title: Direct evidence that prostate tumors show high sensitivity to fractionation (low alpha/beta ratio), similar to late-responding normal tissue.
abstract: OBJECTIVE
  A direct approach to the question of whether prostate tumors have an atypically high sensitivity to fractionation (low alpha/beta ratio), more typical of the surrounding late-responding normal tissue.
  
  
  METHODS
  Earlier estimates of alpha/beta for prostate cancer have relied on comparing results from external beam radiotherapy (EBRT) and brachytherapy, an approach with significant pitfalls due to the many differences between the treatments. To circumvent this, we analyze recent data from a single EBRT + high-dose-rate (HDR) brachytherapy protocol, in which the brachytherapy was given in either 2 or 3 implants, and at various doses. For the analysis, standard models of tumor cure based on Poisson statistics were used in conjunction with the linear-quadratic formalism. Biochemical control at 3 years was the clinical endpoint. Patients were matched between the 3 HDR vs. 2 HDR implants by clinical stage, pretreatment prostate-specific antigen (PSA), Gleason score, length of follow-up, and age.
  
  
  RESULTS
  The estimated value of alpha/beta from the current analysis of 1.2 Gy (95% CI: 0.03, 4.1 Gy) is consistent with previous estimates for prostate tumor control. This alpha/beta value is considerably less than typical values for tumors (> or =8 Gy), and more comparable to values in surrounding late-responding normal tissues.
  
  
  CONCLUSIONS
  This analysis provides strong supporting evidence that alpha/beta values for prostate tumor control are atypically low, as indicated by previous analyses and radiobiological considerations. If true, hypofractionation or HDR regimens for prostate radiotherapy (with appropriate doses) should produce tumor control and late sequelae that are at least as good or even better than currently achieved, with the added possibility that early sequelae may be reduced.
authors.affiliation: Center for Radiological Research, Department of Radiation Oncology, Columbia University, New York, NY 10032, USA. djb3@columbia.edu
authors.forename: David J
authors.initials: DJ
authors.lastname: Brenner
authors.forename: Alvaro A
authors.initials: AA
authors.lastname: Martinez
authors.forename: Gregory K
authors.initials: GK
authors.lastname: Edmundson
authors.forename: Christina
authors.initials: C
authors.lastname: Mitchell
authors.forename: Howard D
authors.initials: HD
authors.lastname: Thames
authors.forename: Elwood P
authors.initials: EP
authors.lastname: Armour
mesh_terms: D000368:Aged; D001918:Brachytherapy / Q000379:methods; D019583:Dose Fractionation, Radiation; D005500:Follow-Up Studies; D006801:Humans; D007496:Iridium Radioisotopes / Q000627:therapeutic use; D008297:Male; D016012:Poisson Distribution; D011446:Prospective Studies; D011471:Prostatic Neoplasms / Q000532:radiotherapy*; D018787:Radiation Oncology / Q000379:methods; D020266:Radiotherapy, Conformal / Q000379:methods; D017211:Treatment Failure
chemical_list: D007496:Iridium Radioisotopes