{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T13:42:33Z","timestamp":1791380553102,"version":"4.3.3"},"reference-count":13,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2024,11,6]],"date-time":"2024-11-06T00:00:00Z","timestamp":1730851200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Canadian Institutes of Health Research and Brain Tumour Charity"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,5,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>We previously developed a DNA methylation\u2013based risk predictor for meningioma, which has been used locally in a prospective fashion since its original publication. As a follow-up, we validate this model using a large prospective cohort and introduce a streamlined next-generation predictor compatible with newer methylation arrays.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Genome-wide methylation profiles were generated with the Illumina EPICArray. The performance of our next-generation predictor was compared with our original model and standard-of-care 2021 WHO grade using time-dependent receiver operating characteristic curves. An nomogram was generated by incorporating our methylation predictor with WHO grade and the extent of resection.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>A total of 1347 meningioma cases were utilized in the study, including 469 prospective cases from 3 institutions and an external cohort of 100 WHO grade 2 cases for model validation. Both the original and next-generation models significantly outperform the 2021 WHO grade in predicting early postoperative recurrence. Dichotomizing patients into grade-specific risk subgroups was predictive of outcomes within both WHO grades 1 and 2 tumors (P\u2005&amp;lt;\u2005.05), whereas all WHO grade 3 tumors were considered high-risk. Multivariable Cox regression demonstrated the benefit of adjuvant radiotherapy (RT) in high-risk cases specifically, reinforcing its informative role in clinical decision-making. Finally, our next-generation predictor contains nearly 10-fold fewer features than the original model, allowing for targeted arrays.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>This next-generation DNA methylation\u2013based meningioma outcome predictor significantly outperforms the 2021 WHO grading in predicting time to recurrence. We make this available as a point-and-click tool that will improve prognostication, inform patient selection for RT, and allow for molecularly stratified clinical trials.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/neuonc\/noae236","type":"journal-article","created":{"date-parts":[[2024,11,6]],"date-time":"2024-11-06T13:04:46Z","timestamp":1730898286000},"page":"1004-1016","source":"Crossref","is-referenced-by-count":17,"title":["Validation and next-generation update of a DNA methylation\u2013based recurrence predictor for meningioma: A multicenter prospective study"],"prefix":"10.1093","volume":"27","author":[{"given":"Alexander P","family":"Landry","sequence":"first","affiliation":[{"name":"Princess Margaret Cancer Centre, University Health Network , Toronto, Ontario ,","place":["Canada"]},{"name":"Division of Neurosurgery, Department of Surgery, University of Toronto , Toronto, Ontario ,","place":["Canada"]},{"name":"MacFeeters Hamilton Neuro-Oncology Program, Princess Margaret Cancer Centre, University Health Network and University of Toronto , Toronto, Ontario ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justin Z","family":"Wang","sequence":"additional","affiliation":[{"name":"Princess Margaret Cancer Centre, University Health Network , Toronto, Ontario ,","place":["Canada"]},{"name":"Division of Neurosurgery, Department of Surgery, University of Toronto , Toronto, Ontario ,","place":["Canada"]},{"name":"MacFeeters Hamilton Neuro-Oncology Program, Princess Margaret Cancer Centre, University Health Network and University of Toronto , Toronto, Ontario ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vikas","family":"Patil","sequence":"additional","affiliation":[{"name":"Princess Margaret Cancer Centre, University Health Network , Toronto, Ontario ,","place":["Canada"]},{"name":"MacFeeters Hamilton Neuro-Oncology Program, Princess Margaret Cancer Centre, University Health 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