 cases of mild pneumothorax but no cases of hemothorax, dyspnea, or pyothorax after the procedure. Grade 3 or 4 acute hematologic toxicity was observed in 5 patients. During follow-up, mild fibrosis around the puncture point was observed on the CT scans of 2 patients, but both patients were asymptomatic. The overall response rates (complete and partial) for the primary mass and positive lymph nodes were 100% and 92.3%, respectively. The 1-year and 2-year overall survival (OS) rates were 90.9% and 67%, respectively, with a median OS of 22.5 months. Conclusion: Our findings suggest that HDR brachytherapy is safe and feasible for peripheral locally advanced NSCLC, justifying a phase 2 clinical trial.

  1. Multi-walled carbon nanotube-induced gene expression in the mouse lung: Association with lung pathology

    SciTech Connect (OSTI)

    Pacurari, M.; Qian, Y.; Porter, D.W.; Wolfarth, M.; Wan, Y.; Luo, D.; Ding, M.; Castranova, V.; Guo, N.L.

    2011-08-15

    Due to the fibrous shape and durability of multi-walled carbon nanotubes (MWCNT), concerns regarding their potential for producing environmental and human health risks, including carcinogenesis, have been raised. This study sought to investigate how previously identified lung cancer prognostic biomarkers and the related cancer signaling pathways are affected in the mouse lung following pharyngeal aspiration of well-dispersed MWCNT. A total of 63 identified lung cancer prognostic biomarker genes and major signaling biomarker genes were analyzed in mouse lungs (n = 80) exposed to 0, 10, 20, 40, or 80 {mu}g of MWCNT by pharyngeal aspiration at 7 and 56 days post-exposure using quantitative PCR assays. At 7 and 56 days post-exposure, a set of 7 genes and a set of 11 genes, respectively, showed differential expression in the lungs of mice exposed to MWCNT vs. the control group. Additionally, these significant genes could separate the control group from the treated group over the time series in a hierarchical gene clustering analysis. Furthermore, 4 genes from these two sets of significant genes, coiled-coil domain containing-99 (Ccdc99), muscle segment homeobox gene-2 (Msx2), nitric oxide synthase-2 (Nos2), and wingless-type inhibitory factor-1 (Wif1), showed significant mRNA expression perturbations at both time points. It was also found that the expression changes of these 4 overlapping genes at 7 days post-exposure were attenuated at 56 days post-exposure. Ingenuity Pathway Analysis (IPA) found that several carcinogenic-related signaling pathways and carcinogenesis itself were associated with both the 7 and 11 gene signatures. Taken together, this study identifies that MWCNT exposure affects a subset of lung cancer biomarkers in mouse lungs. - Research Highlights: > Multi-Walled Carbon Nanotubes affect lung cancer biomarkers in mouse lungs. > The results suggest potentially harmful effects of MWCNT exposure on human lungs. > The results could potentially be used for

  2. 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.

  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

  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. 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.

  6. 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.

  7. 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.

  8. Joshua DeLung

    Broader source: Energy.gov [DOE]

    Joshua DeLung is an Account Manager at ENC Marketing & Communications and the Executive Editor at Relatively Journalizing.

  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. Admin Chg 1 dated 9-1-09; Admin Chg 2 dated 12-22-09. Canceled by DOE O 205.1B.

  10. 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

  11. Phase 2 Study of Concurrent Cetuximab Plus Definitive Thoracic Radiation Therapy Followed by Consolidation Docetaxel Plus Cetuximab in Poor Prognosis or Elderly Patients With Locally Advanced Non-Small Cell Lung Cancer

    SciTech Connect (OSTI)

    Dilling, Thomas J.; Extermann, Martine; Kim, Jongphil; Thompson, Lora M.; Yue, Binglin; Stevens, Craig W.; Antonia, Scott; Gray, Jhanelle; Williams, Charles; Haura, Eric; Pinder-Schenck, Mary; Tanvetyanon, Tawee; Kim, Sungjune; Chiappori, Alberto

