Discrepant longitudinal volumetric and metabolic evolution of diffuse intrinsic Pontine gliomas during treatment: implications for current response assessment strategies

Neuroradiology. 2016 Oct;58(10):1027-1034. doi: 10.1007/s00234-016-1724-8. Epub 2016 Jul 20.


Introduction: Based on clinical observations, we hypothesized that in infiltrative high-grade brainstem neoplasms, such as diffuse intrinsic pontine glioma (DIPG), longitudinal metabolic evaluation of the tumor by magnetic resonance spectroscopy (MRS) may be more accurate than volumetric data for monitoring the tumor's biological evolution during standard treatment.

Methods: We evaluated longitudinal MRS data and corresponding tumor volumes of 31 children with DIPG. We statistically analyzed correlations between tumor volume and ratios of Cho/NAA, Cho/Cr, and NAA/Cr at key time points during the course of the disease through the end of the progression-free survival period.

Results: By the end of RT, tumor volume had significantly decreased from the baseline (P < .0001) and remained decreased through the last available follow-up magnetic resonance imaging study (P = .007632). However, the metabolic profile of the tumor tissue (Cho/Cr, NAA/Cr, and Cho/NAA ratios) did not change significantly over time.

Conclusion: Our data show that longitudinal tumor volume and metabolic profile changes are dissociated in patients with DIPG during progression-free survival. Volume changes, therefore, may not accurately reflect treatment-related changes in tumor burden. This study adds to the existing body of evidence that the value of conventional MRI metrics, including volumetric data, needs to be reevaluated critically and, in infiltrative tumors in particular, may not be useful as study end-points in clinical trials. We submit that advanced quantitative MRI data, including robust, MRS-based metabolic ratios and diffusion and perfusion metrics, may be better surrogate markers of key end-points in clinical trials.

Keywords: Brainstem tumor; Diffuse intrinsic pontine glioma; Magnetic resonance imaging; Proton spectroscopy; Response criteria.

MeSH terms

  • Adolescent
  • Aging / pathology*
  • Aspartic Acid / analogs & derivatives*
  • Aspartic Acid / metabolism
  • Biomarkers, Tumor / metabolism
  • Brain Stem / diagnostic imaging
  • Brain Stem / metabolism
  • Brain Stem / pathology
  • Brain Stem Neoplasms / diagnostic imaging
  • Brain Stem Neoplasms / metabolism*
  • Brain Stem Neoplasms / pathology*
  • Child
  • Child, Preschool
  • Choline / metabolism*
  • Creatine / metabolism*
  • Disease Progression
  • Female
  • Humans
  • Magnetic Resonance Imaging / methods
  • Magnetic Resonance Spectroscopy / methods*
  • Male
  • Molecular Imaging / methods
  • Outcome Assessment, Health Care / methods
  • Reproducibility of Results
  • Sensitivity and Specificity
  • Tumor Burden


  • Biomarkers, Tumor
  • Aspartic Acid
  • N-acetylaspartate
  • Creatine
  • Choline