Fractionated SRS Improves Local Control After Brain Metastasis Resection

A multicenter randomized trial found that fractionated stereotactic radiosurgery (SRS) provided better one-year control at the surgical site than single-fraction SRS after removal of a larger brain metastasis. The A071801 trial also reported longer median overall survival and fewer patients needing salvage whole-brain radiation therapy, with similar rates of radiation necrosis and cerebral edema in the two groups. The findings were presented September 29 at the American Society for Radiation Oncology annual meeting in Boston.

Researchers randomized 242 patients with up to four brain metastases, including at least one resected metastasis measuring 2 centimeters or more. Of those enrolled, 223 were evaluable for the primary endpoint: control of the surgical bed at one year. That rate was 87% with fractionated SRS and 81% with single-fraction SRS. The trial reported a 47% reduction in the hazard of surgical-bed failure with fractionated treatment (95% confidence interval 0.28 to 1.00; P=0.046).

In the fractionated group, patients received either 27 Gy in three sessions or 30 Gy in five sessions to the surgical bed and any unresected lesions; the dose depended on lesion size. Single-fraction doses also varied by lesion size. At one year, 94% of patients in the fractionated group remained free of salvage whole-brain radiation therapy, compared with 84% in the single-fraction group. The most common intracranial recurrence in both groups was a new brain metastasis, reported in 38% and 34%, respectively.

Median overall survival, a key secondary endpoint, was 28.6 months with fractionated SRS and 20.2 months with single-fraction SRS. The reported hazard ratio was 0.66 (95% confidence interval 0.46 to 0.94; P=0.02). Radiation necrosis occurred in 13% of the fractionated group and 11% of the single-fraction group; cerebral edema occurred in 8% and 9%, respectively. The report said the benefits occurred without an apparent increase in toxicity.

Control After Metastasis Surgery

The results address a treatment problem after surgery: the surgical bed can remain a site of recurrence, particularly after removal of a larger metastasis. Better local control could mean fewer patients need additional treatment to the whole brain, which can affect the course of care. In this trial, freedom from salvage whole-brain radiation at one year was higher in the fractionated group.

The survival finding may also matter, but it needs careful interpretation. Overall survival was a secondary endpoint, and the trial report does not establish why median survival differed between groups. ASTRO discussant Rupesh Kotecha said that difference requires more study. The local-control result is the study’s primary finding; the survival result is encouraging evidence from the same trial, not a settled explanation of treatment effect.

Ayal Aizer, the trial presenter, said the randomized results add stronger evidence to prior retrospective studies supporting fractionated treatment. He said postoperative fractionated SRS should be considered standard care for patients with larger brain metastases. Kotecha framed his recommendation more narrowly: when external-beam radiation is chosen after upfront resection, he said, fractionated radiosurgery is the new standard of care.

Why Fractionation Was Studied

Earlier randomized studies established single-fraction SRS as a standard approach after surgery for brain metastases. Aizer said those studies still reported one-year surgical-bed recurrence rates of 40% and 28%. A subset analysis from one study suggested that larger metastases were especially prone to poorer control with a single fraction.

Retrospective studies had reported good local control with fractionated SRS, commonly delivered over three to five sessions. A071801, sponsored by the Alliance Clinical Network, was designed to test that approach against single-fraction treatment in a randomized multicenter study. Its eligibility criteria allowed up to four brain metastases and required one resected lesion of at least 2 centimeters. The trial therefore speaks most directly to patients who fit those criteria, rather than every person undergoing surgery for a brain metastasis.

Radiation approaches have different advantages and disadvantages. Kotecha said trials directly comparing modalities are needed to identify an optimal approach. The current results compare two SRS schedules; they do not establish that SRS is preferable to every other postoperative radiation strategy.

“Fractionated stereotactic radiosurgery improves surgical-bed control compared with single-fraction stereotactic radiosurgery after resection of a brain metastasis, and the improvement in surgical-bed control was achieved without an apparent increase in toxicity.”

— Ayal Aizer, MD, trial presenter

Questions About Survival and Scope

The trial report does not explain why median overall survival differed, and the discussant called for further study of possible explanations. The findings also do not settle which postoperative radiation option is best across all patients or clinical situations. A071801 included patients with up to four metastases and at least one resected lesion measuring 2 centimeters or more, so the results should be read within that study population.

The report gives one-year surgical-bed control and freedom from salvage whole-brain radiation, but it does not provide longer-term estimates in the material available here. It also does not detail how results varied by tumor type, patient characteristics, or the specific fractionated schedule used. The reported toxicity rates were similar, but those figures do not answer every question about longer-term effects or individual treatment choices.

How Practice May Respond

Clinicians and cancer centers will assess the randomized results alongside each patient’s situation and the other available radiation approaches. Aizer said three to five SRS sessions should be considered standard postoperative treatment for patients with larger brain metastases; Kotecha’s statement likewise tied that standard to cases where postoperative external-beam radiotherapy is chosen.

The next evidence needed includes further analysis of the survival difference and direct comparisons among postoperative radiation options, as Kotecha noted. The meeting report does not specify a date for additional trial results or a change to treatment guidelines. For now, the findings support fractionated SRS as an evidence-backed option for patients resembling those enrolled, while leaving broader treatment comparisons and the survival explanation unresolved.

Key Questions

What did the A071801 trial compare?

It compared single-fraction SRS with fractionated SRS after surgery in patients with up to four brain metastases, including one resected lesion at least 2 centimeters in size.

How much did one-year surgical-bed control differ?

Control at one year was 87% with fractionated SRS and 81% with single-fraction SRS among patients evaluable for the primary endpoint.

Did fractionated SRS improve overall survival?

Median overall survival was 28.6 months with fractionated treatment and 20.2 months with single-fraction treatment. Overall survival was a secondary endpoint, and the reason for the difference remains unclear.

Were toxicity rates higher with fractionated SRS?

The report found similar rates of radiation necrosis and cerebral edema in the two groups. It did not establish that every possible short- or long-term side effect is the same.

How was fractionated SRS delivered?

Patients received either 27 Gy over three sessions or 30 Gy over five sessions, with the regimen depending on lesion size.

Source: rss