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

Authors
Justin Wang,Vikas Patil
Alexander Landry,Chloe Gui,Andrew Ajisebutu,Jeff Liu,Olli Saarela,Stephanie Pugh,Minhee Won,Zeel Patel,Rebecca Yakubov,Ramneet Kaloti,Christopher Wilson,Aaron Cohen‐Gadol,Mohamed Zaazoue,Ghazaleh Tabatabai,Marcos Tatagiba,Felix Behling,Damian Bonnin,Eric Holland,Tim Kruser,Jill Barnholtz‐Sloan,Andrew Sloan,Craig Horbinski,Silky Chotai,Lola Chambless,Andrew Gao,Alexander Rebchuk,Serge Makarenko,Stephen Yip,Felix Sahm,Sybren Maas,Derek Tsang,Michael McDermott,Thomas Santarius,Warren Selman,Marta Couce,Bruno Carvalho,Patrick Wen,Kyle Walsh,Eelke Bos,Wenya Bi,Raymond Huang,Priscilla Brastianos,Helen Shih,Tobias Walbert,Ian Lee,Michelle Felicella,Ana Castro,Houtan Noushmehr,James Snyder,Francesco DiMeco,Andrea Saladino,Bianca Pollo,Christian Schichor,Jörg‐Christian Tonn,Felix Ehret,Timothy Kaufmann,Daniel Lachance,Caterina Giannini,Evanthia Galanis,Aditya Raghunathan,Michael Vogelbaum,Patrick Cimino,Mark Youngblood,Matija Snuderl,Sylvia Kurz,Erik Sulman,Ian Dunn,C. Hanemann,Mohsen Javadpour,Ho‐Keung Ng,Gary Bader,Richard Everson,Alkiviadis Tzannis,Konstantinos Fountas,Nils Schmidt,Karolyn Au,Roland Goldbrunner,Norbert Galldiks,Marco Timmer,Tiit Mathiesen,Manfred Westphal,Katrin Lamszus,Franz Ricklefs,Christel Herold‐Mende,Christine Jungk,Gerhard Jungwirth,Andreas Deimling,Maximilian Deng,Susan Short,Michael Jenkinson,Christian Mawrin,Abdurrahman Islim,Daniel Fountain,Omar Pathmanaban,Katharine Drummond,Andrew Morokoff,David Raleigh,Arie Perry,Nicholas Butowski,Tathiane Malta,Viktor Zherebitskiy,Luke Hnenny,Gabriel Zada,Mirjam Renovanz,Antonio Santacroce,Christian Fougère,Jens Schittenhelm,Paul Passlack,Jennifer Moliterno,Alper Dincer,Leland Rogers,Kenneth Aldape,Farshad Nassiri,Gelareh Zadeh,Aaron Cohen-Gadol
+115 authors
,Ho Ng
Published
Aug 21, 2024
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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. 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.

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