title: Venous thromboembolism, interleukin-6 and survival outcomes in patients with advanced ovarian clear cell carcinoma.
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.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  Advanced OCCC is associated with an increased incidence of VTE and decreased survival outcomes, which has major implications for clinical management of OCCC.
authors.affiliation: 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.
authors.forename: Koji
authors.initials: K
authors.lastname: Matsuo
authors.affiliation: Department of Gynecologic Oncology, Saitama Medical University International Medical Center, Saitama, Japan.
authors.forename: Kosei
authors.initials: K
authors.lastname: Hasegawa
authors.affiliation: Department of Obstetrics and Gynecology, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Yoshino
authors.affiliation: Department of Gynecology and Obstetrics, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Ryusuke
authors.initials: R
authors.lastname: Murakami
authors.affiliation: 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.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Hisamatsu
authors.affiliation: Department of Obstetrics and Gynecology, The Johns Hopkins University, Baltimore, MD, USA.
authors.forename: Rebecca L
authors.initials: RL
authors.lastname: Stone
authors.affiliation: Department of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Rebecca A
authors.initials: RA
authors.lastname: Previs
authors.affiliation: Department of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Jean M
authors.initials: JM
authors.lastname: Hansen
authors.affiliation: 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.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Ikeda
authors.affiliation: Department of Gynecologic Oncology, Saitama Medical University International Medical Center, Saitama, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Miyara
authors.affiliation: Department of Obstetrics and Gynecology, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Kosuke
authors.initials: K
authors.lastname: Hiramatsu
authors.affiliation: Department of Obstetrics and Gynecology, Niigata University Graduate School of Medicine, Niigata, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Enomoto
authors.affiliation: Department of Gynecologic Oncology, Saitama Medical University International Medical Center, Saitama, Japan.
authors.forename: Keiichi
authors.initials: K
authors.lastname: Fujiwara
authors.affiliation: Department of Gynecology and Obstetrics, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Noriomi
authors.initials: N
authors.lastname: Matsumura
authors.affiliation: Department of Gynecology and Obstetrics, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Ikuo
authors.initials: I
authors.lastname: Konishi
authors.affiliation: 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.
authors.forename: Lynda D
authors.initials: LD
authors.lastname: Roman
authors.affiliation: Ovarian Cancer Action Research Centre, Department of Surgery and Cancer, Imperial College London, London, UK.
authors.forename: Hani
authors.initials: H
authors.lastname: Gabra
authors.affiliation: Ovarian Cancer Action Research Centre, Department of Surgery and Cancer, Imperial College London, London, UK.
authors.forename: Christina
authors.initials: C
authors.lastname: Fotopoulou
authors.affiliation: 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.
authors.forename: Anil K
authors.initials: AK
authors.lastname: Sood
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood*; D002277:Carcinoma / Q000097:blood / Q000150:complications* / Q000401:mortality / Q000473:pathology; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D015994:Incidence; D015850:Interleukin-6 / Q000097:blood*; D007564:Japan; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D015999:Multivariate Analysis; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D018297:Neoplasms, Cystic, Mucinous, and Serous / Q000097:blood / Q000150:complications* / Q000401:mortality / Q000473:pathology; D010051:Ovarian Neoplasms / Q000097:blood / Q000150:complications* / Q000401:mortality / Q000473:pathology; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D012307:Risk Factors; D013997:Time Factors; D014481:United States; D015854:Up-Regulation; D054556:Venous Thromboembolism / Q000175:diagnosis / Q000209:etiology* / Q000401:mortality
chemical_list: D014408:Biomarkers, Tumor; C508600:IL6 protein, human; D015850:Interleukin-6
keywords: Clear cell carcinoma; IL-6; Ovarian cancer; Survival outcome; Venous thromboembolism