학술논문
Targeted gene expression profiling predicts meningioma outcomes and radiotherapy responses
Document Type
article
Author
Chen, William C; Choudhury, Abrar; Youngblood, Mark W; Polley, Mei-Yin C; Lucas, Calixto-Hope G; Mirchia, Kanish; Maas, Sybren LN; Suwala, Abigail K; Won, Minhee; Bayley, James C; Harmanci, Akdes S; Harmanci, Arif O; Klisch, Tiemo J; Nguyen, Minh P; Vasudevan, Harish N; McCortney, Kathleen; Yu, Theresa J; Bhave, Varun; Lam, Tai-Chung; Pu, Jenny Kan-Suen; Li, Lai-Fung; Leung, Gilberto Ka-Kit; Chan, Jason W; Perlow, Haley K; Palmer, Joshua D; Haberler, Christine; Berghoff, Anna S; Preusser, Matthias; Nicolaides, Theodore P; Mawrin, Christian; Agnihotri, Sameer; Resnick, Adam; Rood, Brian R; Chew, Jessica; Young, Jacob S; Boreta, Lauren; Braunstein, Steve E; Schulte, Jessica; Butowski, Nicholas; Santagata, Sandro; Spetzler, David; Bush, Nancy Ann Oberheim; Villanueva-Meyer, Javier E; Chandler, James P; Solomon, David A; Rogers, C Leland; Pugh, Stephanie L; Mehta, Minesh P; Sneed, Penny K; Berger, Mitchel S; Horbinski, Craig M; McDermott, Michael W; Perry, Arie; Bi, Wenya Linda; Patel, Akash J; Sahm, Felix; Magill, Stephen T; Raleigh, David R
Source
Nature Medicine. 29(12)
Subject
Language
Abstract
Surgery is the mainstay of treatment for meningioma, the most common primary intracranial tumor, but improvements in meningioma risk stratification are needed and indications for postoperative radiotherapy are controversial. Here we develop a targeted gene expression biomarker that predicts meningioma outcomes and radiotherapy responses. Using a discovery cohort of 173 meningiomas, we developed a 34-gene expression risk score and performed clinical and analytical validation of this biomarker on independent meningiomas from 12 institutions across 3 continents (N = 1,856), including 103 meningiomas from a prospective clinical trial. The gene expression biomarker improved discrimination of outcomes compared with all other systems tested (N = 9) in the clinical validation cohort for local recurrence (5-year area under the curve (AUC) 0.81) and overall survival (5-year AUC 0.80). The increase in AUC compared with the standard of care, World Health Organization 2021 grade, was 0.11 for local recurrence (95% confidence interval 0.07 to 0.17, P