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REVIEW article

Front. Oncol.
Sec. Pediatric Oncology
Volume 14 - 2024 | doi: 10.3389/fonc.2024.1504440
This article is part of the Research Topic Recent Biological Insights into Pediatric Brain Tumors View all 3 articles

The Role of Brainstem Biopsy and Targeted Therapies in Pediatric Diffuse Midline Glioma/ Diffuse Intrinsic Pontine Glioma (DMG/DIPG)

Provisionally accepted
Shehryar R Sheikh Shehryar R Sheikh 1,2Violette M R Recinos Violette M R Recinos 1Eric M Thompson Eric M Thompson 3Ross Mangum Ross Mangum 4Mariah Wright- Nadkarni Mariah Wright- Nadkarni 5Bradley Gampel Bradley Gampel 6Neha J Patel Neha J Patel 7*
  • 1 Department of Neurosurgery, Cleveland Clinic, Cleveland, OH, United States
  • 2 Department of Molecular Medicine, Case Western Reserve University, Cleveland, OH, United States
  • 3 Department of Neurosurgery, Washington University, St Louis, MO, United States
  • 4 Center for Cancer and Blood Disorders, Phoenix Children's Hospital, Phoenix, AZ, United States
  • 5 Nationwide Children's Hospital, Columbus, OH, United States
  • 6 Department of Pediatrics, Sylvester Comprehensive Cancer Center, Miami, FL, United States
  • 7 Department of Pediatric Hematology-Oncology and Blood & Marrow Transplant, Cleveland Clinic, Cleveland, OH, United States

The final, formatted version of the article will be published soon.

    Pediatric diffuse midline glioma (DMG), including diffuse intrinsic pontine glioma (DIPG), are aggressive brainstem tumors with a dire prognosis, traditionally diagnosed based on MRI characteristics. The recognition that molecular characteristics may determine prognosis and response to therapy has led to a reevaluation of biopsy necessity. This comprehensive review addresses the evolving role of brainstem biopsies in diagnosing and managing these tumors -both within the context of a clinical trial and in routine clinical care. We examine practice variability around brainstem biopsies for DMG/DIPG, revealing a global inconsistency in biopsy application and perceptions amongst providers. We show that safety profiles from contemporary studies demonstrate a high diagnostic success rate with minimal permanent morbidity, supporting the feasibility of biopsies in expert centers. Beyond the safety angle, we discuss the utility of biopsies in enabling personalized medicine, highlighting how molecular profiling has been used in multiple centers to guide targeted therapies. We present initial evidence from case studies and registry reports to address whether these molecularly targeted approaches are 1) clinically feasible, and 2) likely to extend survival. Furthermore, we present evidence to support the notion that biopsies facilitate the design of more refined clinical trials, shifting from a one-size-fits-all model to molecularly stratified studies. We discuss how this new paradigm for trial design is likely necessary in the context of DMG/DIPG given the lack of progress in this disease for the last several decades. Future directions discussed in the review include liquid biopsy techniques to complement or replace tissue sampling, aiming to enhance diagnostic precision and treatment monitoring.

    Keywords: DMG, dipg, diffuse midline glioma, diffuse intrinsic pontine glioma, brainstem biopsy, targeted therapy, H3K27M

    Received: 30 Sep 2024; Accepted: 03 Dec 2024.

    Copyright: © 2024 Sheikh, Recinos, Thompson, Mangum, Wright- Nadkarni, Gampel and Patel. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Neha J Patel, Department of Pediatric Hematology-Oncology and Blood & Marrow Transplant, Cleveland Clinic, Cleveland, OH, United States

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.