Correlation between time to postoperative seizure onset and time to tumor progression in a cohort of adult-type diffuse gliomas with molecular characterization.

Abstract

Objective: Seizure is frequently a presenting symptom for patients with diffuse glioma, and seizures can remain common throughout the disease course. Patients can develop seizures despite resection, and the relationship among postoperative seizures, tumor genetics, and tumor progression is unclear. The aim of this study was to characterize the clinical and genetic factors associated with delayed postoperative seizures in adult patients who had undergone resection of diffuse gliomas and to investigate the relationship between time to seizure onset and progression-free survival (PFS).

Methods: The authors performed a retrospective registry chart review of adults who had undergone resection of diffuse gliomas at a single institution up until 2020 and for whom targeted next-generation sequencing was available. Linear regression was used to model the relationship between time to postoperative seizure and time to tumor progression. Cox proportional hazards regression was performed to identify factors associated with time to postoperative seizures. Seizures within 72 hours of surgery were considered immediate postoperative seizures and were excluded from this study.

Results: Five hundred thirty-one patients were identified and included in the study. Among these patients, 176 IDH-mutant and 355 IDH-wildtype gliomas were resected up until 2020. The median follow-up was 28.3 months. In the patients with IDH-mutant tumors, seizures that occurred at least 17 months after surgery were strongly correlated with tumor progression; for patients with IDH-wildtype tumors, this correlation occurred at least 2 months after surgery. Male sex, seizure at initial presentation, and MDM2 mutation were significantly associated with worse seizure-free survival in patients with IDH-wildtype gliomas, whereas the SETD2 mutation was associated with improved seizure freedom. In IDH-mutant glioma cases, a higher preoperative Karnofsky Performance Status and NIPBL mutation predicted longer seizure freedom. More than 12 months of postoperative seizure freedom was associated with improved PFS and overall survival regardless of IDH mutation status.

Conclusions: The development of seizures after surgery might predict a risk of tumor progression if they occur beyond a postoperative period unique to IDH status. Specifically, an MDM2 mutation and presentation with seizures were strong predictors of tumor progression in glioblastoma (GBM). SETD2 and NIPBL mutations might predict greater seizure freedom in GBM and IDH-mutant gliomas, respectively.