title: Dosimetric explanations of fatigue in head and neck radiotherapy: an analysis from the PARSPORT Phase III trial.
abstract: BACKGROUND
  An unexpected finding from the phase III parotid sparing radiotherapy trial, PARSPORT (ISRCTN48243537, CRUK/03/005), was a statistically significant increase in acute fatigue for those patients who were treated with intensity-modulated radiotherapy (IMRT) compared to standard conventional radiotherapy (CRT). One possible explanation was the difference in dose to central nervous system (CNS) structures due to differing beam portals. Using data from the trial, a dosimetric analysis of individual CNS structures was performed.
  
  
  METHODS
  Dosimetric and toxicity data were available for 67 patients (27 CRT, 40 IMRT). Retrospective delineation of the posterior fossa, brainstem, cerebellum, pituitary gland, pineal gland, hypothalamus, hippocampus and basal ganglia was performed. Dosimetry was reviewed using summary statistics and dose-volume atlases.
  
  
  RESULTS
  A statistically significant increase in maximum and mean doses to each structure was observed for patients who received IMRT compared to those who received CRT. Both maximum and mean doses were significantly higher for the posterior fossa, brainstem and cerebellum for the 42 patients who reported acute fatigue of Grade 2 or higher (p ≤ 0.01) compared to the 25 who did not. Dose-volume atlases of the same structures indicated that regions representing larger volumes and higher doses to each structure were consistent with a higher incidence of acute fatigue. There was no association between the dose distribution and acute fatigue for the other structures tested.
  
  
  CONCLUSIONS
  The excess fatigue reported in the IMRT arm of the trial may, at least in part, be attributed to the dose distribution to the posterior fossa, cerebellum and brainstem. Future studies that modify dose delivery to these structures may allow us to test the hypothesis that radiation-induced fatigue is avoidable.
authors.affiliation: Institute of Cancer Research, UK. sarahg@icr.ac.uk
authors.forename: Sarah L
authors.initials: SL
authors.lastname: Gulliford
authors.forename: Aisha B
authors.initials: AB
authors.lastname: Miah
authors.forename: Sinead
authors.initials: S
authors.lastname: Brennan
authors.forename: Dualta
authors.initials: D
authors.lastname: McQuaid
authors.forename: Catharine H
authors.initials: CH
authors.lastname: Clark
authors.forename: Mike
authors.initials: M
authors.lastname: Partridge
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Harrington
authors.forename: James P
authors.initials: JP
authors.lastname: Morden
authors.forename: Emma
authors.initials: E
authors.lastname: Hall
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Nutting
mesh_terms: D000368:Aged; D002490:Central Nervous System / Q000528:radiation effects; D004307:Dose-Response Relationship, Radiation; D005221:Fatigue / Q000453:epidemiology / Q000209:etiology* / Q000503:physiopathology; D005260:Female; D005500:Follow-Up Studies; D006258:Head and Neck Neoplasms / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000473:pathology; D009367:Neoplasm Staging; D010307:Parotid Neoplasms / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D011874:Radiometry / Q000379:methods; D011878:Radiotherapy / Q000009:adverse effects / Q000379:methods; D011879:Radiotherapy Dosage; D050397:Radiotherapy, Intensity-Modulated / Q000009:adverse effects* / Q000379:methods*; D018570:Risk Assessment; D015996:Survival Rate; D016896:Treatment Outcome