Correlation of multimodal 18F-DOPA PET and conventional MRI with treatment response and survival in children with diffuse intrinsic pontine gliomas

Theranostics. 2020 Oct 25;10(26):11881-11891. doi: 10.7150/thno.50598. eCollection 2020.

Abstract

To evaluate the contribution of 18F-dihydroxyphenylalanine (DOPA) PET in association with conventional MRI in predicting treatment response and survival outcome of pediatric patients with diffuse intrinsic pontine gliomas (DIPGs). Methods: We retrospectively analyzed 19 children with newly diagnosed DIPGs who underwent 18F-DOPA PET/CT and conventional MRI within one week of each other at admission and subsequent MRI follow-up. Following co-registration and fusion of PET and MRI, 18F-DOPA uptake avidity and extent (PET tumor volume and uniformity) at admission, along with MRI indices including presence of ring contrast-enhancement, tumor volume at admission and at maximum response following first-line treatment, were evaluated and correlated with overall survival (OS). The association between 18F-DOPA uptake tumor volume at admission and MRI tumor volume following treatment was evaluated. Statistics included Wilcoxon signed-rank and Mann-Whitney U tests, Kaplan-Meier OS curve and Cox analysis. Results: DIPGs with a 18F-DOPA uptake Tumor/Striatum (T/S) ratio >1 presented an OS ≤ 12 months and lower degree of tumor volume reduction following treatment (p = 0.001). On multivariate analysis, T/S (p = 0.001), ring enhancement (p = 0.01) and the degree of MRI tumor volume reduction (p = 0.01) independently correlated with OS. In all patients, areas of increased 18F-DOPA uptake overlapped with regions demonstrating more prominent residual components/lack of response following treatment. Conclusions:18F-DOPA PET provides useful information for evaluating the metabolism of DIPGs. T/S ratio is an independent predictor of outcome. 18F-DOPA uptake extent delineates tumoral regions with a more aggressive biological behaviour, less sensitive to first line treatment.

Keywords: DIPG; DOPA PET; MRI; Pediatric; diffuse midline glioma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Monoclonal, Humanized / pharmacology
  • Antibodies, Monoclonal, Humanized / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols / pharmacology
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Biopsy
  • Brain Stem Neoplasms / diagnosis
  • Brain Stem Neoplasms / genetics
  • Brain Stem Neoplasms / mortality
  • Brain Stem Neoplasms / therapy*
  • Chemoradiotherapy / methods*
  • Child
  • Child, Preschool
  • Corpus Striatum / diagnostic imaging
  • Diffuse Intrinsic Pontine Glioma / diagnosis
  • Diffuse Intrinsic Pontine Glioma / genetics
  • Diffuse Intrinsic Pontine Glioma / mortality
  • Diffuse Intrinsic Pontine Glioma / therapy*
  • Dihydroxyphenylalanine / administration & dosage
  • Dihydroxyphenylalanine / analogs & derivatives
  • Feasibility Studies
  • Female
  • Follow-Up Studies
  • Histones / genetics
  • Humans
  • Kaplan-Meier Estimate
  • Magnetic Resonance Imaging
  • Male
  • Mutation
  • Pons / diagnostic imaging*
  • Pons / pathology
  • Positron-Emission Tomography
  • Retrospective Studies
  • Risk Assessment / methods
  • Tumor Burden / drug effects
  • Tumor Burden / radiation effects
  • Vinorelbine / pharmacology
  • Vinorelbine / therapeutic use

Substances

  • Antibodies, Monoclonal, Humanized
  • Histones
  • fluorodopa F 18
  • Dihydroxyphenylalanine
  • nimotuzumab
  • Vinorelbine