title: The Cambridge Breast Intensity-modulated Radiotherapy Trial: patient- and treatment-related factors that influence late toxicity.
abstract: OBJECTIVE
  The effect of patient- and treatment-related factors in the development of late normal tissue toxicity after radiotherapy is not yet fully established. The aim of this study was to elucidate the relative importance of such factors in the development of late toxicity after breast-conserving surgery and adjuvant breast radiotherapy.
  
  
  METHODS
  Patient- and treatment-related factors were analysed in 1014 patients who had received adjuvant radiotherapy to the breast in the Cambridge Breast Intensity-modulated Radiotherapy (IMRT) Trial. Late toxicity data were collected using photographic and clinical assessments and patient-reported questionnaires at 2 years after radiotherapy.
  
  
  RESULTS
  On multivariate analysis, a larger breast volume was statistically significantly associated with the development of breast shrinkage assessed by serial photographs (odds ratio per litre increase in breast volume = 1.98, 95% confidence interval 1.41, 2.78; P < 0.0005), telangiectasia (odds ratio = 3.94, 95% confidence interval 2.49, 6.24; P < 0.0005), breast oedema (odds ratio = 3.65, 95% confidence interval 2.54, 5.24; P < 0.0005) and pigmentation (odds ratio = 1.75, 95% confidence interval 1.21, 2.51; P = 0.003). Current smokers had an increased risk of developing pigmentation (odds ratio = 2.09, 95% confidence interval 1.23, 3.54; P = 0.006). Patients with a moderate or poor post-surgical cosmesis had a greatly increased risk of moderate or poor overall cosmesis (odds ratio = 38.19; 95% confidence interval 21.9, 66.7; P < 0.0005). Postoperative infection requiring antibiotics was associated with increased risk of telangiectasia (odds ratio = 3.39, 95% confidence interval 1.94, 5.91; P < 0.0005) and breast oversensitivity (odds ratio = 1.78, 95% confidence interval 1.27, 2.49; P = 0.001).
  
  
  CONCLUSIONS
  In this study, the greatest risk factors for the development of late toxicity 2 years after breast-conserving surgery and adjuvant radiotherapy were larger breast volume, baseline pre-radiotherapy surgical cosmesis, postoperative infection and possibly smoking. These factors seem to be more important than relatively small differences in dose inhomogeneity and the addition of boost radiotherapy at 2 years after the completion of radiotherapy. The modification of potentially preventable risk factors, such as postoperative infection and smoking, may limit the development of late toxicity after breast radiotherapy.
authors.affiliation: University of Cambridge Department of Oncology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK.
authors.forename: G C
authors.initials: GC
authors.lastname: Barnett
authors.forename: J S
authors.initials: JS
authors.lastname: Wilkinson
authors.forename: A M
authors.initials: AM
authors.lastname: Moody
authors.forename: C B
authors.initials: CB
authors.lastname: Wilson
authors.forename: N
authors.initials: N
authors.lastname: Twyman
authors.forename: G C
authors.initials: GC
authors.lastname: Wishart
authors.forename: N G
authors.initials: NG
authors.lastname: Burnet
authors.forename: C E
authors.initials: CE
authors.lastname: Coles
mesh_terms: D000293:Adolescent; D000328:Adult; D001943:Breast Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery; D005260:Female; D006801:Humans; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D011832:Radiation Injuries / Q000209:etiology*; D018714:Radiotherapy, Adjuvant; D050397:Radiotherapy, Intensity-Modulated / Q000009:adverse effects* / Q000379:methods; D016896:Treatment Outcome; D055815:Young Adult