title: TGF-beta1 in serum and induced sputum for predicting radiation pneumonitis in patients with non-small cell lung cancer after radiotherapy.
abstract: OBJECTIVE
  Research has confirmed that transforming growth factor-beta1 (TGF-beta1) is one of the cytokines related to radiation pneumonitis. But the level of TGF-beta1 in serum needed to predict radiation pneumonitis is still not clear. This study assessed the value of TGF-beta1 in both serum and induced sputum in predicting radiation pneumonitis, providing a reference for the radiotherapy of patients with non-small cell lung cancer (NSCLC).
  
  
  METHODS
  A total of 23 patients with NSCLC treated with three-dimensional conformal radiotherapy (3D-CRT) or intensity-modulated radiation therapy (IMRT) in our department between November 2007 and January 2009 were analyzed and evaluated. TGF-beta1 levels in both serum and sputum were detected before and near the end of radiotherapy for all the patients. The TGF-beta1 level in serum was measured with enzyme-linked immunosorbent assay (ELISA). Immunocytochemistry assays were used to detect TGF-beta1 expression in sputum sediment. Radiation pneumonitis was graded according to Radiation Therapy Oncology Group (RTOG) radiation scoring criteria every 3 weeks from the start to 3 months after the end of treatment.
  
  
  RESULTS
  Radiation pneumonitis was noted in 9 patients in this cohort. The total incidence of radiation pneumonitis was 39.1% (9/23) and those with Grade II or worse was 30.4% (7/23). The absolute TGF-beta1 level in serum after radiotherapy was higher than before radiotherapy, but there was no statistical difference (P = 0.139). Patients with increased levels of TGF-beta1 had a higher incidence of radiation pneumonitis (45.5%) than those with decreased TGF-beta1 levels post-radiotherapy (40.0%). Though there was a tendency of higher incidence of radiation pneumonitis with increases in TGF-beta1 level, no statistical difference was found (P = 1.000). Patients with tumor response had higher incidence of radiation pneumonitis (50.0%) than patients without when TGF-beta1 levels in serum increased, but there was no statistical difference (P = 0.792). TGF-beta1 was positively expressed (brown yellow) in sputum on immunocytochemistry assays and located in the cytoplasm of either macrophages or epithelial cells. Macrophages were the main cells expressing TGF-beta1. A significantly higher positive expression rate (71.4%) was found in sputum post-radiotherapy than pre-radiotherapy (28.6%) (P = 0.015). The higher incidence of radiation pneumonitis (46.7%) was found in patients with positive TGF-beta1 expression in sputum post-radiotherapy than those with negative expression post-radiotherapy (14.3%) (P = 0.193).
  
  
  CONCLUSIONS
  It may be more reasonable to predict radiation pneumonitis by combining the change of TGF-beta1 levels in serum with tumor response than just the change of TGF-beta1 levels in serum alone. TGF-beta1 can positively express in the sputum of patients with NSCLC, located in macrophages and epithelial cells, with macrophages as the main areas of expression. Patients with positively expressed TGF-beta1 in sputum after radiotherapy have a higher incidence of radiation pneumonitis than those with negative expressions. The positive expression of TGF-beta1 in sputum is expected to become a factor for predicting radiation pneumonitis.
authors.affiliation: Department of Radiation Oncology, Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, P. R. China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.forename: Xue-Ying
authors.initials: XY
authors.lastname: Qiao
authors.forename: Fu-He
authors.initials: FH
authors.lastname: Lu
authors.forename: Zhi-Guo
authors.initials: ZG
authors.lastname: Zhou
authors.forename: Yu-Zhi
authors.initials: YZ
authors.lastname: Song
authors.forename: Jun-Jie
authors.initials: JJ
authors.lastname: Huo
authors.forename: Xin
authors.initials: X
authors.lastname: Liu
mesh_terms: D000328:Adult; D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood / Q000378:metabolism / Q000532:radiotherapy*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008175:Lung Neoplasms / Q000097:blood / Q000378:metabolism / Q000532:radiotherapy*; D008264:Macrophages / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D017564:Radiation Pneumonitis / Q000097:blood / Q000209:etiology* / Q000378:metabolism; D020266:Radiotherapy, Conformal / Q000009:adverse effects; D050397:Radiotherapy, Intensity-Modulated / Q000009:adverse effects; D013183:Sputum / Q000737:chemistry*; D053773:Transforming Growth Factor beta1 / Q000097:blood / Q000378:metabolism*
chemical_list: D053773:Transforming Growth Factor beta1