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Influence of stem-cell cycle time on accelerated re-population during radiotherapy in head and neck cancer

Authors

  • L. G. Marcu,

    Corresponding author
    1. Faculty of Science, University of Oradea, Oradea, Romania
    2. School of Chemistry and Physics, University of Adelaide, Adelaide, SA, Australia
    • Department of Medical Physics, Royal Adelaide Hospital, North Terrace, SA, Australia
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  • E. Bezak

    1. Department of Medical Physics, Royal Adelaide Hospital, North Terrace, SA, Australia
    2. School of Chemistry and Physics, University of Adelaide, Adelaide, SA, Australia
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Correspondence: L. G. Marcu, Department of Medical Physics, Royal Adelaide Hospital, North Terrace, SA 5000, Australia. Tel.: +61 8 8222 5539; Fax: +61 8 8222 5937; E-mail: loredana.marcu@health.sa.gov.au; Alternative E-mail: loredana@marcunet.com

Abstract

Objectives

Tumour re-population during radiotherapy was identified as an important reason for treatment failure in head and neck cancers. The process of re-population is suggested to be caused by various mechanisms, one of the most plausible one being accelerated division of stem-cells (i.e. drastic shortening of cell cycle duration). However, the literature lacks quantitative data regarding the length of tumour stem-cell cycle time during irradiation.

Materials and methods

The presented work suggests that if accelerated stem-cell division is indeed a key mechanism behind tumour re-population, the stem-cell cycle time can drop below 10 h during radiotherapy. To illustrate the possible implications, the mechanism of accelerated division was implemented into a Monte Carlo model of tumour growth and response to radiotherapy. Tumour response to radiotherapy was simulated with different stem-cell cycle times (between 2 and 10 h) after the initiation of radiotherapy.

Results

It was found that very short stem-cell cycle times lead to tumour re-population during treatment, which cannot be overcome by radiation-induced cell kill. Increasing the number of radiation dose fractions per week might be effective, but only for longer cell cycle times.

Conclusion

It is of crucial importance to quantitatively assess the mechanisms responsible for tumour re-population, given that conventional treatment regimens are not efficient in delivering lethal doses to advanced head and neck tumours.

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