PATH-09. NEXT-GENERATION SEQUENCING OF GLIOBLASTOMA MULTIFORME ‘EXTREME RESPONDERS’

Abstract

Abstract BACKGROUND Glioblastoma Multiforme (GBM) is the most common primary brain among adults. Despite steady advances in treatment, the outcome remains universally lethal. Median overall survival in a population-based study is approximately 10 to 12 months. Prognostic factors in GBM patients include age, performance score, extent of surgical resection, IDH1 mutation status and MGMT methylation status. Survival > 2 years is rare; for the purpose of this study we have defined these patients ‘extreme responders.’ This study aims to identify genomic signatures and gene alterations that may have contributed to ‘extreme response’ to standard adjuvant chemoradiotherapy. METHODS A total of 12 out of 141 primary GBM patients were identified as ‘extreme responders’ as part of a retrospective chart review between 2005 - 2016. Of the 12 suitable for NGS testing, 9 were analyzed using the Foundation One CDx® (next-generation sequencing platform) which interrogates 324 genes, microsatellite status and tumour mutational burden (TMB). Baseline demographics, clinical characteristics, and NGS results were compared. RESULTS Of the 9 patients tested, over half were female (5, 55%) and median age at diagnosis was 53 years. Gross total resection was performed at diagnosis in 3 cases. MGMT status was available for 5 patients and was methylated in 3. NGS results revealed: MSI stable in all patients, median TMB 3 muts/Mb and most common gene alterations were TP53 (5/9); ATRX (4/9); EGFR (3/9); CDKN2A/B (3/9); IDH1(3/9); PIK3R1(3/9) and PTEN (3/9). CONCLUSION Acknowledging the fact that our sample size was small and no control group was tested, our study infers a higher incidence of IDH1, TP53 and ATRX mutations which are more common in secondary glioblastomas and this may be a contributing factor towards longer survival in our cohort. We did not identify any universal molecular marker predictive of improved prognosis or exquisite sensitivity to chemoradiotherapy.