title: Moderate Hypofractionation with Simultaneous Integrated Boost in Prostate Cancer: Long-term Results of a Phase I-II Study.
abstract: To report 5 year outcome and late toxicity in prostate cancer patients treated with image-guided tomotherapy with a moderate hypofractionated simultaneous integrated boost approach.
  
  
  
  In total, 211 prostate cancer patients, 78 low risk, 53 intermediate risk and 80 high risk were treated between 2005 and 2011. Intermediate- and high-risk patients received 51.8 Gy to pelvic lymph nodes and concomitant simultaneous integrated boost to prostate up to 74.2 Gy/28 fractions, whereas low-risk patients were treated to the prostate only with 71.4 Gy/28 fractions. Daily megavoltage computed tomography (MVCT) image guidance was applied. Androgen deprivation was prescribed for a median duration of 6 months for low-risk patients (for downsizing), 12 months for intermediate-risk and 36 months for high-risk patients. The 5 year biochemical relapse-free survival (bRFS), cancer-specific survival (CSS), overall survival and late gastrointestinal and genitourinary CTCAE.v3 toxicity were assessed. The effect of several clinical variables on both outcome and gastrointestinal/genitourinary toxicity was tested by uni- and multivariate Cox regression analyses.
  
  
  
  After a median follow-up of 5 years, the late toxicity actuarial incidence was: genitourinary ≥ grade 2: 20.2%; genitourinary ≥ grade 3: 5.9%; gastrointestinal ≥ grade 2: 17%; gastrointestinal ≥ grade 3: 6.3% with lower prevalence at the last follow-up visit (≥ grade 3: genitourinary: 1.9%; gastrointestinal: 1.9%). Major predictors of ≥ grade 3 genitourinary and gastrointestinal late toxicity were genitourinary acute toxicity ≥ grade 2 (hazard ratio: 4.9) and previous surgery (hazard ratio: 3.4). The overall 5 year bRFS was 93.7% (low risk: 94.6%; intermediate risk: 96.2%; high risk: 91.1%), overall survival and CSS were 88.6% (low risk: 90.5%; intermediate risk: 87.4%; high risk: 87%) and 97.5% (low risk: 98.7%; intermediate risk: 95%; high risk: 94.3%), respectively. Risk classes and androgen deprivation were not significantly correlated with either bRFS, overall survival or CSS. Twelve patients experienced a biochemical relapse but none experienced clinically proven local and/or pelvic recurrence.
  
  
  
  A satisfactory 5 year outcome with an acceptable toxicity profile was observed. The combination of image-guided radiotherapy-intensity-modulated radiotherapy, high equivalent 2 Gy dose (EQD2) with a moderate hypofractionated approach and extensive prophylactic lymph node irradiation also leads to very good outcome in high-risk patients.
authors.affiliation: Department of Radiation Oncology, San Raffaele Scientific Institute, Milan, Italy. Electronic address: dimuzio.nadia@hsr.it.
authors.forename: N G
authors.initials: NG
authors.lastname: Di Muzio
authors.affiliation: Department of Radiation Oncology, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Fodor
authors.affiliation: Department of Radiation Oncology, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: B
authors.initials: B
authors.lastname: Noris Chiorda
authors.affiliation: Medical Physics, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Broggi
authors.affiliation: Medical Physics, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Mangili
authors.affiliation: Fondazione IRCCS Istituto Nazionale dei Tumori, Radiotherapy, Milan, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Valdagni
authors.affiliation: Department of Radiation Oncology, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: I
authors.initials: I
authors.lastname: Dell'Oca
authors.affiliation: Department of Radiation Oncology, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Pasetti
authors.affiliation: Department of Radiation Oncology, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: C L
authors.initials: CL
authors.lastname: Deantoni
authors.affiliation: Department of Radiation Oncology, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Chiara
authors.affiliation: Department of Radiation Oncology, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Berardi
authors.affiliation: Department of Urology, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Briganti
authors.affiliation: Medical Physics, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Calandrino
authors.affiliation: Department of Radiation Oncology, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Cozzarini
authors.affiliation: Medical Physics, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Fiorino
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D054893:Cone-Beam Computed Tomography / Q000379:methods; D006801:Humans; D008297:Male; D008875:Middle Aged; D011471:Prostatic Neoplasms / Q000401:mortality / Q000532:radiotherapy*; D000069473:Radiation Dose Hypofractionation; D061089:Radiotherapy, Image-Guided / Q000009:adverse effects / Q000379:methods*; D050397:Radiotherapy, Intensity-Modulated / Q000009:adverse effects* / Q000379:methods*; D016896:Treatment Outcome
keywords: Moderate hypofractionation; prostate cancer; simultaneous integrated boost; tomotherapy