title: Predictive factors of late radiation fibrosis: a prospective study in non-small cell lung cancer.
abstract: OBJECTIVE
  To determine predictive factors of late radiation fibrosis (RF) after conformal radiotherapy (3D-RT) in non-small cell lung cancer (NSCLC).
  
  
  METHODS
  Ninety-six patients with Stage IA-IIIB NSCLC were included in a prospective trial. Clinical evaluation, chest X-ray, and pulmonary functional tests including diffusion parameters were performed before and 6 months after radiotherapy. An independent panel of experts prospectively analyzed RF, using Late Effects in Normal Tissues-Subjective, Objective, Management and Analytic scales classification. Logistic regression analysis was performed to identify relationships between clinical, functional, or treatment parameters and incidence of RF. Variations of circulating serum levels of pro-inflammatory (interleukin-6, tumor necrosis factor alpha, tumor growth factor beta1) and anti-inflammatory (interleukin-10) cytokines during 3D-RT were examined to identify correlations with RF.
  
  
  RESULTS
  Of the 96 patients included, 72 were evaluable for RF at 6 months. Thirty-seven (51.4%) developed RF (Grade >or=1), including six severe RF (Grades 2-3; 8.3%). In univariate analysis, only poor Karnofsky Performance Status and previous acute radiation pneumonitis were associated with RF (p < 0.05). Dosimetric factors (mean lung dose, percentage of lung volume receiving more than 10, 20, 30, 40, and 50 Gy) were highly correlated with RF (p < 0.001). In multivariate analysis, previous acute radiation pneumonitis and dosimetric parameters were significantly correlated with RF occurrence. It was not significantly correlated either with cytokines at baseline or with their variation during 3D-RT.
  
  
  CONCLUSIONS
  This study confirms the importance of dosimetric parameters to limit the risk of RF. Contrary to acute radiation pneumonitis, RF was not correlated to cytokine variations during 3D-RT.
authors.affiliation: University of Lyon, Centre Léon Bérard, Department of Radiation Oncology, Lyon, France.
authors.forename: Renaud
authors.initials: R
authors.lastname: Mazeron
authors.forename: Bénédicte
authors.initials: B
authors.lastname: Etienne-Mastroianni
authors.forename: David
authors.initials: D
authors.lastname: Pérol
authors.forename: Dominique
authors.initials: D
authors.lastname: Arpin
authors.forename: Michel
authors.initials: M
authors.lastname: Vincent
authors.forename: Lionel
authors.initials: L
authors.lastname: Falchero
authors.forename: Isabelle
authors.initials: I
authors.lastname: Martel-Lafay
authors.forename: Christian
authors.initials: C
authors.lastname: Carrie
authors.forename: Line
authors.initials: L
authors.lastname: Claude
mesh_terms: D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D015415:Biomarkers / Q000097:blood; D002289:Carcinoma, Non-Small-Cell Lung / Q000473:pathology / Q000532:radiotherapy*; D005260:Female; D006801:Humans; D016753:Interleukin-10 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D017567:Karnofsky Performance Status; D016015:Logistic Models; D008175:Lung Neoplasms / Q000473:pathology / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D017564:Radiation Pneumonitis / Q000097:blood / Q000209:etiology* / Q000473:pathology / Q000517:prevention & control; D011879:Radiotherapy Dosage; D020266:Radiotherapy, Conformal / Q000009:adverse effects* / Q000379:methods; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D015415:Biomarkers; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10