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

作者：Justin Z. Wang, Vikas S. Patil, Alexander Landry, Chloe Gui, Andrew A. Ajisebutu, Jeff Liu, Olli Saarela, Stephanie L. Pugh, Minhee Won, Zeel Patel, Rebeca Yakubov, Ramneet Kaloti, Christopher D. Wilson, Aaron Cohen‐Gadol, Mohamed A. Zaazoue, Ghazaleh Tabatabai, Marcos Soares Tatagiba, Felix Behling, Damian A. Almiron Bonnin, Eric C. Holland, Tim J. Kruser, Jill S. Barnholtz‐Sloan, Andrew Edward Sloan, Craig Horbinski, Silky Chotai, Lola Blackwell Chambless, Andrew F. Gao, Alexander D. Rebchuk, Serge Makarenko, Stephen S. F. Yip, Felix Sahm, Sybren L. N. Maas, Derek S. Tsang, Michael William McDermott, Thomas Santarius, Warren R. Selman, Marta Couce, Andrew Edward Sloan, Bruno Carvalho, Patrick Yung Wen, Kyle M. Walsh, Eelke Marijn Bos, Wenya Linda Bi, Raymond Y. Huang, Priscilla Kaliopi Brastianos, Helen Alice Shih, Tobias Walbert, Ian Y. Lee, Michelle Madden Felicella, Ana Valéria Castro, Houtan Noushmehr, James Matthew Snyder, Francesco DiMeco, Andrea Saladino, Bianca Pollo, Christian Schichor, Jörg‐Christian Tonn, Felix Ehret, Timothy J. Kaufmann, Daniel Honore Lachance, Caterina Giannini, Evanthia Galanis, Aditya Raghunathan, Michael A. Vogelbaum, Jill S. Barnholtz‐Sloan, Patrick Joseph Cimino, Craig Horbinski, Mark W. Youngblood, Matija Snuderl, Sylvia Christine Kurz, Erik P. Sulman, Ian F. Dunn, Clemens Oliver Hanemann, Mohsen Javadpour, Ho‐Keung Ng, Paul Christopher Boutros, Richard G. Everson, Alkiviadis Tzannis, Konstantinos N. Fountas, Nils Ole Schmidt, Karolyn Au, Roland Goldbrunner, Norbert Galldiks, Marco Timmer, Tiit Illimar Mathiesen, Manfred Westphal, Katrin Lamszus, Franz Lennard Ricklefs, Christel C. Herold‐Mende, Felix Sahm, Christine Jungk, Gerhard Jungwirth, Andreas von Deimling, Maximilian Y. Deng, Susan C Short, Michael D. Jenkinson, Christian Mawrin, Abdurrahman I. Islim, Daniel Mark Fountain, Omar Nathan Pathmanaban, Katharine Jann Drummond, Andrew P. Morokoff, David Ronan Raleigh, Arie Perry, Nicholas Arthur Butowski, Tathiane Maistro Malta, Viktor A. Zherebitskiy, Luke Hnenny, Gabriel Zada, Mirjam Renovanz, Antonio Santacroce, Christian la Fougère, Jens Schittenhelm, Paul Passlack, Jennifer A. Moliterno, Alper Dincer, Leland Rogers, Kenneth Aldape, Farshad Nassiri, Gelareh Mohammed Zadeh · 发表于：Nature Medicine · 年份：2024 · DOI：10.1038/s41591-024-03167-4 · 被引用次数：80 · 研究领域：Meningioma and schwannoma management、Glioma Diagnosis and Treatment、Brain Metastases and Treatment

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. In a large, partially prospective cohort of patients with molecularly profiled and clinically annotated meningioma, the extent of surgical resection and radiotherapy (RT) response correlate with molecular classification, which can be used in a molecular model to predict clinical outcomes in response to RT.