2026 Proffered Presentations
S267: ASSESSMENT OF MOLECULAR TOOLS IN PEDIATRIC, ADOLESCENT AND YOUNG ADULT MENINGIOMA HIGHLIGHTS THE NEED FOR LIFESPAN PRECISION IN NEURO-ONCOLOGY
Leo S Yefet1; Alex Landry1; Justin Wang1; Jeff Liu2; Vikas Patil2; Chloe Gui1; Andrew Ajisebutu1; Yosef Ellenbogen1; Yasin Mamatjan3; Rebecca Yakubov1; Ramneet Kaloti1; Phooja Persaud1; Qingxia Wei2; Olivia Singh2; Sheila Mansouri2; Severa Bunda2; Aaron A Cohen-Gadol4; Ghazaleh Tabatabai5; Marcos Tatagiba5; Felix Behling5; Jill S Barnholtz-Sloan6; Andrew E Sloan7; Silky Chotai8; Lola B Chambless8; Alireza Mansouri9; Sameer Agnihotri10; Serge Makarenko11; Stephen Yip11; Derek S Tsang2; Kenneth Aldape6; Andrew Gao2; Farshad Nassiri2; Gelareh Zadeh12; 1University of Toronto; 2University Health Network; 3Thompson Rivers University; 4Keck School of Medicine; 5Eberhard Karls University Tübingen; 6National Cancer Institute; 7Piedmont Brain Tumor Center; 8Vanderbilt University Medical Center; 9Penn State Milton S. Hershey Medical Center; 10University of Pittsburgh; 11University of British Columbia; 12Mayo Clinic
Background: Adolescent and young adult (AYA) patients remain underrepresented in neuro-oncology research. Despite being the second most common primary brain tumor in this population, meningiomas have not been studied using age-specific molecular analyses. DNA methylation–based classification and prognostic tools have transformed meningioma care. This study aimed to evaluate the performance of these tools across age groups.
Methods: We analyzed 1,568 meningiomas with DNA methylation and clinical data, including 18 pediatric patients (<15 years), 195 AYA patients (15–39 years), and 1,355 adult patients (>39 years). Pediatric and AYA (P/AYA) tumors were combined and compared with adult tumors. The performance of established molecular classifiers and recurrence predictors, as well as differences in chromosomal copy number alterations were compared across age groups.
Results: While histologic grading was comparable between cohorts, P/AYA tumors displayed significantly fewer aggressive molecular groups and lower frequencies of chromosomal arm losses, including 1p, 6q, and 14q. The adult-trained recurrence predictor failed in the P/AYA population (AUC 0.57), despite similar score distributions. Retraining the model on an age-specific cohort using an identical analytic framework improved performance (AUC 0.79) and enabled effective stratification of progression-free survival (p = 0.00054). Importantly, 1p loss retained prognostic significance within the P/AYA group, supporting its clinical utility.
Conclusions: Molecular tools developed in adult-dominant cohorts do not generalize to younger patients due to both biological divergence and exclusion from model development. These findings underscore the need for age-specific molecular frameworks and highlight the imperative of including P/AYA populations in precision neuro-oncology research to ensure lifespan-equitable care.