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A multicenter randomized phase III trial (A071801) presented at the ASTRO 2026 annual meeting found that fractionated stereotactic radiosurgery after resection of larger brain metastases improved 1-year surgical-bed control (87% vs 81%) and median overall survival (28.6 vs 20.2 months) compared with single-fraction SRS, without added toxicity. Investigators called fractionated SRS a new standard of care for this setting.
Fractionated stereotactic radiosurgery (SRS) significantly improved local control of the surgical bed after removal of larger brain metastases compared with single-fraction SRS, according to the randomized phase III A071801 trial presented at the ASTRO annual meeting in Boston on September 29, 2026. One-year surgical-bed control rose from 81% to 87%, fewer patients needed salvage whole-brain radiation therapy (WBRT), and median overall survival — a secondary endpoint — improved from 20.2 to 28.6 months, all without an apparent increase in toxicity.
The trial, sponsored by the Alliance Clinical Network, enrolled 242 patients with up to four brain metastases, including one resected metastasis measuring ≥2 cm. A total of 223 patients were evaluable for the primary endpoint. Patients in the single-fraction arm received variable doses to resected and unresected lesions depending on lesion size, while those in the fractionated arm received 27 Gy in three fractions or 30 Gy in five fractions to the surgical bed and unresected lesions, also size-dependent.
The primary endpoint — surgical-bed control at 1 year — favored fractionated SRS, which reduced the hazard of surgical-bed failure by 47% (95% CI 0.28–1.00, P=0.046). Freedom from salvage WBRT at 1 year was also better in the fractionated arm (94% vs 84%). The 8.4-month difference in median overall survival corresponded to a hazard ratio of 0.66 in favor of fractionated SRS (95% CI 0.46–0.94, P=0.02). Patterns and rates of intracranial recurrence were similar between groups, with new brain metastases the most common recurrence type (38% vs 34%).
Toxicity profiles were comparable: radiation necrosis occurred in 11% of single-fraction patients versus 13% with fractionated SRS, and cerebral edema rates were 9% versus 8%, respectively. Ayal Aizer, MD, of Mass General Brigham and Dana-Farber Cancer Institute, who reported the findings, said the improvement in surgical-bed control was achieved “without an apparent increase in toxicity.”
A New Postoperative Standard for Larger Metastases
Single-fraction SRS had been the accepted standard after resection of brain metastases based on two prior randomized trials, but recurrence in the surgical bed remained common — 1-year surgical-bed recurrence rates of 40% and 28% in those earlier studies. Subset analysis of the single-center trial suggested larger metastases were especially prone to poor control after single-fraction treatment, motivating the current trial.
The findings matter because they provide randomized evidence that splitting the radiation dose over three to five sessions improves outcomes specifically for patients with larger resected metastases — a common clinical scenario — without adding toxicity or requiring more invasive treatment. Fewer patients needing salvage WBRT is also meaningful, since whole-brain radiation is associated with cognitive side effects that clinicians try to avoid. Aizer said the study “moves fractionated radiosurgery from a reasonable practice supported by retrospective data to one backed by a randomized phase III trial.” ASTRO discussant Rupesh Kotecha, MD, of Baptist Health Herbert Wertheim Cancer Institute in Miami, concurred: “If postoperative external beam radiotherapy is chosen after upfront resection, then postoperative fractionated radiosurgery is the new standard of care.”
How the Trial Built on Earlier SRS Evidence
Before this trial, two randomized studies — a multicenter North American trial and a single-center study — established single-fraction SRS as standard care after surgical resection of brain metastases. However, both reported substantial surgical-bed recurrence, and retrospective analyses across multiple institutions suggested that fractionated SRS, typically delivered in three to five treatments, achieved better local control for larger cavities. The Alliance A071801 trial was designed to confirm those retrospective observations in a randomized, multicenter setting, focusing on patients whose resected metastasis was at least 2 cm — the group where single-fraction control was weakest.
“For patients undergoing resection of a larger brain metastasis, postoperative fractionated stereotactic radiosurgery should be considered the standard of care.”
— Ayal Aizer, MD
Open Questions on the Survival Benefit
Although the overall survival difference was statistically significant, it was a secondary endpoint, and the reasons for the 8.4-month improvement are not established. Kotecha said the OS difference “requires more study to explore potential explanations.” It is not yet clear whether the survival advantage stems directly from better surgical-bed control, from reduced use of salvage whole-brain radiation, from imbalances in patient characteristics, or from other factors.
Kotecha also noted that all existing radiotherapy approaches have distinct advantages and disadvantages, and that clinical trials directly comparing different modalities are still needed to determine the optimal approach. The trial’s borderline primary-endpoint P-value (P=0.046) and the conference-presentation format — full peer-reviewed publication details are pending — mean some details may evolve with final reporting.
Peer-Reviewed Publication and Practice Uptake
The findings were presented at a scientific meeting, and clinicians will look for full peer-reviewed publication of A071801 with longer follow-up, subgroup analyses, and quality-of-life or cognitive outcomes. Future research directions include exploring the mechanisms behind the overall survival difference and running head-to-head comparisons of fractionated SRS against other postoperative radiotherapy modalities, as Kotecha suggested. In the near term, radiation oncology teams treating patients with resected brain metastases ≥2 cm are likely to shift toward three-to-five-fraction SRS schedules, consistent with the investigators’ and discussant’s conclusions.
Key Questions
What is fractionated stereotactic radiosurgery?
It is a form of precisely targeted radiation delivered in multiple sessions — in this trial, 27 Gy in three fractions or 30 Gy in five fractions — rather than in a single high-dose treatment. Delivering radiation over several sessions can improve control of larger tumors while sparing healthy tissue.
How much did fractionated SRS improve outcomes compared with single-fraction SRS?
One-year surgical-bed control improved from 81% to 87%, freedom from salvage whole-brain radiation at 1 year was 94% versus 84%, and median overall survival increased from 20.2 to 28.6 months. Fractionated SRS reduced the hazard of surgical-bed control failure by 47%.
Did fractionated SRS cause more side effects?
No increase in toxicity was observed. Rates of radiation necrosis were 11% (single-fraction) versus 13% (fractionated), and cerebral edema rates were 9% versus 8% — differences investigators described as similar between the groups.
Does this apply to all brain metastasis patients?
The trial enrolled patients with up to four brain metastases, including one resected metastasis of at least 2 cm. The conclusions about fractionated SRS as a standard of care apply specifically to patients undergoing resection of larger brain metastases; other patient groups may require different approaches, and patients should discuss their options with their treatment team.
Why did fractionated SRS improve survival if that wasn’t the main endpoint?
That remains unclear. Overall survival was a secondary endpoint, and the ASTRO discussant said the survival difference “requires more study to explore potential explanations.” Possible contributors such as better local control or less salvage whole-brain radiation have not been confirmed as the cause.
Source: rss
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