Incorporating an NCCN-Based Systemic Therapy CNS Activity Score Into SRS Decision-Making for Patients With 5 or More...

Historically, patients with ≥5 brain metastases (BM) were considered borderline or poor candidates for stereotactic radiosurgery (SRS). With increased survival and expanded treatment options for BM in the modern era, paradigms of BM management warrant reevaluation. Our objective was to determine whether overall survival (OS) differs between patients receiving SRS for 5 to 9 BMs versus ≥10 BMs and to identify factors associated with favorable outcomes.

We identified patients with ≥5 BMs treated with SRS at a single institution between 2015 and 2022 who had not received prior central nervous system (CNS) radiation. The CNS activity of systemic regimens was classified according to the 2024 NCCN Guidelines. Outcomes included OS, whole-brain radiation therapy-free survival (WBRT-FS), and CNS progression-free survival (CNS-PFS).

A total of 557 patients received Gamma knife surgery to ≥5 BMs (range, 5-23). Median OS time was 11.0 months and did not differ for patients with 5 to 9 BMs (n=440) and those with ≥10 BMs (n=117) (P=.52). On multivariable analysis, improved performance status (hazard ratio [HR], 0.956; P<.001) and receipt of CNS-active systemic therapy after SRS (HR, 0.518; P<.001) were associated with improved OS. Lesion number was not associated with OS (HR, 1.012; P=.466). We created a nomogram predicting 6- and 12-month WBRT-FS that performed well on a validation cohort of (area under receiver operating characteristic curve, 0.8).

Lesion number did not influence OS in patients with ≥5 BMs. Good performance status, receipt of CNS-active systemic therapy after SRS, and stable systemic disease predicted improved OS and WBRT-FS. Our publicly available online nomogram can inform patient-specific treatment decisions for individuals with ≥5 BMs (https://medcalc.mdanderson.org/WbrtCalc).