# Risk Factors and Prognostic Implications of Tumor‐Related Epilepsy in Diffuse Glioma Patients: A Real‐World Multicenter Study

## TL;DR

This study finds that tumor-related epilepsy in brain cancer patients may not independently predict survival, but is linked to other factors like age and tumor location.

## Contribution

The study provides new insights into how tumor-related epilepsy correlates with survival outcomes in different glioma subtypes using a large multicenter dataset.

## Key findings

- TRE incidence was highest in lower-grade oligodendroglioma/astrocytoma (44.4%) and lowest in high-grade gliomas (16.5%).
- Age was an independent predictor of TRE in lower-grade gliomas, while absence of deep structure involvement was linked to TRE in unclassified and high-grade gliomas.
- TRE was associated with longer survival in univariate analysis but not in multivariate models, suggesting it is not an independent prognostic factor.

## Abstract

The relevance of tumor‐related epilepsy (TRE) to glioma survival is controversial. This study aimed to assess the risk factors and prognostic impact of TRE in adult patients with diffuse gliomas by integrating clinical, radiological, and molecular data.

This multicenter retrospective study included 1036 adult patients with diffuse gliomas from local hospitals and the POLA Network. Patients were categorized into three prognostic groups: lower‐grade oligodendroglioma/astrocytoma (OD/AC, II–III, IDH‐MT), not otherwise specified or not elsewhere classified (NOS/NEC, II–III, IDH‐WT), and high‐grade gliomas (HGG, IV). Clinico‐radiological, molecular, and therapeutic factors were analyzed using univariate and multivariate logistic regression, with the Cox proportional hazards model applied to identify independent prognostic factors for progression‐free survival (PFS) and overall survival (OS).

TRE occurred in 44.4% of OD/AC patients, 25.8% of NOS/NEC patients, and 16.5% of HGG patients. Multivariate analysis identified age as the only significant independent correlate of TRE in the OD/AC group (OR = 0.961; p = 0.004), while the absence of deep structure involvement was independently associated with TRE in the NOS/NEC and HGG groups. In univariate analysis, the presence of TRE was associated with longer PFS and OS across all groups, particularly in the NOS/NEC group, where patients with TRE had a median PFS of 35.2 months compared to 13.6 months in those without TRE (p = 0.02), but was not a significant predictor in multivariate analyses. TRE was the only factor significantly associated with maintaining histological grade at recurrence (HR = 0.094; p = 0.005).

TRE was not a strong independent prognostic factor after controlling for clinical and molecular tumor features, suggesting that the prognostic relevance of TRE is likely driven by underlying glioma biology and other associated clinical factors.

This multi‐center retrospective study evaluated the risk factors and prognostic impact of tumor‐related epilepsy (TRE) in 1,036 adult patients with diffuse gliomas. Patients were classified into three prognostic groups: OD/AC (IDH‐MT, lower‐grade gliomas), NOS/NEC (IDH‐WT, unclassified grade II‐III), and HGG (high‐grade gliomas). TRE incidence was highest in OD/AC (44.4%) and lowest in HGG (16.5%). Age was an independent predictor of TRE in OD/AC, while the absence of deep structure involvement was linked to TRE in NOS/NEC and HGG. Univariate analysis showed TRE was associated with longer progression‐free survival (PFS) and overall survival (OS), particularly in NOS/NEC patients (median PFS: 35.2 vs. 13.6 months, P = 0.02). However, TRE was not a significant prognostic factor in multivariate models. These findings suggest TRE's prognostic role is likely influenced by glioma biology and clinical factors rather than being an independent predictor of survival outcomes.