Daniela Svetlovska1, Viera Miskovska2, Dana Cholujova3, Paulina Gronesova3, Silvia Cingelova4, Michal Chovanec5, Zuzana Sycova-Mila6, Jana Obertova5, Patrik Palacka5, Jan Rajec5, Katarina Kalavska7, Vanda Usakova8, Jan Luha9, Dalibor Ondrus2, Stanislav Spanik10, Jozef Mardiak5, Michal Mego11. 1. Translational Research Unit, Comenius University, Faculty of Medicine, Bratislava, Slovakia; Department of Clinical Trials, National Cancer Institute, Bratislava, Slovakia. 2. 1st Department of Oncology, Comenius University, Faculty of Medicine and St. Elisabeth Cancer Institute, Bratislava, Slovakia. 3. Cancer Research Institute, Biomedical Center, Slovak Academy of Sciences, Bratislava, Slovakia. 4. Oncohematology Clinic, National Cancer Institute, Bratislava, Slovakia. 5. 2nd Department of Oncology, Comenius University, Faculty of Medicine and National Cancer Institute, Bratislava, Slovakia; Clinic of Clinical Oncology, National Cancer Institute, Bratislava, Slovakia. 6. Clinic of Clinical Oncology, National Cancer Institute, Bratislava, Slovakia. 7. Translational Research Unit, Comenius University, Faculty of Medicine, Bratislava, Slovakia. 8. Department of Medical Oncology of St. Elizabeth University of Health and Social Sciences and St. Elisabeth Cancer Institute, Bratislava, Slovakia. 9. Institute of Medical Biology, Genetics and Clinical Genetics, Comenius University, Faculty of Medicine, Bratislava, Slovakia. 10. 1st Department of Oncology, Comenius University, Faculty of Medicine and St. Elisabeth Cancer Institute, Bratislava, Slovakia; Department of Medical Oncology of St. Elizabeth University of Health and Social Sciences and St. Elisabeth Cancer Institute, Bratislava, Slovakia. 11. Translational Research Unit, Comenius University, Faculty of Medicine, Bratislava, Slovakia; 2nd Department of Oncology, Comenius University, Faculty of Medicine and National Cancer Institute, Bratislava, Slovakia; Clinic of Clinical Oncology, National Cancer Institute, Bratislava, Slovakia. Electronic address: misomego@gmail.com.
Abstract
BACKGROUND: Cytokines are the communicators of immune system and are involved in all immune responses. The aim of this study was to assess the correlation among plasma cytokines, patient and tumor characteristics, and clinical outcome in chemonaive testicular germ-cell tumor (TGCT) patients. PATIENTS AND METHODS: This study included 92 metastatic chemotherapy-naive TGCT patients treated with platinum-based chemotherapy from July 2010 to March 2014. Plasma was isolated before first administration of chemotherapy, and the concentration of 51 plasma cytokines were analyzed using multiplex bead arrays. RESULTS: At a median follow-up of 33.2 months (range, 0.1-54.8 months), 10.9% of patients experienced disease progression, and 7.6% died. Several cytokines were associated with different baseline clinicopathologic features. Elevated plasma levels of interferon (IFN)-α2, interleukin (IL)-2Rα, IL-16, hepatocyte growth factor (HGF), and monocyte chemotactic protein (MCP)-3 were significantly associated with worse progression-free survival and overall survival (OS). Moreover, elevated levels of stem-cell growth factor (SCGF)-β were also associated with worse OS. Patients with elevated levels of all 6 cytokines experienced significantly worse outcomes compared to patients who had fewer than 6 cytokines elevated (hazard ratio = 12.06; 95% confidence interval, 7.39-19.49; P = .002 for progression-free survival, and hazard ratio = 39.65; 95% confidence interval, 25.03-62.18; P < .00001 for OS, respectively). Results were independent of International Germ Cell Cancer Collaborative Group criteria. CONCLUSION: We found a correlation among progression free-survival, OS, and circulating cytokines in TGCT. This suggests the existence an association between plasma cytokines and baseline clinicopathologic features in TGCT. Plasma cytokines could be used for identification of high-risk patients who are candidates for new therapeutic approaches.
BACKGROUND: Cytokines are the communicators of immune system and are involved in all immune responses. The aim of this study was to assess the correlation among plasma cytokines, patient and tumor characteristics, and clinical outcome in chemonaive testicular germ-cell tumor (TGCT) patients. PATIENTS AND METHODS: This study included 92 metastatic chemotherapy-naive TGCT patients treated with platinum-based chemotherapy from July 2010 to March 2014. Plasma was isolated before first administration of chemotherapy, and the concentration of 51 plasma cytokines were analyzed using multiplex bead arrays. RESULTS: At a median follow-up of 33.2 months (range, 0.1-54.8 months), 10.9% of patients experienced disease progression, and 7.6% died. Several cytokines were associated with different baseline clinicopathologic features. Elevated plasma levels of interferon (IFN)-α2, interleukin (IL)-2Rα, IL-16, hepatocyte growth factor (HGF), and monocyte chemotactic protein (MCP)-3 were significantly associated with worse progression-free survival and overall survival (OS). Moreover, elevated levels of stem-cell growth factor (SCGF)-β were also associated with worse OS. Patients with elevated levels of all 6 cytokines experienced significantly worse outcomes compared to patients who had fewer than 6 cytokines elevated (hazard ratio = 12.06; 95% confidence interval, 7.39-19.49; P = .002 for progression-free survival, and hazard ratio = 39.65; 95% confidence interval, 25.03-62.18; P < .00001 for OS, respectively). Results were independent of International Germ Cell Cancer Collaborative Group criteria. CONCLUSION: We found a correlation among progression free-survival, OS, and circulating cytokines in TGCT. This suggests the existence an association between plasma cytokines and baseline clinicopathologic features in TGCT. Plasma cytokines could be used for identification of high-risk patients who are candidates for new therapeutic approaches.
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