title: Cytokine levels as biomarkers of radiation fibrosis in patients treated with breast radiotherapy.
abstract: BACKGROUND
  Radiation fibrosis is not easily measurable although clinical scores have been developed for this purpose. Biomarkers present an alternative more objective approach to quantification, and estimation in blood provides accessible samples. We investigated if blood cytokines could be used to measure established fibrosis in patients who have undergone radiotherapy for breast cancer.
  
  
  METHODS
  We studied two cohorts treated by breast-conserving surgery and radiotherapy in the UK START Trial A, one with breast fibrosis (cases) and one with no or minimal fibrosis (controls). Two candidate cytokines, plasma connective tissue growth factor (CTGF) and serum interleukin-6 (IL6) were estimated by ELISA. Comparisons between cases and controls used the t-test or Mann-Whitney test and associations between blood concentration and clinical factors were assessed using the Spearman rank correlation coefficient.
  
  
  RESULTS
  Seventy patients were included (26 cases, 44 controls). Mean time since radiotherapy was 9.9 years (range 8.3-12.0). No statistically significant differences between cases and controls in serum IL6 (median (IQR) 0.84 pg/ml (0.57-1.14), 0.75 pg/ml (0.41-1.43) respectively) or plasma CTGF (331.4 pg/ml (234.8-602.9), 334.5 pg/ml (270.0-452.8) were identified. There were no significant associations between blood cytokine concentration and age, fibrosis severity, breast size or time since radiotherapy.
  
  
  CONCLUSIONS
  No significant difference in IL6 or CTGF concentrations was detected between patients with breast fibrosis and controls with minimal or no fibrosis.
authors.affiliation: Department of Oncology, UCL Cancer Institute, University College London, London, UK. charlotte.westbury@thh.nhs.uk.
authors.forename: Charlotte B
authors.initials: CB
authors.lastname: Westbury
authors.forename: Joanne
authors.initials: J
authors.lastname: Haviland
authors.forename: Sue
authors.initials: S
authors.lastname: Davies
authors.forename: Lone
authors.initials: L
authors.lastname: Gothard
authors.forename: Bahja Ahmed
authors.initials: BA
authors.lastname: Abdi
authors.forename: Mark
authors.initials: M
authors.lastname: Sydenham
authors.forename: Jo
authors.initials: J
authors.lastname: Bowen
authors.forename: Richard
authors.initials: R
authors.lastname: Stratton
authors.forename: Susan C
authors.initials: SC
authors.lastname: Short
authors.forename: John R
authors.initials: JR
authors.lastname: Yarnold
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood*; D001943:Breast Neoplasms / Q000097:blood / Q000150:complications / Q000532:radiotherapy*; D016022:Case-Control Studies; D003131:Combined Modality Therapy; D055513:Connective Tissue Growth Factor / Q000097:blood*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015850:Interleukin-6 / Q000097:blood*; D015412:Mastectomy, Segmental; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D011446:Prospective Studies; D017564:Radiation Pneumonitis / Q000097:blood / Q000175:diagnosis* / Q000209:etiology; D011879:Radiotherapy Dosage
chemical_list: D014408:Biomarkers, Tumor; C526317:CCN2 protein, human; D015850:Interleukin-6; D055513:Connective Tissue Growth Factor