Meta-Analysis of VTE Risk: Ovarian Cancer Patients by Stage, Histology, Cytoreduction, and Ascites at Diagnosis

Abstract

Venous thromboembolisms (VTEs) have been a leading secondary cause of death among ovarian cancer patients, prompting multiple studies of risk factors. The objective of this meta-analysis is to quantify the associations between VTE and the most commonly reported risk factors among ovarian cancer patients. PubMed, Embase, and Cumulative Index to Nursing and Allied Health Literature (CINAHL) were used to identify observational studies. Two reviewers independently abstracted data and assessed quality via the Newcastle–Ottawa tool. A random effects model was used to calculate the pooled odds ratios for VTE with each of the following exposures: advanced cancer stage, clear cell histology, serous histology, ascites at diagnosis, and complete cytoreduction. The I2 and Q tests were used to evaluate heterogeneity. Twenty cohort studies with 6,324 total ovarian cancer patients, 769 of whom experienced a VTE, were included. The odds of VTE in ovarian cancer patients were higher among patients with cancer stage III/IV (versus cancer stage I/II, pooled odds ratio (OR) 2.73; 95% CI 1.84–4.06; I2= 64%), clear cell (versus nonclear cell) histology (OR 2.11; 95% CI 1.55–2.89; I2 = 6%), and ascites (versus no ascites) at diagnosis (OR 2.12; 95% CI 1.51–2.96; I2 = 32%). Serous (versus nonserous) histology (OR 1.26; 95% CI 0.91–1.75; I2 = 42%) and complete (versus incomplete) cytoreduction (OR 1.05; 95% CI 0.27–4.11; I2 = 88%) were not associated with VTE. This meta-analysis quantifies the significantly elevated odds of VTE in ovarian cancer patients with advanced stage at diagnosis, clear cell histology, and ascites at diagnosis. Further studies are needed to account for confounders and inform clinical decision-making tools.

Venous thromboembolism in women with ovarian cancer undergoing neoadjuvant chemotherapy prior to cytoreductive surgery: A retrospective study

“…24,25 In our study, clear cell and carcinosarcomas were associated with VTE, although the numbers are small and do not reach statistical significance in the case of clear cell disease. This reflects their at least 2.5-fold greater VTE risk, which is known from larger studies, 23,26 most likely because of increased ectopic production of tissue factor and factor VII. 9 Our data add to results from other smaller retrospective studies in the field.…”

“…Patients undergoing NACT have a high (usually unresectable) tumor burden with ascites, both significantly associated with VTE risk, likely due to a combination of reduced blood flow from pelvic venous compression, and the ectopic secretion of procoagulant material including tissue factor, membrane-derived microparticles, and cytokines such as interleukin-6 and tumor necrosis factorα. 9,23 In addition, NACT can lead to VTE via pathways including reduced protein C and S expression (from reduced vitamin K absorption), increased factor V expression, and direct injury to vascular endothelium. 24,25 In our study, clear cell and carcinosarcomas were associated with VTE, although the numbers are small and do not reach statistical significance in the case of clear cell disease.…”

Risk of Thrombo-Embolic Events in Ovarian Cancer: Does Bevacizumab Tilt the Scale? A Systematic Review and Meta-Analysis

“…Primary prophylaxis could be considered for newly diagnosed advanced OC patients with BMI > 35 kg/m 2 , hemoglobin < 10 g/dL, leukocytosis > 11 × 10 6 /µL or thrombocytosis > 350,000/µL. When weighing risks and benefits, treatment with bevacizumab can be considered as an additional risk factor besides others such as ascites, clear cell histology or a prior history of VTE [ 79 ].…”

Biologically Active Tissue Factor-Bearing Larger Ectosome-Like Extracellular Vesicles in Malignant Effusions from Ovarian Cancer Patients: Correlation with Incidence of Thrombosis

“…The development of ascites in patients with ovarian carcinoma indicates a massive progression of the disease, and is associated with severely reduced survival prognosis for patients [ 15 ]. In addition, these patients have a high incidence of venous thromboembolic events (VTE), which can also result in a fatal outcome [ 2 ]. In this scenario of tumor progression and activation of the coagulation system, EVs are suspected of playing a major role, especially when they expose membrane-bound TF, as well as PS, which enables them to activate the systemic coagulation system on the one hand, and the PAR2/ERK signaling pathway on the other [ 5 , 10 , 16 ].…”

“…The clinical association between progressive cancer and the development of venous thromboembolic events (VTE) is well known, and represents a life-threatening event in patients [ 1 ]. Patients with ovarian carcinoma are affected particularly often [ 2 ]. The molecular reasons are still unclear, and most certainly are multifactorial.…”