Neoadjuvant Stereotactic Radiosurgery for Large Brain Metastases: An International, Multicenter, Single-Arm Phase II...

Previous reports have suggested that neoadjuvant stereotactic radiosurgery (SRS) for brain metastases (BrMets) mitigates the elevated risks of radiation necrosis (RN) and meningeal recurrence associated with adjuvant SRS. We report treatment outcomes from a multicenter phase II trial (NCT03368625) of single-fraction neoadjuvant SRS for large BrMets.

Patients with 1 index BrMet requiring resection and up to 9 nonindex BrMets not requiring resection were recruited across 3 centers and treated with single-fraction SRS (14-21 Gy) targeting the index lesion with a 2-mm margin, followed by surgical resection. Nonindex lesions were targeted with definitive SRS. The primary end point was 1-year rate of grade 2+ RN affecting the index lesion. Secondary end points included median overall survival, 2-year intracranial progression-free survival, and 1-year rates of local failure (LF) affecting the index lesion, leptomeningeal disease, and pachymeningeal disease.

Between April 2018 and November 2022, 35 patients were enrolled; the median follow-up period was 11.8 months (IQR: 6.14, 15.9). No patients developed grade 2+ RN. Six patients experienced LF (1-year rate: 18.0% [95% CI: 7.03, 32.9]); 1 patient developed classic leptomeningeal disease (1-year rate: 2.9% [95% CI: 0.21, 12.9]), and 1 patient developed pachymeningeal disease (1-year rate: 3.2% [95% CI: 0.22, 14.6]). The median overall survival was 13.8 months (95% CI: 8.15, 22.4), and the 2-year intracranial progression-free survival was 29.5% (95% CI: 13.8, 63.1).

In this study, no patients experienced symptomatic RN and the incidence of meningeal failure was lower than historical rates associated with postoperative SRS. However, the high 1-year rate of LF suggests a potential benefit for higher or fractionated radiation doses or larger clinical target volume margins.