Venous thromboembolism, interleukin-6 and survival outcomes in patients with advanced ovarian clear cell carcinoma

Eur J Cancer. 2015 Sep;51(14):1978-88. doi: 10.1016/j.ejca.2015.07.012. Epub 2015 Jul 31.

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.

Keywords: Clear cell carcinoma; IL-6; Ovarian cancer; Survival outcome; Venous thromboembolism.

Publication types

  • Multicenter Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor / blood*
  • Carcinoma / blood
  • Carcinoma / complications*
  • Carcinoma / mortality
  • Carcinoma / pathology
  • Disease Progression
  • Disease-Free Survival
  • Female
  • Humans
  • Incidence
  • Interleukin-6 / blood*
  • Japan
  • Kaplan-Meier Estimate
  • Middle Aged
  • Multivariate Analysis
  • Neoplasm Recurrence, Local
  • Neoplasm Staging
  • Neoplasms, Cystic, Mucinous, and Serous / blood
  • Neoplasms, Cystic, Mucinous, and Serous / complications*
  • Neoplasms, Cystic, Mucinous, and Serous / mortality
  • Neoplasms, Cystic, Mucinous, and Serous / pathology
  • Ovarian Neoplasms / blood
  • Ovarian Neoplasms / complications*
  • Ovarian Neoplasms / mortality
  • Ovarian Neoplasms / pathology
  • Proportional Hazards Models
  • Retrospective Studies
  • Risk Factors
  • Time Factors
  • United States
  • Up-Regulation
  • Venous Thromboembolism / diagnosis
  • Venous Thromboembolism / etiology*
  • Venous Thromboembolism / mortality

Substances

  • Biomarkers, Tumor
  • IL6 protein, human
  • Interleukin-6