Mmap-15 Surgical Resection Results in Improved Seizure Outcomes in Epileptogenic Brain Metastases Compared to Radiosurgery Alone

BACKGROUND Seizure is a common and potentially disabling complication of brain metastasis (BrM). Local ablative therapies for BrM, including surgical resection with adjuvant stereotactic radiosurgery and stereotactic radiosurgery alone, have undefined seizure outcomes. We sought to define and compare these outcomes in patients with epileptogenic brain metastasis treated with either modality. METHODS Patients who received definitive stereotactic radiosurgery (SRS) or neurosurgical resection (R) plus adjuvant SRS for BrM at an NCI-designated Comprehensive Cancer Center between 2015 and 2023 were retrospectively reviewed. Patients with seizure and semiology attributable to an active, previously untreated metastasis were included. Clinical characteristics were extracted from the medical record. Actuarial estimates and Cox proportional hazards models compared seizure outcomes between modalities. RESULTS R+SRS (n=75) and SRS (n=103) groups were similar in baseline characteristics, but R+SRS patients had larger tumor diameter (mean [SD]: 2.80 [0.833] vs. 1.87 [0.668] cm; p<0.001). Radiation course also differed by treatment (% R+SRS vs. SRS patients [dosage in Gy, fractions]: 57.3% vs. 17.5% [30,5], 30.7% vs. 48.5% [27,3], 1.3% vs. 21.4% [21,1], 10.7% vs. 12.6% [other]; p<0.001). R+SRS patients were more likely to be seizure-free at 6-months post-treatment compared to SRS patients (estimated seizure-free probability [95%CI]: 0.860 [0.784,0.945] vs. 0.667 [0.577,0.770]; p=0.002) despite similar rates of active anticonvulsant use (85.7% vs. 82.6%; p=0.644). Under the univariate Cox model, R+SRS treatment demonstrated a 65.5% reduction in 6-month seizure recurrence hazard relative to SRS treatment (HR=0.345; 95%CI [0.169,0.703]; p=0.003). After adjustment for significant covariates including race, tumor diameter, and radiation dose and fractionation, this trend persisted (HR=0.413; 95%CI [0.179,0.955]; p=0.039). CONCLUSION Patients with BrM-related seizures treated with resection and adjuvant stereotactic radiosurgery demonstrated greater 6-month seizure freedom and reduced post-treatment seizure hazard compared to those treated with radiosurgery alone. This discrepancy should be considered in local treatment planning for BrM.