Noninvasive detection of glutamate predicts survival in pediatric medulloblastoma

Martin Wilson, Simrandip K Gill, Lesley MacPherson, Martin English, Theodoros N Arvanitis, Andrew C Peet

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26 Citations (Scopus)
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Abstract

PURPOSE: Medulloblastoma is the most common malignant brain tumor occurring in childhood and is a significant cause of morbidity and mortality in pediatric oncology. More intense treatment strategies are recommended for patients displaying high-risk factors; however, considerable variation in outcome remains, indicating a need for improved predictive markers. In this study, 1H magnetic resonance spectroscopy (MRS) was used to investigate noninvasive molecular biomarkers of survival in medulloblastoma.

EXPERIMENTAL DESIGN: MRS was performed on a series of 35 biopsy-confirmed medulloblastoma cases. One case was excluded because of poor quality MRS. The prognostic value of MRS detectable biomarkers was investigated using Cox regression, retrospectively (N=15). A subsequent validation analysis (N=19) was also performed to reduce the chance of type I errors. Where available, high-resolution ex vivo MRS of biopsy tissue was used to confirm biomarker assignments.

RESULTS: The retrospective analysis revealed that creatine, glutamate, and glycine were markers of survival (P<0.01). The validation analysis showed that glutamate was a robust marker, with a hazard ration (HR) of 8.0 for the full dataset (P=0.0003, N=34). A good correlation between in vivo and ex vivo MRS glutamate/total-choline was found (P=0.001), validating the in vivo assignment. Ex vivo glutamate/total-choline was also associated with survival (P<0.01).

CONCLUSION: The identification of glutamate as a predictive biomarker of survival in pediatric medulloblastoma provides a clinically viable risk factor and highlights the importance of more detailed studies into the metabolism of this disease. Noninvasive biomarker detection using MRS may offer improved disease monitoring and potential for widespread use following multicenter validation.

Original languageEnglish
Pages (from-to)4532-4539
JournalClinical Cancer Research
Volume20
Issue number17
Early online date19 Jun 2014
DOIs
Publication statusPublished - 1 Sep 2014

Keywords

  • Adolescent
  • Biomarkers, Tumor
  • Brain Neoplasms
  • Child
  • Child, Preschool
  • Female
  • Glutamic Acid
  • Humans
  • Kaplan-Meier Estimate
  • Magnetic Resonance Spectroscopy
  • Male
  • Medulloblastoma
  • Precision Medicine
  • Prognosis

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