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Acute Hypoxia Profile is a Stronger Prognostic Factor than Chronic Hypoxia in Advanced Stage Head and Neck Cancer Patients

1
Division of Cell Biology, The Netherlands Cancer Institute, Plesmanlaan 121, 1006 CX Amsterdam, The Netherlands
2
Department of Head and Neck Oncology and Surgery, The Netherlands Cancer Institute, Plesmanlaan 121, 1006 CX Amsterdam, The Netherlands
3
Department of Radiation Oncology, The Netherlands Cancer Institute, Plesmanlaan 121, 1006 CX Amsterdam, The Netherlands
4
Amsterdam UMC, Vrije Universiteit Amsterdam, Otolaryngology/Head & Neck Surgery, Cancer Center Amsterdam, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands
5
Department of Radiation Oncology (MAASTRO), GROW – School for Oncology and Developmental Biology, Maastricht University Medical Centre, Dr. Tanslaan 12, 6229 ET Maastricht, The Netherlands
6
Department of Radiation Oncology, Radboud University Medical Center, Geert Grooteplein Zuid 10, 6525 GA Nijmegen, The Netherlands
7
Department of Oral and Maxillofacial Surgery, Amsterdam UMC, Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Cancers 2019, 11(4), 583; https://doi.org/10.3390/cancers11040583
Received: 6 March 2019 / Revised: 11 April 2019 / Accepted: 19 April 2019 / Published: 25 April 2019
(This article belongs to the Special Issue Tumor Radioresistance)
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Abstract

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. View Full-Text
Keywords: head and neck cancer; gene expression; hypoxia head and neck cancer; gene expression; hypoxia
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van der Heijden, M.; de Jong, M.C.; Verhagen, C.V.M.; de Roest, R.H.; Sanduleanu, S.; Hoebers, F.; Leemans, C.R.; Brakenhoff, R.H.; Vens, C.; Verheij, M.; van den Brekel, M.W.M. Acute Hypoxia Profile is a Stronger Prognostic Factor than Chronic Hypoxia in Advanced Stage Head and Neck Cancer Patients. Cancers 2019, 11, 583.

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