title: Do acute mucosal reactions lead to consequential late reactions in patients with head and neck cancer?
abstract: OBJECTIVE
  The relationship between acute and late mucosal reactions remains ill defined but is of considerable relevance to efforts to produce therapeutic gains through the use of altered fractionation schemes and concurrent chemotherapy. We therefore investigated whether acute mucosal reactions in patients treated with an accelerated and a conventionally fractionated radiotherapy regime predicted the severity of late mucosal reactions.
  
  
  METHODS
  The study population consisted of 191 patients randomised on a prospective trial comparing conventional fractionation at 2 Gy/fraction per day, 70 Gy over 47 days with an accelerated regimen of 59.4 Gy, 1.8 Gy b.i.d over 24 days for Stage III-IV carcinoma of the head and neck. Acute and late mucosal reactions were scored according to RTOG/EORTC criteria and analyzed using multiple regression techniques.
  
  
  RESULTS
  The duration of time spent by patients at the acute confluent mucositis grade 3 level was inversely related to the time to onset of the reaction for both fractionation schedules. Time to onset was more rapid for patients treated on the accelerated schedule but time spent at the reaction grade did not differ significantly between the schedules. After correction for treatment and patient related factors, anatomical site (oral cavity/oropharynx versus hypopharynx/larynx) and increasing duration of confluent mucositis emerged as independent predictors of the hazard of late mucosal reactions with the latter effect being more pronounced in the accelerated treatment arm. The expected reduction in late mucosal effects in the accelerated fractionation arm, predicted by the LQ model for late effects was identified only in patients whose acute confluent mucosal reactions lasted less than 20 days.
  
  
  CONCLUSIONS
  The presence of individual patient susceptibility factors that determine the severity of acute mucosal reactions is suggested. A link between severe and prolonged acute reactions and the risk of developing late mucosal reactions that is independent of biological dose, has also been found. Purpose designed prospective studies of these issues are necessary.
authors.affiliation: Newcastle Mater Misericordiae Hospital, Newcastle, NSW, Australia.
authors.forename: J W
authors.initials: JW
authors.lastname: Denham
authors.forename: L J
authors.initials: LJ
authors.lastname: Peters
authors.forename: J
authors.initials: J
authors.lastname: Johansen
authors.forename: M
authors.initials: M
authors.lastname: Poulsen
authors.forename: D S
authors.initials: DS
authors.lastname: Lamb
authors.forename: A
authors.initials: A
authors.lastname: Hindley
authors.forename: P C
authors.initials: PC
authors.lastname: O'Brien
authors.forename: N A
authors.initials: NA
authors.lastname: Spry
authors.forename: M
authors.initials: M
authors.lastname: Penniment
authors.forename: H
authors.initials: H
authors.lastname: Krawitz
authors.forename: S
authors.initials: S
authors.lastname: Williamson
authors.forename: J
authors.initials: J
authors.lastname: Bear
authors.forename: L
authors.initials: L
authors.lastname: Tripcony
mesh_terms: D000208:Acute Disease; D000328:Adult; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000532:radiotherapy*; D005260:Female; D006258:Head and Neck Neoplasms / Q000532:radiotherapy*; D006801:Humans; D007013:Hypopharynx / Q000473:pathology / Q000528:radiation effects; D007830:Larynx / Q000473:pathology / Q000528:radiation effects; D008297:Male; D008875:Middle Aged; D009061:Mouth Mucosa / Q000473:pathology / Q000528:radiation effects*; D009092:Mucous Membrane / Q000473:pathology / Q000528:radiation effects; D009960:Oropharynx / Q000473:pathology / Q000528:radiation effects*; D010166:Palliative Care; D011446:Prospective Studies; D011832:Radiation Injuries / Q000473:pathology*; D011878:Radiotherapy / Q000009:adverse effects; D013280:Stomatitis / Q000209:etiology / Q000473:pathology