Hypofractionated vs. standard radiotherapy for locally advanced limited-stage small cell lung cancer

Abstract

Background: Hypofractionated radiotherapy in locally advanced limited-stage small cell lung cancer is preferred in many Western countries but not used regularly in the United States. We examined practice patterns and overall survival with definitive hypofractionated radiotherapy and chemotherapy vs. standard radiotherapy in this setting. Methods: We included patients in the National Cancer Database with unresected primary stage II-III small cell lung cancer in 2008-2016 who underwent chemotherapy within six months of either hypofractionated radiotherapy (40-45 Gy/15 fractions) or standard radiotherapy (45 Gy/30 fractions or 60-70 Gy /30-35 fractions) in this retrospective cohort study. Patient characteristics were assessed with univariable and multivariable logistic regression. Kaplan-Meier estimator, log-rank test, and multivariable Cox regression were used to evaluate overall survival. Propensity score matching (PSM) was performed as a sensitivity analysis. Early concurrent chemotherapy consisted of radiotherapy and chemotherapy initiated within 30 days of each other.Results: Seven thousand and one hundred forty-three patients were included: 97.9% received standard radiotherapy and 2.1% hypofractionated radiotherapy. Multivariable analysis on the whole cohort yielded comparable overall survival (HR for hypofractionated radiotherapy 1.09, CI: 0.90-1.32, P=0.37). On PSM (N=292), median overall survival was similar between standard radiotherapy [22.9 months (95% CI: 18.2-30.4)] vs. hypofractionated radiotherapy [21.2 months (CI: 16.3-24.7); P=0.13]. Overall survival was shorter with hypofractionated radiotherapy in the early concurrent chemotherapy subset (15.8 vs. 22.1 months, P=0.007) and longer with hypofractionated radiotherapy in the non-early concurrent chemotherapy subset (29.5 vs. 18.5 months, P=0.027).Conclusions: Overall survival with hypofractionated radiotherapy appears similar to standard radiotherapy in locally advanced limited-stage small cell lung cancer. Chemotherapy timing may modify the effect of fractionation on overall survival, though larger numbers must confirm. Hypofractionated radiotherapy may be considered in those unable to receive early concurrent chemotherapy.

Progress in radiotherapy for small‐cell lung cancer

“…Most toxicities had similar incidences in both groups; however, the once‐daily group had higher incidence of grade ≥3 acute lymphopenia (71.7% vs. 40.2%; p < 0.001) 13 . Data from the National Cancer Database, 14‐16 suggest that hypofractionated radiation does not appear to be worse than standard radiotherapy. Furthermore, in a meta‐analysis based on the latest pooled phase II trial, 17 hypofractionated radiotherapy was associated with an improvement in OS compared to HFRT ( p = 0.03).…”

“…Alternative approaches to improve the efficacy of TRT include studying the use of hypofractionated regimens (once-daily, higher-dose radiotherapy 13 Data from the National Cancer Database, [14][15][16] suggest that hypofractionated radiation does not appear to be worse than standard radiotherapy. Furthermore, in a meta-analysis based on the latest pooled phase II trial, 17 hypofractionated radiotherapy was associated with an improvement in OS compared to HFRT (p = 0.03).…”