    2014-11-15

    Background: Recursive partitioning analysis has shown that Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) ≥2, male sex, and age ≥70 years are prognostic of poor outcome in locally advanced non-small cell lung cancer (LA-NSCLC) patients. Concurrent chemoradiation therapy (CRT) improves survival, but toxicity is a concern in this frail patient cohort. We therefore opened this trial of concurrent definitive thoracic radiation therapy (XRT) and cetuximab, followed by consolidation docetaxel plus cetuximab. Methods and Materials: Eligible patients had pathologically proven, unresectable LA-NSCLC (stage IIA-“dry” IIIB). They had ECOG PS 2 or weight loss ≥5% in 3 months or were aged ≥70 years. The primary objective was progression-free survival (PFS). Secondary objectives included overall survival (OS) and overall response rate (ORR). Results: From May 2008 to November 2010, a total of 32 patients were evaluated in our single-institution, institutional review board–approved prospective clinical trial. Three patients were screen failures and 2 more withdrew consent before treatment, leaving 27 evaluable patients. One was removed because of poor therapy compliance, and 2 were taken off trial because of grade 3 cetuximab-related toxicities but were followed up under intent-to-treat analysis. The median follow-up and OS were 10.5 months. The median PFS was 7.5 months. The ORR was 59.3%. Eight early/sudden deaths were reported. Upon review, 6 patients developed severe pulmonary complications. Conclusions: Patients enrolled in this trial had improved OS compared with poor-PS historical controls (10.5 vs 6.4 months) and comparable OS to good-PS historical controls (10.5 vs 11.9 months) treated with XRT alone. However, pulmonary toxicity is a concern. Consolidative cetuximab/docetaxel, in conjunction with high-dose radiation therapy, is a putative cause.

  12. 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.

  13. 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.

  14. 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.

  15. 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

  16. Nuclear Incident Team | National Nuclear Security Administration...

    National Nuclear Security Administration (NNSA)

    Incident Team NNSA houses the Nuclear Incident Team (NIT), which is responsible for deploying assets at the request of coordinating agencies in response to a nuclear or ...

  17. ORISE: The Medical Aspects of Radiation Incidents

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

    The Medical Aspects of Radiation Incidents The Medical Aspects of Radiation Incidents provides the basic information needed for the medical management of victims of radiation ...

  18. 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 ...

  19. INCIDENT REPORTING: LEARNING FROM EXPERIENCE

    SciTech Connect (OSTI)

    Weiner, Steven C.; Kinzey, Bruce R.; Dean, Jesse D.; Davis, Patrick B.; Ruiz, Antonio

    2007-09-12

    Experience makes a superior teacher. Sharing the details surrounding safety events is one of the best ways to help prevent their recurrence elsewhere. This approach requires an open, non-punitive environment to achieve broad benefits. The Hydrogen Incident Reporting Tool (www.h2incidents.org) is intended to facilitate the sharing of lessons learned and other relevant information gained from actual experiences using and working with hydrogen and hydrogen systems. Its intended audience includes those involved in virtually any aspect of hydrogen technology, systems and use, with an emphasis towards energy and transportation applications. The database contains records of safety events both publicly available and/or voluntarily submitted. Typical records contain a general description of the occurrence, contributing factors, equipment involved, and some detailing of consequences and changes that have been subsequently implemented to prevent recurrence of similar events in the future. The voluntary and confidential nature and other characteristics surrounding the database mean that any analysis of apparent trends in its contents cannot be considered statistically valid for a universal population. A large portion of reported incidents have occurred in a laboratory setting due to the typical background of the reporting projects, for example. Yet some interesting trends are becoming apparent even at this early stage of the database’s existence and general lessons can already be taken away from these experiences. This paper discusses the database and a few trends that have already become apparent for the reported incidents. Anticipated future uses of this information are also described. This paper is intended to encourage wider participation and usage of the incidents reporting database and to promote the safety benefits offered by its contents.

