Do the benefits of IDH mutations in high-grade glioma persist beyond the first recurrence? A multi-institutional retrospective analysis

Purpose: Recurrence is inevitable in both IDH wild-type glioblastoma and IDH-mutant WHO grade 3 or 4 astrocytoma. While IDH-mutant astrocytomas are associated with longer survival and delayed first progression, less is known about disease course beyond initial treatment. This study examines whether IDH mutation status influences time to second recurrence and identifies additional predictors of recurrence intervals. Methods: This retrospective, multi-institutional study included adults diagnosed with pathologically confirmed high-grade glioma (HGG) between 2015 and 2020. HGG refers to IDH-mutant WHO grade 3 or 4 astrocytomas and IDH wild-type glioblastomas, consistent with WHO CNS5 criteria. Demographics, treatment, extent of resection, and molecular markers were analyzed. Time-to-recurrence was calculated per RANO 2.0 criteria. Statistical tests included Mann‒Whitney U, Fisher’s exact, and Cox regression. Results: Among 319 patients, 121 met inclusion criteria. Fourteen (11.6%) had IDH-mutant astrocytomas, and 107 (88.4%) had IDH wild-type glioblastomas. Mean time to first recurrence was significantly longer in IDH-mutant patients (17.5 months) than IDH wild-type (9.8 months, p = 0.0130). Mean time-to-second recurrence was not significantly different (IDH-mutant: 10.8 months, IDH wild-type: 8.1 months, p = 0.176). Multivariate analysis found IDH wild-type status (p = 0.0491) and Black race (p = 0.0238) predicted shorter time to first recurrence. Conclusions: IDH mutation status significantly affects time to first but not second recurrence. This study offers insight into recurrence patterns and highlights disparities in disease progression.