title: Influence of stem-cell cycle time on accelerated re-population during radiotherapy in head and neck cancer.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors: Department of Medical Physics, Royal Adelaide Hospital, North Terrace, SA, Australia. loredana.marcu@health.sa.gov.au
authors: L G
authors: LG
authors: Marcu
authors: E
authors: E
authors: Bezak
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000473:pathology* / Q000532:radiotherapy; D002453:Cell Cycle / Q000502:physiology / Q000528:radiation effects; D016923:Cell Death / Q000502:physiology / Q000528:radiation effects; D002455:Cell Division / Q000502:physiology / Q000528:radiation effects; D002470:Cell Survival / Q000502:physiology / Q000528:radiation effects; D003198:Computer Simulation; D006258:Head and Neck Neoplasms / Q000473:pathology* / Q000532:radiotherapy; D006801:Humans; D009010:Monte Carlo Method; D009364:Neoplasm Recurrence, Local / Q000209:etiology / Q000473:pathology; D014411:Neoplastic Stem Cells / Q000473:pathology* / Q000528:radiation effects; D013997:Time Factors