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Title: The Impact of Induction Chemotherapy and the Associated Tumor Response on Subsequent Radiation-Related Changes in Lung Function and Tumor Response

Abstract

Purpose: To assess the impact of induction chemotherapy, and associated tumor shrinkage, on the subsequent radiation-related changes in pulmonary function and tumor response. Methods and Materials: As part of a prospective institutional review board-approved study, 91 evaluable patients treated definitively with thoracic radiation therapy (RT) for unresectable lung cancer were analyzed. The rates of RT-associated pulmonary toxicity and tumor response were compared in the patients with and without pre-RT chemotherapy. In the patients receiving induction chemotherapy, the rates of RT-associated pulmonary toxicity and tumor response were compared in the patients with and without a response (modified Response Evaluation Criteria in Solid Tumor criteria) to the pre-RT chemotherapy. Comparisons of the rates of improvements in pulmonary function tests (PFTs) post-RT, dyspnea requiring steroids, and percent declines in PFTs post-RT were compared in patient subgroups using Fisher's exact test, analysis of variance, and linear or logistic regression. Results: The use of pre-RT chemotherapy appears to increase the rate of radiation-induced pneumonitis (p = 0.009-0.07), but has no consistent impact on changes in PFTs. The degree of induction chemotherapy-associated tumor shrinkage is not associated with the rate of subsequent RT-associated pulmonary toxicity. The degree of tumor response to chemotherapy is not related tomore » the degree of tumor response to RT. Conclusions: Additional study is needed to better clarify the impact of chemotherapy on radiation-associated disfunction.« less

Authors:
 [1];  [2];  [1];  [3];  [1];  [4];  [1];  [1];  [1];  [5];  [6];  [7]
  1. Department of Radiation Oncology, Duke University Medical Center, Durham, NC (United States)
  2. (China)
  3. (Turkey)
  4. Department of Medicine, Duke University Medical Center, Durham, NC (United States)
  5. Department of Pulmonary, Allergy, and Critical Care, Duke University Medical Center, Durham, NC (United States)
  6. Department of Biostatistics, Duke University Medical Center, Durham, NC (United States)
  7. Department of Radiation Oncology, Duke University Medical Center, Durham, NC (United States). E-mail: lawrence.marks@duke.edu
Publication Date:
OSTI Identifier:
20951578
Resource Type:
Journal Article
Resource Relation:
Journal Name: International Journal of Radiation Oncology, Biology and Physics; Journal Volume: 67; Journal Issue: 5; Other Information: DOI: 10.1016/j.ijrobp.2006.11.003; PII: S0360-3016(06)03370-0; Copyright (c) 2007 Elsevier Science B.V., Amsterdam, Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE; CARCINOMAS; CHEMOTHERAPY; LUNGS; PATIENTS; PNEUMONITIS; RADIOTHERAPY; REVIEWS; SHRINKAGE; STEROIDS; TOXICITY

