title: Phase 2 trial of guideline-based postoperative image guided intensity modulated radiation therapy for prostate cancer: Toxicity, biochemical, and patient-reported health-related quality-of-life outcomes.
abstract: OBJECTIVE
  The purpose of this study was to characterize treatment-related toxicities, health-related quality of life (HRQOL), and biochemical outcomes in patients treated with postoperative image guided intensity modulated radiation therapy (IMRT) for prostate cancer using a consensus guideline for defining the clinical target volume.
  
  
  METHODS
  Between August 2007 and October 2008, patients considered for radiation therapy (RT) after prostatectomy were enrolled. The clinical target volume (prostate bed) was delineated according to published consensus guidelines, and patients were prescribed a dose of 66 Gy in 33 fractions. Radiation treatment planning prioritized rectal dose constraints over target volume coverage. Treatment was delivered by use of IMRT and daily cone beam computed tomographic guidance. Toxicity (graded according to the National Cancer Institute's Common Terminology Criteria for Adverse Events) and HRQOL assessments according to the Expanded Prostate Cancer Index Composite (EPIC) questionnaire were collected prospectively at baseline, at week 5 (during RT), at 3 months, and at yearly follow-up visits. Cumulative toxicity and biochemical relapse-free rates were calculated by the Kaplan-Meier method. Paired Student t tests with multiple testing correction were used to assess changes in HRQOL.
  
  
  RESULTS
  A total of 68 men were evaluated, with median follow-up of 5.9 years. Fifty-three patients (77.9%) and 15 patients (22.1%) were treated with salvage and adjuvant RT, respectively. Primary planning objectives were met in most cases (97.1%), but planning target volume coverage was compromised in 40% of cases because of large planning target volumes (mean 347.6 cm(3)). There were no grade 3 or 4 acute toxicities. Cumulative 5-year incidence of late gastrointestinal and genitourinary grade 2 toxicities was 12.3% (95% confidence interval [CI], 11.1%-13.5%) and 10.6% (95% CI, 9.5%-11.6%), respectively. No grade 3 or 4 late toxicities were observed. Transient declines in EPIC gastrointestinal domain summary score (mean 87.66 at 3 months vs 92.76 at baseline; P = .006) and genitourinary irritative subscale (week 5 mean score 83.37 vs 89.45 at baseline; P = .007) were observed. Complete recovery occurred between 3 and 12 months after therapy, remaining stable compared with baseline at 5-year follow-up. Sexual HRQOL remained stable at 5 years, with an improving trend in bother subscale. Biochemical relapse-free rate at 5 years was 72.7% (95% CI, 61.9%-83.5%).
  
  
  CONCLUSIONS
  Guideline-based postprostatectomy image guided IMRT with rigid rectal dose constraints resulted in favorable toxicity profiles; long-term stability in gastrointestinal, genitourinary, and sexual HRQOL; and expected biochemical control rates. Concerns regarding toxicity and HRQOL should not preclude recommendation for RT after prostatectomy.
authors.affiliation: Departments of Radiation Oncology, Medical Biophysics, University of Toronto, Toronto, Ontario, Canada; Radiation Medicine Program, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada; Servicio de Radioterapia, Clinica Alemana de Santiago, Santiago, Chile.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Berlin
authors.affiliation: Radiation Medicine Program, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Cho
authors.affiliation: Radiation Medicine Program, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.
authors.forename: Vickie
authors.initials: V
authors.lastname: Kong
authors.affiliation: Radiation Medicine Program, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada; Department of Radiation Oncology, University of Arizona, Tucson, Arizona.
authors.forename: Krisha J
authors.initials: KJ
authors.lastname: Howell
authors.affiliation: Radiation Medicine Program, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.
authors.forename: Bernadeth
authors.initials: B
authors.lastname: Lao
authors.affiliation: Departments of Radiation Oncology, Medical Biophysics, University of Toronto, Toronto, Ontario, Canada; Radiation Medicine Program, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.
authors.forename: Tim
authors.initials: T
authors.lastname: Craig
authors.affiliation: Departments of Radiation Oncology, Medical Biophysics, University of Toronto, Toronto, Ontario, Canada; Radiation Medicine Program, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.
authors.forename: Andrew
authors.initials: A
authors.lastname: Bayley
authors.affiliation: Departments of Radiation Oncology, Medical Biophysics, University of Toronto, Toronto, Ontario, Canada; Radiation Medicine Program, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.
authors.forename: Peter
authors.initials: P
authors.lastname: Chung
authors.affiliation: Departments of Radiation Oncology, Medical Biophysics, University of Toronto, Toronto, Ontario, Canada; Radiation Medicine Program, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.
authors.forename: Mary
authors.initials: M
authors.lastname: Gospodarowicz
authors.affiliation: Departments of Radiation Oncology, Medical Biophysics, University of Toronto, Toronto, Ontario, Canada; Radiation Medicine Program, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.
authors.forename: Padraig
authors.initials: P
authors.lastname: Warde
authors.affiliation: Departments of Radiation Oncology, Medical Biophysics, University of Toronto, Toronto, Ontario, Canada; Radiation Medicine Program, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.
authors.forename: Charles
authors.initials: C
authors.lastname: Catton
authors.affiliation: Departments of Radiation Oncology, Medical Biophysics, University of Toronto, Toronto, Ontario, Canada; Radiation Medicine Program, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.
authors.forename: Robert G
authors.initials: RG
authors.lastname: Bristow
authors.affiliation: Departments of Radiation Oncology, Medical Biophysics, University of Toronto, Toronto, Ontario, Canada; Radiation Medicine Program, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada. Electronic address: Cynthia.Menard@rmp.uhn.on.ca.
authors.forename: Cynthia
authors.initials: C
authors.lastname: Ménard
mesh_terms: D000328:Adult; D000368:Aged; D015331:Cohort Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D011471:Prostatic Neoplasms / Q000532:radiotherapy*; D011788:Quality of Life; D061089:Radiotherapy, Image-Guided / Q000379:methods*; D050397:Radiotherapy, Intensity-Modulated / Q000379:methods*; D016896:Treatment Outcome