title: Noninvasive detection of glutamate predicts survival in pediatric medulloblastoma.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: School of Cancer Sciences, University of Birmingham, Birmingham; Birmingham Children's Hospital NHS Foundation Trust, Birmingham; and martin@pipegrep.co.uk.
authors.forename: Martin
authors.initials: M
authors.lastname: Wilson
authors.affiliation: School of Cancer Sciences, University of Birmingham, Birmingham; Birmingham Children's Hospital NHS Foundation Trust, Birmingham; and.
authors.forename: Simrandip K
authors.initials: SK
authors.lastname: Gill
authors.affiliation: Birmingham Children's Hospital NHS Foundation Trust, Birmingham; and.
authors.forename: Lesley
authors.initials: L
authors.lastname: MacPherson
authors.affiliation: Birmingham Children's Hospital NHS Foundation Trust, Birmingham; and.
authors.forename: Martin
authors.initials: M
authors.lastname: English
authors.affiliation: Birmingham Children's Hospital NHS Foundation Trust, Birmingham; and Institute of Digital Healthcare, WMG, University of Warwick, Coventry, United Kingdom.
authors.forename: Theodoros N
authors.initials: TN
authors.lastname: Arvanitis
authors.affiliation: School of Cancer Sciences, University of Birmingham, Birmingham; Birmingham Children's Hospital NHS Foundation Trust, Birmingham; and.
authors.forename: Andrew C
authors.initials: AC
authors.lastname: Peet
mesh_terms: D000293:Adolescent; D014408:Biomarkers, Tumor / Q000235:genetics*; D001932:Brain Neoplasms / Q000000981:diagnostic imaging / Q000235:genetics* / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D005260:Female; D018698:Glutamic Acid / Q000235:genetics* / Q000302:isolation & purification; D006801:Humans; D053208:Kaplan-Meier Estimate; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008527:Medulloblastoma / Q000000981:diagnostic imaging / Q000235:genetics* / Q000473:pathology; D057285:Precision Medicine; D011379:Prognosis; D011859:Radiography
chemical_list: D014408:Biomarkers, Tumor; D018698:Glutamic Acid