Journal
RADIOTHERAPY AND ONCOLOGY
Volume 119, Issue 3, Pages 487-494Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.radonc.2016.04.024
Keywords
Prognostic model; Blood-biomarkers; NSCLC
Funding
- QuIC-ConCePT project - EFPIA companies
- Innovative Medicine Initiative Joint Undertaking (IMIJU) [115151]
- Dutch technology Foundation STW, applied science division of NWO [10696 DuCAT]
- Technology Programme of the Ministry of Economic Affairs
- CTMM framework (AIRFORCE project) [030-103]
- EU [257144, 601826]
- SME Phase 2 (EU proposal) [673780 - RAIL]
- Kankeronderzoekfonds Limburg from the Health Foundation Limburg
- Dutch Cancer Society [KWF UM 2008-4210, KWF UM 2009-4454]
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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 (alpha 2M), 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 1 s, 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 alpha 2M, 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. (C) 2016 The Authors. Published by Elsevier Ireland Ltd.
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