Predicting radiation pneumonitis after chemoradiation therapy for lung cancer: an international individual patient data meta-analysis

Abstract

Background: Radiation pneumonitis is a dose-limiting toxicity for patients undergoing concurrent chemoradiation therapy (CCRT) for non-small cell lung cancer (NSCLC). We performed an individual patient data meta-analysis to determine factors predictive of clinically significant pneumonitis.

Methods and materials: After a systematic review of the literature, data were obtained on 836 patients who underwent CCRT in Europe, North America, and Asia. Patients were randomly divided into training and validation sets (two-thirds vs one-third of patients). Factors predictive of symptomatic pneumonitis (grade ≥2 by 1 of several scoring systems) or fatal pneumonitis were evaluated using logistic regression. Recursive partitioning analysis (RPA) was used to define risk groups.

Results: The median radiation therapy dose was 60 Gy, and the median follow-up time was 2.3 years. Most patients received concurrent cisplatin/etoposide (38%) or carboplatin/paclitaxel (26%). The overall rate of symptomatic pneumonitis was 29.8% (n=249), with fatal pneumonitis in 1.9% (n=16). In the training set, factors predictive of symptomatic pneumonitis were lung volume receiving ≥20 Gy (V(20)) (odds ratio [OR] 1.03 per 1% increase, P=.008), and carboplatin/paclitaxel chemotherapy (OR 3.33, P<.001), with a trend for age (OR 1.24 per decade, P=.09); the model remained predictive in the validation set with good discrimination in both datasets (c-statistic >0.65). On RPA, the highest risk of pneumonitis (>50%) was in patients >65 years of age receiving carboplatin/paclitaxel. Predictors of fatal pneumonitis were daily dose >2 Gy, V(20), and lower-lobe tumor location.

Conclusions: Several treatment-related risk factors predict the development of symptomatic pneumonitis, and elderly patients who undergo CCRT with carboplatin-paclitaxel chemotherapy are at highest risk. Fatal pneumonitis, although uncommon, is related to dosimetric factors and tumor location.

Conflict of interest statement

Conflict of Interest Statement

Dr. Palma was the recipient of the 2009 Canadian Association of Radiation Oncologists’ Elekta Research Fellowship. Dr. Senan has received research funding from Sanofi-Aventis, speaking honoraria from Varian Medical Systems Inc, has a departmental master research agreement with Varian Medical Systems Inc,, and is a member of the trial management group for the phase III PROCLAIM study, which is sponsored by Eli Lilly.

Copyright © 2013 Elsevier Inc. All rights reserved.

Figures

Figure 1

Recursive partitioning analysis of radiation pneumonitis risk in patients undergoing concurrent chemoradiation therapy (CCRT) for non-small cell lung cancer (NSCLC). Patients were randomly divided into a training set (T) and validation set (V). MLD: mean lung dose; V20: volume of lung receiving ≥ 20 Gy.