Citation Formats

Mao Jingfang, Department of Radiation Oncology, Cancer Hospital, Fudan University, Shanghai, Kocak, Zafer, Department of Radiation Oncology, Trakya University Hospital, Edirne, Zhou Sumin, Garst, Jennifer, Evans, Elizabeth S., Zhang Junan, Larrier, Nicole A., Hollis, Donna R., Folz, Rodney J., and Marks, Lawrence B.. The Impact of Induction Chemotherapy and the Associated Tumor Response on Subsequent Radiation-Related Changes in Lung Function and Tumor Response. United States: N. p., 2007. Web.
Mao Jingfang, Department of Radiation Oncology, Cancer Hospital, Fudan University, Shanghai, Kocak, Zafer, Department of Radiation Oncology, Trakya University Hospital, Edirne, Zhou Sumin, Garst, Jennifer, Evans, Elizabeth S., Zhang Junan, Larrier, Nicole A., Hollis, Donna R., Folz, Rodney J., & Marks, Lawrence B.. The Impact of Induction Chemotherapy and the Associated Tumor Response on Subsequent Radiation-Related Changes in Lung Function and Tumor Response. United States.
Mao Jingfang, Department of Radiation Oncology, Cancer Hospital, Fudan University, Shanghai, Kocak, Zafer, Department of Radiation Oncology, Trakya University Hospital, Edirne, Zhou Sumin, Garst, Jennifer, Evans, Elizabeth S., Zhang Junan, Larrier, Nicole A., Hollis, Donna R., Folz, Rodney J., and Marks, Lawrence B.. Sun . "The Impact of Induction Chemotherapy and the Associated Tumor Response on Subsequent Radiation-Related Changes in Lung Function and Tumor Response". United States. doi:.
@article{osti_20951578,
title = {The Impact of Induction Chemotherapy and the Associated Tumor Response on Subsequent Radiation-Related Changes in Lung Function and Tumor Response},
author = {Mao Jingfang and Department of Radiation Oncology, Cancer Hospital, Fudan University, Shanghai and Kocak, Zafer and Department of Radiation Oncology, Trakya University Hospital, Edirne and Zhou Sumin and Garst, Jennifer and Evans, Elizabeth S. and Zhang Junan and Larrier, Nicole A. and Hollis, Donna R. and Folz, Rodney J. and Marks, Lawrence B.},
abstractNote = {Purpose: To assess the impact of induction chemotherapy, and associated tumor shrinkage, on the subsequent radiation-related changes in pulmonary function and tumor response. Methods and Materials: As part of a prospective institutional review board-approved study, 91 evaluable patients treated definitively with thoracic radiation therapy (RT) for unresectable lung cancer were analyzed. The rates of RT-associated pulmonary toxicity and tumor response were compared in the patients with and without pre-RT chemotherapy. In the patients receiving induction chemotherapy, the rates of RT-associated pulmonary toxicity and tumor response were compared in the patients with and without a response (modified Response Evaluation Criteria in Solid Tumor criteria) to the pre-RT chemotherapy. Comparisons of the rates of improvements in pulmonary function tests (PFTs) post-RT, dyspnea requiring steroids, and percent declines in PFTs post-RT were compared in patient subgroups using Fisher's exact test, analysis of variance, and linear or logistic regression. Results: The use of pre-RT chemotherapy appears to increase the rate of radiation-induced pneumonitis (p = 0.009-0.07), but has no consistent impact on changes in PFTs. The degree of induction chemotherapy-associated tumor shrinkage is not associated with the rate of subsequent RT-associated pulmonary toxicity. The degree of tumor response to chemotherapy is not related to the degree of tumor response to RT. Conclusions: Additional study is needed to better clarify the impact of chemotherapy on radiation-associated disfunction.},
doi = {},
journal = {International Journal of Radiation Oncology, Biology and Physics},
number = 5,
volume = 67,
place = {United States},
year = {Sun Apr 01 00:00:00 EDT 2007},
month = {Sun Apr 01 00:00:00 EDT 2007}
}
  • Purpose: To investigate the roles of radiation therapy and chemotherapy in the occurrence of subsequent leukemia after childhood cancer. Methods and Materials: We analyzed data from a case-control study with 35 cases and 140 controls. The active bone marrow (ABM) was segmented into 19 compartments, and the radiation dose was estimated in each. The chemotherapy drug doses were also estimated to enable adjustments. Models capable of accounting for radiation dose heterogeneity were implemented for analysis. Results: Univariate analysis showed a significant trend in the increase of secondary leukemia risk with radiation dose, after accounting for dose heterogeneity (P=.046). This trendmore » became nonsignificant after adjustment for doses of epipodophyllotoxins, alkylating agents, and platinum compounds and the first cancer on multivariate analysis (P=.388). The role of the radiation dose appeared to be dwarfed, mostly by the alkylating agents (odds ratio 6.9, 95% confidence interval 1.9-25.0). Among the patients who have received >16 Gy to the ABM, the radiogenic risk of secondary leukemia was about 4 times greater in the subgroup with no alkylating agents than in the subgroup receiving ≥10 g/m{sup 2}. Conclusions: Notwithstanding the limitations resulting from the size of our study population and the quite systematic co-treatment with chemotherapy, the use of detailed information on the radiation dose distribution to ABM enabled consideration of the role of radiation therapy in secondary leukemia induction after childhood cancer.« less
