title: Evaluating the effect of reducing the high-dose volume on the toxicity of radiotherapy in the treatment of bladder cancer.
abstract: OBJECTIVE
  The radiation dose used to treat bladder cancer is limited by the risk of inducing severe late bladder toxicity. Retrospective data suggest that radiation tolerance is greater for partial rather than whole bladder irradiation. Limiting the high-dose region to a section of the bladder may reduce toxicity, opening the way for dose escalation. The aims of this study were to establish the efficacy and compare the late toxicity between (1) a two-phase technique limiting the high-dose area and (2) a conventional single-phase radiotherapy to the whole bladder.
  
  
  METHODS
  A cohort study was undertaken of 229 patients with invasive bladder cancer treated with computed tomography-planned radical radiotherapy at the Royal Marsden Hospital from 1984 to 1998. In total, 154 patients received a single-phase treatment to the whole bladder with a 2 cm margin. Seventy-five patients with solitary, well-localised tumours were selected for treatment using a two-phase technique. The first phase (12 Gy) aimed to treat the tumour with a 2 cm margin. A second phase treated the whole bladder with 52 Gy. One hundred and forty-one patients were planned to receive a dose of 60-64 Gy/30-32 fractions over 6-6.5 weeks, whereas 88 patients received an accelerated regime. Data on late bladder and bowel toxicity (using Radiation Therapy Oncology Group criteria) were collected prospectively at the annual review.
  
  
  RESULTS
  At the 5-year follow-up there was no difference in overall survival (hazard ratio = 0.91, 95% confidence interval 0.64-1.3) or failure-free survival (hazard ratio = 1.02, 95% confidence interval 0.73-1.43) between the two techniques. The two-phase reduced volume treatment was less toxic, with a 19% absolute reduction in overall grade 3-4 late toxicity (P = 0.02). These differences were more marked for bladder toxicity compared with bowel toxicity.
  
  
  CONCLUSIONS
  The two-phase reduced volume technique was associated with less bladder and bowel toxicity than conventional whole bladder radiotherapy without evidence of impaired survival.
authors.affiliation: Academic Radiotherapy, Institute of Cancer Research and Royal Marsden NHS Foundation Trust, Sutton, Surrey, UK.
authors.forename: S A
authors.initials: SA
authors.lastname: Mangar
authors.forename: K
authors.initials: K
authors.lastname: Foo
authors.forename: A
authors.initials: A
authors.lastname: Norman
authors.forename: V
authors.initials: V
authors.lastname: Khoo
authors.forename: M
authors.initials: M
authors.lastname: Shahidi
authors.forename: D P
authors.initials: DP
authors.lastname: Dearnaley
authors.forename: A
authors.initials: A
authors.lastname: Horwich
authors.forename: R A
authors.initials: RA
authors.lastname: Huddart
mesh_terms: D015331:Cohort Studies; D004307:Dose-Response Relationship, Radiation; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007422:Intestines / Q000528:radiation effects; D008297:Male; D020714:Maximum Tolerated Dose; D009361:Neoplasm Invasiveness; D011832:Radiation Injuries / Q000517:prevention & control; D011879:Radiotherapy Dosage; D020266:Radiotherapy, Conformal / Q000009:adverse effects / Q000379:methods*; D012189:Retrospective Studies; D012307:Risk Factors; D012680:Sensitivity and Specificity; D015996:Survival Rate; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome; D001743:Urinary Bladder / Q000528:radiation effects*; D001749:Urinary Bladder Neoplasms / Q000000981:diagnostic imaging / Q000532:radiotherapy*