C Jaimes1,2,3, S Vajapeyam1,3, D Brown4, P-C Kao5,6, C Ma5,6,3, L Greenspan5,6, N Gupta7,8, L Goumnerova, P Bandopahayay5,6,3, F Dubois6,3, N F Greenwald9, T Zack8, O Shapira6,10, R Beroukhim5,6,3, K L Ligon6,11,3, S Chi5,6,3, M W Kieran12, K D Wright5,6,3, T Y Poussaint13,3. 1. From the Departments of Radiology (C.J., S.V., T.Y.P.). 2. Fetal-Neonatal Neuroimaging and Developmental Science Center (C.J.), Division of Newborn Medicine; Boston Children's Hospital, Boston, Massachusetts. 3. Harvard Medical School (C.J., S.V., C.M., P.B., F.D., R.B., K.L.L., S.C., K.D.W., T.Y.P.), Boston, Massachusetts. 4. Tumor Imaging Metrics Core (D.B.), Massachusetts General Hospital, Boston, Massachusetts. 5. Pediatrics, Division of Oncology (P.-C.K., C.M., L.G., P.B., R.B., S.C., K.D.W.). 6. Dana Farber Cancer Institute (P.-C.K., C.M., L.G., P.B., F.D., O.S., R.B., K.L.L., S.C., K.D.W.), Boston, Massachusetts. 7. Department of Pediatric Neurosurgery (N.G.), University of California San Francisco Benioff Children's Hospital, San Francisco, California. 8. University of California San Francisco School of Medicine (N.G., T.Z.), San Francisco, California. 9. Stanford University School of Medicine (N.F.G.), Palo Alto, California. 10. Broad Institute of Massachusetts Institute of Technology and Harvard University (O.S.), Cambridge, Massachusetts. 11. Department of Pathology (K.L.L.), Brigham and Women's Hospital, Boston, Massachusetts. 12. Clinical Trials Division (M.W.K.), Bristol-Myers-Squibb, New York, New York. 13. From the Departments of Radiology (C.J., S.V., T.Y.P.) Tinayoung.poussaint@childrens.harvard.edu.
Abstract
BACKGROUND AND PURPOSE: 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. MATERIALS AND METHODS: 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 MGMT mutations were established. Histone mutations were also determined (H3F3A, HIST1H3B, HIST1H3C). 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. RESULTS: 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 MGMT-/epidermal growth factor receptor (EGFR)-, 14 in MGMT-/EGFR+, 3 in MGMT+/EGFR-, and 3 in MGMT+/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 (P = .04), after accounting for the false discovery rate. Tumor volume enhancing, median, mode, skewness, and kurtosis ADC T2-FLAIR/T2 were significantly different (P ≤ .048) between patients with H3F3A and HIST1H3B/C mutations. CONCLUSIONS: MR imaging features including enhancement and ADC histogram parameters are correlated with molecular subgroups and mutations in children with diffuse intrinsic pontine gliomas.
BACKGROUND AND PURPOSE: 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. MATERIALS AND METHODS: 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 MGMT mutations were established. Histone mutations were also determined (H3F3A, HIST1H3B, HIST1H3C). 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. RESULTS: 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 MGMT-/epidermal growth factor receptor (EGFR)-, 14 in MGMT-/EGFR+, 3 in MGMT+/EGFR-, and 3 in MGMT+/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 (P = .04), after accounting for the false discovery rate. Tumor volume enhancing, median, mode, skewness, and kurtosis ADC T2-FLAIR/T2 were significantly different (P ≤ .048) between patients with H3F3A and HIST1H3B/C mutations. CONCLUSIONS: MR imaging features including enhancement and ADC histogram parameters are correlated with molecular subgroups and mutations in children with diffuse intrinsic pontine gliomas.
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