title: High-dose irradiation for prostate cancer via a high-dose-rate brachytherapy boost: results of a phase I to II study.
abstract: OBJECTIVE
  To evaluate outcomes of intermediate- and high-risk prostate cancer patients on a prospective dose-escalation study of pelvic external-beam radiation therapy (EBRT) combined with high-dose-rate (HDR) brachytherapy boost.
  
  
  METHODS
  From November 1991 to April 2003, 197 patients were treated for intermediate- and high-risk disease features. All patients had prostate-specific antigen>10 ng/ml, Gleason score>or=7, or clinical stage>or=T2b, and all received pelvic EBRT (46 Gy) while receiving either two or three HDR boost treatments. HDR dose fractionation increased progressively and was divided into two dose levels. The mean prostate biologic equivalency dose was 88.2 Gy for the low-dose group and 116.8 Gy for the high-dose group (alpha/beta=1.2). Clinical failure was either local failure or distant metastasis; clinical event-free survival (cEFS) was defined as patients who lived free of clinical failure.
  
  
  RESULTS
  Median follow-up was 4.9 years. The 5-year rates were as follows: biologic failure (BF), 18.6%, clinical failure (CF), 9.8%, cEFS 84.8%, cause-specific survival (CSS), 98.3%, and overall survival (OS), 92.9%. Five-year biochemical failure (68.7% vs. 86%, p<0.001), CF (6.1% vs. 15.6%, p=0.04), cEFS (75.5% vs. 91.7%, p=0.003), CSS (95.4% vs. 100%, p=0.02), and OS (86.2% vs. 97.8%, p=0.002) were significantly better for the high-dose group. Multivariate analysis showed that high-dose group (p=0.01, HR 0.35) and Gleason score (p=0.01, HR 1.84) were significant variables for cEFS. Multivariate analysis showed that high-dose group (p=0.01, HR 0.14) and age (p=0.03, HR 1.09 per year) were significant variables for overall survival.
  
  
  CONCLUSIONS
  There is a strong dose-response relationship for intermediate- to high-risk prostate cancer patients. Improved locoregional control with higher radiation doses alone can significantly decrease biochemical and clinical failures.
authors.affiliation: Radiation Oncology Department, William Beaumont Hospital, Royal Oak, MI 48073, USA.
authors.forename: Carlos E
authors.initials: CE
authors.lastname: Vargas
authors.forename: Alvaro A
authors.initials: AA
authors.lastname: Martinez
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Boike
authors.forename: William
authors.initials: W
authors.lastname: Spencer
authors.forename: Neal
authors.initials: N
authors.lastname: Goldstein
authors.forename: Gary S
authors.initials: GS
authors.lastname: Gustafson
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Krauss
authors.forename: José
authors.initials: J
authors.lastname: Gonzalez
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001918:Brachytherapy / Q000379:methods*; D004307:Dose-Response Relationship, Radiation; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011446:Prospective Studies; D011471:Prostatic Neoplasms / Q000097:blood / Q000532:radiotherapy*; D011879:Radiotherapy Dosage; D012062:Relative Biological Effectiveness; D016019:Survival Analysis; D017211:Treatment Failure