title: Confirmation of a low α/β ratio for prostate cancer treated by external beam radiation therapy alone using a post-treatment repeated-measures model for PSA dynamics.
abstract: OBJECTIVE
  To estimate the α/β ratio of prostate cancer treated with external beam radiation only by use of a model of long-term prostate-specific antigen (PSA) dynamics.
  
  
  METHODS
  Repeated measures of PSA from 5,093 patients from 6 institutions treated for localized prostate cancer by external beam radiation therapy (EBRT) without planned androgen deprivation were analyzed. A biphasic linear mixed model described the post-treatment evolution of PSA, rather than a conventional model of time to biochemical recurrence. The model was adjusted for standard prognostic factors (T stage, initial PSA level, and Gleason score) and cohort-specific effects. The radiation dose fractionation effect was estimated from the long-term rate of rise of PSA level.
  
  
  RESULTS
  Adjusted for other factors, total dose of EBRT and sum of squared doses per fraction were associated with long-term rate of change of PSA level (p = 0.0017 and p = 0.0003, respectively), an increase of each being associated with a lower rate of rise. The α/β ratio was estimated at 1.55 Gy (95% confidence band, 0.46-4.52 Gy). This estimate was robust to adjustment of the linear mixed model.
  
  
  CONCLUSIONS
  By analysis of a large EBRT-only cohort along with a method that uses all the repeated measures of PSA after the end of treatment, a low and precise α/β was estimated. These data support the use of hypofractionation at fractional doses up to 2.8 Gy but cannot presently be assumed to accurately represent higher doses per fraction.
authors.affiliation: INSERM, U897, Epidemiology and Biostatistics Research Center, Bordeaux, France. scott.williams@petermac.org
authors.forename: Cécile
authors.initials: C
authors.lastname: Proust-Lima
authors.forename: Jeremy M G
authors.initials: JM
authors.lastname: Taylor
authors.forename: Solène
authors.initials: S
authors.lastname: Sécher
authors.forename: Howard
authors.initials: H
authors.lastname: Sandler
authors.forename: Larry
authors.initials: L
authors.lastname: Kestin
authors.forename: Tom
authors.initials: T
authors.lastname: Pickles
authors.forename: Kyoungwha
authors.initials: K
authors.lastname: Bae
authors.forename: Roger
authors.initials: R
authors.lastname: Allison
authors.forename: Scott
authors.initials: S
authors.lastname: Williams
mesh_terms: D000368:Aged; D015331:Cohort Studies; D019583:Dose Fractionation, Radiation; D006801:Humans; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D017430:Prostate-Specific Antigen / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000532:radiotherapy*; D011836:Radiation Tolerance; D018709:Statistics, Nonparametric
chemical_list: D017430:Prostate-Specific Antigen
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