  20. 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,

  1. Chapter_11_Incidents_of_Security_Concern

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

    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

  2. Tiny plastic lung mimics human pulmonary function

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

    Tiny plastic lung mimics human pulmonary function Tiny plastic lung mimics human pulmonary function Scientists are developing a miniature, tissue-engineered artificial lung that ...

  3. Nuclear Incident Team | National Nuclear Security Administration

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

    Apply for Our Jobs Our Jobs Working at NNSA Blog Home Nuclear Incident Team Nuclear Incident Team Fukushima: Five Years Later After the March 11, 2011, Japan earthquake, tsunami, ...

  4. NFAT5 promotes proliferation and migration of lung adenocarcinoma cells in part through regulating AQP5 expression

    SciTech Connect (OSTI)

    Guo, Kai; Jin, Faguang

    2015-09-25

    The osmoregulated transcription factor nuclear factor of activated T-cells 5(NFAT5), has been found to play important roles in the development of many kinds of human cancers, including breast cancer, colon carcinoma, renal cell carcinoma and melanoma. The aim of the present study was to determine whether NFAT5 is involved in the proliferation and migration of lung adenocarcinoma cells. We found that NFAT5 was upregulated in lung adenocarcinoma cells and knockdown of NFAT5 decreased proliferation and migration of the cells, accompanied by a significant reduction in the expression of AQP5. AQP5 was upregulated in lung adenocarcinoma cells and knockdown of AQP5 also inhibited proliferation and migration of the cells as knockdown of NFAT5 did. Moreover, overexpression of NFAT5 promoted proliferation and migration of lung adenocarcinoma cells, accompanied by a significant increase in the expression of AQP5. These results indicate that NFAT5 plays important roles in proliferation and migration of human lung adenocarcinoma cells through regulating AQP5 expression, providing a new therapeutic option for lung adenocarcinoma therapy. - Highlights: • NFAT5 expression is higher in lung adenocarcinoma cells compared with normal cells. • NFAT5 knockdown decreases proliferation and migration of lung adenocarcinoma cells. • Knockdown of NFAT5 reduces AQP5 expression in human lung adenocarcinoma cells. • Overexpression of NFAT5 promotes proliferation and migration of lung adenocarcinoma cells. • Overexpression of NFAT5 increases AQP5 expression in human lung adenocarcinoma cells.

  5. Lung pair phantom

    DOE Patents [OSTI]

    Olsen, Peter C.; Gordon, N. Ross; Simmons, Kevin L.

    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.

  6. 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.

  7. 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.

  8. 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

  9. 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 ...

  10. 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...

  11. 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

  12. 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.

  13. 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.

  14. 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.

  15. 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

  16. 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.

  17. 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.

  18. 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

  19. 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.

  20. 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

  1. 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.

  2. A common language for computer security incidents

    SciTech Connect (OSTI)

    John D. Howard; Thomas A Longstaff

    1998-10-01

    Much of the computer security information regularly gathered and disseminated by individuals and organizations cannot currently be combined or compared because a common language has yet to emerge in the field of computer security. A common language consists of terms and taxonomies (principles of classification) which enable the gathering, exchange and comparison of information. This paper presents the results of a project to develop such a common language for computer security incidents. This project results from cooperation between the Security and Networking Research Group at the Sandia National Laboratories, Livermore, CA, and the CERT{reg_sign} Coordination Center at Carnegie Mellon University, Pittsburgh, PA. This Common Language Project was not an effort to develop a comprehensive dictionary of terms used in the field of computer security. Instead, the authors developed a minimum set of high-level terms, along with a structure indicating their relationship (a taxonomy), which can be used to classify and understand computer security incident information. They hope these high-level terms and their structure will gain wide acceptance, be useful, and most importantly, enable the exchange and comparison of computer security incident information. They anticipate, however, that individuals and organizations will continue to use their own terms, which may be more specific both in meaning and use. They designed the common language to enable these lower-level terms to be classified within the common language structure.

