title: Normal tissue complication probability (NTCP) parameters for breast fibrosis: pooled results from two randomised trials.
abstract: BACKGROUND
  The dose-volume effect of radiation therapy on breast tissue is poorly understood. We estimate NTCP parameters for breast fibrosis after external beam radiotherapy.
  
  
  METHODS
  We pooled individual patient data of 5856 patients from 2 trials including whole breast irradiation followed with or without a boost. A two-compartment dose volume histogram model was used with boost volume as the first compartment and the remaining breast volume as second compartment. Results from START-pilot trial (n=1410) were used to test the predicted models.
  
  
  RESULTS
  26.8% patients in the Cambridge trial (5 years) and 20.7% patients in the EORTC trial (10 years) developed moderate-severe breast fibrosis. The best fit NTCP parameters were BEUD3(50)=136.4 Gy, γ50=0.9 and n=0.011 for the Niemierko model and BEUD3(50)=132 Gy, m=0.35 and n=0.012 for the Lyman Kutcher Burman model. The observed rates of fibrosis in the START-pilot trial agreed well with the predicted rates.
  
  
  CONCLUSIONS
  This large multi-centre pooled study suggests that the effect of volume parameter is small and the maximum RT dose is the most important parameter to influence breast fibrosis. A small value of volume parameter 'n' does not fit with the hypothesis that breast tissue is a parallel organ. However, this may reflect limitations in our current scoring system of fibrosis.
authors: Oncology Centre, Cambridge University Hospitals NHS Foundation Trust, UK. Electronic address: mukesh.mukesh@addenbrookes.nhs.uk.
authors: Mukesh B
authors: MB
authors: Mukesh
authors: Emma
authors: E
authors: Harris
authors: Sandra
authors: S
authors: Collette
authors: Charlotte E
authors: CE
authors: Coles
authors: Harry
authors: H
authors: Bartelink
authors: Jenny
authors: J
authors: Wilkinson
authors: Philip M
authors: PM
authors: Evans
authors: Peter
authors: P
authors: Graham
authors: Jo
authors: J
authors: Haviland
authors: Philip
authors: P
authors: Poortmans
authors: John
authors: J
authors: Yarnold
authors: Raj
authors: R
authors: Jena
mesh_terms: D000328:Adult; D000368:Aged; D001707:Biopsy, Needle; D001940:Breast / Q000473:pathology* / Q000528:radiation effects*; D001943:Breast Neoplasms / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery; D004307:Dose-Response Relationship, Radiation; D005069:Evaluation Studies as Topic; D005260:Female; D005355:Fibrosis / Q000209:etiology / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D015412:Mastectomy, Segmental / Q000379:methods; D008875:Middle Aged; D010865:Pilot Projects; D011336:Probability; D011879:Radiotherapy Dosage; D018714:Radiotherapy, Adjuvant; D020266:Radiotherapy, Conformal / Q000009:adverse effects* / Q000379:methods; D011882:Radiotherapy, High-Energy / Q000009:adverse effects* / Q000379:methods; D016032:Randomized Controlled Trials as Topic; D012016:Reference Values; D018570:Risk Assessment
keywords: Breast conserving treatment; Breast fibrosis; Breast radiotherapy; Late complications; NTCP