Preoperative Radiosurgery for Resected Brain Metastases: The PROPS-BM Multicenter Cohort Study

Abstract

Preoperative (pre-op) SRS has been demonstrated to be a feasible alternative to postoperative (post-op) SRS primarily based on single institution studies with potential benefits in adverse radiation effect (ARE) and leptomeningeal disease (LMD) compared to post-op SRS. This study (Preoperative Radiosurgery for Brain Metastases - PROPS-BM) reports pre-op SRS treatment details and outcomes from a large multicenter cohort.Patients (pts) with brain metastases (BM) from solid cancers, of which at least 1 lesion was treated with pre-op SRS and underwent planned resection were included from 5 institutions. SRS to synchronous intact BM was allowed. Exclusion criteria included classically radiosensitive or non-solid cancers, prior or planned whole brain radiotherapy (WBRT), and < 3 months of cranial imaging follow-up. SRS dose, fractionation, and interval between pre-op SRS and surgery was as per individual institutional protocol. Intracranial outcomes were estimated using cumulative incidence with competing risk of death and overall survival (OS) was estimated using the Kaplan-Meier method with the date of resection considered time 0. Radiographic LMD was categorized as nodular (nLMD) or classical "sugarcoating" (cLMD).The cohort included 242 pts with 253 pre-op treated index lesions. The majority of pts (62.4%) had a single BM, 93.7% underwent gross total resection (GTR), and 98.8% were treated with a single fraction to a median dose of 15 Gy to a median gross tumor volume (GTV) of 9.9 cc. Median interval between pre-op SRS and surgery was 1 day. Most pts had non-small cell lung (43.4%), breast (20.2%), or melanoma (12.8%) cancer. The table below details 1 and 2-year outcomes. Extent of resection was a strong independent predictor of cavity local recurrence (LR) with LR occurring in 7 of 16 cavities (43.8%) status post subtotal resection (STR) compared with 32 of 237 (13.5%) cavities status post GTR (P = 0.005). The majority of LMD was cLMD type (13 of 19 pts with LMD, 68.4%). Ten of 242 pts (4.1%) experienced grade ≥3 post-op surgical complications.This multicenter cohort study represents the largest population of pts treated with pre-op SRS to our knowledge. Approximately half of the pts included are from previously unpublished cohorts. The favorable oncologic outcomes, especially the notably low rates of LMD and ARE, previously demonstrated in single institution studies are confirmed in this expanded multicenter analysis without evidence of excessive post-op surgical complications. STR, though infrequent, is associated with significantly worse cavity LR in this setting. A randomized trial between pre-op and post-op SRS is warranted and is currently being designed.