title: Moderate Hypofractionated Protracted Radiation Therapy and Dose Escalation for Prostate Cancer: Do Dose and Overall Treatment Time Matter?
abstract: OBJECTIVE
  This was a retrospective study of 2 sequential dose escalation regimens of twice-weekly 4 Gy/fractions hypofractionated intensity modulated radiation therapy (IMRT): 56 Gy and 60 Gy delivered within a protracted overall treatment time (OTT) of 6.5 and 7 weeks, respectively.
  
  
  METHODS
  163 prostate cancer patients with cT1c-T3a disease and nodal involvement risk ≤20% (Roach index) were treated twice weekly to the prostate ± seminal vesicles with 2 sequential dose-escalated IMRT schedules: 56 Gy (14 × 4 Gy, n=81) from 2003 to 2007 and 60 Gy (15 × 4 Gy, n=82) from 2006 to 2010. Patient repositioning was made with bone matching on portal images. Gastrointestinal (GI) and genitourinary (GU) toxicities were scored according to the Common Terminology Criteria for Adverse Events version 3.0 grading scale.
  
  
  RESULTS
  There were no significant differences regarding the acute GU and GI toxicities in the 2 dose groups. The median follow-up times were 80.2 months (range, 4.5-121 months) and 56.5 months (range, 1.4-91.2 months) for patients treated to 56 and 60 Gy, respectively. The 5-year grade ≥2 late GU toxicity-free survivals with 56 Gy and 60 Gy were 96 ± 2.3% and 78.2 ± 5.1% (P=.001), respectively. The 5-year grade ≥2 late GI toxicity-free survivals with 56 Gy and 60 Gy were 98.6 ± 1.3% and 85.1 ± 4.5% (P=.005), respectively. Patients treated with 56 Gy showed a 5-year biochemical progression-free survival (bPFS) of 80.8 ± 4.7%, worse than patients treated with 60 Gy (93.2 ± 3.9%, P=.007). A trend for a better 5-year distant metastasis-free survival was observed among patients treated in the high-dose group (95.3 ± 2.7% vs 100%, P=.073, respectively). On multivariate analysis, only the 60-Gy group predicted for a better bPFS (P=.016, hazard ratio = 4.58).
  
  
  CONCLUSIONS
  A single 4-Gy additional fraction in patients treated with a hypofractionated protracted IMRT schedule of 14 × 4 Gy resulted in a similar and minimal acute toxicity, in worse moderate to severe urinary and GI late effects, but a significantly better biochemical control.
authors: Department of Radiation Oncology, Geneva University Hospital, Geneva, Switzerland.
authors: Melpomeni
authors: M
authors: Kountouri
authors: Department of Radiation Oncology, Geneva University Hospital, Geneva, Switzerland.
authors: Thomas
authors: T
authors: Zilli
authors: Department of Radiation Oncology, Geneva University Hospital, Geneva, Switzerland.
authors: Michel
authors: M
authors: Rouzaud
authors: Department of Radiation Oncology, Geneva University Hospital, Geneva, Switzerland.
authors: Angèle
authors: A
authors: Dubouloz
authors: Radiation Oncology, Teknon Oncologic Institute, Barcelona, Spain.
authors: Dolors
authors: D
authors: Linero
authors: Radiation Oncology, Teknon Oncologic Institute, Barcelona, Spain.
authors: Lluís
authors: L
authors: Escudé
authors: Radiation Oncology, Teknon Oncologic Institute, Barcelona, Spain.
authors: Sandra
authors: S
authors: Jorcano
authors: Department of Radiation Oncology, Geneva University Hospital, Geneva, Switzerland; Radiation Oncology, Teknon Oncologic Institute, Barcelona, Spain. Electronic address: Raymond.Miralbell@hcuge.ch.
authors: Raymond
authors: R
authors: Miralbell
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D018572:Disease-Free Survival; D053159:Dysuria / Q000209:etiology; D005500:Follow-Up Studies; D006417:Hematuria / Q000209:etiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D011471:Prostatic Neoplasms / Q000473:pathology / Q000532:radiotherapy*; D000069473:Radiation Dose Hypofractionation; D011832:Radiation Injuries / Q000401:mortality; D011879:Radiotherapy Dosage; D050397:Radiotherapy, Intensity-Modulated / Q000009:adverse effects / Q000379:methods*; D012189:Retrospective Studies; D013997:Time Factors