Epidemiology, Diagnostic Strategies, and Therapeutic Advances in Diffuse Midline Glioma

Abstract

Object: Diffuse midline glioma (DMG) is a highly aggressive and lethal brain tumor predominantly affecting children and young adults. Previously known as diffuse intrinsic pontine glioma (DIPG) or grade IV brain stem glioma, DMG has recently been reclassified as “diffuse midline glioma” according to the WHO CNS5 nomenclature, expanding the DMG demographic. Limited therapeutic options result in a poor prognosis, despite advances in diagnosis and treatment. Radiotherapy has historically been the primary treatment modality to improve patient survival. Methods: This systematic literature review aims to comprehensively compile information on the diagnosis and treatment of DMG from 1 January 2012 to 31 July 2023. The review followed the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement and utilized databases such as PubMed, Cochrane Library, and SciELO. Results: Currently, molecular classification of DMG plays an increasingly vital role in determining prognosis and treatment options. Emerging therapeutic avenues, including immunomodulatory agents, anti-GD2 CAR T-cell and anti-GD2 CAR-NK therapies, techniques to increase blood–brain barrier permeability, isocitrate dehydrogenase inhibitors, oncolytic and peptide vaccines, are being explored based on the tumor’s molecular composition. However, more clinical trials are required to establish solid guidelines for toxicity, dosage, and efficacy. Conclusions: The identification of the H3K27 genetic mutation has led to the reclassification of certain midline tumors, expanding the DMG demographic. The field of DMG research continues to evolve, with encouraging findings that underscore the importance of highly specific and tailored therapeutic strategies to achieve therapeutic success.

Radiotherapy plus temozolomide with or without anlotinib in H3K27M‐mutant diffuse midline glioma: A retrospective cohort study

“…Previous studies indicated that H3K27M‐DMG predominantly occurs in children and adolescents and was relatively rarely found in adults 3 . Owing to the high mortality, H3K27M‐DMG is the leading cause of CNS tumor‐related death in the pediatric population, accounting for about 10%–15% of all brain tumor deaths 4 . Although comprehensive treatments containing surgical resection and chemoradiotherapy are adopted, the median overall survival (OS) of children with H3K27M‐DMG is only 9–12 months, with 2‐year survival of less than 10% since the time of diagnosis 3,5 .…”

“… 3 Owing to the high mortality, H3K27M‐DMG is the leading cause of CNS tumor‐related death in the pediatric population, accounting for about 10%–15% of all brain tumor deaths. 4 Although comprehensive treatments containing surgical resection and chemoradiotherapy are adopted, the median overall survival (OS) of children with H3K27M‐DMG is only 9–12 months, with 2‐year survival of less than 10% since the time of diagnosis. 3 , 5 Moreover, several studies showed the prognosis differed significantly between tumors in different anatomical localizations.…”