Utilization of Hyperfractionated Radiation in Small-Cell Lung Cancer and Its Impact on Survival

Twice-daily radiation with concurrent chemotherapy is recognized as the standard of care for the treatment of limited stage small-cell lung carcinoma (SCLC), but its utilization in this setting is unclear. The objective of this study was to analyze modern patterns of treatment for limited stage SCLC and the impact on survival utilizing the National Cancer Database.

Between 1999 and 2012, there were 25,045 patients diagnosed with nonmetastatic SCLC who met the selection criteria, of whom 22,626 had survival data. Those receiving 45 Gy in 1.5 Gy fractions twice-daily (BID) were compared with those receiving 45 to 72 Gy in 1.8 or 2.0 Gy fractions. Overall survival was analyzed via Kaplan-Meier analysis and compared using the log-rank test. Multivariate Cox regression analysis was used to identify covariates associated with survival.

The utilization of BID radiation overall was 11.3%. Treatment at an academic center was associated with a higher likelihood of receiving BID treatment (odds ratio: 2.29, 95% confidence interval [CI]: 1.95-2.69; p < 0.001). Median survival was 22.1, 17.2, 18.3, 19.2, and 19.5 months for patients receiving 45 Gy BID, 45 Gy once-daily, 46 to 59.4 Gy once-daily, 60 to 61.2 Gy once-daily, and 62 to 72 Gy once-daily, respectively (p < 0.001 for all pairwise comparisons to BID). On multivariate analysis, treatment at an academic center (hazard ratio: 0.88, 95% CI: 0.83-0.93; p < 0.001) and receipt of BID radiation (hazard ratio: 0.92, 95% CI: 0.86-0.98; p = 0.008) were associated with improved survival.

The adoption of BID radiation remains very limited, but is more commonly utilized in the academic setting. In this hospital-based study, BID fractionation was associated with improved survival over once-daily fractionation, even at doses ≥60 Gy.