title: A randomized hypofractionation dose escalation trial for high risk prostate cancer patients: interim analysis of acute toxicity and quality of life in 124 patients.
abstract: BACKGROUND
  The α/β ratio for prostate cancer is postulated being in the range of 0.8 to 2.2 Gy, giving rise to the hypothesis that there may be a therapeutic advantage to hypofractionation. To do so, we carried out a randomized trial comparing hypofractionated and conventionally fractionated image-guided intensity modulated radiotherapy (IG-IMRT) in high-risk prostate cancer. Here, we report on acute toxicity and quality of life (QOL) for the first 124 randomized patients.
  
  
  METHODS
  The trial compares 76 Gy in 38 fractions (5 fractions/week) (Arm 1) to 63 Gy in 20 fractions (4 fractions/week) (Arm 2) (IG-IMRT). Prophylactic pelvic lymph node irradiation with 46 Gy in 23 fractions sequentially (Arm 1) and 44 Gy in 20 fractions simultaneously (Arm 2) was applied. All patients had long term androgen deprivation therapy (ADT) started before RT. Both physician-rated acute toxicity and patient-reported QOL using EPIC questionnaire are described.
  
  
  RESULTS
  There were no differences in overall maximum acute gastrointestinal (GI) or genitourinary (GU) toxicity. Compared to conventional fractionation (Arm 1), GI and GU toxicity both developed significantly earlier but also disappeared earlier in the Arm 2, reaching significant differences from Arm 1 at week 8 and 9. In multivariate analyses, only parameter shown to be related to increased acute Grade ≥1 GU toxicity was the study Arm 2 (p = 0.049). There were no statistically significant differences of mean EPIC scores in any domain and sub-scales. The clinically relevant decrease (CRD) in EPIC urinary domain was significantly higher in Arm 2 at month 1 with a faster recovery at month 3 as compared to Arm 1.
  
  
  CONCLUSIONS
  Hypofractionation at 3.15 Gy per fraction to 63 Gy within 5 weeks was well tolerated. The GI and GU physician-rated acute toxicity both developed earlier but recovered faster using hypofractionation. There was a correlation between acute toxicity and bowel and urinary QOL outcomes. Longer follow-up is needed to determine the significance of these associations with late toxicity.
authors.affiliation: Department of Radiotherapy, Institute of Oncology, Vilnius University, Vilnius, Lithuania. dnorkus@takas.lt.
authors.forename: Darius
authors.initials: D
authors.lastname: Norkus
authors.forename: Agata
authors.initials: A
authors.lastname: Karklelyte
authors.forename: Benedikt
authors.initials: B
authors.lastname: Engels
authors.forename: Harijati
authors.initials: H
authors.lastname: Versmessen
authors.forename: Romas
authors.initials: R
authors.lastname: Griskevicius
authors.forename: Mark
authors.initials: M
authors.lastname: De Ridder
authors.forename: Guy
authors.initials: G
authors.lastname: Storme
authors.forename: Eduardas
authors.initials: E
authors.lastname: Aleknavicius
authors.forename: Ernestas
authors.initials: E
authors.lastname: Janulionis
authors.forename: Konstantinas Povilas
authors.initials: KP
authors.lastname: Valuckas
mesh_terms: D000230:Adenocarcinoma / Q000532:radiotherapy*; D000368:Aged; D019583:Dose Fractionation, Radiation; D004307:Dose-Response Relationship, Radiation; D006801:Humans; D008297:Male; D008875:Middle Aged; D011471:Prostatic Neoplasms / Q000532:radiotherapy*; D011788:Quality of Life; D061089:Radiotherapy, Image-Guided / Q000009:adverse effects / Q000379:methods; D050397:Radiotherapy, Intensity-Modulated / Q000009:adverse effects* / Q000379:methods*