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

Abstract

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), medianmore » 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 months). There was an increase in grades III to V lung toxicity associated with ID (13.0% vs 4.9%, respectively). Conclusions: No significant overall survival benefits were found with intermediate DE; however, more grade III or greater lung toxicity was observed. The separation of survival curves after 15 months of follow-up suggests that a small overall survival improvement associated with intermediate DE cannot be excluded.« less

Authors:
 [1];  [2];  [3];  [4];  [2];  [5];  [6];  [7];  [8];  [9];  [10];  [11];  [12];  [1];  [13];  [1]
  1. London Health Sciences Centre, London, Ontario (Canada)
  2. MAASTRO Clinic, Maastricht (Netherlands)
  3. VU University Medical Center, Amsterdam (Netherlands)
  4. Hyogo Cancer Center, Akashi (Japan)
  5. Universidad de Navarra, Pamplona (Spain)
  6. National Cancer Center, Goyang-si, Gy eonggi (Korea, Republic of)
  7. University of North Carolina, Chapel Hill, North Carolina (United States)
  8. University of Washington, Seattle, Washington (United States)
  9. Karolinska University Hospital, Stockholm (Sweden)
  10. Campus Bio-Medico University, Rome (Italy)
  11. Ghent University, Ghent (Belgium)
  12. Universidad Pompeu Fabra, Barcelona (Spain)
  13. Washington University School of Medicine, St. Louis, Missouri (United States)
Publication Date:
OSTI Identifier:
22423848
Resource Type:
Journal Article
Resource Relation:
Journal Name: International Journal of Radiation Oncology, Biology and Physics; Journal Volume: 91; Journal Issue: 1; Other Information: Copyright (c) 2015 Elsevier Science B.V., Amsterdam, The 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; CHEMOTHERAPY; FRACTIONATED IRRADIATION; LUNGS; MATERIALS; NEOPLASMS; PATIENTS; PLATINUM; RADIATION DOSES; RADIOTHERAPY; REGRESSION ANALYSIS; SURVIVAL CURVES; TOXICITY

Citation Formats

Rodrigues, George, E-mail: george.rodrigues@lhsc.on.ca, 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., and Palma, David A. Is Intermediate Radiation Dose Escalation With Concurrent Chemotherapy for Stage III Non–Small-Cell Lung Cancer Beneficial? A Multi-Institutional Propensity Score Matched Analysis. United States: N. p., 2015. Web. doi:10.1016/J.IJROBP.2014.09.033.
Rodrigues, George, E-mail: george.rodrigues@lhsc.on.ca, 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. Is Intermediate Radiation Dose Escalation With Concurrent Chemotherapy for Stage III Non–Small-Cell Lung Cancer Beneficial? A Multi-Institutional Propensity Score Matched Analysis. United States. doi:10.1016/J.IJROBP.2014.09.033.
Rodrigues, George, E-mail: george.rodrigues@lhsc.on.ca, 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., and Palma, David A. Thu . "Is Intermediate Radiation Dose Escalation With Concurrent Chemotherapy for Stage III Non–Small-Cell Lung Cancer Beneficial? A Multi-Institutional Propensity Score Matched Analysis". United States. doi:10.1016/J.IJROBP.2014.09.033.
@article{osti_22423848,
title = {Is Intermediate Radiation Dose Escalation With Concurrent Chemotherapy for Stage III Non–Small-Cell Lung Cancer Beneficial? A Multi-Institutional Propensity Score Matched Analysis},
author = {Rodrigues, George, E-mail: george.rodrigues@lhsc.on.ca and Oberije, Cary and Senan, Suresh and Tsujino, Kayoko and Wiersma, Terry and Moreno-Jimenez, Marta and Kim, Tae Hyun and Marks, Lawrence B. and Rengan, Ramesh and De Petris, Luigi and Ramella, Sara and DeRuyck, Kim and De Dios, Núria Rodriguez and Warner, Andrew and Bradley, Jeffrey D. and Palma, David A.},
abstractNote = {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 months). There was an increase in grades III to V lung toxicity associated with ID (13.0% vs 4.9%, respectively). Conclusions: No significant overall survival benefits were found with intermediate DE; however, more grade III or greater lung toxicity was observed. The separation of survival curves after 15 months of follow-up suggests that a small overall survival improvement associated with intermediate DE cannot be excluded.},
doi = {10.1016/J.IJROBP.2014.09.033},
journal = {International Journal of Radiation Oncology, Biology and Physics},
number = 1,
volume = 91,
place = {United States},
year = {Thu Jan 01 00:00:00 EST 2015},
month = {Thu Jan 01 00:00:00 EST 2015}
}