title: Risk of late toxicity in men receiving dose-escalated hypofractionated intensity modulated prostate radiation therapy: results from a randomized trial.
abstract: OBJECTIVE
  To report late toxicity outcomes from a randomized trial comparing conventional and hypofractionated prostate radiation therapy and to identify dosimetric and clinical parameters associated with late toxicity after hypofractionated treatment.
  
  
  METHODS
  Men with localized prostate cancer were enrolled in a trial that randomized men to either conventionally fractionated intensity modulated radiation therapy (CIMRT, 75.6 Gy in 1.8-Gy fractions) or to dose-escalated hypofractionated IMRT (HIMRT, 72 Gy in 2.4-Gy fractions). Late (≥90 days after completion of radiation therapy) genitourinary (GU) and gastrointestinal (GI) toxicity were prospectively evaluated and scored according to modified Radiation Therapy Oncology Group criteria.
  
  
  RESULTS
  101 men received CIMRT and 102 men received HIMRT. The median age was 68, and the median follow-up time was 6.0 years. Twenty-eight percent had low-risk, 71% had intermediate-risk, and 1% had high-risk disease. There was no difference in late GU toxicity in men treated with CIMRT and HIMRT. The actuarial 5-year grade ≥2 GU toxicity was 16.5% after CIMRT and 15.8% after HIMRT (P=.97). There was a nonsignificant numeric increase in late GI toxicity in men treated with HIMRT compared with men treated with CIMRT. The actuarial 5-year grade ≥2 GI toxicity was 5.1% after CIMRT and 10.0% after HIMRT (P=.11). In men receiving HIMRT, the proportion of rectum receiving 36.9 Gy, 46.2 Gy, 64.6 Gy, and 73.9 Gy was associated with the development of late GI toxicity (P<.05). The 5-year actuarial grade ≥2 GI toxicity was 27.3% in men with R64.6Gy ≥ 20% but only 6.0% in men with R64.6Gy < 20% (P=.016).
  
  
  CONCLUSIONS
  Dose-escalated IMRT using a moderate hypofractionation regimen (72 Gy in 2.4-Gy fractions) can be delivered safely with limited grade 2 or 3 late toxicity. Minimizing the proportion of rectum that receives moderate and high dose decreases the risk of late rectal toxicity after this hypofractionation regimen.
authors.affiliation: Departments of Radiation Oncology and Radiation Physics, The University of Texas, MD Anderson Cancer Center, Houston, Texas. Electronic address: khoffman1@mdanderson.org.
authors.forename: Karen E
authors.initials: KE
authors.lastname: Hoffman
authors.affiliation: Departments of Radiation Oncology and Radiation Physics, The University of Texas, MD Anderson Cancer Center, Houston, Texas.
authors.forename: K Ranh
authors.initials: KR
authors.lastname: Voong
authors.affiliation: Departments of Radiation Oncology and Radiation Physics, The University of Texas, MD Anderson Cancer Center, Houston, Texas.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Pugh
authors.affiliation: Departments of Radiation Oncology and Radiation Physics, The University of Texas, MD Anderson Cancer Center, Houston, Texas.
authors.forename: Heath
authors.initials: H
authors.lastname: Skinner
authors.affiliation: Departments of Radiation Oncology and Radiation Physics, The University of Texas, MD Anderson Cancer Center, Houston, Texas.
authors.forename: Lawrence B
authors.initials: LB
authors.lastname: Levy
authors.affiliation: Departments of Radiation Oncology and Radiation Physics, The University of Texas, MD Anderson Cancer Center, Houston, Texas.
authors.forename: Vinita
authors.initials: V
authors.lastname: Takiar
authors.affiliation: Departments of Radiation Oncology and Radiation Physics, The University of Texas, MD Anderson Cancer Center, Houston, Texas.
authors.forename: Seungtaek
authors.initials: S
authors.lastname: Choi
authors.affiliation: Departments of Radiation Oncology and Radiation Physics, The University of Texas, MD Anderson Cancer Center, Houston, Texas.
authors.forename: Weiliang
authors.initials: W
authors.lastname: Du
authors.affiliation: Departments of Radiation Oncology and Radiation Physics, The University of Texas, MD Anderson Cancer Center, Houston, Texas.
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Frank
authors.affiliation: Departments of Radiation Oncology and Radiation Physics, The University of Texas, MD Anderson Cancer Center, Houston, Texas.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Johnson
authors.affiliation: Departments of Radiation Oncology and Radiation Physics, The University of Texas, MD Anderson Cancer Center, Houston, Texas.
authors.forename: James
authors.initials: J
authors.lastname: Kanke
authors.affiliation: Departments of Radiation Oncology and Radiation Physics, The University of Texas, MD Anderson Cancer Center, Houston, Texas.
authors.forename: Rajat J
authors.initials: RJ
authors.lastname: Kudchadker
authors.affiliation: Departments of Radiation Oncology and Radiation Physics, The University of Texas, MD Anderson Cancer Center, Houston, Texas.
authors.forename: Andrew K
authors.initials: AK
authors.lastname: Lee
authors.affiliation: Departments of Radiation Oncology and Radiation Physics, The University of Texas, MD Anderson Cancer Center, Houston, Texas.
authors.forename: Usama
authors.initials: U
authors.lastname: Mahmood
authors.affiliation: Departments of Radiation Oncology and Radiation Physics, The University of Texas, MD Anderson Cancer Center, Houston, Texas.
authors.forename: Sean E
authors.initials: SE
authors.lastname: McGuire
authors.affiliation: Departments of Radiation Oncology and Radiation Physics, The University of Texas, MD Anderson Cancer Center, Houston, Texas.
authors.forename: Deborah A
authors.initials: DA
authors.lastname: Kuban
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019583:Dose Fractionation, Radiation; D004307:Dose-Response Relationship, Radiation; D041981:Gastrointestinal Tract / Q000528:radiation effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D011446:Prospective Studies; D011467:Prostate / Q000528:radiation effects; D011471:Prostatic Neoplasms / Q000532:radiotherapy*; D011829:Radiation Dosage; D011832:Radiation Injuries / Q000209:etiology; D011874:Radiometry; D050397:Radiotherapy, Intensity-Modulated / Q000009:adverse effects* / Q000379:methods*; D012007:Rectum / Q000528:radiation effects; D012306:Risk; D001743:Urinary Bladder / Q000528:radiation effects