  • Purpose: To investigate whether changes in the volume transfer coefficient (K{sup trans}) in a growing tumor could be used as a surrogate marker for predicting tumor responses to radiation therapy (RT) and chemotherapy (CT). Methods and Materials: Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) was consecutively performed on tumor-bearing mice, and temporal and spatial changes of K{sup trans} values were measured along with tumor growth. Tumor responses to RT and CT were studied before and after observed changes in K{sup trans} values with time. Results: Dynamic changes with an initial increase and subsequent decline in K{sup trans} values were found tomore » be associated with tumor growth. When each tumor was divided into core and peripheral regions, the K{sup trans} decline was greater in core, although neither vascular structure or necrosis could be linked to this spatial difference. Tumor responses to RT were worse if applied after the decline of K{sup trans}, and there was less drug distribution and cell death in the tumor core after CT. Conclusion: The K{sup trans} value in growing tumors, reflecting the changes of tumor microenvironment and vascular function, is strongly associated with tumor responses to RT and CT and could be a potential surrogate marker for predicting the tumor response to these treatments.« less
  • Purpose: Clinical and magnetic resonance imaging (MRI) characteristics at baseline and following chemoradiation therapy (CRT) most strongly associated with histopathologic response were investigated and survival outcomes evaluated in accordance with imaging and pathological response. Methods and Materials: Responders were defined as mrT3c/d-4 downstaged to ypT0-2 on pathology or low at risk mrT2 downstaged to ypT1 or T0. Multivariate logistic regression of baseline and posttreatment MRI: T, N, extramural venous invasion (EMVI), circumferential resection margin, craniocaudal length <5 cm, and MRI tumor height ≤5 cm were used to identify independent predictor(s) for response. An association between induction chemotherapy and EMVI statusmore » was analyzed. Survival outcomes for pathologic and MRI responders and nonresponders were analyzed. Results: Two hundred eighty-one patients were eligible; 114 (41%) patients were pathology responders. Baseline MRI negative EMVI (odds ratio 2.94, P=.007), tumor height ≤5 cm (OR 1.96, P=.02), and mrEMVI status change (positive to negative) following CRT (OR 3.09, P<.001) were the only predictors for response. There was a strong association detected between induction chemotherapy and ymrEMVI status change after CRT (OR 9.0, P<.003). ymrT0-2 gave a positive predictive value of 80% and OR of 9.1 for ypT0-2. ymrN stage accuracy of ypN stage was 75%. Three-year disease-free survival for pathology and MRI responders were similar at 80% and 79% and significantly better than poor responders. Conclusions: Tumor height and mrEMVI status are more important than baseline size and stage of the tumor as predictors of response to CRT. Both MRI- and pathologic-defined responders have significantly improved survival. “Good response” to CRT in locally advanced rectal cancer with ypT0-2 carries significantly better 3-year overall survival and disease-free survival. Use of induction chemotherapy for improving mrEMVI status and knowledge of MRI predictive factors could be taken into account in the pursuit of individualized neoadjuvant treatments for patients with rectal cancer.« less
  • A two-institution Phase II Pilot Study for the Eastern Cooperative Oncology Group (ECOG) used standard induction chemotherapy (cyclophosphamide and CCNU) followed by consolidation radiation therapy (RT) (600 rad of upper half-body irradiation plus 2000 rad in one week of localized chest irradiation) followed by maintenance chemotherapy in patients with extensive small cell bronchogenic carcinoma (SCBC). Nineteen patients were entered and 9 (47%) had partial responses (PR) after induction chemotherapy. No complete responses (CR) were seen. The 10 patients whose disease progressed were ineligible for consolidation RT and died with a short median survival time (MST) of 15 weeks. Of themore » 9 patients who were consolidated, 7 (78%) had complete responses in the chest; five (63%) became overall complete responders. The MST of all consolidated responders was 44 weeks. At this writing, two of the 5 patients who achieved CR after RT consolidation were alive without disease for more than one year; another patient was alive with disease for almost one year. A control group consisting of patients with extensive SCBC was used for comparison; these patients were treated by the two participating institutions in an earlier ECOG protocol with the same chemotherapy regimen but without RT consolidation.« less
  • Purpose: To quantify the impact that changes in tumor volume after induction chemotherapy have on radiotherapy treatment planning for locally advanced non-small-cell lung cancer. Methods and Materials: An analysis of coregistered pre- and postchemotherapy tumor volumes in a Phase II study of induction chemotherapy delivered before radical radiotherapy. Results: Using the Response Evaluation Criteria In Solid Tumors measurement, 35% of patients had a partial response and 62% had stable disease after chemotherapy. Conversely, volumetric decreases in tumor size were seen in 95% of patients. Mean decreases in gross tumor volume and planning target volume were 37% and 26%, respectively. Usingmore » the smaller postchemotherapy tumor volume to plan radiotherapy treatment leads to a mean decrease in volume of lung receiving 20 Gy or greater of 3% (p < 0.005). Targeting the postchemotherapy volume also results in the delivery of a significant, although inhomogeneous, incidental dose of radiation to the rind of tissue formed around the shrinking tumor. Disease shrinkage is anisotropic, with greater displacements observed along anterior, posterior, and lateral margins. After chemotherapy, there is measurable blurring of the tumor's radiologic edge. Conclusions: Modest decreases in tumor volume that are not reflected by the Response Evaluation Criteria In Solid Tumors measurement occur in most patients. Although targeting the postchemotherapy tumor may decrease lung toxicity, the magnitude of the benefit is small. Because this strategy runs the risk of increasing the marginal recurrence rate, it should be used with caution. Quantification of tumor shrinkage and margin blurring permits more accurate reconstruction of the prechemotherapy target volume.« less