Is there a Role for Hypofractionated Thoracic Radiotherapy in Limited-Stage Small Cell Lung Cancer? A Propensity Score Matched Analysis

Zayed, Sondos; Chen, Hanbo; Ali, Emma; Rodrigues, George B.; Warner, Andrew; Palma, David A.; Louie, Alexander V.

ABSTRACT Introduction Various radiation schedules are used in concurrent chemoradiotherapy for limited-stage small cell lung cancer (LS-SCLC). As there is currently no randomized evidence comparing hypofractionated (HFRT) and conventionally-fractionated radiotherapy (CFRT), the aim of this study was to compare overall survival (OS), progression-free survival (PFS), and toxicity of HFRT and CFRT in LS-SCLC. Methods LS-SCLC patients treated between 2000-2013 with HFRT (40Gy/15, 45Gy/15, 45Gy/20 fractions) or CFRT (60Gy/30 or 66Gy/33 fractions) were included. Propensity scores were generated using a multivariable logistic regression model. Patients were matched on a 1:1 ratio with a caliper distance of 0.20. OS and PFS were estimated by the Kaplan-Meier method and compared using log-rank tests. As a sensitivity analysis, univariable and multivariable Cox regression was performed including all patients without matching. Logistic regression was performed to identify predictors of pulmonary and esophageal adverse events. Results In the overall group of 117 patients, there were significant baseline differences between the HFRT and CFRT cohorts. Patients who received CFRT were older, smoked more often concurrently with treatment, had higher ECOG performance status, different T and N stage patterns, and more commonly received concurrent chemoradiotherapy and prophylactic cranial irradiation. After propensity score matching for these differences, 72 patients were included, 36 in the HFRT and CFRT cohorts respectively. There was no difference in OS (P=0.724), PFS (P=0.862), any pulmonary (P=0.350), or esophageal (P=0.097) adverse events between cohorts. Skin adverse events were significantly higher for CFRT (41.7%) compared with HFRT (16.7%, P=0.020). Multivariable Cox regression also revealed no differences in OS (P=0.886) or PFS (P=0.717) between all HFRT and CFRT patients, without matching. No grade 5 adverse events were observed. Conclusion In LS-SCLC patients, HFRT was associated with comparable survival and toxicity outcomes and may be considered as an alternative to CFRT, should its efficacy be confirmed in prospective studies.