title: The impact of clinical factors on the development of late radiation toxicity: results from the Medical Research Council RT01 trial (ISRCTN47772397).
abstract: OBJECTIVE
  A variety of dosimetric parameters have been shown to influence the incidence of late radiation toxicity. The effect of other treatment- and patient-related factors is less well established. The aim of this study was to elucidate the influence of such factors in the development of late symptoms after radical radiotherapy to the prostate.
  
  
  METHODS
  Patient- and treatment-related factors that are thought to influence the development of late toxicity were analysed in 788 patients who had received radical radiotherapy to the prostate in the Medical Research Council RT01 trial. Late toxicity data were recorded using the Radiation Therapy Oncology Group, Late Effects of Normal Tissues/Subjective, Objective, Management, Analytic, Royal Marsden Hospital and the University of California, Los Angeles, Prostate Cancer Index. Acute toxicity was measured using the Radiation Therapy Oncology Group grading system.
  
  
  RESULTS
  On multivariate analysis, acute bowel toxicity was statistically significantly associated with increased proctitis (hazard ratio=1.63, 95% confidence interval 1.18, 2.24; P=0.003) and increased stool frequency (hazard ratio=1.77, 95% confidence interval 1.27, 2.46; P=0.001). Hypertension was strongly associated with a decreased risk of poor urinary stream (hazard ratio=0.25, 95% confidence interval 0.09, 0.71; P=0.009). There was an increased risk of rectal bleeding with increased age (hazard ratio=1.04 per year of age, 95% confidence interval 1.01, 1.08; P=0.009). As expected, a higher prescribed dose increased the risk of several late toxicity end points. Although acute bladder toxicity was associated with the presence of bladder symptoms at 5 years, the effect disappeared for all symptoms except increased urinary frequency and haematuria when a change in bladder function from baseline was calculated. Patients with any pretreatment bladder symptoms were more likely to report increased urinary frequency (hazard ratio=2.09, 95% confidence interval 1.48, 2.95; P<0.0005), increased urinary incontinence (hazard ratio=4.22, 95% confidence interval 2.13, 8.35; P<0.0005) and decreased stream (hazard ratio=2.64, 95% confidence interval 1.62, 4.31; P<0.0005), after treatment and before the most recent follow-up assessment.
  
  
  CONCLUSIONS
  In this study, increased acute gastrointestinal and bladder symptoms and prescribed dose were associated with increased late radiation toxicity. The presence of hypertension seemed to be protective for the development of late effects. Baseline symptoms should be taken into account when radiation toxicity is analysed.
authors.affiliation: University of Cambridge, Department of Oncology, Oncology Centre, Cambridge University Hospital NHS Foundation Trust, Cambridge, UK. gillbarnett@doctors.org.uk
authors.forename: G C
authors.initials: GC
authors.lastname: Barnett
authors.forename: G
authors.initials: G
authors.lastname: De Meerleer
authors.forename: S L
authors.initials: SL
authors.lastname: Gulliford
authors.forename: M R
authors.initials: MR
authors.lastname: Sydes
authors.forename: R M
authors.initials: RM
authors.lastname: Elliott
authors.forename: D P
authors.initials: DP
authors.lastname: Dearnaley
mesh_terms: D004307:Dose-Response Relationship, Radiation; D005767:Gastrointestinal Diseases / Q000209:etiology; D006801:Humans; D008297:Male; D015999:Multivariate Analysis; D016016:Proportional Hazards Models; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000532:radiotherapy*; D011832:Radiation Injuries / Q000150:complications* / Q000209:etiology*; D011874:Radiometry; D011879:Radiotherapy Dosage; D020266:Radiotherapy, Conformal / Q000009:adverse effects; D001745:Urinary Bladder Diseases / Q000209:etiology