title: Prognostic value of blood-biomarkers related to hypoxia, inflammation, immune response and tumour load in non-small cell lung cancer - A survival model with external validation.
abstract: Improve the prognostic prediction of clinical variables for non-small cell lung cancer (NSCLC), by selecting from blood-biomarkers, non-invasively describing hypoxia, inflammation and tumour load.
  
  
  
  Model development and validation included 182 and 181 inoperable stage I-IIIB NSCLC patients treated radically with radiotherapy (55.2%) or chemo-radiotherapy (44.8%). Least absolute shrinkage and selection operator (LASSO), selected from blood-biomarkers related to hypoxia [osteopontin (OPN) and carbonic anhydrase IX (CA-IX)], inflammation [interleukin-6 (IL-6), IL-8, and C-reactive protein (CRP)], and tumour load [carcinoembryonic antigen (CEA), and cytokeratin fragment 21-1 (Cyfra 21-1)]. Sequent model extension selected from alpha-2-macroglobulin (α2M), serum interleukin-2 receptor (sIL2r), toll-like receptor 4 (TLR4), and vascular endothelial growth factor (VEGF). Discrimination was reported by concordance-index.
  
  
  
  OPN and Cyfra 21-1 (hazard ratios of 3.3 and 1.7) significantly improved a clinical model comprising gender, World Health Organization performance-status, forced expiratory volume in 1s, number of positive lymph node stations, and gross tumour volume, from a concordance-index of 0.66 to 0.70 (validation=0.62 and 0.66). Extension of the validated model yielded a concordance-index of 0.67, including α2M, sIL2r and VEGF (hazard ratios of 4.6, 3.1, and 1.4).
  
  
  
  Improvement of a clinical model including hypoxia and tumour load blood-biomarkers was validated. New immunological markers were associated with overall survival. Data and models can be found at www.cancerdata.org (http://dx.doi.org/10.17195/candat.2016.04.1) and www.predictcancer.org.
authors.affiliation: Department of Radiation Oncology (MAASTRO), GROW - School for Oncology and Developmental Biology, Maastricht University Medical Center (MUMC+), The Netherlands. Electronic address: sara.carvalho@maastro.nl.
authors.forename: Sara
authors.initials: S
authors.lastname: Carvalho
authors.affiliation: Department of Radiation Oncology (MAASTRO), GROW - School for Oncology and Developmental Biology, Maastricht University Medical Center (MUMC+), The Netherlands; Institute of Radiooncology, Helmholtz Zentrum Dresden-Rossendorf, Germany; OncoRay, National Center for Radiation Research in Oncology, Dresden, Germany; Department of Radiooncology, Universitätsklinik Carl Gustav Carus der Technischen Universität Dresden, Germany.
authors.forename: Esther G C
authors.initials: EG
authors.lastname: Troost
authors.affiliation: Central Diagnostic Laboratory, Laboratory for Immunodiagnostics, Maastricht University Medical Centre, Maastricht, The Netherlands.
authors.forename: Judith
authors.initials: J
authors.lastname: Bons
authors.affiliation: Central Diagnostic Laboratory, Laboratory for Immunodiagnostics, Maastricht University Medical Centre, Maastricht, The Netherlands.
authors.forename: Paul
authors.initials: P
authors.lastname: Menheere
authors.affiliation: Department of Radiation Oncology (MAASTRO), GROW - School for Oncology and Developmental Biology, Maastricht University Medical Center (MUMC+), The Netherlands.
authors.forename: Philippe
authors.initials: P
authors.lastname: Lambin
authors.affiliation: Department of Radiation Oncology (MAASTRO), GROW - School for Oncology and Developmental Biology, Maastricht University Medical Center (MUMC+), The Netherlands.
authors.forename: Cary
authors.initials: C
authors.lastname: Oberije
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000097:blood; D014408:Biomarkers, Tumor / Q000097:blood*; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood / Q000401:mortality*; D015687:Cell Hypoxia; D005260:Female; D006801:Humans; D007249:Inflammation / Q000097:blood*; D053539:Keratin-19 / Q000097:blood; D008175:Lung Neoplasms / Q000097:blood / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D053495:Osteopontin / Q000097:blood; D011379:Prognosis; D047368:Tumor Burden
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D053539:Keratin-19; C102012:antigen CYFRA21.1; D053495:Osteopontin
keywords: Blood-biomarkers; NSCLC; Prognostic model