title: High-dose-rate brachytherapy may be radiobiologically superior to low-dose rate due to slow repair of late-responding normal tissue cells.
abstract: OBJECTIVE
  Recent analysis of morbidity for patients treated with the continuous hyperfractionated accelerated radiotherapy (CHART) regimen demonstrates that repair half-times for late-reacting normal tissue cells are of the order of 4-5 h, which is considerably longer than previously believed. This would reduce repair of these tissue cells during a course of low-dose rate (LDR) brachytherapy, but have no effect at high-dose-rate (HDR), where there is no repair during, and full repair between fractions, regardless of repair half-time. The effect this has upon radiobiologic comparison of LDR and HDR is the topic of this paper.
  
  
  METHODS
  The linear-quadratic (L-Q) model is used to compare late-effect biologically effective doses (BEDs) of LDR and HDR, for constant BED (tumor). The effects of dose rate (for LDR), fractionation (for HDR), and geometrical sparing of normal tissues are all considered. Repair half-times observed in the CHART study are used to investigate the potential impact of long repair times on the comparison of LDR and HDR.
  
  
  RESULTS
  It is demonstrated that, for a repair half-time of 1.5 h for tumor cells, if the half-time for repair of late-reacting normal tissue cells exceeds about 2.5 h, LDR becomes radiobiologically inferior to HDR. Even with the least HDR-favorable combinations of parameters, HDR at over about 5 Gy/fraction ought to be radiobiologically superior to LDR at 0.5 Gy/h, so long as the time between HDR fractions is long compared to the repair half time. It is also shown that any geometrical sparing of normal tissues will benefit HDR more than LDR.
  
  
  CONCLUSIONS
  The previously held belief that LDR must be inherently superior radiobiologically to HDR is wrong if the long repair times demonstrated in the recent CHART study are applicable to other late-reacting normal tissues. This could explain why HDR has been so successful in clinical practice, especially for the treatment of cervical cancer, despite previous convictions of radiobiologic inferiority of this modality.
authors.affiliation: Karmanos Cancer Institute, Detroit, MI, USA. ortonc@kci.wayne.edu
authors.forename: C G
authors.initials: CG
authors.lastname: Orton
mesh_terms: D001918:Brachytherapy / Q000379:methods*; D002470:Cell Survival; D004260:DNA Repair / Q000502:physiology / Q000528:radiation effects*; D019583:Dose Fractionation, Radiation; D006801:Humans; D016014:Linear Models; D008954:Models, Biological; D011853:Radiobiology; D012062:Relative Biological Effectiveness; D013997:Time Factors