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Purpose Preoperative stereotactic radiosurgery (SRS) has been proposed as a strategy to reduce nodular leptomeningeal disease (nLMD) after resection of brain metastases by devitalizing tumor cells prior to surgical manipulation. This study aimed to determine the safety of preoperative SRS via a phase 1 dose escalation trial and compare outcomes—including nLMD, classical LMD (cLMD), local control, and overall survival (OS)—between preoperative and postoperative treatment cohorts. Methods A phase 1 trial evaluated the safety of single-fraction preoperative SRS at escalating doses (12 and 15 Gy) in patients with tumors 2–6 cm. Adverse events (AEs) were assessed per CTCAE v4.0, with dose-limiting toxicity (DLT) defined as high-grade neurologic or wound complications. Retrospective analysis included an expanded preoperative cohort (n=95) and a historical postoperative cohort (n=107). Outcomes were analyzed with Kaplan-Meier and Cox proportional hazards models. Results Fifteen Gy was well tolerated in the phase 1 cohort, with no DLTs in larger tumors (4–6 cm) and three DLTs in smaller tumors, not meeting thresholds for dose de-escalation. In the expanded analysis, preoperative SRS significantly reduced rates of nLMD (7.4% vs 27.1%, p=0.002), while rates of cLMD (4.2% vs 4.5%) and local failure (14.6% vs 18.7%) were similar between groups. OS was also similar (median 12.8 vs 12.3 months). Multivariable analysis confirmed preoperative SRS as protective against nLMD (HR=0.18, 95%CI: 0.07–0.43, p<0.001). Conclusions Preoperative SRS to 15 Gy is safe for tumors 2–6 cm and significantly reduces nLMD without compromising local control or OS. These findings support preoperative SRS as a viable treatment strategy and justify further investigation into optimal dosing and patient selection.
Hoyle et al. (Fri,) studied this question.