Elsevier

Gynecologic Oncology

Volume 105, Issue 3, June 2007, Pages 784-790
Gynecologic Oncology

Venous thromboembolism in ovarian cancer

https://doi.org/10.1016/j.ygyno.2007.02.024Get rights and content

Abstract

Objective.

To determine the incidence, time-course, and risk factors associated with the development of thromboembolism (VTE) in a population-based study of women with ovarian cancer.

Methods.

Using the California Cancer Registry, cases diagnosed with ovarian cancer for a 6-year period were identified. These cases were linked with the California Patient Discharge Data Set to determine the incidence of VTE. Proportional hazards modeling was performed to analyze the strength of specified risk factors to predict development of VTE or death within 2 years.

Results.

Among 13,031 cases with ovarian cancer, 5.2% were diagnosed with a VTE event within 24 months after diagnosis. The cumulative incidence varied from 1.4% among women with local stage disease to 6.7% among women with advanced disease. The person-time incidence rate of VTE decreased over time, with the highest rate noted during the first 3 months. In a multivariate model, significant risk factors for VTE included advancing age, increasing number of chronic comorbid conditions, more advanced cancer stage, invasive histology, and absence of any major surgery. For all stages of cancer, development of VTE within 2 years was a significant risk factor for decreased survival, and the magnitude of the risk was greatest among the cases diagnosed with localized disease (HR 4.7, 95% CI: 2.3–9.5).

Conclusions.

VTE occurred in a significant proportion of ovarian cancer patients and adversely impacted survival, particularly among cases with local or regional stage cancer.

Introduction

Most women with ovarian cancer present with advanced disease and undergo complicated treatment regimens, including one or more major surgeries and several courses of chemotherapy. During this extended treatment course, many women suffer a variety of complications, including venous thromboembolism (VTE, deep vein thrombosis or pulmonary embolism). In a recent retrospective study of 253 women with epithelial ovarian cancer who underwent both surgery and chemotherapy and who were followed for a median of 2.6 years, the reported incidence of VTE was 16.6%, 15% with deep vein thrombosis (DVT) and 1.6% with pulmonary embolism (PE) [1]. The risk factors for VTE depended on the length of time between the cancer diagnosis and the VTE diagnosis. Early VTE events were associated with surgery and chemotherapy, whereas later VTE events were associated with older age, prior history of DVT, FIGO stage IIC–IV, and presence of residual tumor after initial surgery [1]. In a recent study, the incidence of VTE in 12 common cancers in California was evaluated. This population-based study reported that among 5347 patients with advanced ovarian cancer, the 2-year incidence of VTE was 3.3%, with a 2-year survival of 50% [2]. This trial did not analyze in detail the differences in incidence and outcome specific to the ovarian cancer population based on histology, comorbidities, or type of surgery. In the present study, our aims were to define the incidence and time-course of VTE in a large population based cohort of women with ovarian cancer, to analyze the strength of potential risk factors associated with the occurrence of VTE, and to determine the effect of VTE on overall survival.

Section snippets

Materials and methods

Ovarian cancer cases were identified using the comprehensive California Cancer Registry, which identifies 99% of all cancers diagnosed in California [3]. Venous thromboembolic events were determined by linking the registry cases to the California Patient Discharge Data Set using patient-specific identifiers. The California Patient Discharge Data Set contains serial linked medical–diagnostic and procedural data from July 1990 to the present for all patients admitted to hospitals in California [4]

Results

Over the 6-year period, there were 13,031 cases of ovarian cancer in the cancer registry that could be linked to the discharge database. Table 2 outlines the demographic characteristics of this cohort including mean age, race, stage, histologic type, and the total number of patients with episodes of VTE. Overall, the 24-month cumulative incidence of VTE was 672 (5.2%), 1.4% with PE and 3.7% with DVT. 30% of the VTE events occurred within 3 months of major pelvic or abdominal cancer surgery, 5%

Discussion

Prior studies that have analyzed VTE in women with ovarian cancer have had significant methodological limitations. Levitan et al. who analyzed only medicare patients with cancer who required hospitalization reported that the highest incidence of VTE was in women with ovarian cancer [8]. Other studies have reported the cumulative occurrence rates of asymptomatic VTE in patients with a variety of types of gynecologic cancer, usually in the postoperative period. For example, Clarke-Pearson et al.

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