Molecular classification to refine surgical and radiotherapeutic decision-making in meningioma
Authors: Justin Z. Wang, Vikas Patil, Alexander P. Landry, Chloe Gui, Andrew Ajisebutu, Jeff Liu, Olli Saarela, Stephanie L. Pugh, Minhee Won, Zeel Patel, Rebeca Yakubov, Ramneet Kaloti, Christopher Wilson, Aaron Cohen-Gadol, Mohamed A. Zaazoue, Ghazaleh Tabatabai, Marcos Tatagiba, Felix Behling, Damian A. Almiron Bonnin, Eric C. Holland, Tim J. Kruser, Jill S. Barnholtz-Sloan, Andrew E. Sloan, Craig Horbinski, Silky Chotai, Lola B. Chambless, Andrew Gao, Alexander D. Rebchuk, Serge Makarenko, Stephen Yip, Felix Sahm, Sybren L. N. Maas, Derek S. Tsang, Michael W. McDermott, Thomas Santarius, Warren Selman, Marta Couce, Andrew E. Sloan, Bruno Carvalho, Patrick Y. Wen, Kyle M. Walsh, Eelke M. Bos, Wenya Linda Bi, Raymond Y. Huang, Priscilla K. Brastianos, Helen A. Shih, Tobias Walbert, Ian Lee, Michelle M. Felicella, Ana Valeria Castro, Houtan Noushmehr, James M. Snyder, Francesco Dimeco, Andrea Saladino, Bianca Pollo, Christian Schichor, Jörg-Christian Tonn, Felix Ehret, Timothy J. Kaufmann, Daniel H. Lachance, Caterina Giannini, Evanthia Galanis, Aditya Raghunathan, Michael A. Vogelbaum, Jill Barnholtz-Sloan, Patrick J. Cimino, Craig M. Horbinski, Mark Youngblood, Matija Snuderl, Sylvia C. Kurz, Erik P. Sulman, Ian F. Dunn, C. Oliver Hanemann, Mohsen Javadpour, Ho-Keung Ng, Paul C. 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 L. Ricklefs, Christel Herold-Mende, Felix Sahm, Christine Jungk, Gerhard Jungwirth, Andreas von Deimling, Maximilian Deng, Susan C. Short, Michael D. Jenkinson, Christian Mawrin, Abdurrahman I. Islim, Daniel M. Fountain, Omar N. Pathmanaban, Katharine J. Drummond, Andrew Morokoff, David R. Raleigh, Arie Perry, Nicholas A. Butowski, Tathiane M. Malta, Viktor Zherebitskiy, Luke Hnenny, Gabriel Zada, Mirjam Renovanz, Antonio Santacroce, Christian la Fougère, Jens Schittenhelm, Paul Passlack, Jennifer Moliterno, Alper Dincer, C. Leland Rogers, Kenneth Aldape, Farshad Nassiri, Gelareh Zadeh
Journal: Nature Medicine (2024)

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.