title: Monte Carlo radiotherapy simulations of accelerated repopulation and reoxygenation for hypoxic head and neck cancer.
abstract: OBJECTIVE
  A temporal Monte Carlo tumour growth and radiotherapy effect model (HYP-RT) simulating hypoxia in head and neck cancer has been developed and used to analyse parameters influencing cell kill during conventionally fractionated radiotherapy. The model was designed to simulate individual cell division up to 10(8) cells, while incorporating radiobiological effects, including accelerated repopulation and reoxygenation during treatment.
  
  
  METHODS
  Reoxygenation of hypoxic tumours has been modelled using randomised increments of oxygen to tumour cells after each treatment fraction. The process of accelerated repopulation has been modelled by increasing the symmetrical stem cell division probability. Both phenomena were onset immediately or after a number of weeks of simulated treatment.
  
  
  RESULTS
  The extra dose required to control (total cell kill) hypoxic vs oxic tumours was 15-25% (8-20 Gy for 5 × 2 Gy per week) depending on the timing of accelerated repopulation onset. Reoxygenation of hypoxic tumours resulted in resensitisation and reduction in total dose required by approximately 10%, depending on the time of onset. When modelled simultaneously, accelerated repopulation and reoxygenation affected cell kill in hypoxic tumours in a similar manner to when the phenomena were modelled individually; however, the degree was altered, with non-additive results. Simulation results were in good agreement with standard linear quadratic theory; however, differed for more complex comparisons where hypoxia, reoxygenation as well as accelerated repopulation effects were considered.
  
  
  CONCLUSIONS
  Simulations have quantitatively confirmed the need for patient individualisation in radiotherapy for hypoxic head and neck tumours, and have shown the benefits of modelling complex and dynamic processes using Monte Carlo methods.
authors.affiliation: Department of Medical Physics, Royal Adelaide Hospital Cancer Centre, Adelaide, SA, Australia. wendy.harriss@health.sa.gov.au
authors.forename: W M
authors.initials: WM
authors.lastname: Harriss-Phillips
authors.forename: E
authors.initials: E
authors.lastname: Bezak
authors.forename: E K
authors.initials: EK
authors.lastname: Yeoh
mesh_terms: D000465:Algorithms; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000532:radiotherapy*; D002455:Cell Division; D045744:Cell Line, Tumor; D003198:Computer Simulation; D019583:Dose Fractionation, Radiation; D006258:Head and Neck Neoplasms / Q000235:genetics / Q000532:radiotherapy*; D006801:Humans; D000860:Hypoxia / Q000378:metabolism*; D008954:Models, Biological; D009010:Monte Carlo Method; D010100:Oxygen / Q000378:metabolism*; D011853:Radiobiology; D011880:Radiotherapy Planning, Computer-Assisted
chemical_list: D010100:Oxygen