Blood serum proteins as biomarkers for prediction of survival, locoregional control and distant metastasis rate in radiotherapy and radio-chemotherapy for non-small cell lung cancer

Abstract

Abstract Background Several studies have documented that blood biomarkers can improve basic prognostic models in radiotherapy and radio-chemotherapy for non-small cell lung cancer. The current study evaluated the prognostic impact of six markers focusing on their utility in homogenous subsets, compared to the significance in a large heterogeneous group. Methods Blood samples of 337 patients who were referred for curative or palliative external beam thoracic radiotherapy for non-small cell lung cancer were collected. The concentration of osteopontin (OPN), vascular endothelial growth factor (VEGF), erythropoetin (EPO), high mobility group box 1 protein (HMGB1), insulin-like growth factor 1 (IGF-1) and platelet-derived growth factor (PDGF) in serum were measured by ELISA assay and the prognostic potential was assessed using univariable and multivariable survival models. Results Multivariable analysis revealed that out of several variables studied six dichotomized features: namely: cigarette smoking, lack of chemotherapy, palliative doses of radiotherapy, high OPN concentration, advanced T stage and high VEGF concentration had a highly significant (p < 0.005) and independent influence on overall survival in the group of 337 patients. In a subset of patients treated with curative radio-chemotherapy or radiotherapy (N = 148) tumor pathology, EPO concentration and VEGF concentration, significantly and independently influenced overall survival. In a subset of patients with squamous cell cancer (N = 206) OPN had a highly significant impact on overall survival. In contrast, in a subset of patients with nonsquamous histology (N = 131) only VEGF had a significant influence on survival. Conclusions Blood serum proteins appear to be clinically useful prognosticators of overall survival in radio-chemotherapy and radiotherapy for non-small cell lung cancer. In unselected heterogeneous groups, dichotomized concentrations of OPN and VEGF emerged among the strongest independent prognosticators of overall survival. VEGF and EPO concentration (dichotomized) were found to be independent prognostic factors among the patients treated with curative doses of radiotherapy. The utility of OPN as a prognostic marker appeared restricted to the patients with squamous histology.

Keywords

• Lung cancer
• Radiotherapy
• Biomarkers
• Survival
• Osteopontin
• Vascular endothelial growth factor