title: Dose escalation improves cancer-related events at 10 years for intermediate- and high-risk prostate cancer patients treated with hypofractionated high-dose-rate boost and external beam radiotherapy.
abstract: OBJECTIVE
  To evaluate the 10-year outcomes of intermediate- and high-risk prostate cancer patients treated with a prospective dose escalation hypofractionated trial of pelvic external beam radiation therapy (P-EBRT) with a high-dose-rate (HDR) brachytherapy boost.
  
  
  METHODS
  From 1992 to 2007, 472 patients were treated with a HDR boost at William Beaumont Hospital. They had at least one of the following: a prostate-specific antigen (PSA) level of >10 ng/ml, a Gleason score of ≥7, or clinical stage ≥T2b. Patients received 46-Gy P-EBRT and an HDR boost. The HDR dose fractionation was divided into two dose levels. The prostate biologically equivalent dose (BED) low-dose-level group received <268 Gy, and the high-dose group received >268 Gy . Phoenix biochemical failure (BF) definition was used.
  
  
  RESULTS
  Median follow-up was 8.2 years (range, 0.4-17 years). The 10-year biochemical failure rate of 43.1% vs. 18.9%, (p < 0.001), the clinical failure rate of 23.4% vs. 7.7%, (p < 0.001), and the distant metastasis of 12.4% vs. 5.7%, (p = 0.028) were all significantly better for the high-dose level group. On Cox multivariate analysis, higher BED levels (p = 0.017; hazard ratio [HR] = 0.586), pretreatment PSA assays (p < 0.001, HR = 1.022), and Gleason scores (p = 0.004) were significant variables for reduced biochemical failure. Higher dose levels (p, 0.002; HR, 0.397) and Gleason scores (p < 0.001) were significant for clinical failure. Grade 3 genitourinary complications were 2% and 3%, respectively, and grade 3 gastrointestinal complication was <0.5%.
  
  
  CONCLUSIONS
  This prospective trial using P-EBRT with HDR boost and hypofractionated dose escalation demonstrates a strong dose-response relationship for intermediate- and high-risk prostate cancer patients. The improvement at 10 years for locoregional control with higher radiation doses (BED, > 268 Gy) has significantly decreased biochemical and clinical failures as well as distant metastasis.
authors.affiliation: Radiation Oncology Department, William Beaumont Hospital, Royal Oak, Michigan 48073, USA. amartinez@beaumont.edu
authors.forename: Alvaro A
authors.initials: AA
authors.lastname: Martinez
authors.forename: Jose
authors.initials: J
authors.lastname: Gonzalez
authors.forename: Hong
authors.initials: H
authors.lastname: Ye
authors.forename: Mihai
authors.initials: M
authors.lastname: Ghilezan
authors.forename: Sugandh
authors.initials: S
authors.lastname: Shetty
authors.forename: Kenneth
authors.initials: K
authors.lastname: Kernen
authors.forename: Gary
authors.initials: G
authors.lastname: Gustafson
authors.forename: Daniel
authors.initials: D
authors.lastname: Krauss
authors.forename: Frank
authors.initials: F
authors.lastname: Vicini
authors.forename: Larry
authors.initials: L
authors.lastname: Kestin
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000512:Alpha Particles / Q000627:therapeutic use; D001610:Beta Particles / Q000627:therapeutic use; D001918:Brachytherapy / Q000379:methods*; D019583:Dose Fractionation, Radiation; D004307:Dose-Response Relationship, Radiation; D005500:Follow-Up Studies; D006801:Humans; D007496:Iridium Radioisotopes / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011446:Prospective Studies; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000097:blood / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy*; D012306:Risk
chemical_list: D007496:Iridium Radioisotopes; D017430:Prostate-Specific Antigen