title: Perioperative cerebral ischemia promote infiltrative recurrence in glioblastoma.
abstract: BACKGROUND
  Hypoxia is a key driver for infiltrative growth in experimental gliomas. It has remained elusive whether tumor hypoxia in glioblastoma patients contributes to distant or diffuse recurrences. We therefore investigated the influence of perioperative cerebral ischemia on patterns of progression in glioblastoma patients.
  
  
  METHODS
  We retrospectively screened MRI scans of 245 patients with newly diagnosed glioblastoma undergoing resection for perioperative ischemia near the resection cavity. 46 showed relevant ischemia nearby the resection cavity. A control cohort without perioperative ischemia was generated by a 1:1 matching using an algorithm based on gender, age and adjuvant treatment. Both cohorts were analyzed for patterns of progression by a blinded neuroradiologist.
  
  
  RESULTS
  The percentage of diffuse or distant recurrences at first relapse was significantly higher in the cohort with perioperative ischemia (61.1%) compared to the control cohort (19.4%). The results of the control cohort matched well with historical data. The change in patterns of progression was not associated with a difference in survival.
  
  
  CONCLUSIONS
  This study reveals an unrecognized association of perioperative cerebral ischemia with distant or diffuse recurrence in glioblastoma. It is the first clinical study supporting the concept that hypoxia is a key driver of infiltrative tumor growth in glioblastoma patients.
authors.affiliation: Dr. Senckenberg Institute of Neurooncology, Goethe-University Hospital, Frankfurt, Germany.
authors.forename: Anna-Luisa
authors.initials: AL
authors.lastname: Thiepold
authors.affiliation: Department of Neurology, Goethe-University Hospital, Frankfurt, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Luger
authors.affiliation: Institute of Neuroradiology, Goethe-University Hospital, Frankfurt, Germany.
authors.forename: Marlies
authors.initials: M
authors.lastname: Wagner
authors.affiliation: Institute of Biostatistics and Mathematical Modeling, Goethe-University Hospital, Frankfurt, Germany.
authors.forename: Natalie
authors.initials: N
authors.lastname: Filmann
authors.affiliation: Dr. Senckenberg Institute of Neurooncology, Goethe-University Hospital, Frankfurt, Germany.
authors.forename: Michael W
authors.initials: MW
authors.lastname: Ronellenfitsch
authors.affiliation: Edinger Institute, Institute of Neurology, Goethe-University Hospital, Frankfurt, Germany.
authors.forename: Patrick N
authors.initials: PN
authors.lastname: Harter
authors.affiliation: Edinger Institute, Institute of Neurology, Goethe-University Hospital, Frankfurt, Germany.
authors.forename: Anne K
authors.initials: AK
authors.lastname: Braczynski
authors.affiliation: Department of Neurosurgery, Goethe-University Hospital, Frankfurt, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Dützmann
authors.affiliation: Institute of Neuroradiology, Goethe-University Hospital, Frankfurt, Germany.
authors.forename: Elke
authors.initials: E
authors.lastname: Hattingen
authors.affiliation: Dr. Senckenberg Institute of Neurooncology, Goethe-University Hospital, Frankfurt, Germany.
authors.forename: Joachim P
authors.initials: JP
authors.lastname: Steinbach
authors.affiliation: Department of Neurosurgery, Goethe-University Hospital, Frankfurt, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Senft
authors.affiliation: Dr. Senckenberg Institute of Neurooncology, Goethe-University Hospital, Frankfurt, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Rieger
authors.affiliation: Dr. Senckenberg Institute of Neurooncology, Goethe-University Hospital, Frankfurt, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Bähr
mesh_terms: D000328:Adult; D000368:Aged; D002545:Brain Ischemia; D001932:Brain Neoplasms / Q000150:complications* / Q000401:mortality / Q000473:pathology; D015687:Cell Hypoxia / Q000502:physiology*; D015331:Cohort Studies; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D005909:Glioblastoma / Q000150:complications* / Q000401:mortality / Q000473:pathology; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000473:pathology; D059035:Perioperative Period; D012189:Retrospective Studies; D016019:Survival Analysis
keywords: MRI; glioblastoma; hypoxia; patterns of progression; perioperative ischemia