Research Papers:

Perioperative cerebral ischemia promote infiltrative recurrence in glioblastoma

Anna-Luisa Thiepold, Sebastian Luger, Marlies Wagner, Natalie Filmann, Michael W. Ronellenfitsch, Patrick N. Harter, Anne K. Braczynski, Stephan Dützmann, Elke Hattingen, Joachim P. Steinbach, Christian Senft, Johannes Rieger and Oliver Bähr _

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Oncotarget. 2015; 6:14537-14544. https://doi.org/10.18632/oncotarget.3994

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Anna-Luisa Thiepold1, Sebastian Luger2, Marlies Wagner3, Natalie Filmann4, Michael W. Ronellenfitsch1, Patrick N. Harter5, Anne K. Braczynski5, Stephan Dützmann6, Elke Hattingen3, Joachim P. Steinbach1, Christian Senft6, Johannes Rieger1 and Oliver Bähr1

1 Dr. Senckenberg Institute of Neurooncology, Goethe-University Hospital, Frankfurt, Germany

2 Department of Neurology, Goethe-University Hospital, Frankfurt, Germany

3 Institute of Neuroradiology, Goethe-University Hospital, Frankfurt, Germany

4 Institute of Biostatistics and Mathematical Modeling, Goethe-University Hospital, Frankfurt, Germany

5 Edinger Institute, Institute of Neurology, Goethe-University Hospital, Frankfurt, Germany

6 Department of Neurosurgery, Goethe-University Hospital, Frankfurt, Germany

Correspondence to:

Oliver Bähr, email:

Keywords: glioblastoma, hypoxia, patterns of progression, perioperative ischemia, MRI

Received: March 24, 2015 Accepted: April 11, 2015 Published: May 04, 2015


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.

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