title: Acute toxicity of image-guided hypofractionated radiotherapy for prostate cancer: nonrandomized comparison with conventional fractionation.
abstract: OBJECTIVE
  To compare acute toxicity of prostate cancer image-guided hypofractionated radiotherapy (hypo-IGRT) with conventional fractionation without image-guidance (non-IGRT). To test the hypothesis that the potentially injurious effect of hypofractionation can be counterbalanced by the reduced irradiated normal tissue volume using IGRT approach.
  
  
  METHODS
  One hundred seventy-nine cT1-T2N0M0 prostate cancer patients were treated within the prospective study with 70.2 Gy/26 fractions (equivalent to 84 Gy/42 fractions, α/β 1.5 Gy) using IGRT (transabdominal ultrasound, ExacTrac X-Ray system, or cone-beam computer tomography). Their prospectively collected data were compared with data of 174 patients treated to 80 Gy/40 fractions with non-IGRT. The difference between hypo-IGRT and non-IGRT cohorts included fractionation (hypofractionation vs. conventional fractionation), margins (hypo-IGRT margins: 7 mm and 3 mm, for all but posterior margins; respectively; non-IGRT margins: 10 and 5 mm, for all but posterior margins, respectively), and use of image-guidance or not. Multivariate analysis was performed to define the tumor-, patient-, and treatment-related predictors for acute toxicity.
  
  
  RESULTS
  All patients completed the prescribed radiotherapy course. Acute toxicity in the hypo-IGRT cohort included rectal (G1: 29.1%; G2: 11.2%; G3: 1.1%) and urinary events (G1: 33.5%; G2: 39.1%; G3: 5%). Acute toxicity in the non-IGRT patients included rectal (G1: 16.1%; G2: 6.3%) and urinary events (G1: 36.2%; G2: 20.7%; G3: 0.6%). In 1 hypo-IGRT and 2 non-IGRT patients, radiotherapy was temporarily interrupted due to acute toxicity. The incidence of mild (G1-2) rectal and bladder complications was significantly higher for hypo-IGRT (P = 0.0014 and P < 0.0001, respectively). Multivariate analysis showed that hypo-IGRT (P = 0.001) and higher PSA (P = 0.046) are correlated with higher acute urinary toxicity. No independent factor was identified for acute rectal toxicity. No significant impact of IGRT system on acute toxicity was observed.
  
  
  CONCLUSIONS
  The acute toxicity rates were low and similar in both study groups with some increase in mild acute urinary injury in the hypo-IGRT patients (most probably due to the under-reporting in the retrospectively analyzed non-IGRT cohort). The higher incidence of acute bowel reactions observed in hypo-IGRT group was not significant in the multivariate analysis. Further investigation is warranted in order to exclude the bias due to the nonrandomized character of the study.
authors.affiliation: Department of Radiation Oncology, European Institute of Oncology, Milan, Italy. barbara.jereczek@ieo.it
authors.forename: Barbara Alicja
authors.initials: BA
authors.lastname: Jereczek-Fossa
authors.forename: Dario
authors.initials: D
authors.lastname: Zerini
authors.forename: Cristiana
authors.initials: C
authors.lastname: Fodor
authors.forename: Luigi
authors.initials: L
authors.lastname: Santoro
authors.forename: Raffaella
authors.initials: R
authors.lastname: Cambria
authors.forename: Cristina
authors.initials: C
authors.lastname: Garibaldi
authors.forename: Barbara
authors.initials: B
authors.lastname: Tagaste
authors.forename: Andrea
authors.initials: A
authors.lastname: Vavassori
authors.forename: Federica
authors.initials: F
authors.lastname: Cattani
authors.forename: Daniela
authors.initials: D
authors.lastname: Alterio
authors.forename: Federica
authors.initials: F
authors.lastname: Gherardi
authors.forename: Flavia
authors.initials: F
authors.lastname: Serafini
authors.forename: Bernardo
authors.initials: B
authors.lastname: Rocco
authors.forename: Gennaro
authors.initials: G
authors.lastname: Musi
authors.forename: Ottavio
authors.initials: O
authors.lastname: De Cobelli
authors.forename: Roberto
authors.initials: R
authors.lastname: Orecchia
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D019583:Dose Fractionation, Radiation; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D011471:Prostatic Neoplasms / Q000000981:diagnostic imaging* / Q000532:radiotherapy*; D011832:Radiation Injuries / Q000000981:diagnostic imaging* / Q000209:etiology; D011880:Radiotherapy Planning, Computer-Assisted; D020266:Radiotherapy, Conformal / Q000009:adverse effects*; D012189:Retrospective Studies; D015996:Survival Rate; D014057:Tomography, X-Ray Computed