Abstract Background Adult IDH-mutant brainstem gliomas (BSGs) are rare and appear molecularly distinct from H3K27-altered diffuse midline gliomas. We aimed to provide a comprehensive characterization by integrating an institutional cohort with a pooled individual-patient analysis. Methods Adults with IDH-mutant BSGs diagnosed at our institution were identified. A PRISMA-guided search of PubMed and Scopus captured additional cases. Individual-level demographic, radiographic, molecular, treatment, and outcome data were abstracted. Kaplan-Meier and log-rank testing evaluated survival associations with age, sex, WHO grade, surgery, chemoradiation, IDH variant, MGMT methylation, ATRX status, and location. Results Eighty-four patients were analyzed (n = 7 institutional, n = 77 literature-derived). Mean age was 37.8 years; 68.6% male. Most tumors involved the pons/medulla (90.4% astrocytomas; 68.7% WHO grade 2). Among evaluable cases, MGMT methylation was present in 47.5%, ATRX loss in 53.2%, and TP53 mutation in 84.3%. Non-canonical IDH variants accounted for 45.3% of cases. Median overall survival (OS) was 77.3 months. In multivariate analysis, non-canonical IDH variants independently predicted improved OS (HR = 0.37, P = .012), while surgical resection showed a strong clinical trend toward improved OS (HR = 0.48, P = .073). Chi-squared analysis confirmed no significant difference in high-grade tumor distribution between resection and biopsy groups (P = .52), suggesting the trend was not driven by selection bias. Conclusions Adult IDH-mutant BSGs represent a clinically meaningful subgroup with outcomes more favorable than H3K27-altered gliomas but shorter than supratentorial IDH-mutant gliomas. Their recurrent molecular features, including frequent non-canonical IDH variants, warrant study in larger cohorts to clarify biological significance, refine prognostication, and inform the potential role of IDH-targeted therapies.
Ghoche et al. (Sat,) studied this question.