Risk Factors for Progression and Toxic Effects After Preoperative Stereotactic Radiosurgery for Patients With Resected Brain Metastases

Abstract

ImportancePreoperative stereotactic radiosurgery (SRS) has been demonstrated as a feasible alternative to postoperative SRS for resectable brain metastases (BMs) with potential benefits in adverse radiation effects (AREs) and meningeal disease (MD). However, mature large-cohort multicenter data are lacking.ObjectiveTo evaluate preoperative SRS outcomes and prognostic factors from a large international multicenter cohort (Preoperative Radiosurgery for Brain Metastases–PROPS-BM).Design, Setting, and ParticipantsThis multicenter cohort study included patients with BMs from solid cancers, of which at least 1 lesion received preoperative SRS and a planned resection, from 8 institutions. Radiosurgery to synchronous intact BMs was allowed. Exclusion criteria included prior or planned whole-brain radiotherapy and no cranial imaging follow-up. Patients were treated between 2005 and 2021, with most treated between 2017 and 2021.ExposuresPreoperative SRS to a median dose to 15 Gy in 1 fraction or 24 Gy in 3 fractions delivered at a median (IQR) of 2 (1-4) days before resection.Main Outcomes and MeasuresThe primary end points were cavity local recurrence (LR), MD, ARE, overall survival (OS), and multivariable analysis of prognostic factors associated with these outcomes.ResultsThe study cohort included 404 patients (214 women [53%]; median [IQR] age, 60.6 [54.0-69.6] years) with 416 resected index lesions. The 2-year cavity LR rate was 13.7%. Systemic disease status, extent of resection, SRS fractionation, type of surgery (piecemeal vs en bloc), and primary tumor type were associated with cavity LR risk. The 2-year MD rate was 5.8%, with extent of resection, primary tumor type, and posterior fossa location being associated with MD risk. The 2-year any-grade ARE rate was 7.4%, with target margin expansion greater than 1 mm and melanoma primary being associated with ARE risk. Median OS was 17.2 months (95% CI, 14.1-21.3 months), with systemic disease status, extent of resection, and primary tumor type being the strongest prognostic factors associated with OS.Conclusions and RelevanceIn this cohort study, the rates of cavity LR, ARE, and MD after preoperative SRS were found to be notably low. Several tumor and treatment factors were identified that are associated with risk of cavity LR, ARE, MD, and OS after treatment with preoperative SRS. A phase 3 randomized clinical trial of preoperative vs postoperative SRS (NRG BN012) has began enrolling (NCT05438212).

Symptomatic radionecrosis after postoperative but not preoperative stereotactic radiosurgery in a single patient: illustrative case

“…Early studies demonstrated low rates of LMD after preoperative SRS, sparking large randomized clinical trials (NCT05438212) to further establish the possible benefits of preoperative SRS. 2 , 3 , 5 , 16 It has been postulated that preoperative SRS may reduce LMD rates by treating the lesion prior to potential tumor spillage during surgery, thereby making cellular spread into the leptomeninges unviable. 2 , 3 , 5 , 14–16 …”

Stereotactic Radiosurgery in the Management of Brain Metastases: A Case-Based Radiosurgery Society Practice Guideline

“… 21 , 22 This risk provides a rationale for preoperative SRS, which is hypothesized to decrease the risk of LMD, with initial studies demonstrating meningeal disease rates of 5.8% compared with 16% to 21% in the postoperative setting. 48 , 49 , 50 Other potential benefits of preoperative SRS include improved logistics due to not having to coordinate postoperative treatment, earlier initiation of systemic therapy, and ability to treat to doses that are about 20% to 25% lower. 49 , 51 A potential disadvantage of preoperative SRS is the risk of irradiation of benign or primary CNS lesions, which has been reported to occur in 2% to 11% of patients.…”