title: A review of in vitro experimental evidence for the effect of spatial and temporal modulation of radiation dose on response.
abstract: BACKGROUND
  Intensity modulated radiation therapy introduces strong spatial and temporal modulation of the dose delivery that may have therapeutic benefits, as yet unrealized.
  
  
  METHODS
  Experimental evidence for spatial and temporal modulation affecting the cell survival following in vitro irradiation has been derived using clonogenic assays.
  
  
  CONCLUSIONS
  The experimental results show that the survival status of a cell is strongly influenced by the spatial dose modulation. The classical bystander effect of decreased survival has now been supplemented by observations of increased survival, which may result from the same or different signaling mechanisms. Temporal dose modulation experiments show that dose protraction significantly increases cell survival. An appropriate choice of temporal dose modulation pattern enables cell death to be maximized or minimized for a constant dose and delivery time.
  
  
  CONCLUSIONS
  Bystander effects challenge the assumption that outcome is solely dependent on local dose. Intra-fractional temporal modulation via protracted treatments and time varying dose delivery both affect the cell survival. The presence of bystander and temporal effects emphasize the need for a mathematical framework which incorporates their influence on cell survival.
authors.affiliation: Department of Radiation Oncology, Royal Prince Alfred Hospital, New South Wales, Australia. Natalka@email.cs.nsw.gov.au
authors.forename: Natalka
authors.initials: N
authors.lastname: Suchowerska
authors.forename: Martin A
authors.initials: MA
authors.lastname: Ebert
authors.forename: David R
authors.initials: DR
authors.lastname: McKenzie
authors.forename: Michael
authors.initials: M
authors.lastname: Jackson
mesh_terms: D000818:Animals; D024201:Bystander Effect / Q000528:radiation effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000528:radiation effects*; D004307:Dose-Response Relationship, Radiation; D006801:Humans; D008545:Melanoma / Q000532:radiotherapy; D015233:Models, Statistical; D009369:Neoplasms / Q000532:radiotherapy*; D011829:Radiation Dosage; D050397:Radiotherapy, Intensity-Modulated; D012878:Skin Neoplasms / Q000532:radiotherapy; D013997:Time Factors