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Diffuse Intrinsic Pontine Glioma: From Diagnosis to Next-Generation Clinical Trials

  • Neuro-oncology (R Soffietti, Section Editor)
  • Published:
Current Treatment Options in Neurology Aims and scope Submit manuscript

Abstract

Purpose of review

This review of diffuse intrinsic pontine glioma (DIPG) provides clinical background, a systematic approach to diagnosis and initial care, and synthesizes historical, modern, and future directions for treatment. We present evidence supporting neurosurgical biopsy, early palliative care involvement, limitation of glucocorticoid use, and the leveraging of preclinical DIPG models as a pipeline to next-generation clinical trials.

Recent findings

New molecular understanding of pediatric high-grade gliomas has led to the reclassification of DIPG as one member of a family of diffuse gliomas occurring in the midline of the central nervous system that exhibit pathognomonic mutations in genes encoding histone 3 (H3 K27M). DIPG remains a clinically relevant term, though diagnostically the 80% of DIPG cases that exhibit the H3 K27M mutation have been reclassified as diffuse midline glioma, H3 K27M-mutant. Re-irradiation has been shown to be well-tolerated and of potential benefit. Epigenetic targeting of transcriptional dependencies in preclinical models is fueling molecularly targeted clinical trials. Chimeric antigen receptor T cell immunotherapy has also demonstrated efficacy in preclinical models and provides a promising new clinical strategy.

Summary

DIPG is a universally fatal, epigenetically driven tumor of the pons that is considered part of a broader class of diffuse midline gliomas sharing H3 K27M mutations. Radiation remains the standard of care, single-agent temozolomide is not recommended, and glucocorticoids should be used only sparingly. A rapid evolution of understanding in the chromatin, signaling, and immunological biology of DIPG may soon result in clinical breakthroughs.

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Acknowledgements

The authors gratefully acknowledge support from the National Institute of Neurological Disorders and Stroke (R01NS092597), NIH Director’s Pioneer Award (DP1NS111132), Unravel Pediatric Cancer, McKenna Claire Foundation, Virginia and D.K. Ludwig Fund for Cancer Research, ChadTough Foundation, Defeat DIPG, and Abbie’s Army Foundation.

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  1. Division of Hematology/Oncology, Department of Pediatrics, Seattle Children’s Hospital, University of Washington, Seattle, WA, USA

    Nicholas A. Vitanza MD

  2. Center for Clinical and Translational Research, Seattle Children’s Research Institute, Seattle, WA, USA

    Nicholas A. Vitanza MD

  3. Fred Hutchinson Cancer Research Center, Seattle, WA, USA

    Nicholas A. Vitanza MD

  4. Departments of Neurology and Neurological Sciences, Pediatrics, Stanford University Medical School, 265 Campus Drive, G3077, Stanford, CA, 94305, USA

    Michelle Monje MD, PhD

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Correspondence to Michelle Monje MD, PhD.

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Nicholas A. Vitanza declares no potential conflicts of interest. Michelle Monje has a pending patent entitled “CAR T cell therapy to treat H3K27M midline gliomas.”

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Vitanza, N.A., Monje, M. Diffuse Intrinsic Pontine Glioma: From Diagnosis to Next-Generation Clinical Trials. Curr Treat Options Neurol 21, 37 (2019). https://doi.org/10.1007/s11940-019-0577-y

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