NIMG-36. PERFUSION, DIFFUSION, AND ANATOMICAL MRI BIOMARKERS FOR ASSESSING HISTOLOGICALLY-CONFIRMED MALIGNANT TRANSFORMATION IN MOLECULAR SUBTYPES OF IDH-MUTANT GLIOMAS

Abstract BACKGROUND Isocitrate dehydrogenase-mutant (IDHm) gliomas often initially present as low-grade (grade 2) gliomas but are expected to later progress into more aggressive higher-grade (grade 3-4) gliomas through malignant transformation (MT). MT is often determined non-invasively by emergence of contrast-enhancement on post-contrast T1-weighted magnetic resonance imaging (MRI), but contrast-enhancement is an imperfect surrogate for histologically-confirmed MT. This study explored perfusion, diffusion, and anatomical MRI biomarkers besides contrast-enhancement to study histologically-confirmed MT in IDHm 1p/19q-intact astrocytomas (IDHm-A) and IDHm 1p/19q-co-deleted oligodendrogliomas (IDHm-O). METHODS N=64 patients with initial histopathological grade 2 IDH-mutant glioma diagnosis who underwent repeated tissue sampling and were classified as histologically-confirmed MT (n=35) or non-MT (n=29) were retrospectively studied. Pre-surgical anatomical MRI (n=64) and, if available, diffusion-weighted imaging (n=61) and dynamic susceptibility contrast perfusion MRI (n=53) were analyzed. Tumor volumes of interest were segmented on the whole T2/FLAIR-hyperintense tumor. Measurable contrast enhancement (>1000mm3), tumor volume, sphericity, median apparent diffusion coefficient (ADC), and normalized relative cerebral blood volume (nrCBV) were compared between MT vs. non-MT IDHm-A and IDHm-O. RESULTS 81% of contrast-enhancing IDHm-A and 100% of contrast-enhancing IDHm-O underwent MT, while 41% of MT IDHm-A and 62% of MT IDHm-O were non-enhancing. Tumor volumes were significantly larger in the MT vs. non-MT groups for both IDHm-A (P=0.02) and IDHm-O (P=0.04). Whole tumor nrCBV was significantly higher (P=0.002), whole tumor ADC trended lower (P=0.06), and non-enhancing tumor sphericity was significantly lower (P=0.03) in MT vs. non-MT IDHm-A. There were no significant differences in ADC, nrCBV, nor sphericity when comparing MT vs. non-MT IDHm-O (P>0.05). CONCLUSIONS Many MT IDHm-gliomas remain non-enhancing. Tumor volumes can determine MT for both IDHm-A and IDHm-O. Diffusion and perfusion MRI show differences for MT in IDHm-A but not IDHm-O, which may reflect the different tumor biology of these IDHm molecular subtypes and their need for separate imaging biomarkers.