BIOM-55. TARGETED GENE EXPRESSION PROFILING PREDICTS MENINGIOMA OUTCOMES AND RADIOTHERAPY RESPONSES

Abstract

Abstract INTRODUCTION Improvements in meningioma risk stratification are needed and current indications for postoperative radiotherapy are controversial. Here we report multicenter clinical and analytical validation of a gene expression biomarker using clinical and genomic data from 1856 meningiomas from 12 institutions across 3 continents. METHODS A previously-developed 34-gene expression biomarker was applied to 3 validation cohorts: (1) a multicenter retrospective clinical validation cohort (N = 6 centers, N = 866 meningiomas, median follow-up 5.2 years), (2) a prospective investigator-blinded clinical validation cohort from RTOG 0539 (N = 103 meningiomas, median follow-up 8.4 years), and (3) an analytical validation cohort for test/re-test and FFPE/frozen analyses, and comparison across platforms for gene expression quantification (N = 8 centers, N = 1219 meningiomas). Biomarker performance was compared to 9 other meningioma classification systems. Favorable versus unfavorable cases were defined as (1) gene expression low risk with any resection, or gene expression intermediate risk with GTR (favorable), versus (2) gene expression intermediate risk with STR, or gene expression high risk with any resection (unfavorable). RESULTS The biomarker improved on WHO 2021 grade (5-year local freedom from recurrence [LFFR] delta-AUC 0.11, 95% CI 0.07-0.17, p< 0.001) and all other classification systems for LFFR and OS on multivariate analysis, achieving a negative predictive value for recurrence at 5-years of 91.9%. The biomarker predicted LFFR after postoperative radiotherapy, with a hazard ratio of 0.33 for unfavorable primary WHO grade 2 meningiomas (95% CI 0.14-0.76, P = 0.009), and 0.54 for unfavorable propensity-matched meningiomas across all WHO grades (95% CI 0.37-0.78, p = 0.0001). The biomarker reclassified 39.8% of meningiomas from RTOG 0539, including downstaging 30.5% of patients who received postoperative radiotherapy, and was independently prognostic for overall survival on multivariate analysis. CONCLUSIONS A 34-gene expression biomarker improves prognostication of meningioma outcomes and predicts postoperative radiotherapy responses.