title: Changes in tumor cell response due to prolonged dose delivery times in fractionated radiation therapy.
abstract: OBJECTIVE
  Dynamic radiation therapy, such as intensity-modulated radiation therapy, delivers more complex treatment fields than conventional techniques. The increased complexity causes longer dose delivery times for each fraction. The cellular damage after a full treatment may depend on the dose rate, because sublethal radiation damage can be repaired more efficiently during prolonged dose delivery. The goal of this study was to investigate the significance of this effect in fractionated radiation therapy.
  
  
  METHODS
  The lethal/potentially lethal model was used to calculate lesion induction rates for repairable and nonrepairable lesions. Dose rate effects were analyzed for 9 different cell lines (8 human tumor xenografts and a C3H10T1/2 cell line). The effects of single-fraction as well as fractionated irradiation for different dose rates were studied.
  
  
  RESULTS
  Significant differences can be seen for dose rates lower than about 0.1 Gy/min for all cell lines considered. For 60 Gy delivered in 30 fractions, the equivalent dose is reduced by between 1.3% and 12% comparing 2 Gy delivery over 30 min per fraction with 2 Gy delivery over 1 min per fraction. The effect is higher for higher doses per fraction. Furthermore, the results show that dose rate effects do not show a simple correlation with the alpha/beta ratio for ratios between 3 Gy and 31 Gy.
  
  
  CONCLUSIONS
  If the total dose delivery time for a treatment fraction in radiation therapy increases to about 20 min, a correction for dose rate effects may have to be considered in treatment planning. Adjustments in effective dose may be necessary when comparing intensity-modulated radiation therapy with conventional treatment plans.
authors.affiliation: Massachusetts General Hospital, and Harvard Medical School, Boston, MA 02114, USA. hpaganetti@partners.org
authors.forename: Harald
authors.initials: H
authors.lastname: Paganetti
mesh_terms: D000465:Algorithms; D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000502:physiology / Q000528:radiation effects*; D019583:Dose Fractionation, Radiation; D004307:Dose-Response Relationship, Radiation; D006801:Humans; D008954:Models, Biological; D009369:Neoplasms / Q000473:pathology / Q000532:radiotherapy*; D011836:Radiation Tolerance; D050397:Radiotherapy, Intensity-Modulated; D013997:Time Factors