Journal
CLINICAL CANCER RESEARCH
Volume 20, Issue 17, Pages 4532-4539Publisher
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/1078-0432.CCR-13-2320
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Funding
- Medical Research Council [G0601327]
- EU FP6 projects eTUMOUR and Health Agents
- CR-UK& EPSRC Cancer Imaging Programme at the CCLG
- MRC and Department of Health (England)
- NIHR
- Birmingham Children's Hospital Research Foundation
- Poppyfields
- National Institutes of Health Research (NIHR) [NIHR-RP-02-12-019] Funding Source: National Institutes of Health Research (NIHR)
- MRC [G0601327] Funding Source: UKRI
- Action Medical Research [2181] Funding Source: researchfish
- Cancer Research UK [10342] Funding Source: researchfish
- Medical Research Council [G0601327] Funding Source: researchfish
- National Institute for Health Research [NIHR-RP-02-12-019] Funding Source: researchfish
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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, 1 H 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 ofMRSdetectable 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. (C) 2014 AACR.
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