Comparison of First-Line Radiosurgery for Small-Cell and Non-Small Cell Lung Cancer Brain Metastases (Cross-FIRE)

Introduction Historical reservations regarding radiosurgery (SRS) for small-cell-lung-cancer (SCLC) brain metastases (BrM) include concerns for short-interval/diffuse CNS-progression, poor prognoses, and increased neurological mortality specific to SCLC histology. We compared SRS outcomes for SCLC and non-small-cell-lung-cancer (NSCLC) where SRS is well established. Methods Multicenter first-line SRS outcomes for SCLC and NSCLC from 2000-2022 were retrospectively collected (N=892-SCLC/N=4,785-NSCLC). Data from the prospective JLGK0901 SRS trial were analyzed as a comparison cohort (N=98-SCLC/N=794-NSCLC). OS and CNS-progression were analyzed using Cox-Proportional-Hazard and Fine-Gray models, respectively, with multivariable (MV) adjustment (including age/sex/performance-status/year/extracranial disease/BrM-number/BrM-volume). Mutation-stratified analyses were performed in propensity score-matched (PSM) retrospective cohorts of EGFR/ALK-positive-NSCLC, mutation-negative-NSCLC, and SCLC. Results OS was superior with NSCLC over SCLC in the retrospective dataset (median-OS, 10.5 vs 8.6 months, MV-p Conclusion After SRS, SCLC was associated with shorter OS compared to NSCLC. CNS progression occurred earlier in SCLC overall but was similar in patients matched on baseline characteristics. Neurological mortality, lesions at CNS-progression, and leptomeningeal-progression were comparable. These findings may better inform clinical decision-making for SCLC patients.