Royal College of Surgeons in Ireland
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Molecular classification to refine surgical and radiotherapeutic decision-making in meningioma

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posted on 2025-02-04, 13:09 authored by Justin Z Wang, International Consortium on Meningiomas (ICOM), Mohsen JavadpourMohsen Javadpour, Gelareh Zadeh

Treatment of the tumor and dural margin with surgery and sometimes radiation are cornerstones of therapy for meningioma. Molecular classifications have provided insights into the biology of disease; however, response to treatment remains heterogeneous. In this study, we used retrospective data on 2,824 meningiomas, including molecular data on 1,686 tumors and 100 prospective meningiomas, from the RTOG-0539 phase 2 trial to define molecular biomarkers of treatment response. Using propensity score matching, we found that gross tumor resection was associated with longer progression-free survival (PFS) across all molecular groups and longer overall survival in proliferative meningiomas. Dural margin treatment (Simpson grade 1/2) prolonged PFS compared to no treatment (Simpson grade 3). Molecular group classification predicted response to radiotherapy, including in the RTOG-0539 cohort. We subsequently developed a molecular model to predict response to radiotherapy that discriminates outcome better than standard-of-care classification. This study highlights the potential for molecular profiling to refine surgical and radiotherapy decision-making.

Funding

National Cancer Institute, National Institutes of Health, under the Cancer Moonshot Initiative (contract number HHSN261201500003I; task order number HHSN26100039)

Canadian Institutes of Health Research (CIHR) Project Fund (RN482811-481519)

Deciphering the genetic and epigenetic landscape of clinically aggressive meningiomas

Brain Tumour Charity

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Establishing NOvel predictive and NOn-invasive epigenetic biomarkers to transform meningioma management

Brain Tumour Charity

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UHN Foundation

Mary Hunter Meningioma Research Fund

V Foundation for Cancer Research

CIHR Vanier Scholarship

American Association of Neurological Surgeons Neurosurgery Education & Research Foundation Research Fellowship

Congress of Neurological Surgeons Tumor Section

Princess Margaret Hospital Foundation Hold ‘em For Life Oncology Fellowship

History

Data Availability Statement

DNA methylation data and gene expression data (RNA sequencing) generated for this study are deposited in the National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO) (https://www.ncbi.nlm.nih.gov/geo/) under the superseries accession number GSE270375. Unprocessed DNA methylation data from the retrospective meningioma tumors are available under the accession number GSE270371 and gene expression counts data are available under the accession number GSE270638. Unprocessed RNA sequencing data (FASTQ) are deposited in the NCBI Sequence Read Archive (https://www.ncbi.nlm.nih.gov/sra) under the project number PRJNA1127224 for the retrospective meningiomas. Unprocessed DNA methylation data and gene expression data (RNA sequencing) for the prospective NRG RTOG-0539 clinical trial cases are deposited in the database of Genotypes and Phenotypes (dbGaP) under the project no. phs003707.v1.p1 entitled MP2PRT-MNG: identifying novel molecular markers of response to radiotherapy in meningiomas using samples from the RTOG-0539 (NCT00895622). Previously published, publicly available data were downloaded from the GEO database (https://ncbi.nlm.nih.gov/geo) under the following accession numbers: GSE189521 (Bayley et al. DNA methylation) and GSE183656 (Choudhury et al. DNA methylation and RNA sequencing)25,26.

Comments

The original article is available at https://www.nature.com/

Published Citation

Wang JZ, et al. Molecular classification to refine surgical and radiotherapeutic decision-making in meningioma. Nat Med. 2024;30(11):3173-3183.

Publication Date

21 August 2024

PubMed ID

39169220

Department/Unit

  • Surgery

Research Area

  • Neurological and Psychiatric Disorders

Publisher

Springer Nature Limited

Version

  • Published Version (Version of Record)