title: Optimal fractionation in radiotherapy for non-small cell lung cancer--a modelling approach.
abstract: BACKGROUND
  Conventionally fractionated radiotherapy (CFRT) has proven ineffective in treating non-small cell lung cancer while more promising results have been obtained with stereotactic body radiotherapy (SBRT). Hypoxic tumours, however, might present a challenge to extremely hypofractionated schedules due to the decreased possibility for inter-fraction fast reoxygenation. A potentially successful compromise might be found in schedules employing several fractions of varying fractional doses. In this modelling study, a wide range of fractionation schedules from single-fraction treatments to heterogeneous, multifraction schedules taking into account repair, repopulation, reoxygenation and radiosensitivity of the tumour cells, has been explored with respect to the probability of controlling lung tumours.
  
  
  METHODS
  The response to radiation of tumours with heterogeneous spatial and temporal oxygenation was simulated including the effects of accelerated repopulation and intra-fraction repair. Various treatments with respect to time, dose and fractionation were considered and the outcome was estimated as Poisson-based tumour control probability for local control.
  
  
  RESULTS
  For well oxygenated tumours, heterogeneous fractionation could increase local control while hypoxic tumours are not efficiently targeted by such treatments despite reoxygenation. For hypofractionated treatments employing large doses per fraction, a synergistic effect was observed between intra-fraction repair and inter-fraction fast reoxygenation of the hypoxic cells as demonstrated by a reduction in D50 from 53.3 Gy for 2 fractions to 52.7 Gy for 5 fractions.
  
  
  CONCLUSIONS
  For well oxygenated tumours, heterogeneous fractionation schedules could increase local control rates substantially compared to CFRT. For hypoxic tumours, SBRT-like hypofractionated schedules might be optimal despite the increased risk of intra-fraction repair due to a synergistic effect with inter-fraction reoxygenation.
authors.affiliation: a Medical Radiation Physics, Department of Physics , Stockholm University , Stockholm , Sweden.
authors.forename: Emely
authors.initials: E
authors.lastname: Lindblom
authors.affiliation: b Department of Radiation Physics and Department of Medical and Health Sciences , Linköping University , Linköping , Sweden.
authors.forename: Alexandru
authors.initials: A
authors.lastname: Dasu
authors.affiliation: a Medical Radiation Physics, Department of Physics , Stockholm University , Stockholm , Sweden.|c Medical Radiation Physics, Department of Oncology and Pathology , Karolinska Institutet , Stockholm , Sweden.
authors.forename: Iuliana
authors.initials: I
authors.lastname: Toma-Dasu
mesh_terms: D002289:Carcinoma, Non-Small-Cell Lung / Q000503:physiopathology / Q000532:radiotherapy*; D015687:Cell Hypoxia; D003198:Computer Simulation; D006801:Humans; D008175:Lung Neoplasms / Q000503:physiopathology / Q000532:radiotherapy*; D008954:Models, Biological; D010100:Oxygen / Q000378:metabolism; D010101:Oxygen Consumption; D000069473:Radiation Dose Hypofractionation; D011836:Radiation Tolerance
chemical_list: D010100:Oxygen