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. 2022 Apr 29;30(1):99-106.
doi: 10.3171/2022.3.PEDS2250. Print 2022 Jul 1.

Risk stratification of H3 K27M-mutant diffuse midline gliomas based on anatomical locations: an integrated systematic review of individual participant data

Huy Gia Vuong  1 , Hieu Trong Le  2 , Andrew Jea  1 , Rene McNall-Knapp  3 , Ian F Dunn  1
Affiliations

Risk stratification of H3 K27M-mutant diffuse midline gliomas based on anatomical locations: an integrated systematic review of individual participant data

Huy Gia Vuong et al. J Neurosurg Pediatr. .

Abstract

Objective: The prognostic significance and genetic characteristics of H3 K27M-mutant diffuse midline gliomas (DMGs) in different anatomical locations requires further clarification. In this study, the authors integrated published data to investigate the differences between brainstem, thalamic, and spinal cord tumors.

Methods: PubMed and Web of Science databases were used to search for eligible articles. Studies were included if they provided individual patient data of H3 K27M-mutant DMGs with available tumor locations. Hazard ratios (HRs) and 95% confidence intervals (CIs) were computed to investigate the survival of each subgroup.

Results: Eight hundred four tumors were identified, including 467, 228, and 109 in the brainstem, thalamus, and spine, respectively. Brainstem tumors were primarily observed in young children, while patients with thalamic and spinal cord tumors afflicted older patients. The Ki-67 labeling index was highest in brainstem tumors. Compared to patients with brainstem tumors, those with thalamic (HR 0.573, 95% CI 0.463-0.709; p < 0.001) and spinal cord lesions (HR 0.460, 95% CI 0.341-0.621; p < 0.001) had a significantly better survival. When patients were stratified by age groups, superior overall survival (OS) of thalamic tumors was observed in comparison to brainstem tumors in young children and adolescents, whereas adult tumors had uniform OS regardless of anatomical sites. Genetically, mutations in HIST1H3B/C (H3.1) and ACVR1 genes were mostly detected in brainstem tumors, whereas spinal cord tumors were characterized by a higher incidence of mutations in the TERT promoter.

Conclusions: This study demonstrated that H3 K27M-mutant DMGs have distinct clinical characteristics, prognoses, and molecular profiles in different anatomical locations.

Keywords: H3 K27M; brainstem; diffuse midline glioma; oncology; overall survival; spinal cord; thalamus.

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Conflict of interest statement

The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper.

Figures

FIG. 1.
FIG. 1.
Study flow chart.
FIG. 2.
FIG. 2.
Kaplan-Meier curves illustrating the survival of H3 K27M–mutant DMGs in the brainstem, thalamus, and spinal cord.
See this image and copyright information in PMC

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