title: Revised radiobiological modelling of the contribution of synchronous chemotherapy to the rate of grades 3-4 mucositis in head and neck cancer.
abstract: BACKGROUND
  Biological effective dose (BED) calculations modelled on reduced accelerated repopulation when synchronous chemotherapy is delivered significantly correlate with observed differences in local control in randomised trials of platinum-based chemoradiation. The purpose of this study was to examine whether a similar relationship existed in the context of grades 3-4 mucositis.
  
  
  METHODS
  Biological effective dose from radiotherapy and synchronous chemotherapy was calculated using three different models: AB using the additional BED attributable to chemotherapy and standard repopulation parameters; zero repopulation (ZRP) using zero correction for repopulation; and variable t(p) (Vt(p)) using a variable doubling time for mucosal stem cell repopulation. The correlation between the percentage change in biological effective dose between trial arms, and the observed percentage change in the rate of grades 3-4 mucositis was examined by using the Pearson product-moment correlation.
  
  
  RESULTS
  With the AB model, there were no significant correlations with observed differences in rates of grades 3-4 mucositis. With either the ZRP or Vt(p) models, significant correlations were observed. A value of 5 days for the doubling time during repopulation (T(p)) was associated with the most significant correlation (P = 0.002).
  
  
  CONCLUSIONS
  Models where the dose lost due to accelerated repopulation is reduced imply a therapeutic loss from the use of synchronous chemotherapy when only local control and the rate of acute grades 3-4 mucositis are considered.
authors.affiliation: Hall-Edwards Radiotherapy Research Group, Queen Elizabeth Hospital.
authors.forename: Sara
authors.initials: S
authors.lastname: Meade
authors.forename: Chris
authors.initials: C
authors.lastname: McConkey
authors.forename: Paul
authors.initials: P
authors.lastname: Sanghera
authors.forename: Hisham
authors.initials: H
authors.lastname: Mehanna
authors.forename: Andrew
authors.initials: A
authors.lastname: Hartley
mesh_terms: D001822:Body Burden; D002294:Carcinoma, Squamous Cell / Q000453:epidemiology* / Q000473:pathology / Q000628:therapy*; D015984:Causality; D059248:Chemoradiotherapy; D003198:Computer Simulation; D006258:Head and Neck Neoplasms / Q000453:epidemiology* / Q000473:pathology / Q000628:therapy*; D006801:Humans; D015233:Models, Statistical; D052016:Mucositis / Q000453:epidemiology*; D060787:Neoplasm Grading; D015995:Prevalence; D011379:Prognosis; D016016:Proportional Hazards Models; D011832:Radiation Injuries / Q000453:epidemiology*; D011879:Radiotherapy Dosage; D018570:Risk Assessment; D000077195:Squamous Cell Carcinoma of Head and Neck; D016896:Treatment Outcome
keywords: head and neck; radiation oncology