  3. 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

  4. A new role of SNAI2 in postlactational involution of the mammary gland links it to luminal breast cancer development

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

    Castillo-Lluva, Sonia; Hontecillas-Prieto, Lourdes; Blanco-Gómez, Adrian; del Mar Sáez-Freire, María; García-Cenador, Begona; García-Criado, Javier; Pérez-Andrés, Martín; Orfao, Alberto; Cañamero, Marta; Mao, Jian-Hua; et al

    2015-06-22

    Breast cancer is a major cause of mortality in women. The transcription factor SNAI2 has been implicated in the pathogenesis of several types of cancer, including breast cancer of basal origin. Here we show that SNAI2 is also important in the development of breast cancer of luminal origin in MMTV-ErbB2 mice. SNAI2 deficiency leads to longer latency and fewer luminal tumors, both of these being characteristics of pretumoral origin. These effects were associated with reduced proliferation and a decreased ability to generate mammospheres in normal mammary glands. However, the capacity to metastasize was not modified. Under conditions of increased ERBB2more » oncogenic activity after pregnancy plus SNAI2 deficiency, both pretumoral defects-latency and tumor load-were compensated. However, the incidence of lung metastases was dramatically reduced. Furthermore, SNAI2 was required for proper postlactational involution of the breast. At 3 days post lactational involution, the mammary glands of Snai2-deficient mice exhibited lower levels of pSTAT3 and higher levels of pAKT1, resulting in decreased apoptosis. Abundant noninvoluted ducts were still present at 30 days post lactation, with a greater number of residual ERBB2+ cells. These results suggest that this defect in involution leads to an increase in the number of susceptible target cells for transformation, to the recovery of the capacity to generate mammospheres and to an increase in the number of tumors. In conclusion, our work demonstrates the participation of SNAI2 in the pathogenesis of luminal breast cancer, and reveals an unexpected connection between the processes of postlactational involution and breast tumorigenesis in Snai2-null mutant mice.« less

  5. A new role of SNAI2 in postlactational involution of the mammary gland links it to luminal breast cancer development

    SciTech Connect (OSTI)

    Castillo-Lluva, Sonia; Hontecillas-Prieto, Lourdes; Blanco-Gómez, Adrian; del Mar Sáez-Freire, María; García-Cenador, Begona; García-Criado, Javier; Pérez-Andrés, Martín; Orfao, Alberto; Cañamero, Marta; Mao, Jian-Hua; Gridley, Thomas; Castellanos-Martín, Andres; Pérez-Losada, Jesus

    2015-06-22

    Breast cancer is a major cause of mortality in women. The transcription factor SNAI2 has been implicated in the pathogenesis of several types of cancer, including breast cancer of basal origin. Here we show that SNAI2 is also important in the development of breast cancer of luminal origin in MMTV-ErbB2 mice. SNAI2 deficiency leads to longer latency and fewer luminal tumors, both of these being characteristics of pretumoral origin. These effects were associated with reduced proliferation and a decreased ability to generate mammospheres in normal mammary glands. However, the capacity to metastasize was not modified. Under conditions of increased ERBB2 oncogenic activity after pregnancy plus SNAI2 deficiency, both pretumoral defects-latency and tumor load-were compensated. However, the incidence of lung metastases was dramatically reduced. Furthermore, SNAI2 was required for proper postlactational involution of the breast. At 3 days post lactational involution, the mammary glands of Snai2-deficient mice exhibited lower levels of pSTAT3 and higher levels of pAKT1, resulting in decreased apoptosis. Abundant noninvoluted ducts were still present at 30 days post lactation, with a greater number of residual ERBB2+ cells. These results suggest that this defect in involution leads to an increase in the number of susceptible target cells for transformation, to the recovery of the capacity to generate mammospheres and to an increase in the number of tumors. In conclusion, our work demonstrates the participation of SNAI2 in the pathogenesis of luminal breast cancer, and reveals an unexpected connection between the processes of postlactational involution and breast tumorigenesis in Snai2-null mutant mice.

  6. 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

  7. 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.

  8. Carbon-initiated effluent tank overpressure incident

    SciTech Connect (OSTI)

    Sherman, R.E.; Crawford, K.C.; Cusick, T.M.; Csengery, L.V.

