KS03.7.A INDEPENDENT PROGNOSTIC ROLE OF METHYLATION CLASS IN ATYPICAL AND MALIGNANT MENINGIOMA UNDERGOING ADJUVANT HIGH-DOSE RADIOTHERAPY: COMPREHENSIVE MOLECULAR ANALYSIS OF EORTC TRIAL 22042-26042

Abstract

Abstract BACKGROUND In EORTC trial 22042-2604 WHO grade 2 and 3 meningioma patients underwent adjuvant high dose radiotherapy. The current study investigated clinicopathological correlations and the prognostic impact of genetic and epigenetic molecular factors in EORTC 22042-26042 trial patients. METHODS For patients that gave consent for additional molecular analysis of the resected tumor specimens (53 of 78 enrolled patients), Illumina Infinium Methylation EPIC BeadChip DNA methylation arrays and next generation sequencing (NGS) panels were performed to investigate the meningioma methylation class, and the presence of mutations in AKT1, TRAF7, BAP1, NF2 and the TERT-promotor as well as loss of chromosomes 1p and 22q and/or homozygous loss of CDKN2A/B. The cohort included 50 atypical and 3 malignant meningiomas per local assessment according to WHO classification at the time of patient enrollment. Factors significant at 10% significance in the univariate and interaction factor analyses were included in multivariate analyses with stepwise selection at the same significance. RESULTS The Cox multivariate analyses identified meningioma methylation class as a significant independent prognostic factor for progression-free survival (PFS) and overall survival (OS) measured from patient registration in the trial, respectively Chromosome 1p loss was significantly associated with PFS but not with OS. Age was significantly associated with OS but not with PFS. Due to small number of cases and/or events the prognostic value of homozygous deletion of CDKN2A/B (n=2) and TERT-promotor mutation (n=2) could not be adequately studied. CONCLUSIONS In this cohort of WHO grade 2 and 3 meningioma undergoing high-dose adjuvant radiotherapy, meningioma methylation class was identified as an independent prognostic factor for PFS and OS. Chromosome 1p loss was associated with reduced PFS but not OS. Larger cohorts are required to validate our findings.