title: Variations of circulating endothelial progenitor cells and transforming growth factor-beta-1 (TGF-β1) during thoracic radiotherapy are predictive for radiation pneumonitis.
abstract: BACKGROUND
  The vascular endothelial cells are important targets of radiotherapy, which may be involved in the pathogenesis of radiation pneumonitis (RP). This study investigated the variations of circulating endothelial progenitor cells (EPCs) and transforming growth factor-beta-1 (TGF-β1) during three-dimensional conformal radiation therapy (3D-CRT) in patients with non-small-cell lung cancer (NSCLC) and analyzed the correlation between these variations with the occurrence of RP.
  
  
  METHODS
  From November 2008 to November 2009, eighty-four consecutive patients receiving 3D-CRT for stage III disease were evaluated prospectively. Circulating EPCs and TGF-β1 levels were measured at baseline, every 2 weeks during, and at the end of treatment. RP was evaluated prospectively at 6 weeks after 3D-CRT.
  
  
  RESULTS
  Thirty-eight patients (47.5%) experienced score 1 or more of RP. The baseline levels of EPCs and TGF-β1 were analyzed, no difference was found between patients with and without RP during and after 3D-CRT. By serial measurement of TGF-β1 and EPCs levels, we found that the mean levels of EPCs in the whole population remained stable during radiotherapy, but the mean levels of TGF-β1 increased slowly during radiotherapy. TGF-β1 and EPCs levels were all significantly higher at week 2, week 4 and week 6 in patients with RP than that in patients without RP, respectively. During the period of radiation treatment, TGF-β1 levels began to increase in the first 2 weeks and became significantly higher at week 6 (P < 0.01). EPCs levels also began to increase in the first 2 weeks and reached a peak at week 4. Using an ANOVA model for repeated-measures, we found significant associations between the levels of TGF-β1 and EPCs during the course of 3D-CRT and the risk of developing RP (P < 0.01). Most of the dosimetric factors showed a significant association with RP.
  
  
  CONCLUSIONS
  Early variations of TGF-β1 and EPCs levels during 3D-CRT are significantly associated with the risk of RP. Variations of circulating TGF-β1 and EPCs levels during 3D-CRT may serve as independent predictive factors for RP.
  
  
  BACKGROUND
  Trials registration number: 20070618.
authors.affiliation: Department of Radiotherapy, Capital Medical University Affiliated Beijing Chao- yang Hospital, Beijing 100020, China. huiming740512@126.com.
authors.forename: Yunfang
authors.initials: Y
authors.lastname: Liu
authors.forename: Tingyi
authors.initials: T
authors.lastname: Xia
authors.forename: Wenjun
authors.initials: W
authors.lastname: Zhang
authors.forename: Yongjie
authors.initials: Y
authors.lastname: Zhong
authors.forename: Luhua
authors.initials: L
authors.lastname: Zhang
authors.forename: Xuan
authors.initials: X
authors.lastname: Wang
authors.forename: Huiming
authors.initials: H
authors.lastname: Yu
mesh_terms: D000328:Adult; D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood / Q000532:radiotherapy*; D002465:Cell Movement; D066026:Endothelial Progenitor Cells / Q000166:cytology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008175:Lung Neoplasms / Q000097:blood / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D017564:Radiation Pneumonitis / Q000097:blood*; D020266:Radiotherapy, Conformal / Q000009:adverse effects; D053773:Transforming Growth Factor beta1 / Q000097:blood*
chemical_list: D053773:Transforming Growth Factor beta1