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Leif Østergaard

Assessment of tumor oxygenation and its impact on treatment response in bevacizumab-treated recurrent glioblastoma

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Assessment of tumor oxygenation and its impact on treatment response in bevacizumab-treated recurrent glioblastoma. / Bonekamp, David; Mouridsen, Kim; Radbruch, Alexander; Kurz, Felix T; Eidel, Oliver; Wick, Antje; Schlemmer, Heinz-Peter; Wick, Wolfgang; Bendszus, Martin; Østergaard, Leif; Kickingereder, Philipp.

In: Journal of Cerebral Blood Flow and Metabolism, 01.02.2017.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

Harvard

Bonekamp, D, Mouridsen, K, Radbruch, A, Kurz, FT, Eidel, O, Wick, A, Schlemmer, H-P, Wick, W, Bendszus, M, Østergaard, L & Kickingereder, P 2017, 'Assessment of tumor oxygenation and its impact on treatment response in bevacizumab-treated recurrent glioblastoma', Journal of Cerebral Blood Flow and Metabolism. https://doi.org/10.1177/0271678X16630322

APA

Bonekamp, D., Mouridsen, K., Radbruch, A., Kurz, F. T., Eidel, O., Wick, A., Schlemmer, H-P., Wick, W., Bendszus, M., Østergaard, L., & Kickingereder, P. (2017). Assessment of tumor oxygenation and its impact on treatment response in bevacizumab-treated recurrent glioblastoma. Journal of Cerebral Blood Flow and Metabolism. https://doi.org/10.1177/0271678X16630322

CBE

Bonekamp D, Mouridsen K, Radbruch A, Kurz FT, Eidel O, Wick A, Schlemmer H-P, Wick W, Bendszus M, Østergaard L, Kickingereder P. 2017. Assessment of tumor oxygenation and its impact on treatment response in bevacizumab-treated recurrent glioblastoma. Journal of Cerebral Blood Flow and Metabolism. https://doi.org/10.1177/0271678X16630322

MLA

Vancouver

Bonekamp D, Mouridsen K, Radbruch A, Kurz FT, Eidel O, Wick A et al. Assessment of tumor oxygenation and its impact on treatment response in bevacizumab-treated recurrent glioblastoma. Journal of Cerebral Blood Flow and Metabolism. 2017 Feb 1. https://doi.org/10.1177/0271678X16630322

Author

Bonekamp, David ; Mouridsen, Kim ; Radbruch, Alexander ; Kurz, Felix T ; Eidel, Oliver ; Wick, Antje ; Schlemmer, Heinz-Peter ; Wick, Wolfgang ; Bendszus, Martin ; Østergaard, Leif ; Kickingereder, Philipp. / Assessment of tumor oxygenation and its impact on treatment response in bevacizumab-treated recurrent glioblastoma. In: Journal of Cerebral Blood Flow and Metabolism. 2017.

Bibtex

@article{68fe7ee6d88b424888ea8c38725a928b,
title = "Assessment of tumor oxygenation and its impact on treatment response in bevacizumab-treated recurrent glioblastoma",
abstract = "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.",
author = "David Bonekamp and Kim Mouridsen and Alexander Radbruch and Kurz, {Felix T} and Oliver Eidel and Antje Wick and Heinz-Peter Schlemmer and Wolfgang Wick and Martin Bendszus and Leif {\O}stergaard and Philipp Kickingereder",
note = "{\textcopyright} The Author(s) 2016.",
year = "2017",
month = feb,
day = "1",
doi = "10.1177/0271678X16630322",
language = "English",
journal = "Journal of Cerebral Blood Flow and Metabolism",
issn = "0271-678X",
publisher = "SAGE Publications Ltd",

}

RIS

TY - JOUR

T1 - Assessment of tumor oxygenation and its impact on treatment response in bevacizumab-treated recurrent glioblastoma

AU - Bonekamp, David

AU - Mouridsen, Kim

AU - Radbruch, Alexander

AU - Kurz, Felix T

AU - Eidel, Oliver

AU - Wick, Antje

AU - Schlemmer, Heinz-Peter

AU - Wick, Wolfgang

AU - Bendszus, Martin

AU - Østergaard, Leif

AU - Kickingereder, Philipp

N1 - © The Author(s) 2016.

PY - 2017/2/1

Y1 - 2017/2/1

N2 - 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.

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.

U2 - 10.1177/0271678X16630322

DO - 10.1177/0271678X16630322

M3 - Journal article

C2 - 26861817

JO - Journal of Cerebral Blood Flow and Metabolism

JF - Journal of Cerebral Blood Flow and Metabolism

SN - 0271-678X

ER -