Molecular classification to refine surgical and radiotherapeutic decision-making in meningioma
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
Find out more...Establishing NOvel predictive and NOn-invasive epigenetic biomarkers to transform meningioma management
Brain Tumour Charity
Find out more...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 2024External DOI
PubMed ID
39169220Department/Unit
- Surgery
Research Area
- Neurological and Psychiatric Disorders
Publisher
Springer Nature LimitedVersion
- Published Version (Version of Record)