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Advanced ovarian clear cell carcinoma increases risk for VTE
Advanced ovarian clear cell carcinoma appeared associated with an increased incidence of venous thromboembolism and poorer survival, according to findings from a multicenter case-control study.
This association appeared to be linked to proinflammatory cytokine interleukin 6 (IL-6) expression, results showed.
IL-6 — known to be highly expressed in ovarian clear cell carcinoma (OCCC) — may increase the risk for VTE by inducing procoagulant factors or by inducing thrombocytosis.
“Management of OCCC has been always challenging in that OCCC is associated with a high risk for VTE and has a high rate of resistance to chemotherapy,” Koji Matsuo, MD, PhD, an adjunct assistant professor of clinical obstetrics and gynecology at the Keck School of Medicine at University of Southern California, told HemOnc Today. “Both of these factors likely contribute to poorer survival outcomes compared to other types of ovarian cancer. Atlhough these two phenomenon seem separate clinical entities, our study examining more than 1,300 cases of ovarian cancer identified IL-6 as a key marker to link the two distinct characteristics — VTE and aggressive tumor behavior — in OCCC.”
Matsuo and colleagues identified 370 patients with OCCC and 938 patients with serous ovarian carcinoma (SOC) from 10 institutions in the United States, the United Kingdom and Japan between 2000 and 2012. Researchers also examined pretreatment plasma IL-6 levels in a subset of 200 cases.
Overall, 16.4% of the patients experienced VTE. The highest 2-year cumulative VTE rate was in the advanced-OCCC patients (43.1%), whereas 16.2% of VTE cases occurred in patients with advanced SOC, 11.9% occurred in patients with early-stage OCCC, and 6.45% occurred in patients with early-stage SOC (P < .0001).
Patients with advanced-stage OCCC also had significantly higher median levels of IL-6 (17.8 pg/mL) than patients with advanced-stage SOC (9 pg/mL), early-stage OCCC (4.2 pg/mL) and early-stage SOC (5 pg/mL; P = .006).
In a multivariable analysis, the researchers identified advanced OCCC (HR = 3.38; 95% CI, 2.28-5.01), thrombocytosis (HR = 1.42; 95% CI, 1.03-1.96) and overexpression of IL-6 (HR = 8.9; 95% CI, 1.04-76) as independent predictors of VTE.
The rates of 5-year PFS and OS appeared significantly poorer among patients with advanced-stage OCCC (PFS = 13.3%; OS = 28.2%) than among patients with advanced-stage SOC (PFS = 19.7%; OS = 39.8%; P < .01 for both).
Anil K. Sood
However, among patients with early-stage disease, a greater proportion of patients with OCCC than SOC achieved 5-year PFS (84.7% vs. 66.9%) and 5-year OS (89.5% vs. 82.1%; P < .01 for both).
When stratified by disease subtype, the association with worse 2-year PFS and higher IL-6 expression (≥ 10 pg/mL vs. ˂ 10 pg/mL) appeared greater among patients with OCCC (50% vs. 87.5%; HR = 4.89; 95% CI, 1.17-20.5) than SOC (24.9% vs. 40.8%; HR = 1.4; 95% CI, 0.97-2.03).
Limitations of the study include its retrospective design, which inherently has confounding factors. In this instance, standard case record forms were not used to capture VTE events. Additionally, central pathology review was not conducted to confirm OCCC and central histopathologic slide review was not available to grade the serous tumors.
“High IL-6 levels closely parallel increased VTE risk and decreased survival outcome in advanced-stage OCCC,” Anil K. Sood, MD, professor of gynecologic oncology and reproductive medicine and director of ovarian cancer research at The University of Texas MD Anderson Cancer Center told HemOnc Today. “Conversely, OCCCs without high IL-6 level were more likely to be early-stage. These results suggest that anti-IL-6 therapy (eg, monoclonal antibody or statin) may be relevant for VTE and anti-tumor effects in the management of OCCC.”– by Anthony SanFilippo
Disclosure: The researchers report no relevant financial disclosures.