title: Early mucosal reactions during and after head-and-neck radiotherapy: dependence of treatment tolerance on radiation dose and schedule duration.
abstract: OBJECTIVE
  To more precisely localize the dose-time boundary between head-and-neck radiotherapy schedules inducing tolerable and intolerable early mucosal reactions.
  
  
  METHODS
  Total cell-kill biologically effective doses (BED(CK)) have been calculated for 84 schedules, including incomplete repair effects, but making no other corrections for the effect of schedule duration T. [BED(CK),T] scatterplots are graphed, overlying BED(CKboundary)(T) curves on the plots and using discriminant analysis to optimize BED(CKboundary)(T) to best represent the boundary between the tolerable and intolerable schedules.
  
  
  RESULTS
  More overlap than expected is seen between the tolerable and intolerable treatments in the 84-schedule [BED(CK),T] scatterplot, but this was largely eliminated by removing gap and tolerated accelerating schedules from the plot. For the remaining 57 predominantly regular schedules, the BED(CKboundary)(T) boundary increases with increasing T (p = 0.0001), curving upwards significantly nonlinearly (p = 0.00007) and continuing to curve beyond 15 days (p = 0.035). The regular schedule BED(CKboundary)(T) boundary does not describe tolerability well for accelerating schedules (p = 0.002), with several tolerated accelerating schedules lying above the boundary where regular schedules would be intolerable. Gap schedule tolerability also is not adequately described by the regular schedule boundary (p = 0.04), although no systematic offset exists between the regular boundary and the overall gap schedule tolerability pattern.
  
  
  CONCLUSIONS
  All schedules analyzed (regular, gap, and accelerating) with BED(CK) values below BED(CKboundary)(T)=69.5x(T/32.2)/sin((T/32.2)((radians)))-3.5Gy(10)(forT< or =50 days) are tolerable, and many lying above the boundary are intolerable. The accelerating schedules analyzed were tolerated better overall than are the regular schedules with similar [BED(CK),T] values.
authors.affiliation: Department of Medical Physics, Clatterbridge Centre for Oncology, Wirral, United Kingdom. john.fenwick@ccotrust.nhs.uk
authors.forename: John D
authors.initials: JD
authors.lastname: Fenwick
authors.forename: Geoff P
authors.initials: GP
authors.lastname: Lawrence
authors.forename: Zafar
authors.initials: Z
authors.lastname: Malik
authors.forename: Alan E
authors.initials: AE
authors.lastname: Nahum
authors.forename: W Philip M
authors.initials: WP
authors.lastname: Mayles
mesh_terms: D000465:Algorithms; D016923:Cell Death; D016002:Discriminant Analysis; D006258:Head and Neck Neoplasms / Q000532:radiotherapy*; D006801:Humans; D009061:Mouth Mucosa / Q000528:radiation effects*; D011832:Radiation Injuries / Q000473:pathology*; D011879:Radiotherapy Dosage; D012062:Relative Biological Effectiveness; D013280:Stomatitis / Q000209:etiology / Q000473:pathology*