Sara Carvalho1, Esther G C Troost2, Judith Bons3, Paul Menheere3, Philippe Lambin4, Cary Oberije4. 1. 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. 2. 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. 3. Central Diagnostic Laboratory, Laboratory for Immunodiagnostics, Maastricht University Medical Centre, Maastricht, The Netherlands. 4. Department of Radiation Oncology (MAASTRO), GROW - School for Oncology and Developmental Biology, Maastricht University Medical Center (MUMC+), The Netherlands.
Abstract
AIM: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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.
AIM: 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. METHODS: Model development and validation included 182 and 181 inoperable stage I-IIIB NSCLCpatients 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. RESULTS: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). CONCLUSION: 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.
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