P12.13.B PROGNOSTIC IMPACT OF NEUROTRANSMISSION-MODULATING CONCOMITANT TREATMENTS IN HIGH-GRADE GLIOMA: A RETROSPECTIVE COHORT STUDY

Abstract BACKGROUND Emerging insights from cancer neuroscience highlight that neuronal activity and neuron-tumor interactions could significantly influence glioma progression. Commonly prescribed systemic medications—such as antiepileptics, antidepressants, benzodiazepines, calcium channel blockers and beta-blockers—modulate neurotransmission and may affect clinical outcomes in patients with high-grade glioma (HGG). This study aims to evaluate the prognostic impact of these treatments using real-world data. MATERIAL AND METHODS We retrospectively analyzed a monocentric cohort of HGG patients treated between 2009 and 2021 at Gustave Roussy. Collected data included clinical, pathological, molecular, and imaging parameters, as well as information on concomitant medications with potential neuroactive effects (e.g., serotoninergic antidepressants, antiepileptics, benzodiazepines, calcium channel blockers and beta-blockers). Survival outcomes, including progression-free survival (PFS) and overall survival (OS), were analyzed using Cox proportional hazards regression models. For the multivariate analysis, variables that demonstrated a p-value ≤ 0.05 in univariate analyses were included in the model. Hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated to assess the association between covariates and survival outcomes. RESULTS A total of 335 patients were analyzed. Median OS was 20.2 months (3.0-134.5), PFS 9.6 months (1.9-125.9), and follow-up 19.1 months. Regarding concomitant treatments, 300 patients (90%) patients received antiepileptics, 203 (61)% benzodiazepines, 76 (23%) calcium channel blockers, 63 (19%) serotoninergic antidepressant, and 22 (7%) received beta-blockers In multivariable Cox analysis for OS, four independent prognostic factors were identified: Greater extent of surgery (HR = 0.82, 95% CI [0.71-0.96], p = 0.01), adjuvant temozolomide (HR = 0.56, 95% CI [0.40-0.78], p < 0.005), and antiepileptic use (HR = 1.55, 95% CI [1.01-2.38], p = 0.05). For PFS, only adjuvant temozolomide was independently associated with improved outcome (HR = 0.36, 95% CI [0.26-0.50], p < 0.005. CONCLUSION In this cohort of 335 high-grade glioma patients, antiepileptic drug use was independently associated with worse overall survival—an unexpected result, given prior reports suggesting neutral or beneficial effects. This paradox highlights the need to further explore specific molecules and their interactions with tumor biology. No survival impact was found for benzodiazepines or serotonergic antidepressants, despite preclinical evidence of potential glioma-modulating effects. These findings call for a re-evaluation of the clinical relevance of neurotransmission-modulating treatments in the context of neuron-tumor interactions.