Low fractional tumor burden volume obtained from perfusion mri reveals significant survival benefit in mgmt unmethylated glioblastoma.

Abstract INTRODUCTION Standard imaging remains inadequate for the determination of GBM response within the first 3 months following upfront chemoradiation therapy (CRT). Since advanced diffusion and DSC perfusion (pMRI) MRI are currently not included in RANO criteria, greater reliance is placed on MGMT methylation status, with methylated tumors demonstrating survival benefit. While pMRI has demonstrated usefulness following CRT, a newer pMRI biomarker termed Fractional Tumor Burden (FTB) provides both spatial and quantifiable information. The purpose of this study was to evaluate whether advanced MRI including FTB informs a survival benefit beyond MGMT promoter methylation status in newly diagnosed GBM (nGBM). METHODS Consented subjects with nGBM, and known MGMT status who completed standard upfront therapy and had MRI within 6 weeks of CRT completion, were included. Known IDH-mutant tumors were excluded. DSC was collected with the consensus protocol and leakage-corrected relative cerebral blood volume (rCBV) generated. Apparent diffusion coefficient (ADC) was calculated from diffusion MRI (b-value: 0,1000 s/mm2). FTB-defined tumor volumes were calculated from rCBV and delta T1w enhancement. Kaplan-Meier 24-month overall survival (OS) was evaluated for MGMT status and stratified by cohort mean for rCBV (1.3 a.u.) and ADC (1300 x10-6mm2/s), and empirically for FTB (5 ml) (significance: P >.05). RESULTS A total of 43 subjects were included (male/female=21/22; age=57(23-74)). MRI was acquired an average of 29 (12-42) days following CRT. Significant OS differences were confirmed for MGMT methylation (OS=19.08 vs. 10.18 mo; P=.0129). No significant survival differences were found (P >.05) when stratified by rCBV or ADC. While FTB did not provide further OS distinctions in methylated GBM, those with unmethylated MGMT had significant OS benefit when FTB volume was < 5 ml (OS=16.15 vs 8.39 mo; P=.0054). CONCLUSION FTB further informs OS in MGMT promoter unmethylated GBM, where those with lower volume had survival approaching that of methylated subjects.