title: A prospective dose escalation trial of high-dose-rate brachytherapy boost for prostate cancer: Evidence of hypofractionation efficacy?
abstract: OBJECTIVE
  The study aimed to evaluate mature outcomes of a Phase I/II high-dose-rate brachytherapy (HDRB) boost protocol.
  
  
  METHODS
  We analyzed data from 88 patients with T1a-T3a, N0, M0 prostate adenocarcinoma treated on a prospective Phase I/II HDRB boost protocol of 16 (n = 47) or 20 Gy (n = 41) in four fractions, without planned androgen deprivation therapy. HDRB was added to 46 Gy of external beam radiotherapy (EBRT). Outcomes were compared to a contemporaneous retrospective cohort of 104 patients receiving 66 Gy EBRT monotherapy. The primary endpoint was freedom from biochemical failure, defined as a 2 ng/mL rise above the lowest prostate-specific antigen (PSA) (FFbFn2), whereas the American Society of Therapeutic Radiology and Oncology consensus definition (ACD) was used for comparative purposes.
  
  
  RESULTS
  For the HDRB cohort, the overall actuarial 5-year FFbFn2 was 67.4% (95% CI: 58.2-75.5%). For the HDRB doses of 16 and 20 Gy, the 5-year FFbFn2 rates were 58.8% (95% CI: 41.9-72.5%) and 77.3% (95% CI: 64.4-88.3%), respectively (log-rank test p = 0.07). Compared to men treated with 66 Gy EBRT, using multivariate analysis, there was no significant benefit to using HDRB with the FFbFn2 outcome (p = 0.52), yet the ACD suggested a significant advantage (hazard ratio 0.50, 95% CI: 0.29-0.86, p = 0.011). There was a trend to better FFbFn2 outcomes with increasing biologically effective doses (p = 0.09), which was significant using the ACD (p = 0.0003).
  
  
  CONCLUSIONS
  The data support HDRB boost as a potential means of dose escalation in prostate cancer. Significant findings using the ACD need to be validated with contemporary biochemical failure definitions. Prospective trials to optimize fractionation and evaluate outcomes in comparison to contemporary EBRT techniques are warranted.
authors.affiliation: Department of Radiation Oncology, The Cancer Institute, National University Hospital, Singapore.
authors.forename: Johann I
authors.initials: JI
authors.lastname: Tang
authors.forename: Scott G
authors.initials: SG
authors.lastname: Williams
authors.forename: Keen Hun
authors.initials: KH
authors.lastname: Tai
authors.forename: Joanne
authors.initials: J
authors.lastname: Dean
authors.forename: Gillian M
authors.initials: GM
authors.lastname: Duchesne
mesh_terms: D000230:Adenocarcinoma / Q000532:radiotherapy*; D000368:Aged; D000369:Aged, 80 and over; D001918:Brachytherapy / Q000379:methods*; D006801:Humans; D008297:Male; D008875:Middle Aged; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000532:radiotherapy*; D011879:Radiotherapy Dosage; D012189:Retrospective Studies
chemical_list: D017430:Prostate-Specific Antigen