Early Mortality in Patients with Biopsy-Only Glioblastoma: Clinical, Radiological and Molecular Predictors from a Retrospective Cohort

Abstract

Background/Objectives: Patients with unresectable glioblastoma (GBM) undergoing biopsy alone represent a clinically heterogeneous population with poor survival and limited access to standard oncological treatment. We investigated clinical, radiological, and histomolecular factors associated with early mortality after biopsy. Methods: We retrospectively analyzed 93 consecutive cases of patients with IDH-wildtype GBM who underwent biopsy without tumor resection between 2013 and 2025. Early death was defined as death within three months of biopsy. Baseline clinical, radiological, and molecular variables were evaluated using univariable analyses and exploratory multivariable logistic regression. Results: Median overall survival was 3 months, and 48/89 patients with available survival data (53.9%) died within three months. Preoperative Karnofsky Performance Status (KPS) and MGMT promoter methylation status (available for 71/93 patients) were nominally associated with early mortality in univariable analyses, although these associations did not remain significant after FDR correction. Age was not significant in univariable analysis but was associated with early mortality after adjustment in the exploratory multivariable model based on 62 complete cases. Conventional radiological parameters showed no consistent association with early death. Exploratory analysis suggested a high-risk phenotype combining KPS ≤ 60 and FLAIR signal crossing the midline. Overall, 23/93 patients (24.7%) did not initiate any adjuvant treatment, while only 17/93 (18.3%) completed the Stupp regimen. Conclusions: Early mortality is frequent in biopsy-only GBM. Clinical and molecular factors may help identify particularly vulnerable patients at diagnosis, supporting individualized treatment planning and shared decision-making. External validation in larger multicenter cohorts is warranted.