The Role of Thoracic Radiation Therapy Dosing in the Treatment of Limited-Stage Small Cell Lung Cancer: A Study Based on the National Cancer Database

PURPOSE: Small cell lung cancer (SCLC) is a highly fatal disease, but its treatment has remained relatively unchanged for decades. Randomized clinical trials evaluating radiation therapy (RT) dosing and fractionation have yielded mixed results on overall survival (OS). METHODS AND MATERIALS: We identified 2261 patients with limited-stage (LS) SCLC undergoing definitive RT at 1.5, 1.8, and 2.0 Gy dose per fraction, concurrently with chemotherapy, between 2004 and 2015 within the National Cancer Database. Overall survival (OS) was evaluated using the Kaplan-Meier method, and Cox proportional hazards regression was used to investigate whether there was any survival difference among patients who received hyperfractionated, twice-daily RT at 1.5 Gy per fraction (HF1.5) and once-daily, standard fractionation RT at 1.8 Gy (SF1.8) or 2.0 Gy (SF2.0) per fraction. Subgroup analyses by age, sex, race, time to RT, facility type, and Charlson comorbidity index were also performed. RESULTS: All stage median OS rates for HF1.5, SF1.8, and SF2.0 Gy groups were 21.6, 18.9, and 19.4 months, respectively (log-rank P = .0079). Multivariate analyses adjusting for demographic factors, socioeconomic status, tumor characteristics, and year of diagnosis showed SF1.8 (hazard ratio [HR] = 1.30, 1.03-1.63) and SF2.0 (HR = 1.20, 1.00-1.45) was associated with worse 1-year survival compared with HF1.5. This association was more evident in stage IIb-stage III than stage I to stage IIa patients. Propensity score–weighted analysis showed similar results. Stratified analyses showed the significant associations were confined to male or black patients, those aged >65 years, with 1 comorbidity, who had waited >60 days to start RT or were treated at an academic medical center. CONCLUSIONS: Analyses of real-world treatment outcome data showed that receiving hyperfractionated, twice-daily RT was associated with improved survival among patients with LS-SCLC compared with standard, once-daily fractionation regimens at 1 year after diagnosis, particularly for subsets of patients. Some associations retained statistical significance 3 years postdiagnosis.