Abstract
<title>Abstract</title> <p>Background Preoperative prognostication in glioblastoma remains challenging despite advances in histomolecular classification. Navigated transcranial magnetic stimulation (nTMS) enables non-invasive assessment of cortical excitability, but its role as a survival biomarker remains unclear. Objective To determine whether preoperative nTMS-derived cortical excitability metrics independently predict overall survival (OS) in patients with WHO grade 4 IDH-wildtype glioblastoma. Methods This single-centre retrospective cohort study included patients undergoing resection for motor-eloquent WHO grade 4 IDH-wildtype glioblastoma between 2018 and 2024. Preoperative nTMS mapping was used to derive the IntraM1 Excitability Score (IMES) and Cortical Excitability Score (CES). Cox regression adjusted for age, sex, neurological deficit, MGMT methylation, and extent of resection. Results Seventy-seven patients were included (mean age 55.4 ± 16.0 years; 41 males; mean OS 20.5 months). Lower IMES and higher CES were associated with worse OS on univariate analysis and remained independently prognostic on multivariate analysis: IMES (HR 0.15, p = 0.003) and CES (HR 2.52, p = 0.031). Bilateral nTMS improved 12-month survival prediction over unilateral mapping. Conclusions Preoperative nTMS-derived cortical excitability metrics independently predict OS after adjustment for established prognostic factors, supporting excitability profiling as a clinically actionable prognostic tool in glioblastoma.</p>