Clinical and molecular characteristics of thalamic gliomas in adults: prognostic impact of TERT promoter mutation

Abstract

BACKGROUND: Adult thalamic gliomas (ATGs) are rare and biologically heterogeneous tumors. Although the 2021 World Health Organization (WHO) classification designates all diffuse midline gliomas (DMGs), H3-altered, as grade 4, accumulating evidence suggests that adult thalamic DMGs may exhibit more indolent clinical behavior, compared with glioblastomas or pediatric DMGs. In this study, we aimed to characterize the clinical, radiological, pathological, and molecular features of ATGs and identify clinically relevant prognostic markers, with particular focus on H3K27M and TERT promoter (TERTp) mutations. METHODS: We retrospectively analyzed 45 adult patients (≥ 18 years) who underwent surgical resection or biopsy for ATGs between 2007 and 2023. Clinical, radiological, pathological, and molecular data were collected, and prognostic factors for overall survival were evaluated. RESULTS: Patients with thalamic DMG demonstrated significantly longer overall survival (OS) than those with glioblastoma (median OS, 24.6 vs. 12.4 months; p = 0.035). In multivariate Cox regression analysis adjusted for age, WHO grade, H3K27M status, and TERTp status, TERTp mutation emerged as an independent predictor of poor survival (hazard ratio [HR], 1.81; p = 0.026), whereas H3K27M mutation was not significantly associated with outcome (HR, 0.93; p = 0.77). Younger age (< 45 years) was independently associated with longer OS, and WHO grade 4 with shorter survival; however, the survival curves overlapped substantially across histological grades. CONCLUSIONS: In ATGs, TERTp mutation was an independent predictor of poor survival and provided prognostic information beyond H3K27M status. These findings support incorporating TERTp status into risk stratification for ATGs.