MR Imaging Correlates for Molecular and Mutational Analyses in Children with Diffuse Intrinsic Pontine Glioma

Abstract

<h3>BACKGROUND AND PURPOSE:</h3> Recent advances in molecular techniques have characterized distinct subtypes of diffuse intrinsic pontine gliomas. Our aim was the identification of MR imaging correlates of these subtypes. <h3>MATERIALS AND METHODS:</h3> Initial MRIs from subjects with diffuse intrinsic pontine gliomas recruited for a prospective clinical trial before treatment were analyzed. Retrospective imaging analyses included FLAIR/T2 tumor volume, tumor volume enhancing, the presence of cyst and/or necrosis, median, mean, mode, skewness, kurtosis of ADC tumor volume based on FLAIR, and enhancement at baseline. Molecular subgroups based on EGFR and <i>MGMT</i> mutations were established. Histone mutations were also determined (<i>H3F3A, HIST1H3B, HIST1H3C</i>). Univariate Cox proportional hazards regression was used to test the association of imaging predictors with overall and progression-free survival. Wilcoxon rank sum, Kruskal-Wallis, and Fisher exact tests were used to compare imaging measures among groups. <h3>RESULTS:</h3> Fifty patients had biopsy and MR imaging. The median age at trial registration was 6 years (range, 3.3–17.5 years); 52% were female. On the basis of immunohistochemical results, 48 patients were assigned to 1 of 4 subgroups: 28 in <i>MGMT</i>–/<i>epidermal growth factor receptor</i> (<i>EGFR</i>)–, 14 in <i>MGM</i>T–/EGFR+, 3 in <i>MGMT</i>+/EGFR–, and 3 in <i>MGMT</i>+/EGFR+. Twenty-three patients had histone mutations in H3F3A, 8 in HIST1H3B, and 3 in HIST1H3C. Enhancing tumor volume was near-significantly different across molecular subgroups (<i>P </i>= .04), after accounting for the false discovery rate. Tumor volume enhancing, median, mode, skewness, and kurtosis ADC T2-FLAIR/T2 were significantly different (<i>P </i>≤ .048) between patients with H3F3A and HIST1H3B/C mutations. <h3>CONCLUSIONS:</h3> MR imaging features including enhancement and ADC histogram parameters are correlated with molecular subgroups and mutations in children with diffuse intrinsic pontine gliomas.