Fractionated SRS Improves Local Control and Survival in Resected Brain Metastases
Fractionated stereotactic radiosurgery significantly improves surgical bed control compared with single-fraction treatment after the removal of large brain metastases, according to findings presented at the 2026 ASTRO Annual Meeting in Boston. Investigators evaluated patients enrolled in the multicenter Alliance A071801 randomized trial between October 2019 and October 2022 to determine the most effective postoperative radiation therapy approach.
Key Clinical Takeaways:
- Surgical-bed control at 1 year improved from 81% with single-fraction SRS to 87% with fractionated SRS, according to data presented from the Alliance A071801 trial.
- Overall survival as a secondary endpoint increased from a median of 20.2 months with single-fraction treatment to 28.6 months with fractionated delivery.
- Rates of radiation necrosis and cerebral edema remained comparable between the two treatment arms, establishing the safety of the fractionated schedule.
Alliance A071801 Trial Design and Patient Cohort
Sponsored by the Alliance Clinical Network, the phase III trial enrolled 254 pre-registered individuals to compare single-fraction radiosurgery directly against fractionated stereotactic radiosurgery delivered across three to five sessions. Investigators established eligibility criteria requiring participants to be aged 18 years or older with one to four brain metastases, including a completely resected lesion measuring at least 2 cm within 30 days of registration. The study excluded patients with small cell carcinoma, germ cell tumors, lymphoma, leptomeningeal disease, and those with lesions located within 5 mm of the optic apparatus or brainstem. Randomization was stratified by age, cavity diameter, and the use of targeted therapy or immunotherapy.
Fractionated Radiosurgery Improves Surgical-Bed Control
Out of 242 randomly assigned patients, 113 in the single-fraction arm and 110 in the fractionated arm proved evaluable for the primary endpoint. The primary analysis showed fractionated radiosurgery reduced the hazard for surgical-bed control by 47%. The 1-year rate of freedom from salvage whole-brain radiation therapy reached 94% in the fractionated group compared with 84% in the single-fraction cohort. A stratified multivariable Cox model adjusting for Karnofsky performance status, primary tumor site, gender, race, and the number of unresected brain metastases demonstrated a significant association between the fractionated study arm and overall survival, with a hazard ratio of 0.66.
Toxicity Profiles and Quality of Life Assessments
Side effect rates remained consistent across both treatment groups despite the multi-fraction schedule. Radiation necrosis occurred in 13% of patients receiving fractionated radiosurgery and 11% of those receiving single-fraction treatment, while cerebral edema rates were 8% and 9% respectively. Patient-reported outcomes evaluated via functional indices and quality-of-life questionnaires showed no statistically significant differences between the cohorts. Investigators concluded that delivering stereotactic radiosurgery across multiple fractions achieves superior local control for larger resected brain metastases without imposing additional clinical toxicity.
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