Once Versus Twice Daily Fractionation for Limited Stage SCLC

Abstract

Despite phase III data indicating improved survival with twice daily fractionation for limited stage small cell lung cancer (SCLC), logistics of twice daily treatment and potential for increased toxicity have limited its utilization. We sought to compare overall and lung cancer specific survival between once daily and twice daily fractionation for limited stage SCLC. Using the VA Central Cancer Registry (VACCR), limited stage SCLC patients diagnosed from 1/2001-12/2010 were identified. Data regarding fractionation, co-morbidities, and treatment toxicity were obtained from the VA Corporate Data Warehouse (VACDW). Cause of death was obtained from the National Death Index. Radiation fractionation was determined by CPT codes for treatment limited to within 180 days of diagnosis or by review of VACDW abstracted data. Charlson Comorbidity Index (CCI) was calculated using ICD-10 codes in the year before diagnosis. Treatment toxicity was determined based on ICD-10 codes up to 180 days after treatment. 3,512 patients were identified with limited stage SCLC; radiation fractionation was able to be determined for 942 patients. 822 patients had once daily fractionation and 120 had twice daily fractionation. Median follow-up was 78 months. Mean age was 64.6 years, 97.9% were male and 84.8% were white. 96.0% were current/former smokers. 73.1% had stage III disease. Overall survival (HR 1.19, 95% CI 0.96-1.47, p=0.12) and lung cancer specific survival (HR 1.11, 95% CI 0.87-1.40, p=0.39) were similar between the two fractionation schedules. Overall survival of propensity score matched cohorts was also similar between daily and twice daily treatment (HR 0.87, 95% CI 0.65-1.16, p=0.33). There were higher rates of mucositis/esophagitis (27.5% vs 14.6%), nausea (28.3% vs 11.4%), and acute kidney injury (40.0% vs 25.7%, p<0.05 for all) with twice daily fractionation. In this VA population of limited stage SCLC patients diagnosed from 2001-2010, there was no difference in overall survival or lung cancer specific survival with twice daily versus daily radiation fractionation schedules, although toxicity was worse with twice daily treatment. These data agree with a preliminary report of an ongoing phase III study and suggest no benefit to a twice daily fractionation schedule for limited stage SCLC.