Fractionated SRS Tops Single-Fraction SRS After Brain Metastasis Resection

Ayal Aizer, MD, MHS, director of Central Nervous System Radiation Oncology at Brigham and Women’s Hospital and Dana-Farber Cancer Institute and associate professor of radiation oncology at Harvard Medical School, spoke with CancerNetwork® about data from the phase 3 Alliance A071801 trial (NCT04114981), which he presented as a late-breaking abstract during the plenary session at the 2026 American Society for Radiation Oncology (ASTRO) Annual Meeting.

The trial randomly assigned 242 patients with 1 to 4 brain metastases, including a resected lesion, to postoperative single-fraction stereotactic radiosurgery (SRS) or fractionated SRS. At 1-year, surgical bed control was 87% with fractionated SRS vs 81% with single-fraction SRS (P = .046), and the median overall survival was 29 vs 20 months, respectively (P = .035). Aizer said the result was not a surprise, as large resection cavities limit the dose that can be safely delivered in a single fraction. He also discussed possible explanations for the benefit, including biologic dose, contouring practices, and an interaction with fractionation, all of which warrant further investigation.

Transcript:

CancerNetwork: Your data showed that fractionated SRS beat single-fraction SRS for local control after resection. Did that surprise you, given the momentum single-fraction SRS has had?

Aizer: The result was not a surprise per se, but it was nice to see that the study hypothesis in fact came to fruition. We know that when metastases are resected, the cavities can be large, and you can’t give a large amount of dose to a big target in the brain without causing significant necrosis. Dosing is an issue with single-fraction stereotactic radiosurgery. What fractionation can accomplish is a more tolerable dose, but one that can be effective against the tumor as well. There had been prior retrospective series supporting fractionated radiosurgery with good control rates, whereas the single-fraction data, which came mainly from prospective randomized series, were not as encouraging. The study confirmed the hypothesis, and in some ways, the study designers should be commended, Dr Paul D. Brown in particular, for constructing the hypothesis that they did.

CancerNetwork: What was the driving difference: dose-fractionation biology, or something about how the resection cavity behaves?

Aizer: We ultimately don’t know, and that needs to be investigated further. It may be the case that the biologic dose that’s imparted with single-fraction SRS is simply too low to achieve durable control. It may be something about the way people contour when they have to administer 1 fraction vs multiple fractions. Although there were no meaningful differences in the size of the target by arm, there may be subtleties in the way people do the contouring with regard to 1 vs multiple fractions, or there could be some sort of interaction with the fractionation. Ultimately, it can’t be determined with certainty, but this is something that needs to be explored further.

Reference

Brown PD, Ballman KV, Aizer AA, et al. Alliance A071801 phase III trial postoperative single fraction stereotactic radiosurgery (SRS) vs fractionated SRS (fSRS) for resected brain metastasis. Presented at: 2026 ASTRO Annual Meeting; September 26–30, 2026; Boston, MA. Abstract LBA 01.