title: Impact of prolonged fraction delivery times on tumor control: a note of caution for intensity-modulated radiation therapy (IMRT).
abstract: OBJECTIVE
  Intensity-modulated radiation therapy (IMRT) allows greater dose conformity to the tumor target. However, IMRT, especially static delivery, usually requires more time to deliver a dose fraction than conventional external beam radiotherapy (EBRT). The purpose of this work is to explore the potential impact of such prolonged fraction delivery times on treatment outcome.
  
  
  METHODS
  The generalized linear-quadratic (LQ) model, which accounts for sublethal damage repair and clonogen proliferation, was used to calculate the cell-killing efficiency of various simulated and clinical IMRT plans. LQ parameters derived from compiled clinical data for prostate cancer (alpha = 0.15 Gy(-1), alpha/beta = 3.1 Gy, and a 16-min repair half-time) were used to compute changes in the equivalent uniform dose (EUD) and tumor control probability (TCP) due to prolonged delivery time of IMRT as compared with conventional EBRT. EUD and TCP calculations were also evaluated for a wide range of radiosensitivity parameters. The effects of fraction delivery times ranging from 0 to 45 min on cell killing were studied.
  
  
  RESULTS
  Our calculations indicate that fraction delivery times in the range of 15-45 min may significantly decrease cell killing. For a prescription dose of 81 Gy in 1.8 Gy fractions, the EUD for prostate cancer decreases from 78 Gy for a conventional EBRT to 69 Gy for an IMRT with a fraction delivery time of 30 min. The values of EUD are sensitive to the alpha/beta ratio, the repair half-time, and the fraction delivery time. The instantaneous dose-rate, beam-on time, number of leaf shapes (segments), and leaf-sequencing patterns given the same overall fraction delivery time were found to have negligible effect on cell killing.
  
  
  CONCLUSIONS
  The total time to deliver a single fraction may have a significant impact on IMRT treatment outcome for tumors with a low alpha/beta ratio and a short repair half-time, such as prostate cancer. These effects, if confirmed by clinical studies, should be considered in designing IMRT treatments.
authors.affiliation: Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore 21201-1595, USA.
authors.forename: Jian Z
authors.initials: JZ
authors.lastname: Wang
authors.forename: X Allen
authors.initials: XA
authors.lastname: Li
authors.forename: Warren D
authors.initials: WD
authors.lastname: D'Souza
authors.forename: Robert D
authors.initials: RD
authors.lastname: Stewart
mesh_terms: D004249:DNA Damage; D004260:DNA Repair; D019583:Dose Fractionation, Radiation; D006801:Humans; D016014:Linear Models; D008297:Male; D008954:Models, Biological; D011471:Prostatic Neoplasms / Q000503:physiopathology / Q000532:radiotherapy*; D011836:Radiation Tolerance; D011853:Radiobiology; D020266:Radiotherapy, Conformal / Q000379:methods*; D013997:Time Factors