PO69: THE IMPACT OF MGMT METHYLATION AND IDH-1 MUTATION ON LONG TERM OUTCOME FOR GLIOBLASTOMA TREATED WITH CHEMORADIOTHERAPY

INTRODUCTION: Biomarkers have been identified which correlate with improved OS and PFS in Glioblastoma, including MGMT methylation status and mutations in the IDH1 gene. In this study, we investigated the clinical and biological factors associated with long-term survival in glioblastoma patients treated with chemoradiotherapy. METHOD: Demographic and clinical data was collected for all patients with Glioblastoma diagnosed between May 2004 and September 2007, treated with chemoradiotherapy and with associated tissue samples available for biomarker analysis. MGMT methylation was determined by pyrosequencing. IDH1 mutation was identified by R132H immunohistochemistry. RESULTS: 100 patients were included in the study. Median follow-up was 1 year (range 0.1-8.5). Median OS was 12.1 months (95%CI: 10.8-13.3) and PFS was 8.2 months (95%CI: 6.8-9.5). 2, 3 and 5-year survival was 18%, 9% and 6% respectively. Three patients are still alive at 7.4, 8.3 and 8.5 years after diagnosis. Kaplan-Meier survival analysis showed that MGMTmethylated/IDH1 + ve was associated with significantly longer OS 66.8 months (0.0 - 167.8) and PFS 16.9 months (11.1 - 22.7), when compared with MGMTmethylated/IDH1-ve OS 15.5 (11.6 - 19.4) and PFS 9.4 (8 - 10.8) (P = 0.000), and MGMTunmethylated/IDH1-ve OS 11.1 (8.5 - 13.7) and PFS 6.3 (4.4 - 8.3) (P = 0.000). CONCLUSION: We have shown that the combination of MGMTmethylated/IDH1 + ve is associated with considerably longer OS and PFS in this series of chemoradiotherapy treated Glioblastoma tumours. The long-term cognitive function and quality of life in these long-term survivors warrants investigation.