Diffuse brainstem gliomas across the pediatric, adolescent, and adult age spectrum: Clinical and radiological features, molecular profile, and determinants of survival in a multicenter retrospective cohort of 42 patients
Andrea Garcia-Bitar, Guillermo Axayacalt Gutierrez-Aceves, Alejandro Rodriguez-Camacho, Jorge Alejandro Torres-Rios, Jose Guillermo Flores-Vazquez, Lilian Zavala-Romero, Gerardo Gomez-Castro, Alejandro Salazar-Pigeon, Sergio Moreno-JiménezBackground:
Diffuse brainstem gliomas are infiltrative neoplasms classically described in children as diffuse intrinsic pontine glioma, but increasingly recognized in adults. We describe the clinical, radiological, molecular, and survival characteristics of a cohort spanning the full age spectrum and identify determinants of overall survival (OS).
Methods:
Retrospective analysis of 42 consecutive patients with a clinical-radiological diagnosis of diffuse brainstem glioma treated between 1996 and 2025 at two neuro-oncology referral centers in Mexico. Demographic, clinical, imaging, biopsy, molecular (histone H3 lysine-27-to-methionine mutation [H3 K27M], isocitrate dehydrogenase 1 [IDH1], O 2 -methylguanine-DNA methyltransferase [MGMT], codeletion of chromosome arms 1p and 19q [1p/19q], epidermal growth factor receptor [EGFR], and tumour protein 53 gene [TP53]), and treatment variables were analyzed after a database audit. OS was estimated by Kaplan–Meier, compared by log-rank test, and modeled by multivariable Cox regression.
Results:
Median age at onset was 31.1 years (range 7.8–65.7); 10 patients (23.8%) were younger than 18 years, and 33 (78.6%) were male. Stereotactic biopsy was performed in 32 patients (76.2%). H3 K27M was mutant in 12 (28.6%). Median OS was 23.3 months (95% confidence interval [CI] 14.7–32.5). H3 K27M mutation (hazard ratio [HR] 10.35; 95% CI 3.77–28.40) and contrast enhancement (HR 2.71; 95% CI 1.28–5.71) were independent adverse prognostic factors (concordance index 0.76). A score combining both features separated low-, high-, and very-high-risk groups, with median OS of 36.3, 20.5, and 9.7 months ( p < 0.001).
Conclusion:
H3 K27M status and contrast enhancement were the strongest independent determinants of survival and jointly provide an accessible prognostic score. These findings support systematic molecular characterization, aided by stereotactic biopsy when safely feasible, for prognostic stratification and access to targeted therapies.