Koji Matsuo1, Kosei Hasegawa2, Kiyoshi Yoshino3, Ryusuke Murakami4, Takeshi Hisamatsu5, Rebecca L Stone6, Rebecca A Previs7, Jean M Hansen7, Yuji Ikeda8, Akiko Miyara2, Kosuke Hiramatsu3, Takayuki Enomoto9, Keiichi Fujiwara2, Noriomi Matsumura4, Ikuo Konishi4, Lynda D Roman10, Hani Gabra11, Christina Fotopoulou11, Anil K Sood12. 1. Department of Obstetrics and Gynecology, University of Southern California, Los Angeles, CA, USA; Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, USA. Electronic address: koji.matsuo@med.usc.edu. 2. Department of Gynecologic Oncology, Saitama Medical University International Medical Center, Saitama, Japan. 3. Department of Obstetrics and Gynecology, Osaka University Graduate School of Medicine, Osaka, Japan. 4. Department of Gynecology and Obstetrics, Kyoto University Graduate School of Medicine, Kyoto, Japan. 5. Department of Obstetrics and Gynecology, Osaka University Graduate School of Medicine, Osaka, Japan; Department of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. 6. Department of Obstetrics and Gynecology, The Johns Hopkins University, Baltimore, MD, USA. 7. Department of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. 8. Department of Gynecologic Oncology, Saitama Medical University International Medical Center, Saitama, Japan; Department of Obstetrics and Gynecology, The University of Tokyo Faculty of Medicine, Tokyo, Japan. 9. Department of Obstetrics and Gynecology, Niigata University Graduate School of Medicine, Niigata, Japan. 10. Department of Obstetrics and Gynecology, University of Southern California, Los Angeles, CA, USA; Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, USA. 11. Ovarian Cancer Action Research Centre, Department of Surgery and Cancer, Imperial College London, London, UK. 12. Department of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; Center for RNA Interference and Non-Coding RNAs, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Abstract
BACKGROUND: We compared survival outcomes and risk of venous thromboembolism (VTE) among patients with advanced and early-stage ovarian clear cell carcinoma (OCCC) and serous ovarian carcinoma (SOC), as well as potential links with interleukin-6 (IL-6) levels. METHODS: A multicenter case-control study was conducted in 370 patients with OCCC and 938 with SOC. In a subset of 200 cases, pretreatment plasma IL-6 levels were examined. FINDINGS: Patients with advanced OCCC had the highest 2-year cumulative VTE rates (advanced OCCC 43.1%, advanced SOC 16.2%, early-stage OCCC 11.9% and early-stage SOC 6.4%, P<0.0001) and the highest median levels of IL-6 (advanced OCCC 17.8 pg/mL, advanced SOC 9.0 pg/mL, early-stage OCCC 4.2 pg/mL and early-stage SOC 5.0 pg/mL, P=0.006). Advanced OCCC (hazard ratio [HR] 3.38, P<0.0001), thrombocytosis (HR 1.42, P=0.032) and elevated IL-6 (HR 8.90, P=0.046) were independent predictors of VTE. In multivariate analysis, patients with advanced OCCC had significantly poorer 5-year progression-free and overall survival rates than those with advanced SOC (P<0.01), and thrombocytosis was an independent predictor of decreased survival outcomes (P<0.01). Elevated IL-6 levels led to poorer 2-year progression-free survival rates in patients with OCCC (50% versus 87.5%, HR 4.89, P=0.016) than in those with SOC (24.9% versus 40.8%, HR 1.40, P=0.07). INTERPRETATION: Advanced OCCC is associated with an increased incidence of VTE and decreased survival outcomes, which has major implications for clinical management of OCCC.
BACKGROUND: We compared survival outcomes and risk of venous thromboembolism (VTE) among patients with advanced and early-stage ovarian clear cell carcinoma (OCCC) and serous ovarian carcinoma (SOC), as well as potential links with interleukin-6 (IL-6) levels. METHODS: A multicenter case-control study was conducted in 370 patients with OCCC and 938 with SOC. In a subset of 200 cases, pretreatment plasma IL-6 levels were examined. FINDINGS:Patients with advanced OCCC had the highest 2-year cumulative VTE rates (advanced OCCC 43.1%, advanced SOC 16.2%, early-stage OCCC 11.9% and early-stage SOC 6.4%, P<0.0001) and the highest median levels of IL-6 (advanced OCCC 17.8 pg/mL, advanced SOC 9.0 pg/mL, early-stage OCCC 4.2 pg/mL and early-stage SOC 5.0 pg/mL, P=0.006). Advanced OCCC (hazard ratio [HR] 3.38, P<0.0001), thrombocytosis (HR 1.42, P=0.032) and elevated IL-6 (HR 8.90, P=0.046) were independent predictors of VTE. In multivariate analysis, patients with advanced OCCC had significantly poorer 5-year progression-free and overall survival rates than those with advanced SOC (P<0.01), and thrombocytosis was an independent predictor of decreased survival outcomes (P<0.01). Elevated IL-6 levels led to poorer 2-year progression-free survival rates in patients with OCCC (50% versus 87.5%, HR 4.89, P=0.016) than in those with SOC (24.9% versus 40.8%, HR 1.40, P=0.07). INTERPRETATION: Advanced OCCC is associated with an increased incidence of VTE and decreased survival outcomes, which has major implications for clinical management of OCCC.
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