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

  • Paediatric Neuroradiology
  • Published:
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Abstract

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.

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Acknowledgments

This work was supported in part by Grant P30 CA021765 from the National Cancer Institute and by the American Lebanese Syrian Associated Charities (ALSAC). The authors thank Dr. Cherise Guess of the Department of Scientific Editing at St. Jude Children’s Research Hospital for editing the manuscript.

Author information

Authors and Affiliations

  1. Department of Diagnostic and Interventional Neuroradiology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

    U. Löbel

  2. Department of Diagnostic Imaging, St. Jude Children’s Research Hospital, 262 Danny Thomas Place, MS220, Memphis, TN, 38105, USA

    U. Löbel, S. Hwang, A. Edwards & Z. Patay

  3. Department of Biostatistics, St. Jude Children’s Research Hospital, Memphis, TN, USA

    Y. Li & X. Li

  4. Department of Oncology, St. Jude Children’s Research Hospital, Memphis, TN, USA

    A. Broniscer

  5. Department of Pediatrics, University of Tennessee Health Science Center, Memphis, TN, USA

    A. Broniscer

Authors
  1. U. Löbel
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  2. S. Hwang
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  3. A. Edwards
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  4. Y. Li
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  5. X. Li
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  7. Z. Patay
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Corresponding author

Correspondence to Z. Patay.

Ethics declarations

We declare that all human studies have been approved by the local ethics committee and have therefore been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. We declare that all patients gave informed consent prior to inclusion in this study.

Conflict of interest

AB received partial financial support from AstraZeneca to conduct this clinical trial.

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Löbel, U., Hwang, S., Edwards, A. et al. Discrepant longitudinal volumetric and metabolic evolution of diffuse intrinsic Pontine gliomas during treatment: implications for current response assessment strategies. Neuroradiology 58, 1027–1034 (2016). https://doi.org/10.1007/s00234-016-1724-8

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  • DOI: https://doi.org/10.1007/s00234-016-1724-8

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