    1996-12-31

    This report provides, for information purposes, a description of an unusual event and the corrective actions undertaken by the Shell facility involved. Shell and the authors hope that this information will help personnel associated with other facilities understand a non-obvious failure mechanism and take action to prevent their experiencing similar incidents. While drawn from actual experience, the information provided should be considered illustrative. Each company should be considered illustrative. Each company should review their own facilities, materials or processes to determine the appropriate equipment and procedures for their own specific circumstances.

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

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

    Personnel Accountability for Non-COOP Incidents Personnel Accountability for Non-COOP Incidents This document establishes reporting requirements for non-COOP incidents. Personnel Accountability for Non-COOP Incidents (1.26 MB) 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 Fiscal Year 2013 Department of Energy Annual Occupational Safety and Health Report for

  10. Nuclear Incident Team | National Nuclear Security Administration | (NNSA)

    National Nuclear Security Administration (NNSA)

    Incident Team NNSA houses the Nuclear Incident Team (NIT), which is responsible for deploying assets at the request of coordinating agencies in response to a nuclear or radiological incident. The NIT's mission is to coordinate NNSA assets for deployment, continually monitor deployment activities, and provide situational awareness of activities to NNSA management. The NIT is staffed and fully operational within two hours of notification

  11. 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.

  12. Security incidents on the Internet, 1989--1995

    SciTech Connect (OSTI)

    Howard, J.D.

    1995-12-31

    This paper presents an analysis of trends in Internet security based on an investigation of 4,299 Internet security-related incidents reported to the CERT{reg_sign} Coordination Center (CERT{reg_sign}/CC) from 1989 through 1995. Prior to this research, knowledge of actual Internet security incidents was limited and primarily anecdotal. This research: (1) developed a taxonomy to classify Internet attacks and incidents, (2) organized, classified, and analyzed CERT{reg_sign}/CC incident records, (3) summarized the relative frequency of the use of tools and vulnerabilities, success in achieving access, and results of attacks, (4) estimated total Internet incident activity, (5) developed recommendations for Internet users and suppliers, and (6) developed recommendations for future research. With the exception of denial-of-service attacks, security incidents were found to be increasing at a rate less than Internet growth. Estimates showed that most, if not all, severe incidents were reported to the CERT{reg_sign}/CC, and that more than one out of three above average incidents (in terms of duration and number of sites) were reported. Estimates also indicated that a typical Internet site was involved in, at most, around one incident (of any kind) per year, and a typical Internet host in, at most, around one incident in 45 years. The probability of unauthorized privileged access was around an order of magnitude less likely. As a result, simple and reasonable security precautions should be sufficient for most Internet users.

  13. 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

  14. 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.

  15. 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

  16. Source term estimation during incident response to severe nuclear...

    Office of Scientific and Technical Information (OSTI)

    response to severe nuclear power plant accidents Citation Details In-Document Search Title: Source term estimation during incident response to severe nuclear power plant ...

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

    Office of Environmental Management (EM)

    Security Plan - Chapter 11, Incidents of Security Concern Whenever a failure to properly protect classified matter is detected, it must be formally reported and investigated. ...

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

    National Nuclear Security Administration (NNSA)

    NNSA NuclearRadiological Incident Response December 01, 2008 The National Nuclear Security Administration (NNSA) has over 60 years of nuclear weapons experience in responding to ...

  19. 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...

  20. 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...

  1. Laser Incident Lessons Learned and Action List (Technical Report...

    Office of Scientific and Technical Information (OSTI)

    Laser Incident Lessons Learned and Action List Citation Details In-Document Search Title: ... output into two work areas in which qualified operators conduct research experiments. ...

  2. Laser Incident Lessons Learned and Action List (Technical Report...

    Office of Scientific and Technical Information (OSTI)

    Title: Laser Incident Lessons Learned and Action List You are accessing a document from ... output into two work areas in which qualified operators conduct research experiments. ...

