title: Thrombin generation as a predictor of radiotherapy induced skin erythema.
abstract: OBJECTIVE
  Biological mechanisms underlying radiation induced erythema remain largely unknown, with no simple way to accurately predict or prevent extreme cases. Based on the recent findings in patients suffering from chronic urticaria, we sought to determine if similar mechanisms of hypercoagulation contributed to comparable skin reactions during radiotherapy.
  
  
  METHODS
  Plasma levels of prothrombin factor 1+2 (F1+2), D-dimers and plasminogen activator inhibitor-1 (Pai-1) were tested in 32 women undergoing irradiation following breast conserving surgery for early breast cancer. Reflectance spectrophotometry was used to objectively assess erythema throughout the treatment by measuring the amount of light reflected from the skin surface as a function of wavelength. Correlations between peak levels of erythema and plasma biomarkers were then assessed.
  
  
  RESULTS
  Individual peak reflectance readings generally occurred between day 29 of treatment and 2 weeks post radiotherapy, and represented a median increase of 66% (range: 11-146%; p<0.001) from baseline. Peak reflectance correlated with F1+2 and Pai-1 levels measured both at baseline and day 29 of treatment, and multivariate analysis indicated that these two baseline measurements were the best predictors of peak reflectance, accounting for 59% of the variability in erythema (p=0.000004).
  
  
  CONCLUSIONS
  Patients with signs of intravascular thrombin generation are at higher risk of radiotherapy-induced skin reactions, providing a new therapeutic avenue for possibly predicting and preventing this side effect of cancer treatment.
authors.affiliation: Department of Haematology, Calvary Mater Newcastle, NSW, Australia. Lisa.Lincz@newcastle.edu.au
authors.forename: Lisa F
authors.initials: LF
authors.lastname: Lincz
authors.forename: Sanjiv A
authors.initials: SA
authors.lastname: Gupta
authors.forename: Christopher R
authors.initials: CR
authors.lastname: Wratten
authors.forename: Janice
authors.initials: J
authors.lastname: Kilmurray
authors.forename: Sharon
authors.initials: S
authors.lastname: Nash
authors.forename: Michael
authors.initials: M
authors.lastname: Seldon
authors.forename: Peter C
authors.initials: PC
authors.lastname: O'Brien
authors.forename: Katy J L
authors.initials: KJ
authors.lastname: Bell
authors.forename: James W
authors.initials: JW
authors.lastname: Denham
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D001943:Breast Neoplasms / Q000097:blood* / Q000532:radiotherapy* / Q000601:surgery; D004797:Enzyme-Linked Immunosorbent Assay; D004890:Erythema / Q000209:etiology*; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism*; D006801:Humans; D008875:Middle Aged; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood*; D011516:Prothrombin / Q000378:metabolism*; D012044:Regression Analysis; D012307:Risk Factors; D012867:Skin / Q000528:radiation effects*; D018709:Statistics, Nonparametric
chemical_list: D015415:Biomarkers; D005338:Fibrin Fibrinogen Degradation Products; D017395:Plasminogen Activator Inhibitor 1; C036309:fibrin fragment D; D011516:Prothrombin