Influence of stem-cell cycle time on accelerated re-population during radiotherapy in head and neck cancer.
Cell Prolif. 2012 Jul 7. Epub 2012 Jul 7. PMID: 22775509
Department of Medical Physics, Royal Adelaide Hospital, North Terrace, SA, Australia; Faculty of Science, University of Oradea, Oradea, Romania; School of Chemistry and Physics, University of Adelaide, Adelaide, SA, Australia.
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.