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.

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Publication Details

Journal
Nature Medicine
Published
2024-08-21
DOI
https://doi.org/10.1038/s41591-024-03167-4
Citations
55
Primary Topic
Meningioma and schwannoma management
Type
article
Field-Weighted Citation Impact
21.26
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article

Molecular classification to refine surgical and radiotherapeutic decision-making in meningioma

Bianca Pollo, Mirjam Renovanz, Sybren L. N. Maas, Luke Hnenny et al.
55 citations
Nature Medicine
Meningioma and schwannoma management
21.26
article

Molecular classification to refine surgical and radiotherapeutic decision-making in meningioma

Bianca Pollo, Mirjam Renovanz, Sybren L. N. Maas, Luke Hnenny, Aditya Raghunathan, Jennifer Moliterno, Jeff Liu, Farshad Nassiri, Tiit Illimar Mathiesen, David Ronan Raleigh, Paul C. Boutros, Craig Horbinski, Maximilian Deng, Aaron Cohen‐Gadol, Priscilla Kaliopi Brastianos, Viktor Zherebitskiy, Olli Saarela, Evanthia Galanis, Katrin Lamszus, Roland Goldbrunner, Mark W. Youngblood, Richard G. Everson, Patrick Y. Wen, Christel C. Herold‐Mende, Christian la Fougère, Tobias Walbert, Francesco DiMeco, Tim J. Kruser, Christian Mawrin, Andrew Morokoff, Zeel Patel, Patrick J. Cimino, Felix Behling, Chloe Gui, Alkiviadis Tzannis, Silky Chotai, Alexander D. Rebchuk, Christian Schichor, Katharine J. Drummond, Jens Schittenhelm, Damian A. Almiron Bonnin, Marco Timmer, Michelle M. Felicella, Marcos Soares Tatagiba, Stephen Yip, C. Oliver Hanemann, Helen Alice Shih, Wenya Linda Bi, Norbert Galldiks, Mohamed A. Zaazoue, Kyle M. Walsh, Daniel H. Lachance, Derek S. Tsang, Jill S. Barnholtz‐Sloan, Serge Makarenko, Andreas von Deimling, Arie Perry, Andrew Ajisebutu, Erik P. Sulman, Justin Z. Wang, Karolyn Au, Minhee Won, Timothy J. Kaufmann, Michael D. Jenkinson, Ana Valéria Castro, Kenneth Aldape, Gerhard Jungwirth, Nils Ole Schmidt, Felix Sahm, Manfred Westphal, Raymond Y. Huang, Thomas Santarius, Daniel M. Fountain, Ramneet Kaloti, Marta Couce, Caterina Giannini, Ho‐Keung Ng, Mohsen Javadpour, Gelareh Mohammed Zadeh, Antonio Santacroce, Franz Ricklefs, Felix Ehret, Abdurrahman I. Islim, Sylvia C. Kurz, Eric C. Holland, Vikas Patil, Tathiane M. Malta, Lola B. Chambless, Matija Snuderl, Houtan Noushmehr, Leland Rogers, Konstantinos Fountas, Eelke M. Bos, Susan C Short, Gabriel Zada, Omar Pathmanaban, Andrew Edward Sloan, Nicholas Butowski, Ghazaleh Tabatabai, Bruno Carvalho, Ian Lee, Andrew Gao, Michael McDermott, Andrea Saladino, Ian F. Dunn, Alexander Landry, Alper Dincer, Paul Passlack, Warren R. Selman, Michael A. Vogelbaum, James M. Snyder, Rebeca Yakubov, Christopher D. Wilson, Stephanie L. Pugh, Jörg‐Christian Tonn
article en
55 citations

Abstract

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.

Nature MedicineVol. 30(11)
Northwestern University (US), University of Southern California (US), Brigham and Women's Hospital (US), Tufts Medical Center (US), National Institutes of Health (US), University of Leeds (GB), The Royal Melbourne Hospital (AU), University Health Network (CA), Harvard University (US), University of British Columbia (CA), Royal College of Surgeons in Ireland (IE), University of Thessaly (GR), University of Liverpool (GB), University of Alberta (CA), Universität Hamburg (DE), University of California, Los Angeles (US), Duke University (US), Chinese University of Hong Kong (HK), German Cancer Research Center (DE), Universidade de São Paulo (BR), University of California, San Francisco (US), University of Cologne (DE), University of Toronto (CA), Washington University in St. Louis (US), Heidelberg University (DE), University Hospitals of Cleveland (US), UW Health University Hospital (US), Leiden University Medical Center (NL), Royal University Hospital (CA), Salford Royal NHS Foundation Trust (GB), Hospital for Sick Children (CA), St James's University Hospital (GB), Toronto General Hospital (CA), Erasmus MC (NL), University Hospital Heidelberg (DE), Copenhagen University Hospital (DK), Princess Margaret Cancer Centre (CA), Rigshospitalet (DK), Walton Centre (GB), Hospital de São João (PT), LMU Klinikum (DE), Moffitt Cancer Center (US), University Hospital Regensburg (DE), University of Saskatchewan (CA), Yale University (US), Humboldt-Universität zu Berlin (DE), NYU Langone Health (US), Massachusetts General Hospital (US), Fred Hutch Cancer Center (US), Utah Cancer Specialists (US), Baptist Health South Florida (US), Brain Tumour Research (GB), Center for Neuro-Oncology (US), University Hospital of Larissa (GR), University Medical Center Hamburg-Eppendorf (DE), University Hospitals Cleveland Medical Center (US), National Institute of Neurological Disorders and Stroke (US), Salford Royal Hospital (GB), Dana-Farber Cancer Institute (US), Mayo Clinic in Arizona (US), Public Health Ontario (CA), Central Brain Tumor Registry of the United States (US), Bernstein Center for Computational Neuroscience Tübingen (DE), National Cancer Institute (US), SickKids Foundation (CA), Hertie Institute for Clinical Brain Research (DE), Evangelisches Krankenhaus Hamm (DE), Northwestern Medicine (US), Center for Cancer Research (US), Erasmus MC Cancer Institute (NL), University Hospital Cologne (DE), Piedmont HealthCare (US), Addenbrooke's Hospital (GB), Neurological Surgery (US), Dana-Farber Brigham Cancer Center (US), NRG Oncology (US), Fondazione IRCCS Istituto Neurologico Carlo Besta (IT), Division of Cancer Epidemiology and Genetics, Deutsches Konsortium für Translationale Krebsforschung (DE), Indiana University School of Medicine, University of Oklahoma Health Sciences Center (US), The University of Texas Medical Branch at Galveston (US), Indiana University – Purdue University Indianapolis (US), Case Western Reserve University (US), Freie Universität Berlin (DE), University of San Francisco (US), Charité - Universitätsmedizin Berlin (DE), University of Tübingen (DE), Ludwig-Maximilians-Universität München (DE), Vanderbilt University Medical Center (US), Otto-von-Guericke-Universität Magdeburg (DE)
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