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PATH-09. MGMT PROMOTER METHYLATION IS A STRONG PROGNOSTIC FACTOR FOR SURVIVAL AFTER PROGRESSION IN HIGH GRADE GLIOMAS


 High grade gliomas (HGGs: anaplastic gliomas and GBM) are the most lethal type of primary brain tumor. Maximal resection and postoperative concurrent chemoradiotherapy, and followed with adjuvant chemotherapy is the standard treatment. But patients with HGGs have a relapse rapidly and short survival. Studies have identified many clinical characteristics and biomarkers were associated with progression free survival (PFS) and over survival (OS). However, there has not yet a comprehensive study on the effects of these factors to survival after the first progression (SAP). 319 patients with HGGs were conducted maximum resection followed by radiotherapy and/or temozolomide chemotherapy and have been confirmed the first progression. Clinical characteristics, biomarkers (IDH1/2 mutation, MGMT promoter methylation, LOH1p/19q, TP53 mutation, EGFR amplification, Ki-67 expression) and clinical interventions (extent of resection, chemoradiotherapy, operation after progression) were analyzed in accordance with SAP. The 1-year SAP was 14.2% (median SAP: 5.1 months). Significant prognostic factors of improved SAP were tumor grade, MGMT promoter methylation and Ki-67 expression in univariate analysis (p< 0.05). Further multivariate analysis showed that MGMT promoter methylation and Ki-67 expression were independently prognostic markers for SAP (p< 0.05). In our data, HGGs could be divided into low, intermediate and high risk groups for SAP by MGMT promoter methylation and Ki-67 expression. However, analysis of 308 patients with GBM from The Cancer Genome Atlas (TCGA) found that MGMT promoter methylation is the only prognostic marker for SAP in multivariate analysis (p< 0.05). Consequently, MGMT promoter methylation is independently prognostic marker for SAP in patients with HGGs. MGMT promoter methylation, combined with Ki-67 expression, might establish a risk model for SAP and this stratification may aid in treatment strategy selection and clinical prognosis evaluation in HGGs.