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Combined modality therapy (CMT) is the standard of care for patients with unresectable stage III non-small-cell lung cancer (NSCLC); however, insufficient data are available regarding prognostic factors in this disease setting.Six hundred and ninety-four patients included in five trials conducted by the Cancer and Leukemia Group B evaluating CMT in stage III NSCLC were included in this analysis. The primary objective was to identify factors that were predictors of survival and selected radiation-related toxicities using Cox regression models and logistic regression analysis.The Cox model shows that performance status (PS) 1 [hazard ratio (HR) 1.24; 95% confidence interval (CI) 1.06–1.45; P=0.009] and thoracic radiation therapy (TRT) only (HR 1.58; 95% CI 1.22–2.05; P=0.001) predicted for poorer survival, while baseline hemoglobin ≥12 g/dl predicted for improved survival (HR 0.67; 95% CI 0.55–0.81; P ≤0.0001). Multivariate logistic regression showed an increase of grade 3 * esophagitis among patients with PS 0 [odds ratio (OR) 1.7; 95% CI 1.1–2.7; P=0.029), >5% weight loss (OR 2.9; 95% CI 1.3–6.6; P=0.008) and patients receiving concurrent chemoradiation (OR 7.3; 95% CI 3.4–15.6; P=0.0001).Baseline hemoglobin and PS, as well as the use of CMT, have the greatest effect on survival in unresectable stage III NSCLC. The use of concurrent chemoradiation increases the risk of esophagitis, which remains the primary radiation-related toxicity.