Background: Diffuse midline glioma with histone H3K27M mutation (H3K27M DMG) is a recently recognized World Health Organization grade IV glioma with a dismal prognosis. Despite maximal treatment, this high-grade glioma exhibits an estimated median survival of 9-12 months. However, little is known with regards to prognostic risk factors for overall survival (OS) for patients with this malignant tumor. The aim of the present study is to characterize risk factors influencing survival in H3K27M DMG.
Methods: This is a population-based retrospective study of survival in patients with H3K27M DMG. The Surveillance, Epidemiology, and End Results database was examined from the years 2018 to 2019 and data from 137 patients were collected. Basic demographics, tumor site, and treatments regimens were retrieved. Univariate and multivariable analyses were conducted to assess for factors associated with OS. Nomograms were built based on the results of the multivariable analyses.
Results: Median OS of the entire cohort was 13 months. Patients with infratentorial H3K27M DMG exhibited worse OS compared to their supratentorial counterparts. Any form of radiation treatment resulted in a significantly improved OS. Most combination treatments significantly improved OS with the exception of the surgery plus chemotherapy group. The combination of surgery and radiation had the greatest impact on OS.
Conclusions: Overall, the infratentorial location of H3K27M DMG portends a worse prognosis compared to their supratentorial counterparts. The combination of surgery and radiation had the greatest impact on OS. These data highlight the survival benefit in utilizing a multimodal treatment approach for H3K27M DMG.
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http://dx.doi.org/10.1016/j.wneu.2023.07.001 | DOI Listing |
bioRxiv
December 2024
Yale University, Department of Molecular, Cellular and Developmental Biology, Faculty of Arts and Sciences; 260 Whitney Avenue, New Haven, Connecticut 06511, USA.
The oncomutation lysine 27-to-methionine in histone H3 (H3K27M) is frequently identified in tumors of patients with diffuse midline glioma-H3K27 altered (DMG-H3K27a). H3K27M inhibits the deposition of the histone mark H3K27me3, which affects the maintenance of transcriptional programs and cell identity. Cells expressing H3K27M are also characterized by defects in genome integrity, but the mechanisms linking expression of the oncohistone to DNA damage remain mostly unknown.
View Article and Find Full Text PDFGenome Biol
December 2024
Department of Pathology, Stanford University, Stanford, CA, 94305, USA.
Background: The fatal diffuse midline gliomas (DMG) are characterized by an undruggable H3K27M mutation in H3.1 or H3.3.
View Article and Find Full Text PDFEur J Cancer
December 2024
Department of Pediatric and Adolescent Oncology, Gustave Roussy, Villejuif, France; Team Genomics and Oncogenesis of Brain Tumors, INSERM U981, Paris Saclay University, Villejuif, France.
Introduction: H3K27-altered diffuse midline gliomas (DMG) have limited therapeutic options and a very poor prognosis. Encouraging responses were observed in early clinical trials with ONC201. As ONC201 was unavailable in Europe, a compassionate use program supported by the French Authorities was launched for patients at progression after standard of care radiotherapy.
View Article and Find Full Text PDFNeuro Oncol
November 2024
Department of Neurosurgery, Boston Children's Hospital, Boston, MA, USA.
Background: Pediatric high-grade gliomas, such as diffuse midline glioma (DMG), have a poor prognosis and lack curative treatments. Current research models of DMG primarily rely on human DMG cell lines cultured in vitro or xenografted into the brains of immunodeficient mice. However, these models are insufficient to recapitulate the complex cell-cell interactions between DMG and the tumor immune microenvironment (TIME), therefore fall short of accurately reflecting how efficacious therapeutic agents or combinations will be in the clinical setting.
View Article and Find Full Text PDFNature
November 2024
Division of Pediatric Hematology/Oncology/Stem Cell Transplant and Regenerative Medicine, Department of Pediatrics, Stanford University, Stanford, CA, USA.
H3K27M-mutant diffuse midline gliomas (DMGs) express high levels of the disialoganglioside GD2 (ref. ). Chimeric antigen receptor-modified T cells targeting GD2 (GD2-CART) eradicated DMGs in preclinical models.
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