TY  - JOUR
AU  - Bonekamp, David
AU  - Mouridsen, Kim
AU  - Radbruch, Alexander
AU  - Kurz, Felix Tobias
AU  - Eidel, Oliver
AU  - Wick, Antje
AU  - Schlemmer, Heinz-Peter
AU  - Wick, Wolfgang
AU  - Bendszus, Martin
AU  - Østergaard, Leif
AU  - Kickingereder, Philipp
TI  - Assessment of tumor oxygenation and its impact on treatment response in bevacizumab-treated recurrent glioblastoma.
JO  - Journal of cerebral blood flow & metabolism
VL  - 37
IS  - 2
SN  - 1559-7016
CY  - Thousands Oaks, Calilf.
PB  - Sage
M1  - DKFZ-2017-00074
SP  - 485 - 494
PY  - 2017
AB  - Antiantiogenic therapy with bevacizumab in recurrent glioblastoma is currently understood to both reduce microvascular density and to prune abnormal tumor microvessels. Microvascular pruning and the resulting vascular normalization are hypothesized to reduce tumor hypoxia and increase supply of systemic therapy to the tumor; however, the underlying pathophysiological changes and their timing after treatment initiation remain controversial. Here, we use a novel dynamic susceptibility contrast MRI-based method, which allows simultaneous assessment of tumor net oxygenation changes reflected by the tumor metabolic rate of oxygen and vascular normalization represented by the capillary transit time heterogeneity. We find that capillary transit time heterogeneity, and hence the oxygen extraction fraction combine with the tumoral blood flow (cerebral blood flow) in such a way that the overall tumor oxygenation appears to be worsened despite vascular normalization. Accordingly, hazards for both progression and death are found elevated in patients with a greater reduction of tumor metabolic rate of oxygen in response to bevacizumab and patients with higher intratumoral tumor metabolic rate of oxygen at baseline. This implies that tumors with a higher degree of angiogenesis prior to bevacizumab-treatment retain a higher level of angiogenesis during therapy despite a greater antiangiogenic effect of bevacizumab, hinting at evasive mechanisms limiting bevacizumab efficacy in that a reversal of their biological behavior and relative prognosis does not occur.
LB  - PUB:(DE-HGF)16
C6  - pmid:26861817
DO  - DOI:10.1177/0271678X16630322
UR  - https://inrepo02.dkfz.de/record/119319
ER  -