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

• Published in: Neuroradiology Vol. 58; no. 10; pp. 1027 - 1034
• Main Authors: Löbel, U., Hwang, S., Edwards, A., Li, Y., Li, X., Broniscer, A., Patay, Z.
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.10.2016; Springer Nature B.V
• Subjects: Adolescent; Aging - pathology; Aspartic Acid - analogs & derivatives; Aspartic Acid - metabolism; Biomarkers, Tumor - metabolism; Brain cancer; 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; Imaging; Magnetic Resonance Imaging - methods; Magnetic Resonance Spectroscopy - methods; Male; Medicine; Medicine & Public Health; Molecular Imaging - methods; Nervous system; Neurology; Neuroradiology; Neurosciences; Neurosurgery; NMR; Nuclear magnetic resonance; Outcome Assessment (Health Care) - methods; Paediatric Neuroradiology; Pediatrics; Radiology; Reproducibility of Results; Sensitivity and Specificity; Tumor Burden; Tumors; Brainstem tumor; Proton spectroscopy; Magnetic resonance imaging; Diffuse intrinsic pontine glioma; Response criteria
• ISSN: 0028-3940; 1432-1920
• DOI: 10.1007/s00234-016-1724-8

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.