Fractionated SRS Improves Local Control After Brain Metastasis Resection

Local control after surgical removal of large brain metastases improved significantly when patients received fractionated stereotactic radiosurgery (SRS) instead of single-fraction SRS, a randomized trial showed.

Surgical-bed control at 1 year improved from 81% with single-fraction SRS to 87% with fractionated SRS. Fewer patients in the latter group required salvage treatment with whole-brain radiation therapy (WBRT), and overall survival (OS), a secondary endpoint, improved from 20.2 months to 28.6 months, respectively.

The benefits of fractionated SRS occurred with no increase in toxicity, reported Ayal Aizer, MD, of Mass General Brigham and Dana-Farber Cancer Institute in Boston, at the American Society for Radiation Oncology (ASTRO) annual meeting in Boston.

“We can state that 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,” said Aizer. “For patients undergoing resection of a larger brain metastasis, postoperative fractionated stereotactic radiosurgery should be considered the standard of care.”

“This study moves fractionated radiosurgery from a reasonable practice supported by retrospective data to one backed by a randomized phase III trial,” he added. “We now have the strongest evidence to date that three to five sessions [of SRS] should be considered a standard postoperative treatment for patients with larger brain metastases.”

All existing radiotherapy approaches have distinct pros and cons, and clinical trials directly comparing different modalities are needed to determine an optimal approach, said ASTRO discussant Rupesh Kotecha, MD, of Baptist Health Herbert Wertheim Cancer Institute in Miami. Although the results showed a significant improvement in surgical-cavity local control, with no increase in toxicity, the OS difference requires more study to explore potential explanations.

“The bottom line: If postoperative external beam radiotherapy is chosen after upfront resection, then postoperative fractionated radiosurgery is the new standard of care,” said Kotecha.

By way of introduction to the results, Aizer noted that two randomized trials, a multicenter trial conducted in North America and a single-center study, established single-fraction SRS as the standard of care after surgical resection of brain metastases. However, the 1-year surgical-bed recurrence rate was high in both studies (40% and 28%, respectively).

“Subset analysis of [the single-center trial] indicated that larger metastases were especially prone to poorer surgical-bed control after single-fraction SRS,” said Aizer.

Multiple retrospective studies have shown that fractionated SRS achieves good local control, usually with three to five fractions. To confirm those observations, investigators in the Alliance Clinical Network sponsored the multicenter A071801 trial comparing single-fraction SRS versus fractionated SRS in patients with up to four brain metastases, including one resected metastasis ≥2 cm.

Patients assigned to single-fraction SRS received variable doses to the resected and unresected lesions, dependent on lesion size. Patients in the fractionated SRS group received 27 Gy in three fractions or 30 Gy in five fractions to the surgical bed and unresected lesions, also dependent on lesion size. The primary endpoint was surgical-bed control at 1 year, and OS was the key secondary endpoint.

The investigators randomized 242 patients, 223 of whom proved to be evaluable for the primary endpoint. The primary analysis showed that fractionated SRS reduced the hazard for surgical-bed control by 47% (95% CI 0.28-1.00, P=0.046). Patterns and rates of intracranial recurrence were similar between the groups, the most common type of recurrence being new brain metastases (38% vs 34%).

Freedom from salvage WBRT at 1 year also favored the fractionated arm (94% vs 84%). The 8.4-month difference in median OS translated into a hazard ratio of 0.66 in favor of fractionated SRS (95% CI 0.46-0.94, P=0.02).

Rates of radiation necrosis and cerebral edema were similar between the single-fraction SRS (11% and 9%) and fractionated SRS (13% and 8%) groups.