  3. 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.

  4. 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. ...

  5. Incident Management Preparedness and Coordination Toolkit

    SciTech Connect (OSTI)

    Koch, Daniel B.

    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 to 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

  6. 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

  7. Understanding the origins of human cancer

    SciTech Connect (OSTI)

    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 the 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).

  8. 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

  9. 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.

  10. 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

  11. 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.

  12. Boron-Nitride Nanotubes Show Potential in Cancer Treatment | Jefferson Lab

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

    Boron-Nitride Nanotubes Show Potential in Cancer Treatment Boron-Nitride Nanotubes Show Potential in Cancer Treatment NEWPORT NEWS, VA, April 26 - A new study has shown that adding boron-nitride nanotubes to the surface of cancer cells can double the effectiveness of Irreversible Electroporation, a minimally invasive treatment for soft tissue tumors in the liver, lung, prostate, head and neck, kidney and pancreas. Although this research is in the very early stages, it could one day lead to

  13. 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.

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

    SciTech Connect (OSTI)

    Chung, Christine S.; Yock, Torunn I.; Nelson, Kerrie; Xu, Yang; Keating, Nancy L.; Tarbell, Nancy J.

    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

  15. 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.

  16. 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).

  17. Six Degrees-of-Freedom Prostate and Lung Tumor Motion Measurements Using Kilovoltage Intrafraction Monitoring

    SciTech Connect (OSTI)

    Huang, Chen-Yu; Tehrani, Joubin Nasehi; Ng, Jin Aun; Booth, Jeremy; Keall, Paul

    2015-02-01

    Purpose: Tumor positional uncertainty has been identified as a major issue that deteriorates the efficacy of radiation therapy. Tumor rotational movement, which is not well understood, can result in significant geometric and dosimetric inaccuracies. The objective of this study was to measure 6 degrees-of-freedom (6 DoF) prostate and lung tumor motion, focusing on the more novel rotation, using kilovoltage intrafraction monitoring (KIM). Methods and Materials: Continuous kilovoltage (kV) projections of tumors with gold fiducial markers were acquired during radiation therapy for 267 fractions from 10 prostate cancer patients and immediately before or after radiation therapy for 50 fractions from 3 lung cancer patients. The 6 DoF motion measurements were determined from the individual 3-dimensional (3D) marker positions, after using methods to reject spurious and smooth noisy data, using an iterative closest point algorithm. Results: There were large variations in the magnitude of the tumor rotation among different fractions and patients. Various rotational patterns were observed. The average prostate rotation angles around the left-right (LR), superior-inferior (SI), and anterior-posterior (AP) axes were 1.0 ± 5.0°, 0.6 ± 3.3°, and 0.3 ± 2.0°, respectively. For 35% of the time, the prostate rotated more than 5° about the LR axis, indicating the need for intrafractional adaptation during radiation delivery. For lung patients, the average LR, SI, and AP rotation angles were 0.8 ± 4.2°, −0.8 ± 4.5°, and 1.7 ± 3.1°, respectively. For about 30% of the time, the lung tumors rotated more than 5° around the SI axis. Respiration-induced rotation was detected in 2 of the 3 lung patients. Conclusions: The prostate and lung tumors were found to undergo rotations of more than 5° for about a third of the time. The lung tumor data represent the first 6 DoF tumor motion measured by kV images. The 6 DoF KIM method can enable rotational and translational

  18. Imaging of occupational and environmental lung diseases

    SciTech Connect (OSTI)

    Akira, M.

    2008-03-15

    The chest radiograph is the basic tool for identifying occupational and environmental lung diseases; however, its sensitivity and specificity for the diagnosis of occupational and environmental lung diseases are low. High-resolution CT is the optimal method of recognizing parenchymal abnormalities in occupational and environmental disease. With the exception of pleural plaques, the CT findings of occupational and environmental lung diseases are nonspecific. Therefore, correlation of imaging features with history of exposure, other clinical features, and sometimes pathology is needed for the diagnosis of pneumoconiosis.

