Radiation Dose, Local Disease Progression, and Overall Survival in Patients With Inoperable Non-Small Cell Lung Cancer After Concurrent Chemoradiation Therapy

Purpose: To identify predictors of local control and overall survival (OS) for patients with inoperable non-small cell lung cancer treated with concurrent chemoradiation therapy. Methods and Materials: We identified 491 patients with newly diagnosed stage IIIA-IIIB non-small cell lung cancer who had received 60 to 74 Gy (with concurrent chemotherapy) from January 2005 through December 2013 and grouped them by radiation dose received: 60 to 63 Gy, 64 to 66 Gy, 67 to 70 Gy, or 71 to 74 Gy. Local progression (LP) was that appearing within the high-dose volume (planning target volume plus 1-cm margin). Times to events were calculated from the completion of radiation therapy. Potential predictors of LP and OS were analyzed with a Cox regression model. Results: Rates of LP for all patients were 16.2% at 1 year, 26.2% at 2 years, 31.0% at 3 years, 32.9% at 4 years, and 32.9% at 5 years; corresponding OS rates were 85.3%, 61.2%, 44.5%, 37.0%, and 31.6%. Median OS time was 21 months (range, 2.9-99.9 months). In multivariate analysis, receipt of 67 to 70 Gy was associated with improved LP-free survival (LPFS) relative to 60 to 63 Gy (hazard ratio [HR] 1.83, 95% confidence interval [CI] 1.062-3.150, P=.030) or 64 to 66 Gy (HR 2.14, 95% CI 1.159-3.969, P=.015). Non-squamous histology (HR 0.23, 95% CI 0.114-0.478, P=.000), gross tumor volume (HR 1.00, 95% CI 1.000-1.003, P=.018) and induction chemotherapy (HR 1.86, 95% CI 1.239-2.778, P=.003) were independent predictors of LPFS. Local progression–free survival was the only independent predictor of OS (HR 2.71, 95% CI 1.331-5.512, P=.006). Incidence of grade ≥3 radiation pneumonitis was no different among dose groups (P=.307). Conclusions: Squamous histology, large tumor volumes, and receipt of induction chemotherapy all predicted worse LPFS. Doses of 67 to 70 Gy were associated with improved LP-free survival after chemoradiotherapy. The link between LP and reduced OS suggests that more effective local control strategies are warranted.