Population-based analysis of single-fraction versus multi-fraction stereotactic ablative radiotherapy for early-stage non-small cell lung cancer.

OBJECTIVES: Optimal dose fractionation of stereotactic ablative radiotherapy (SABR) in early-stage non-small cell lung cancer (NSCLC) remains unclear. This population-based study compares outcomes and toxicities of single-fraction (SF) versus multi-fraction (MF) SABR. METHODS: All patients in British Columbia, Canada with peripheral T1-2N0 NSCLC treated with either SF-SABR (30 Gy or 34 Gy) or MF-SABR (48 Gy/4 or 54 Gy/3 fractions) between January 2021 and August 2024 were retrospectively reviewed. Local failure (LF) and overall survival (OS) were estimated using Kaplan-Meier method and cumulative incidence functions with death as a competing risk. Toxicity was graded per Common Terminology Criteria for Adverse Events version 5.0. Fine-Gray and Cox regression analyses were used to identify variables associated with LF and OS, respectively. Binary logistic regression was used to assess predictors of chest wall toxicity (CWT). RESULTS: A total of 814 lesions in 778 patients were included (SF-SABR 283 and MF-SABR 531). Median follow-up was 25.8 months (interquartile range, 18.8-36.6). No significant differences were observed in 2-year LF (3.5% vs. 4.8%, p = 0.11) or 2-year OS (79.3% vs. 79.4%, p = 0.62). There were no differences in any grade 2 toxicity (11.5% vs. 12.4%, p = 0.13), any grade 3-5 toxicity (1.5% vs. 3.9%, p = 0.08), or grade 2 + CWT (5.0% vs. 5.0%, p = 0.98). SF-SABR alone did not predict worse LF, OS, any grade 2 + toxicity, or grade 2 + CWT. CONCLUSION: No statistically significant differences were observed in LF, OS, or toxicity between SF-SABR versus MF-SABR. SF-SABR should be considered for this patient population as it is convenient and cost-effective.