Safety and Efficacy of 2-Fraction Stereotactic Radiosurgery for Brain Metastases

Objectives: Stereotactic radiosurgery (SRS) is the predominant modality for treating brain metastases. Fractionated SRS has benefits of improved local control and decreased morbidity over single-fraction SRS for larger lesions, typically performed in 3 to 5 fractions. This series is the first report of 2-fraction SRS for brain metastases. Methods: Patients at a National Cancer Institute-designated cancer center with metastatic brain disease deemed suitable for fractionated SRS from August 2025 to September 2026 were included. Constraints used were the Timmerman 2-fraction tables for organs-at-risk, and brain-planning target volume (PTV) V20 Gy <20 cm 3 to minimize radiation necrosis risk. SRS was performed with mask-based immobilization using either Gamma Knife or a linear accelerator. Results: A total of 65 lesions in 15 patients were treated to 24 Gy in 2-fraction SRS (56 untreated brain metastases, 3 planned preoperative treatment, 6 for postoperative treatment). One lesion (1.8%) developed symptomatic radiation necrosis; another lesion (2.4 cm) required subsequent unplanned operative intervention. Local control was achieved in 92% of lesions with a minimum of 10 months of follow-up. Conclusions: This study provides the first evidence supporting 2-fraction SRS for brain metastases as a safe and efficacious alternative to the longer 3-fraction and 5-fraction regimens. The low radiation necrosis rate (<2%) utilizing the brain-PTV V20 <20 cm 3 constraint is a novel aspect of this series, demonstrating that 2-fraction SRS can be performed with minimal morbidity. As the most expedient fractionated SRS regimen, 2-fraction treatment yields several advantages over longer regimens.