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Title: Predicting Esophagitis After Chemoradiation Therapy for Non-Small Cell Lung Cancer: An Individual Patient Data Meta-Analysis

Purpose: Concurrent chemoradiation therapy (CCRT) improves survival compared with sequential treatment for locally advanced non-small cell lung cancer, but it increases toxicity, particularly radiation esophagitis (RE). Validated predictors of RE for clinical use are lacking. We performed an individual-patient-data meta-analysis to determine factors predictive of clinically significant RE. Methods and Materials: After a systematic review of the literature, data were obtained on 1082 patients who underwent CCRT, including patients from Europe, North America, Asia, and Australia. Patients were randomly divided into training and validation sets (2/3 vs 1/3 of patients). Factors predictive of RE (grade ≥2 and grade ≥3) were assessed using logistic modeling, with the concordance statistic (c statistic) used to evaluate the performance of each model. Results: The median radiation therapy dose delivered was 65 Gy, and the median follow-up time was 2.1 years. Most patients (91%) received platinum-containing CCRT regimens. The development of RE was common, scored as grade 2 in 348 patients (32.2%), grade 3 in 185 (17.1%), and grade 4 in 10 (0.9%). There were no RE-related deaths. On univariable analysis using the training set, several baseline factors were statistically predictive of RE (P<.05), but only dosimetric factors had good discrimination scores (c > .60).more » On multivariable analysis, the esophageal volume receiving ≥60 Gy (V60) alone emerged as the best predictor of grade ≥2 and grade ≥3 RE, with good calibration and discrimination. Recursive partitioning identified 3 risk groups: low (V60 <0.07%), intermediate (V60 0.07% to 16.99%), and high (V60 ≥17%). With use of the validation set, the predictive model performed inferiorly for the grade ≥2 endpoint (c = .58) but performed well for the grade ≥3 endpoint (c = .66). Conclusions: Clinically significant RE is common, but life-threatening complications occur in <1% of patients. Although several factors are statistically predictive of RE, the V60 alone provides the best predictive ability. Efforts to reduce the V60 should be prioritized, with further research needed to identify and validate new predictive factors.« less
 [1] ;  [2] ;  [3] ;  [4] ;  [5] ;  [6] ;  [7] ;  [8] ;  [9] ;  [10] ;  [11] ;  [12] ;  [13] ;  [14] ;
  1. Department of Radiation Oncology, London Regional Cancer Program, London, Ontario (Canada)
  2. Department of Radiation Oncology, VU University Medical Center, Amsterdam (Netherlands)
  3. Department of Radiation Oncology (MAASTRO Clinic), GROW – School for Oncology and Developmental Biology, Maastricht University Medical Centre, Maastricht (Netherlands)
  4. Department of Radiation Oncology, The Netherlands Cancer Institute – Antoni van Leeuwenhoek Hospital, Amsterdam (Netherlands)
  5. Department of Radiation Oncology, Parc de Salut Mar, Barcelona, Universidad Pompeu Fabra, Barcelona (Spain)
  6. Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri (United States)
  7. Department of Radiation Oncology, Indiana University School of Medicine, Indianapolis, Indiana (United States)
  8. Department of Oncology, Radiation Oncology Division, Clínica Universidad de Navarra, University of Navarra, Pamplona (Spain)
  9. Center for Proton Therapy, Research Institute and Hospital, National Cancer Center, Goyang, Gyeonggi (Korea, Republic of)
  10. Division of Radiation Oncology, Campus Bio-Medico University, Rome (Italy)
  11. Radiation Therapy Services, Peter MacCallum Cancer Centre, Melbourne, Australia and Department of Medical Imaging and Radiation Sciences, Faculty of Medicine, Nursing and Health Sciences, Monash University (Australia)
  12. Department of Radiation Oncology, University of Pennsylvania, Philadelphia, Pennsylvania (United States)
  13. Department of Radiation Oncology, University of North Carolina, Chapel Hill, North Carolina (United States)
  14. Department of Basic Medical Sciences, Ghent University, Ghent (Belgium)
Publication Date:
OSTI Identifier:
Resource Type:
Journal Article
Resource Relation:
Journal Name: International Journal of Radiation Oncology, Biology and Physics; Journal Volume: 87; Journal Issue: 4; Other Information: Copyright (c) 2013 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States