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Measurement of reoxygenation during fractionated radiotherapy in head and neck squamous cell carcinoma xenografts

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Abstract

Hypoxic tissues lack adequate oxygenation and it has been long established that tumours commonly exhibit hypoxia and that hypoxia is a factor contributing towards resistance to radiotherapy. To develop computer models and make predictions about the affects of tumour hypoxia on treatment outcome, quantitative tumour oxygenation and reoxygenation data from in vivo systems is required. The aim of this study was to investigate the timing and degree of reoxygenation during radiotherapy in a human head and neck squamous cell carcinoma xenograft mouse model (FaDu). Mice were immobilised using a novel restraining system and exposed unanaesthetised in 3 or 5 Gy fractions, up to a maximum of 40 Gy. Partial pressures of oxygen (pO2) measurements were recorded at six time points throughout the 2 week course of radiotherapy, using a fibre optic system. Tumours receiving 0–30 Gy did not exhibit an increase in pO2. However, the mean pO2 after 2 weeks of accelerated fractionated radiotherapy (40 Gy) was significantly increased (P < 0.01) compared to the mean pO2 of tumours not receiving the full schedule (0–30 Gy). These results lead to the conclusion of an average reoxygenation onset time of 2 weeks in this group of xenografts. A relatively large range of pO2 values measured at each dose point in the study indicate a large inter-tumour variation in oxygenation among the tumours. Data from this experimental work will be used to define the range of reoxygenation onset times implemented in a Monte Carlo computer model, simulating hypoxic head and neck cancer growth and radiotherapy.

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Acknowledgements

Authors send thanks to Mrs. D. Beaumont, Dr. T. Lavranos and all staff at Bionomics Ltd, Adelaide, for cell and animal work collaboration, Mr. A. Tran and Mr. J. Schneider, Royal Adelaide Hospital, for engineering assistance, Dr. C. Malcontenti-Wilson of the University of Melbourne for use of the OxyLab System, Dr. C. Cullinane of the Peter MacCallum Cancer Centre, Victoria, for the cell line donation, Prof. A. van der Kogel of the Radboud University, Nijmegen Medical Center, Nijmegen, NL for immunohistochemical study expertise and services, Mr. Brian Lewis and staff at the IMVS Animal Facility, Adelaide and to Mr. Graeme Tucker, Health Statistics Unit Department of Human Services, Government of South Australia.

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Correspondence to Wendy Harriss.

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W. Harriss has previously published in the name of W. Tuckwell.

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Harriss, W., Bezak, E., Yeoh, E. et al. Measurement of reoxygenation during fractionated radiotherapy in head and neck squamous cell carcinoma xenografts. Australas Phys Eng Sci Med 33, 251–263 (2010). https://doi.org/10.1007/s13246-010-0032-6

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  • DOI: https://doi.org/10.1007/s13246-010-0032-6

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