Acute hypoxia profile is a stronger prognostic factor than chronic hypoxia in advanced stage head and neck cancer patients

Martijn Van Der Heijden, Monique C. De Jong, Caroline V.M. Verhagen, Reinout H. De Roest, Sebastian Sanduleanu, Frank Hoebers, C. René Leemans, Ruud H. Brakenhoff, Conchita Vens, Marcel Verheij, Michiel W.M. Van Den Brekel

Research output: Contribution to JournalArticleAcademicpeer-review


Hypoxic head and neck tumors respond poorly to radiotherapy and can be identified using gene expression profiles. However, it is unknown whether treatment outcome is driven by acute or chronic hypoxia. Gene expression data of 398 head and neck cancers was collected. Four clinical hypoxia profiles were compared to in vitro acute and chronic hypoxia profiles. Chronic and acute hypoxia profiles were tested for their association to outcome using Cox proportional hazard analyses. In an initial set of 224 patients, scores of the four clinical hypoxia profiles correlated with each other and with chronic hypoxia. However, the acute hypoxia profile showed a stronger association with local recurrence after chemoradiotherapy (p = 0.02; HR = 3.1) than the four clinical (chronic hypoxia) profiles (p = 0.2; HR = 0.9). An independent set of 174 patients confirmed that acute hypoxia is a stronger prognostic factor than chronic hypoxia for overall survival, progression-free survival, local and locoregional control. Multivariable analyses accounting for known prognostic factors substantiate this finding (p = 0.045; p = 0.042; p = 0.018 and p = 0.003, respectively). In conclusion, the four clinical hypoxia profiles are related to chronic hypoxia and not acute hypoxia. The acute hypoxia profile shows a stronger association with patient outcome and should be incorporated into existing prediction models.

Original languageEnglish
Article number583
Issue number4
Publication statusPublished - Apr 2019

Bibliographical note

Funding Information:
Funding: This study was funded by: EU FP7 programme (Artforce #257144), Brunel, Dutch Cancer Society (Design - KWF-A6C7072) and the Verwelius foundation.

Publisher Copyright:
© 2019 by the authors. Licensee MDPI, Basel, Switzerland.


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