Abstract 4669: Circulating cytokines as biomarkers of BEP toxicity in TGCTs patients
Authors: Svetlovska Daniela , Miskovska Viera , Cholujova Dana , Gronesova Paulina , Cingelova Silvia , Chovanec Michal , Sycova-Mila Zuzana , Obertova Jana , Palacka Patrik , Usakova Vanda , Kalavska Katarina , Luha Jan , Ondrus Dalibor , Spanik Stanislav , Mardiak Jozef , Mego Michal 
Published: July 2017

Abstract
Background: Cytokines are key components in process of inflammation and immune response, what are important processes in many toxicities. Bleomycin, etoposide, cisplatinum (BEP) is a standard treatment in patients with testicular germ cell tumors (TGCTs). Grade 3/4 toxicity can be dose limiting and can highly influence patient’s quality of life. Our aim was to investigate correlation between circulating cytokines and BEP toxicity in TGCTs patients.
Methods: The study population consisted of chemonaive TGCTs patients treated by BEP chemotherapy. Grade 3 and 4 toxicities were assessed according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 after first cycle of chemotherapy. G-CSF was administered to all patients after chemotherapy. Circulating 51 plasma cytokines were analyzed at baseline before chemotherapy administration (94 patients) and on cycle 1 day 22 (57 patients) using multiplex bead arrays. Toxicities were correlated to pretreatment and also postreatment levels of circulating cytokines. Spearman's correlation test was used to analyze the association between cytokines and toxicity.
Results: Significant correlations between grade 3/4 toxicity and cytokines were observed. Neutropenia was associated with elevated pretreatment levels of TGF-beta 2, IL-2R alpha, HGF, MIG, NGF-beta, SDF-1 alpha, IL-1beta, IL-4, IL-5, IL-17, FGF-basic, G-CSF, MIP-1 alpha and postreatment elevated levels of GRO-alpha, TNF-beta. Thrombocytopenia related with higher pretreatment levels of IL-2R alpha, IL-18, M-CSF and higher postreatment IL-3, IL-12p40, GRO-alpha, MCP-3, M-CSF, MIF, NGF -beta. Anemia correlated with elevated pretreatment IL-16, GRO-alpha, HGF, MIF, NGF-beta, SCF, SCGF-beta, MCP-1-MCAF and elevated postreatment levels of IL-16, HGF, M-CSF, SCGF-beta. There were many positive associations between pyelonephritis and pretreatment IL-2R alpha, IL-18, M-CSF, NGF-beta and postreatment IL-2R alpha, IL-3, IL12p40, CTACK, HGF, MCP-3, M-CSF, NGF-beta, SCGF-beta, IL-6. Diarrhea related with higher pretreatment levels of IL-15 and also higher postreatment IL-15, GM-CSF and lower postreatment levels of IFN-alpha, CTACK. Several other associations were detected between elevated postreatment levels of cytokines and toxicities: nausea and SCGF-beta, febrile neutropenia and GRO-alpha, TNF-beta, SIRS and GRO-alpha, PDGF-BB. All correlations were significant P &lt;0.05.
Conclusions: Circulating cytokines are promising and easily detectable biomarker for predicting BEP toxicity in TGCTs patients. This work was supported by the Slovak Research and Development Agency under the contracts No. APVV-0016-11 and APVV-15-0086.
Citation Format: Daniela Svetlovska, Viera Miskovska, Dana Cholujova, Paulina Gronesova, Silvia Cingelova, Michal Chovanec, Zuzana Sycova-Mila, Jana Obertova, Patrik Palacka, Vanda Usakova, Katarina Kalavska, Jan Luha, Dalibor Ondrus, Stanislav Spanik, Jozef Mardiak, Michal Mego. Circulating cytokines as biomarkers of BEP toxicity in TGCTs patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4669. doi:10.1158/1538-7445.AM2017-4669