FRACTIONATED stereotactic radiosurgery prolongs survival and enhances local control in patients with resected brain tumor cavities. Findings from the multi-institutional Alliance A071801 randomized Phase III clinical trial establish fractionated stereotactic radiosurgery as a superior postoperative standard of care over conventional single-session delivery for individuals presenting with resected brain metastases. While surgical resection remains a foundational intervention to alleviate mass effect and obtain definitive histology, post-resection local recurrence rates remain high when adjuvant cavity radiotherapy is omitted. Delivering radiotherapy in a single fraction frequently encounters tumor volume constraints, where escalating target dimensions reduce local control and increase toxicity risk.
The trial enrolled 242 patients with one to four brain metastases who completed surgical resection of a lesion measuring greater than 2 cm. Participants were randomized to receive either single-fraction radiosurgery dosed at 12 to 20 Gy by cavity volume or fractionated stereotactic radiosurgery delivering 27 Gy across three fractions for volumes under 30 cubic centimeters or 30 Gy across five fractions for larger cavities. At a median follow-up of 48 months, one-year surgical bed control reached 87% in the fractionated arm compared to 81% in the single-fraction arm. Crucially, median overall survival significantly favored fractionated stereotactic radiosurgery at 29 months compared to 20 months with single-fraction treatment, demonstrating a meaningful survival benefit with a hazard ratio of 0.68.
Radiobiological advantages underpin the observed clinical gains, as fractionation allows intervening repair of normal neurovascular tissue while maintaining an elevated biologically effective dose to the surgical cavity margins. Untreated intact metastases also trended toward improved control under fractionated dosing, with progression occurring in only 4% of patients compared to 11% in the single-fraction cohort. Importantly, this therapeutic efficacy did not come at the expense of neurotoxicity. Rates of grade 1 or higher radiation necrosis remained comparable between arms at 14% for fractionated regimens and 10% for single-dose treatments, with cerebral edema observed in 8% and 9% of patients, respectively. These Phase III outcomes provide definitive clinical evidence confirming fractionated stereotactic radiosurgery as an essential practice-changing modality in modern oncology.
Reference
Brown PD et al. Alliance A071801 Phase III Trial Postoperative Single Fraction Stereotactic Radiosurgery (SRS) vs. Fractionated SRS (fSRS) for Resected Brain Metastasis. Int J Radiat Oncol Biol Phys. 2026;126(1):e832.
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