BIOM-90. EXPANDED PERIVASCULAR SPACE AS A POTENTIAL RADIOLOGIC SIGN OF TREATMENT RESPONSE IN IDH-MUTATED GLIOMA TREATED WITH IDH-INHIBITORS – A RADIOMICS STUDY

Abstract INTRODUCTION Isocitrate Dehydrogenase (IDH)-mutant gliomas are slow-growing infiltrating tumors of astrocytic (AS) or oligodendroglial (OG) origin. Neomorphic mutations of IDH1/IDH2 and lead to production of 2-hydroxyglutarate (2-HG) that can be measured with optimized in-vivo MRS. Small-molecule IDH inhibitors (IDHi) ivosidenib (inhibits mIDH1 enzyme) and vorasidenib (inhibits mIDH1 and mIDH2 enzymes) showed good tumor penetrance and ~95% 2-HG reduction measured in tumor biopsies. Both ivosidenib and vorasidenib have evidence of responses in tumor growth rate. As volume reductions are often observed, but after a delay of several months, thus an early response biomarker is highly desired. The aim of this study was to explore whether radiomics analysis of MRI can be used to predict response to treatment with IDHmut-inhibiting drugs. METHODS Fourteen patients (Age ≥18y) with a histomolecularly confirmed IDH1 mutated diffuse glioma (AS or OG) received ivosidenib (n=12) or vorasidenib (n=2) therapy as part of their routine clinical care. MRI was performed before treatment (baseline) and repeated (follow-up) with a median on-drug follow-up of 6 months [4, 12 IQR]. Tumors were segmented from FLAIR images in 3D Slicer and volumes were calculated in cm3. Radiomics analysis was performed using the SlicerRadiomics/PyRadiomics module in 3D slicer for both baseline and follow up images. Paired T-tests were used to compare the baseline and follow up radiomics values. Treatment response was defined as a decrease in tumor volume. RESULTS Ten patients (71%) in this study responded to IDH-inhibitor therapy. The radiomics features LowGrayLevelEmphasis (p=0.048), LowGrayLevelRunEmphasis (0.047), and ShortRunLowGrayLevelEmpahasis (p=0.044) significantly increased when comparing baseline to follow up images. On qualitative image review, these radiomic changes manifested as an increase in the presence of perivascular spaces within the tumor volume (Figure 1). CONCLUSIONS The increased prevalence and prominence of perivascular spaces in IDH-mutated tumors was associated with response to IDHi therapy and is therefore a promising radiologic sign of volumetric treatment responses that requires no special imaging tools to recognize.