  19. 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 CenterTraining Site (REACTS) ...

  20. The Department's Cyber Security Incident Management Program, IG-0787 |

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

    Department of Energy Cyber Security Incident Management Program, IG-0787 The Department's Cyber Security Incident Management Program, IG-0787 The Department of Energy operates numerous interconnected computer networks and systems to help accon~plishit s strategic missions in the areas of energy, defense, science, and the environment. These systems are frequently subjected to sophisticated cyber attacks that could potentially affect the Department's ability to carry out its mission. During

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

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

    Administration | (NNSA) December 01, 2008 The National Nuclear Security Administration (NNSA) has over 60 years of nuclear weapons experience in responding to nuclear and radiological accidents and incidents. NNSA provides technical support to the Departments of Homeland Security, Justice, State, and Defense for nuclear terrorism events and domestic nuclear weapon accidents and incidents. The NNSA emergency response assets also provide support to nuclear site and facility accidents and

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

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

    Administration | (NNSA) January 01, 2009 The National Nuclear Security Administration (NNSA) has more than 60 years of nuclear weapons experience in responding to nuclear and radiological accidents and incidents. NNSA provides technical support to the Departments of Homeland Security, Justice, State, and Defense for nuclear terrorism events and domestic nuclear weapon accidents and incidents. The NNSA emergency response assets also provide support to nuclear site and facility accidents and

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

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

    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

  4. 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.

  5. Blockade of lysophosphatidic acid receptors LPAR1/3 ameliorates lung fibrosis induced by irradiation

    SciTech Connect (OSTI)

    Gan, Lu; Xue, Jian-Xin; Laboratory of Stem Cell Biology, West China Hospital, Sichuan University, Chengdu ; Li, Xin; Liu, De-Song; Ge, Yan; Ni, Pei-Yan; Deng, Lin; Lu, You; Department of Thoracic Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu ; Jiang, Wei; Molecular Medicine Research Center, West China Hospital, Sichuan University, Chengdu

    2011-05-27

    Highlights: {yields} Lysophosphatidic acid (LPA) levels and its receptors LPAR1/3 transcripts were elevated during the development of radiation-induced lung fibrosis. {yields} Lung fibrosis was obviously alleviated in mice treated with the dual LPAR1/3 antagonist, VPC12249. {yields} VPC12249 administration effectively inhibited radiation-induced fibroblast accumulation in vivo, and suppressed LPA-induced fibroblast proliferation in vitro. {yields} LPA-LPAR1/3 signaling regulated TGF{beta}1 and CTGF expressions in radiation-challenged lungs, but only influenced CTGF expression in cultured fibroblasts. {yields} LPA-LPAR1/3 signaling induced fibroblast proliferation through a CTGF-dependent pathway, rather than through TGF{beta}1 activation. -- Abstract: Lung fibrosis is a common and serious complication of radiation therapy for lung cancer, for which there are no efficient treatments. Emerging evidence indicates that lysophosphatidic acid (LPA) and its receptors (LPARs) are involved in the pathogenesis of fibrosis. Here, we reported that thoracic radiation with 16 Gy in mice induced development of radiation lung fibrosis (RLF) accompanied by obvious increases in LPA release and LPAR1 and LPAR3 (LPAR1/3) transcripts. RLF was significantly alleviated in mice treated with the dual LPAR1/3 antagonist, VPC12249. VPC12249 administration effectively prolonged animal survival, restored lung structure, inhibited fibroblast accumulation and reduced collagen deposition. Moreover, profibrotic cytokines in radiation-challenged lungs obviously decreased following administration of VPC12249, including transforming growth factor {beta}1 (TGF{beta}1) and connective tissue growth factor (CTGF). In vitro, LPA induced both fibroblast proliferation and CTGF expression in a dose-dependent manner, and both were suppressed by blockade of LPAR1/3. The pro-proliferative activity of LPA on fibroblasts was inhibited by siRNA directed against CTGF. Together, our data suggest that the LPA-LPAR1

