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Clin Cancer Res. 2014 Sep 1;20(17):4532-9. doi: 10.1158/1078-0432.CCR-13-2320. Epub 2014 Jun 19.

Noninvasive detection of glutamate predicts survival in pediatric medulloblastoma.

Author information

1
School of Cancer Sciences, University of Birmingham, Birmingham; Birmingham Children's Hospital NHS Foundation Trust, Birmingham; and martin@pipegrep.co.uk.
2
School of Cancer Sciences, University of Birmingham, Birmingham; Birmingham Children's Hospital NHS Foundation Trust, Birmingham; and.
3
Birmingham Children's Hospital NHS Foundation Trust, Birmingham; and.
4
Birmingham Children's Hospital NHS Foundation Trust, Birmingham; and Institute of Digital Healthcare, WMG, University of Warwick, Coventry, United Kingdom.

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.

PMID:
24947932
PMCID:
PMC4154860
DOI:
10.1158/1078-0432.CCR-13-2320
[Indexed for MEDLINE]
Free PMC Article
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