Alliance A071801 addresses an important question in the postoperative management of brain metastases: single-fraction stereotactic radiosurgery (SRS) or fractionated SRS (fSRS)? Postoperative SRS is an established standard that avoids the neurocognitive effects of whole-brain radiation therapy.1 Local control with single-fraction SRS may decline as cavity size increases, and fSRS is often favored for larger cavities, although largely based on retrospective data.2
This phase III trial randomized 242 patients with one to four brain metastases and a resected lesion >2 cm to single-fraction SRS (12–20 Gy based on volume) or fSRS (27 Gy in 3 fractions for targets <30 cc or 30 Gy in 5 fractions for targets >30 cc). Median cavity volumes were 14.8 cc with SRS and 16.5 cc with fSRS, suggesting that many patients had moderately sized rather than very large postoperative cavities, an important consideration when applying these results to the largest or most complex surgical cavities.
With a median follow-up of 48 months, fSRS significantly improved one-year surgical-bed control compared with SRS (87% versus 81%, p=0.046). The 6% absolute improvement is modest but clinically relevant and supports consideration of fractionation for appropriately selected postoperative cavities.
The most intriguing finding was overall survival, which favored fSRS: median OS was 29 versus 20 months (HR=0.69, p=0.035), with a similar association on multivariable analysis (HR=0.68, p=0.032). However, OS was a secondary endpoint, and a nine-month survival difference is difficult to explain solely by a 6% improvement in one-year surgical-bed control. Further analyses of intracranial failure, salvage therapy, systemic disease control, and systemic treatments are needed to better understand this unexpected finding.
Toxicity was similar between arms. Grade 1 or higher radiation necrosis occurred in 14% with fSRS versus 10% with SRS, while cerebral edema occurred in 8% versus 9%. Failure of treated unresected metastases was numerically lower with fSRS (4% versus 11%, p=0.063), although not statistically significant.
The Alliance investigators should be congratulated for completing an important, randomized trial addressing a question that has long been guided largely by retrospective evidence. Alliance A071801 provides level I evidence that postoperative fSRS improves surgical-bed control without a significant increase in reported toxicity, strengthening the rationale for fractionation, particularly for larger cavities. However, the absolute local-control benefit was modest, and single-fraction SRS remains a reasonable option for appropriately selected patients. Its convenience and lower treatment burden, one treatment rather than three to five visits, should be weighed against the improvement in local control, particularly for smaller postoperative cavities.
The unexpected survival advantage is provocative but should be interpreted cautiously until additional analyses clarify its relationship to fractionation and subsequent cancer therapy. Overall, A071801 is an important practice-informing trial that moves postoperative fSRS from a strategy supported largely by retrospective experience toward one supported by randomized phase III evidence.
References
LBA 01, Alliance A071801 Phase III Trial Postoperative Single Fraction Stereotactic Radiosurgery (SRS) vs. Fractionated SRS (fSRS) for Resected Brain Metastasis, was presented during PL 01- Plenary 01, at ASTRO's 68th Annual Meeting.
Published on: September 29, 2026
