Higher perioperative dexamethasone exposure is associated with shorter survival in glioblastoma

Dexamethasone (DEX) is routinely administered perioperatively to manage tumor-associated vasogenic edema in glioblastoma (GBM), yet increasing evidence suggests that corticosteroid exposure may adversely affect survival. The magnitude of this association during the initial neurosurgical phase of care remains unclear.

We performed a retrospective cohort study of patients with histologically confirmed IDH-wildtype GBM treated at a single tertiary center between 2009 and 2020. All perioperative DEX doses from admission to discharge were extracted from daily medical records. Patients were stratified based on the cumulative dose into low-dose exposure (<34 mg) and high-dose exposure (≥34 mg) groups using maximally selected rank statistics. Overall survival was analyzed using Kaplan-Meier estimates with log-rank test and multivariable Cox proportional hazards models. Adjustment variables were selected using a prespecified, causally informed framework to address confounding.

A total of 420 patients were included. The majority (n = 341; 81.2%) received ≥34 mg DEX perioperatively. Median OS was 13.6 months in the high-dose group and 15.0 months in the low-dose group, with significantly shorter survival observed in the high-dose cohort (log-rank P = .0103). In the adjusted Cox model, cumulative DEX ≥ 34 mg remained independently associated with increased mortality (HR: 1.40, 95% CI: 1.07-1.83; P = .013).

Higher perioperative DEX doses were independently associated with shorter overall survival in GBM patients, emphasizing the need for judicious perioperative use with prompt tapering. Prospective studies are warranted to guide evidence-based DEX management in GBM care.