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

Koji Matsuo, Kosei Hasegawa, Kiyoshi Yoshino, Ryusuke Murakami, Takeshi Hisamatsu, Rebecca L. Stone, Rebecca A. Previs, Jean M. Hansen, Yuji Ikeda, Akiko Miyara, Kosuke Hiramatsu, Takayuki Enomoto, Keiichi Fujiwara, Noriomi Matsumura, Ikuo Konishi, Lynda D. Roman, Hani Gabra, Christina Fotopoulou, Anil K. Sood

Research output: Contribution to journalArticlepeer-review

25 Scopus citations


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.

Original languageEnglish (US)
Article number9546
Pages (from-to)1978-1988
Number of pages11
JournalEuropean Journal of Cancer
Issue number14
StatePublished - Jul 13 2015


  • Clear cell carcinoma
  • IL-6
  • Ovarian cancer
  • Survival outcome
  • Venous thromboembolism

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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