title: Predicting outcome of children with diffuse intrinsic pontine gliomas using multiparametric imaging.
abstract: Noninvasive evaluation using MRI is the primary means to routinely assess children with diffuse intrinsic pontine gliomas (DIPGs). However, no standard MR sequence has correlated with outcome in these patients. In this study, patients with DIPGs were assessed to determine the combined prognostic value via dynamic susceptibility contrast (DSC) MRI, single-voxel spectroscopy (SVS), multivoxel MR spectroscopy (MRS), and T1-weighted post-gadolinium imaging. Eligible patients had clinical and radiographic findings consistent with a DIPG. Imaging studies were acquired on a 1.5T MRI at various time points during each patient's course. Data were evaluated using a Cox proportional hazard model, a time-dependent covariant Cox model, a Wald test, and a Kaplan-Meier analysis. Ninety-eight studies were performed on 34 patients of median age 5.5 years. Median survival from diagnosis was 468 days. At baseline imaging only, increased ratio of choline to n-acetylaspartate (Cho:NAA) on SVS and increased perfusion on DSC-MRI each predicted shorter survival (relative risk [RR] = 1.48, P = .015 and RR = 4.91, P = .0012, respectively). When analyzing all subsequent time points, increased maximum Cho:NAA on MRS (RR = 1.45, P = .042), increased Cho:NAA on SVS (RR = 1.69, P = .003), increased perfusion (RR = 4.68, P = .0016), and the presence of enhancement (RR = 5.69, P = .022) each predicted shorter survival. Kaplan-Meier analysis showed shorter survival associated with increased perfusion at baseline (P = .0004). Increased perfusion at any time point predicts a significantly shorter survival in children with DIPG. In addition, enhancement, increased Cho:NAA on SVS, and increased maximum Cho:NAA on chemical shift imaging are predictive of shorter survival over time. Routine baseline and subsequent imaging for children with DIPG should, at minimum, incorporate DSC-MRI and SVS.
authors.affiliation: Pediatric Oncology Branch, National Cancer Institute, Center for Cancer Research, National Institutes of Health, Bethesda, MD 20892, USA. sean.hipp@us.army.mil
authors.forename: Sean J
authors.initials: SJ
authors.lastname: Hipp
authors.forename: Emilie
authors.initials: E
authors.lastname: Steffen-Smith
authors.forename: Dima
authors.initials: D
authors.lastname: Hammoud
authors.forename: Joanna H
authors.initials: JH
authors.lastname: Shih
authors.forename: Robyn
authors.initials: R
authors.lastname: Bent
authors.forename: Katherine E
authors.initials: KE
authors.lastname: Warren
mesh_terms: D000293:Adolescent; D000328:Adult; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000378:metabolism; D001932:Brain Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000532:radiotherapy; D020295:Brain Stem Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000532:radiotherapy; D002648:Child; D002675:Child, Preschool; D002794:Choline / Q000378:metabolism*; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D011149:Pons; D011446:Prospective Studies; D015996:Survival Rate; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D001224:Aspartic Acid; C000179:N-acetylaspartate; D002794:Choline