T2-FLAIR Mismatch, an Imaging Biomarker for IDH and 1p/19q Status in Lower-grade Gliomas: A TCGA/TCIA Project.

Abstract

<b>Purpose:</b> Lower-grade gliomas (WHO grade II/III) have been classified into clinically relevant molecular subtypes based on <i>IDH</i> and 1p/19q mutation status. The purpose was to investigate whether T2/FLAIR MRI features could distinguish between lower-grade glioma molecular subtypes.<b>Experimental Design:</b> MRI scans from the TCGA/TCIA lower grade glioma database (<i>n</i> = 125) were evaluated by two independent neuroradiologists to assess (i) presence/absence of homogenous signal on T2WI; (ii) presence/absence of "T2-FLAIR mismatch" sign; (iii) sharp or indistinct lesion margins; and (iv) presence/absence of peritumoral edema. Metrics with moderate-substantial agreement underwent consensus review and were correlated with glioma molecular subtypes. Somatic mutation, DNA copy number, DNA methylation, gene expression, and protein array data from the TCGA lower-grade glioma database were analyzed for molecular-radiographic associations. A separate institutional cohort (<i>n</i> = 82) was analyzed to validate the T2-FLAIR mismatch sign.<b>Results:</b> Among TCGA/TCIA cases, interreader agreement was calculated for lesion homogeneity [<i>κ</i> = 0.234 (0.111-0.358)], T2-FLAIR mismatch sign [<i>κ</i> = 0.728 (0.538-0.918)], lesion margins [<i>κ</i> = 0.292 (0.135-0.449)], and peritumoral edema [<i>κ</i> = 0.173 (0.096-0.250)]. All 15 cases that were positive for the T2-FLAIR mismatch sign were <i>IDH</i>-mutant, 1p/19q non-codeleted tumors (<i>P</i> < 0.0001; PPV = 100%, NPV = 54%). Analysis of the validation cohort demonstrated substantial interreader agreement for the T2-FLAIR mismatch sign [<i>κ</i> = 0.747 (0.536-0.958)]; all 10 cases positive for the T2-FLAIR mismatch sign were <i>IDH</i>-mutant, 1p/19q non-codeleted tumors (<i>P</i> < 0.00001; PPV = 100%, NPV = 76%).<b>Conclusions:</b> Among lower-grade gliomas, T2-FLAIR mismatch sign represents a highly specific imaging biomarker for the <i>IDH</i>-mutant, 1p/19q non-codeleted molecular subtype. <i>Clin Cancer Res; 23(20); 6078-85. ©2017 AACR</i>.