Association of partial t2-flair mismatch sign and isocitrate dehydrogenase mutation in who grade 4 glioma/glioblastoma: results from the respond consortium

Abstract PURPOSE T2-FLAIR mismatch (T2FM) is a highly specific imaging biomarker for isocitrate dehydrogenase (IDH) mutation in low-grade gliomas. Previous T2FM studies are inconsistent for glioblastoma (GBM)/grade-4 glioma, partly due to low IDH-mutation prevalence in high-grade gliomas. We leveraged a large multi-institutional GBM/grade-4 glioma cohort to analyze the association of partial T2FM and IDH-mutation (T2-hyperintense, FLAIR-hypointense, nonenhancing, nonedema). METHODS We analyzed preoperative MRI of 1500 pathologically confirmed GBM/grade-4 gliomas with known IDH-mutation status from the ReSPOND consortium, consisting of the following institutions (sample size): Ivy GBM Atlas Project (33), Catalan Institute of Oncology (132), Case Western Reserve University/University Hospitals (132), New York University (55), Ohio State University (25), University of Pennsylvania (641), University Hospital Río Hortega (16), Yonsei University Health System (118), The Cancer Imaging Archive (93), Thomas Jefferson University (48), Tata Memorial Hospital (22), University of Pittsburgh Medical Center (156), and Washington University School of Medicine in St. Louis (57). Sequences were co-registered to a common anatomic atlas. Continuous variables were compared by t-test and categorical variables by Χ 2-test. RESULTS 71 (4.7%) were IDH-mutants, significantly younger (43±1 v. 62±12 years, p=5x10-37), and more likely to exhibit partial T2FM (20% v. 0.4%, p=1x10-43), frontal lobe predominance (68% v. 29%, p=7x10-12), nonenhancing components (T2/FLAIR-intermediate signal, nonedema; 45% v. 9%, p=1x10-22), and cystic components (smooth margins, no/minimal enhancement, homogeneous FLAIR suppression; 17% v. 3%, p=7x10-11) than IDH-wildtypes. 20 cases had partial T2FM (14 IDH-mutant, 6 IDH-wildtype). Sensitivity of partial T2FM for IDH-mutation was 19.7%, specificity 99.6%, positive predictive value 70%, and negative predictive value 96.1%. Subset analysis of 983 IDH-wildtypes with known MGMT methylation status (406 MGMT-hypermethylated) showed frontal lobe predominance was more common in MGMT-hypermethylated than MGMT-unmethylated (39.4% v. 24.3%, p=.02); other imaging characteristics did not significantly differ. CONCLUSIONS Partial T2FM is a highly specific imaging biomarker for IDH-mutation in GBM/grade-4 glioma.