BACKGROUND AND PURPOSE: Selumetinib is a promising MAP (mitogen-activated protein) kinase (MEK) 1/2 inhibitor treatment for pediatric low-grade gliomas. We hypothesized that MR imaging-derived ADC histogram metrics would be associated with survival and response to treatment with selumetinib. MATERIALS AND METHODS:Children with recurrent, refractory, or progressive pediatric low-grade gliomas who had World Health Organization grade I pilocytic astrocytoma with KIAA1549-BRAF fusion or the BRAF V600E mutation (stratum 1), neurofibromatosis type 1-associated pediatric low-grade gliomas (stratum 3), or sporadic non-neurofibromatosis type 1 optic pathway and hypothalamic glioma (OPHG) (stratum 4) were treated with selumetinib for up to 2 years. Quantitative ADC histogram metrics were analyzed for total and enhancing tumor volumes at baseline and during treatment.RESULTS: Each stratum comprised 25 patients. Stratum 1 responders showed lower values of SD of baseline ADC_total as well as a larger decrease with time on treatment in ADC_total mean, mode, and median compared with nonresponders. Stratum 3 responders showed a greater longitudinal decrease in ADC_total. In stratum 4, higher baseline ADC_total skewness and kurtosis were associated with shorter progression-free survival. When all 3 strata were combined, responders showed a greater decrease with time in ADC_total mode and median. Compared with sporadic OPHG, neurofibromatosis type 1-associated OPHG had lower values of ADC_total mean, mode, and median as well as ADC_enhancement mean and median and higher values of ADC_total skewness and kurtosis at baseline. The longitudinal decrease in ADC_total median during treatment was significantly greater in sporadic OPHG compared with neurofibromatosis type 1-associated OPHG.CONCLUSIONS: ADC histogram metrics are associated with progression-free survival and response to treatment with selumetinib in pediatric low-grade gliomas.ABBREVIATIONS: MEK ¼ MAP (mitogen-activated protein) kinase; NF1 ¼ neurofibromatosis type 1; OPHG ¼ optic pathway and hypothalamic glioma; PBTC ¼ Pediatric Brain Tumor Consortium; PFS ¼ progression-free survival; pLGG ¼ pediatric low-grade glioma; WHO ¼ World Health Organization P ediatric low-grade gliomas (pLGGs) are the most commonly occurring childhood brain tumor and comprise 40%-50% of all childhood CNS tumors. 1,2 World Health Organization (WHO) grade I pilocytic astrocytoma is the most frequent primary brain tumor in individuals 0-19 years of age, accounting for 15% of children's and adolescents' (0-19 years) and 17.8% of

BACKGROUND AND PURPOSE: Molecular profiling is a crucial feature in the "integrated diagnosis" of CNS tumors. We aimed to determine whether radiomics could distinguish molecular types of pontine pediatric high-grade gliomas that have similar/overlapping phenotypes on conventional anatomic MR images. MATERIALS AND METHODS:Baseline MR images from children with pontine pediatric high-grade gliomas were analyzed. Retrospective imaging studies included standard precontrast and postcontrast sequences and DTI. Imaging analyses included median, mean, mode, skewness, and kurtosis of the ADC histogram of the tumor volume based on T2 FLAIR and enhancement at baseline. Histone H3 mutations were identified through immunohistochemistry and/or Sanger or next-generation DNA sequencing. The log-rank test identified imaging factors prognostic of survival from the time of diagnosis. Wilcoxon rank-sum and Fisher exact tests compared imaging predictors among groups.RESULTS: Eighty-three patients had pretreatment MR imaging and evaluable tissue sampling. The median age was 6 years (range, 0.7-17 years); 50 tumors had a K27M mutation in H3-3A, and 11, in H3C2/3. Seven tumors had histone H3 K27 alteration, but the specific gene was unknown. Fifteen were H3 wild-type. Overall survival was significantly higher in H3C2/3compared with H3-3A-mutant tumors (P ¼ .003) and in wild-type tumors compared with any histone mutation (P ¼ .001). Lower overall survival was observed in patients with enhancing tumors (P ¼ .02) compared with those without enhancement. H3C2/3-mutant tumors showed higher mean, median, and mode ADC_total values (P , .001) and ADC_enhancement (P , .004), with lower ADC_total skewness and kurtosis (P , .003) relative to H3-3A-mutant tumors. CONCLUSIONS: ADC histogram parameters are correlated with histone H3 mutation status in pontine pediatric high-grade glioma.ABBREVIATIONS: DIPG ¼ diffuse intrinsic pontine glioma; DMG ¼ diffuse midline glioma; HGG ¼ high-grade glioma; IDH ¼ isocitrate dehydrogenase; OS ¼ overall survival; PG ¼ postgadolinium; pHGG ¼ pediatric-type high-grade glioma D iffuse intrinsic pontine glioma (DIPG) is defined as an expansile T1-hypointense, T2-hyperintense nonenhancing pontine tumor involving at least 50% of the ventral pons and engulfing the basilar artery. [1][2][3] These tumors were reclassified in the 2021 World Health Organization classification of CNS tumors, emphasizing that molecular features are as essential as histology in diagnosing pontine tumors. 3,4 Numerous molecular changes of clinicopathologic utility were incorporated, and the designation of a subset of tumors formerly called DIPG as H3 K27-altered diffuse midline glioma highlights the importance of this mutation in defining a disease entity. 2,3 Pontine H3 K27-altered diffuse midline glioma (DMG) is an aggressive pediatric-type high-grade glioma (pHGG) with a median age at diagnosis of 6-7 years and a poor prognosis, with ,10% overall survival (OS) of .2 years. [5][6][7] The diagnosis has historically been based on clinical and MR ...