title: Prognostic information of serial plasma osteopontin measurement in radiotherapy of non-small-cell lung cancer.
abstract: BACKGROUND
  Circulating baseline levels of the plasma-protein osteopontin (OPN) have been suggested as a prognostic indicator in chemotherapy and surgery for lung cancer. However, the role of this hypoxia-related protein in radiotherapy of lung cancer is unclear. We previously demonstrated the prognostic effect of baseline OPN plasma levels which was increased by co-detection with other hypoxia-related proteins in the radical radiotherapy of non-small-cell lung cancer (NSCLC). This prospective clinical study investigated whether serial OPN measurements during and after curative-intent radiotherapy for NSCLC provide additional or superior prognostic information.
  
  
  METHODS
  Sixty-nine patients with inoperable NSCLC were prospectively enrolled (55 M0, 14 M1). OPN plasma levels were measured before (t0), at the end (t1) and four weeks after radiotherapy (t2) by ELISA, compared between M0 and M1 patients and correlated with clinicopathological parameters. OPN levels were monitored over time and correlated with prognosis in M0-stage patients treated by radical 66-Gy radiotherapy ± chemotherapy.
  
  
  RESULTS
  Pre-treatment OPN levels were associated with T stage (p = .03), lung function (p = .002), weight loss (p = .01), tumor volume (p = .02) and hemoglobin concentration (p = 04). M1 patients had significantly elevated OPN levels at all time points (p < .001). Patients with increasing OPN levels after radiotherapy had inferior freedom from relapse (p = .008), overall survival (p = .004) and disease-free survival (p = .001) compared to patients with stable or decreasing OPN levels. The risk of relapse in patients with increasing or stable OPN levels after radiotherapy was increased by a factor of 2.9 (p = .01). Patients with increasing post-treatment OPN levels had a 3.1-fold increased risk of death (p = .003). In an exploratory multivariate model, post-treatment OPN level changes but not absolute baseline OPN levels remained an independent prognostic factor for overall survival (p = .002) with a 3.6-fold increased risk of death, as well as N stage (p = .006).
  
  
  CONCLUSIONS
  Our results suggest that OPN level changes over time, particularly post-treatment, may yield additional prognostic information in curative-intent radiotherapy of NSCLC.
authors.affiliation: Department of Radiation Oncology, Martin Luther University Halle-Wittenberg, Klinik und Poliklinik für Strahlentherapie, Martin Luther Universitaet Halle-Wittenberg, Ernst-Grube-Strasse 40, 06097 Halle (Saale), Germany. Christian.Ostheimer@uk-halle.de.
authors.forename: Christian
authors.initials: C
authors.lastname: Ostheimer
authors.forename: Matthias
authors.initials: M
authors.lastname: Bache
authors.forename: Antje
authors.initials: A
authors.lastname: Güttler
authors.forename: Thomas
authors.initials: T
authors.lastname: Reese
authors.forename: Dirk
authors.initials: D
authors.lastname: Vordermark
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood* / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000097:blood* / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D053495:Osteopontin / Q000097:blood*; D011379:Prognosis; D012307:Risk Factors; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D053495:Osteopontin