title: A pilot study on potential plasma hypoxia markers in the radiotherapy of non-small cell lung cancer. Osteopontin, carbonic anhydrase IX and vascular endothelial growth factor.
abstract: BACKGROUND
  Hypoxic radioresistance plays a critical role in the radiotherapy of cancer and adversely impacts prognosis and treatment response. This prospective study investigated the interrelationship and the prognostic significance of several hypoxia-related proteins in non-small cell lung cancer (NSCLC) patients treated by radiotherapy ± chemotherapy.
  
  
  METHODS
  Pretreatment osteopontin (OPN), vascular endothelial growth factor (VEGF) and carbonic anhydrase IX (CA IX) plasma levels were determined by ELISA in 55 NSCLC (M0) patients receiving 66 Gy curative-intent radiotherapy or chemoradiation. Marker correlation, association with clinicopathological parameters and the prognostic value of a biomarker combination was evaluated.
  
  
  RESULTS
  All biomarkers were linearly correlated and linked to different clinical parameters including lung function, weight loss (OPN), gross tumor volume (VEGF) and T stage (CA IX). High OPN (p = 0.03), VEGF (p = 0.02) and CA IX (p = 0.04) values were significantly associated with poor survival. Double marker combination additively increased the risk of death by a factor of 2 and high plasma levels of the triple combination OPN/VEGF/CA IX yielded a 5.9-fold risk of death (p = 0.009). The combined assessment of OPN/VEGF/CA IX correlated independently with prognosis (p = 0.03) in a multivariate Cox regression model including N stage, T stage and GTV.
  
  
  CONCLUSIONS
  This pilot study suggests that a co-detection augments the prognostic value of single markers and that the integration of OPN, VEGF and CA IX into a hypoxic biomarker profile for the identification of patients with largely hypoxic and radioresistant tumors should be further evaluated.
authors: Department of Radiation Oncology, Martin-Luther-University Halle-Wittenberg, Dryanderstr. 4, 06110, Halle (Saale), Germany, Christian.Ostheimer@uk-halle.de.
authors: C
authors: C
authors: Ostheimer
authors: M
authors: M
authors: Bache
authors: A
authors: A
authors: Güttler
authors: M
authors: M
authors: Kotzsch
authors: D
authors: D
authors: Vordermark
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000097:blood*; D014408:Biomarkers, Tumor / Q000097:blood*; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases / Q000097:blood*; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood* / Q000401:mortality / Q000532:radiotherapy*; D019583:Dose Fractionation, Radiation; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D000860:Hypoxia / Q000097:blood*; D008175:Lung Neoplasms / Q000097:blood* / Q000401:mortality / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging / Q000401:mortality; D053495:Osteopontin / Q000097:blood*; D010865:Pilot Projects; D011379:Prognosis; D011836:Radiation Tolerance; D013223:Statistics as Topic; D015996:Survival Rate; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000097:blood*
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D042461:Vascular Endothelial Growth Factor A; D053495:Osteopontin; C089226:CA9 protein, human; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases