title: Pulse frequency in pulsed brachytherapy based on tissue repair kinetics.
abstract: OBJECTIVE
  Investigation of normal tissue sparing in pulsed brachytherapy (PB) relative to continuous low-dose rate irradiation (CLDR) by adjusting pulse frequency based on tissue repair characteristics.
  
  
  METHODS
  Using the linear quadratic model, the relative effectiveness (RE) of a 20 Gy boost was calculated for tissue with an alpha/beta ratio ranging from 2 to 10 Gy and a half-time of sublethal damage repair between 0.1 and 3 h. The boost dose was considered to be delivered either in a number of pulses varying from 2 to 25, or continuously at a dose rate of 0.50, 0.80, or 1.20 Gy/h.
  
  
  RESULTS
  The RE of 20 Gy was found to be identical for PB in 25 pulses of 0.80 Gy each h and CLDR delivered at 0.80 Gy/h for any alpha/beta value and for a repair half-time > 0.75 h. When normal tissue repair half-times are assumed to be longer than tumor repair half-times, normal tissue sparing can be obtained, within the restriction of a fixed overall treatment time, with higher dose per pulse and longer period time (time elapsed between start of pulse n and start of pulse n + 1). An optimum relative normal tissue sparing larger than 10% was found with 4 pulses of 5 Gy every 8 h. Hence, a therapeutic gain might be obtained when changing from CLDR to PB by adjusting the physical dose in such a way that the biological dose on the tumor is maintained. The normal tissue-sparing phenomenon can be explained by an increase in RE with longer period time for tissue with high alpha/beta ratio and fast or intermediate repair half-time, and the RE for tissue with low alpha/beta ratio and long repair half-time remains almost constant.
  
  
  CONCLUSIONS
  Within the benchmark of the LQ model, advantage in normal tissue-sparing is expected when matching the pulse frequency to the repair kinetics of the normal tissue exposed. A period time longer than 1 h may lead to a reduction of late normal tissue complications. This theoretical advantage emphasizes the need for better knowledge of human tissue-repair kinetics.
authors.affiliation: Academic Medical Center, University of Amsterdam, Department of Radiotherapy, The Netherlands.
authors.forename: P
authors.initials: P
authors.lastname: Sminia
authors.forename: C J
authors.initials: CJ
authors.lastname: Schneider
authors.forename: K
authors.initials: K
authors.lastname: Koedooder
authors.forename: G
authors.initials: G
authors.lastname: van Tienhoven
authors.forename: L E
authors.initials: LE
authors.lastname: Blank
authors.forename: D G
authors.initials: DG
authors.lastname: González
mesh_terms: D000818:Animals; D001918:Brachytherapy / Q000379:methods*; D006801:Humans; D008954:Models, Biological; D011833:Radiation Injuries, Experimental / Q000503:physiopathology*; D011853:Radiobiology / Q000379:methods*; D012062:Relative Biological Effectiveness; D013997:Time Factors; D014945:Wound Healing / Q000502:physiology*