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 After a systematic review of the literature, data was obtained on 836 patients who underwent CCRT in Europe, North America and Asia. Patients were randomly divided into training and validation sets (2/3 vs. 1/3 of patients). Factors predictive of symptomatic pneumonitis (grade ≥ 2 by one 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 radiotherapy dose was 60 Gy, and median follow-up 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 (V20) [OR:1.03 per 1% increase, p=0.008], and carboplatin/paclitaxel chemotherapy [OR:3.33, p<0.001], with a trend for age [OR: 1.24 per decade, p=0.09]; 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, V20, 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.

No abstract

Arm C was equally efficacious and exhibited a more favorable toxicity profile among three arms. Arm C should be considered a standard regimen in the management of locally advanced unresectable NSCLC.