  6. Determination of lung segments in computed tomography images using the Euclidean distance to the pulmonary artery

    SciTech Connect (OSTI)

    Stoecker, Christina; Moltz, Jan H.; Lassen, Bianca; Kuhnigk, Jan-Martin; Krass, Stefan; Welter, Stefan; Peitgen, Heinz-Otto

    2013-09-15

    Purpose: Computed tomography (CT) imaging is the modality of choice for lung cancer diagnostics. With the increasing number of lung interventions on sublobar level in recent years, determining and visualizing pulmonary segments in CT images and, in oncological cases, reliable segment-related information about the location of tumors has become increasingly desirable. Computer-assisted identification of lung segments in CT images is subject of this work.Methods: The authors present a new interactive approach for the segmentation of lung segments that uses the Euclidean distance of each point in the lung to the segmental branches of the pulmonary artery. The aim is to analyze the potential of the method. Detailed manual pulmonary artery segmentations are used to achieve the best possible segment approximation results. A detailed description of the method and its evaluation on 11 CT scans from clinical routine are given.Results: An accuracy of 2–3 mm is measured for the segment boundaries computed by the pulmonary artery-based method. On average, maximum deviations of 8 mm are observed. 135 intersegmental pulmonary veins detected in the 11 test CT scans serve as reference data. Furthermore, a comparison of the presented pulmonary artery-based approach to a similar approach that uses the Euclidean distance to the segmental branches of the bronchial tree is presented. It shows a significantly higher accuracy for the pulmonary artery-based approach in lung regions at least 30 mm distal to the lung hilum.Conclusions: A pulmonary artery-based determination of lung segments in CT images is promising. In the tests, the pulmonary artery-based determination has been shown to be superior to the bronchial tree-based determination. The suitability of the segment approximation method for application in the planning of segment resections in clinical practice has already been verified in experimental cases. However, automation of the method accompanied by an evaluation on a larger

  7. 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

  8. 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.

  9. 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.

  10. TH-E-BRF-07: Raman Spectroscopy for Radiation Treatment Response Assessment in a Lung Metastases Mouse Model

    SciTech Connect (OSTI)

    Devpura, S; Barton, K; Brown, S; Siddiqui, F; Chetty, I; Sethi, S; Klein, M

    2014-06-15

    Purpose: Raman spectroscopy is an optical spectroscopic method used to probe chemical information about a target tissue. Our goal was to investigate whether Raman spectroscopy is able to distinguish lung tumors from normal lung tissue and whether this technique can identify the molecular changes induced by radiation. Methods: 4T1 mouse breast cancer cells were implanted subcutaneously into the flanks of 6 Balb/C female mice. Four additional mice were used as “normal lung” controls. After 14 days, 3 mice bearing tumors received 6Gy to the left lung with 6MV photons and the other three were treated as “unirradiated tumor” controls. At a 24-hour time point, lungs were excised and the specimens were sectioned using a cryostat; alternating sections were either stained with hematoxylin and eosin (H and E) for evaluation by a pathologist or unstained for Raman measurements. 240 total Raman spectra were collected; 84 from normal lung controls; 63 from unirradiated tumors and 64 from tumors irradiated with 6Gy in a single fraction. Raman spectra were also collected from normal lung tissues of mice with unirradiated tumors. Principal component analysis (PCA) and discriminant function analysis (DFA) were performed to analyze the data. Results: Raman bands assignable to DNA/RNA showed prominent contributions in tumor tissues while Raman bands associated with hemoglobin showed strong contributions in normal lung tissue. PCA/DFA analysis identified normal lung tissue and tumor with 100% and 98.4% accuracy, respectively, relative to pathologic scoring. Additionally, normal lung tissues from unirradiated mice bearing tumors were classified as normal with 100% accuracy. In a model consisting of unirradiated and irradiated tumors identification accuracy was 79.4% and 93.8% respectively, relative to pathologic assessment. Conclusion: Initial results demonstrate the promise for Raman spectroscopy in the diagnosis normal vs. lung metastases as well as the assessment of