Abstract 4650: From bench to bedside: are cytokines still relevant biomarkers for staging cancer cachexia.

Abstract Background: We have provided initial evidence1 on the clinical usefulness of the cancer cachexia stages (CCS) proposed by Fearon et al2. However it is still unclear3 if particular molecular phenotypes are also associated with these stages, as well with relevant clinical outcomes. Methods: A candidate list of cytokines (Activin A, Eotaxin, FGF, G-CSF, GDF15, GM-CSF, IFN-g, IL-10, IL-12_p70, IL-13, IL-15, IL-17, IL-1b, IL-1ra, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IP-10, MCP-1_MCAF, MIP-1a, MIP-1b, PDGF-bb, RANTES, TNF-a, VEGF) was measured in 210 blood samples from patients with advanced lung and gastrointestinal cancers, via Luminex and ELISA methods. Non-parametric t-test, Kaplan-Meier and Kruskal-Wallis analyses were used to test the association between cytokines levels with CCS, Patient-Generated Subjective Global Assessment scores (PG-SGA) and survival. Results: Using non-cachectic patients as controls, Activin A and GDF15 were significantly up-regulated in pre-cachectic (p<0.01), cachectic (p<0.05) and refractory cachectic (p<0.001) patients. IL-6, IL-8 and VEGFa were significantly up-regulated only in refractory cachectic (p<0.001) patients. Activin A (p<0.001), GDF15 (p<0.001) and IL-8 (P<0.001) plasma levels correlated with PG-SGA. Quartiles of GDF15 plasma levels identified better survival curves as compared to Activin A, IL-6 and IL-8 quartiles. Conclusions: Activin A and GDF15 appear to be useful aids for the diagnosis of all cachexia stages in advanced cancer. Because of their correlation with nutritional and survival outcomes, these cytokines may also represent useful targets in the development of new compounds for the treatment of cancer cachexia. 1. Vigano A, Del Fabbro E, Bruera E, Borod M. The cachexia clinic: from staging to managing nutritional and functional problems in advancer cancer patients. Critical Reviews in Oncogenesis, 2012 17(3), 293-304 2. Fearon K,Strasser F,Anker SD,Bosaeus I,Bruera E,Fainsinger RL,Jatoi A, Loprinzi C, MacDonald N, Mantovani G, Davis M, Muscaritoli M, Ottery F, Radbruch L, Ravasco P, Walsh D, Wilcock A, Kaasa S, Baracos VE. Definition and classification of cancer cachexia: an international consensus. Lancet Oncol. 2011; 12:489-495. 3. Scheede-Bergdahl, C., Watt, H.L., Trutschnigg, B., Kilgour, R.D., Haggarty, A., Lucar, E., Vigano, A. 2011. Is IL-6 the best pro-inflammatory biomarker of clinical outcomes of cancer cachexia? Clinical Nutrition 31: 85-8. Citation Format: Antonio Vigano, Lorena Lerner, Nianjun Tao, Brian Krieger, Bin Feng, Richard Nicoletti, Qing Liu, Ailin Bai, Zhigang Weng, Thierry Alcindor, Domenico Fuoco, Jeno Gyuris, Maria Isabel Chiu. From bench to bedside: are cytokines still relevant biomarkers for staging cancer cachexia. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4650. doi:10.1158/1538-7445.AM2013-4650