Clinical outcomes and dosimetric factors associated with local control after two-fraction radiosurgery for brain metastases

Purpose: This study aimed to evaluate local control outcomes and dosimetric factors associated with local failure (LF) in patients with brain metastases treated with two-fraction stereotactic radiosurgery (two-fraction SRS). Materials and Methods: We retrospectively analyzed 86 patients with 193 brain metastases who underwent two-fraction SRS between August 2018 and November 2025. LF was the primary endpoint, while distant intracranial failure (DIF) and overall survival (OS) were secondary endpoints. The cumulative incidence of LF and DIF was estimated using competing-risk analysis, with clustered Fine-Gray regression applied to the lesion-level LF analysis to account for intra-patient correlation. Dosimetric parameters, including planning target volume (PTV) coverage indices, were evaluated to identify factors associated with LF. Factors associated with OS were analyzed using Cox proportional hazards models. Results: With a median follow-up of 24.4 months, the cumulative incidence of LF at 6 and 12 months was 11.5% (95% confidence interval [CI], 6.2% to 17.2%) and 17.9% (95% CI, 11.3% to 24.7%), respectively. In the integrated clustered multivariable analysis adjusting for clinical variables, lower PTV D98 (dose covering 98% of the target volume) was independently associated with an increased risk of LF, whereas no other variables remained significant in the final integrated model. The cumulative incidence of DIF was 33.2% at 6 months and 50.2% at 12 months. In multivariable Cox analysis, baseline performance status was the only independent factor significantly associated with OS. Conclusion: Two-fraction SRS achieved reasonable local control in patients with brain metastases. Maintaining an adequate absolute near-minimum dose to the target (PTV D98) was associated with improved local control, while OS was primarily influenced by baseline patient performance status.