title: Strong adverse prognostic impact of hyperglycemic episodes during adjuvant chemoradiotherapy of glioblastoma multiforme.
abstract: BACKGROUND
  In comparison to normal brain tissue, glioblastomas exhibit significantly increased glucose uptake. Brain edema is a common complication during adjuvant chemoradiotherapy, leading to a requirement for glucocorticoid treatment. Glucocorticoid treatment frequently causes considerable deregulation of blood glucose levels. Therefore, episodes of hyperglycemia may contribute to radio- and/or chemoresistance.
  
  
  METHODS
  This study comprises a retrospective analysis of the influence of hyperglycemic episodes (HEs) during adjuvant therapy on the overall survival of 106 glioblastoma multiforme patients.
  
  
  RESULTS
  The occurrence of one or more deregulated blood glucose value(s) > 10 mM is associated with a reduction in median overall survival from 16.7 to 8.8 months. A significantly poorer overall survival of patients with hyperglycemia could also be detected in subgroup analyses of patients with complete tumor resection and complete treatment according to the EORTC 22891/26891 trial protocol, as well as in a multivariate Cox proportional hazards analysis. A history of diabetes mellitus had no influence on prognosis.
  
  
  CONCLUSIONS
  Our data suggest that the observed negative impact of elevated blood glucose levels on overall survival may not solely be explained by the patients' poorer general condition; the elevated blood glucose concentration itself may play a pathogenetic role. This could be due to increased activity of antioxidant systems, elevated expression of DNA damage response proteins and protection of hypoxic tumor cells against apoptosis combined with hypoxia-mediated radioresistance.
  
  
  CONCLUSIONS
  A possible prognostic impact of elevated blood glucose levels during the period of adjuvant (chemo-) radiotherapy of glioblastoma should be evaluated in a prospective clinical trial.
authors.affiliation: Department of Radiooncology and Radiotherapy, University Medical Center, Langenbeckstrasse 1, 55131, Mainz, Germany, arnmayer@uni-mainz.de.
authors.forename: Arnulf
authors.initials: A
authors.lastname: Mayer
authors.forename: Peter
authors.initials: P
authors.lastname: Vaupel
authors.forename: Hans-Garlich
authors.initials: HG
authors.lastname: Struss
authors.forename: Alf
authors.initials: A
authors.lastname: Giese
authors.forename: Marcus
authors.initials: M
authors.lastname: Stockinger
authors.forename: Heinz
authors.initials: H
authors.lastname: Schmidberger
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001932:Brain Neoplasms / Q000628:therapy*; D015984:Causality; D059186:Chemoradiotherapy, Adjuvant / Q000401:mortality*; D015897:Comorbidity; D005260:Female; D005858:Germany / Q000453:epidemiology; D005909:Glioblastoma / Q000401:mortality* / Q000628:therapy*; D006801:Humans; D006943:Hyperglycemia / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D015995:Prevalence; D011379:Prognosis; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D015996:Survival Rate; D016896:Treatment Outcome