Venous thromboembolism in epithelial ovarian cancer. A prospective cohort study

Kahr, Henriette Strøm; Christiansen, Ole Bjarne; Grove, Anni; Iyer, Victor Vishwanath; Torp‐Pedersen, Christian; Knudsen, Aage; Thorlacius-Ussing, Ole

doi:10.1016/j.thromres.2019.07.027

Cited by 17 publications

(16 citation statements)

References 36 publications

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“…Recently published smaller cohort studies propose that chemotherapy might have a higher influence on the risk of VTE than surgery. 11,12,23 The present study found similar HRs of VTE in EOC bleeding risk. 40,41 Gynecologic cancer patients are considered at high risk of developing VTE during chemotherapy according to the Khorana score and need only one other risk factor to fulfill the criteria to receive VTE prophylaxis during ambulant anticancer treatment according to the updated guidelines.…”

Section: Eoc Patients (%) Asupporting

confidence: 82%

“…The heterogeneity of EOC tumors and the complexity of treatment make it difficult to interpret results from smaller cohort studies regarding risk factors and timing of VTE episodes, as demonstrated in a recent prospective study from our group 23 . In the present study, we were able to adjust for several acknowledged VTE risk factors including time‐varying treatment‐related factors due to the possibility of merging clinical data of high quality from validated Danish registers 24‐26 .…”

Section: Discussionmentioning

confidence: 98%

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The timing of venous thromboembolism in ovarian cancer patients: A nationwide Danish cohort study

Kahr

Christiansen

Riddersholm

et al. 2021

Journal of Thrombosis and Haemostasis

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Background and aim: Venous thromboembolism (VTE) is associated with excess mortality and morbidity in cancer, and is influenced by patient-, tumor-, and treatmentrelated factors. We aimed to investigate the impact of such factors in a national cohort of patients with epithelial ovarian cancer (EOC). Methods: Patients in the Danish Gynecologic Cancer Database (DGCD) with EOC from 2005 to 2014 were followed from time of diagnosis to VTE, or censoring. Surgery, chemotherapy, and vascular epithelial growth factor (VEGF)-inhibitors were included as time-varying exposures in Cox proportional hazard regression models. Results: A total of 551 VTE events were registered in 4991 EOC patients. Median follow-up time was 2.9 years. The 2-year cumulative incidence of VTE was 7.2%. Patients were at highest risk during the first year after EOC diagnosis. Previous VTE was associated with a hazard ratio (HR) of 3.26 (95% confidence interval [CI] 2.42-4.39). Exposure to major pelvic surgery was associated with a HR of 3.21 (95% CI 2.29-4.50). Exposure to chemotherapy or (VEGF)-inhibitors were associated with HRs of 1.91 (95% CI 1.56-2.33) and 1.05 (95% CI 0.57-1.93), respectively. Hazard ratios for patients with clear cell histopathology was 1.46 (95% CI 0.97-2.20) and 2.42 for International Federation of Gynaecology and Obstetrics stage III-IV (95% CI 1.93-3.03). Conclusions: EOC is associated with a high risk of VTE, particularly within the first year after diagnosis. Major pelvic surgery and chemotherapy were strongly associated with VTE. Person-related risk factors were increasing age and previous VTE. Advanced stage was an independent tumor-related risk factor. These findings support the indication for thrombosis prophylaxis during chemotherapy. K E Y W O R D S deep vein thrombosis, epithelial ovarian cancer, ovarian cancer, pulmonary embolism, venous thromboembolism, venous thromboprophylaxis | 993 STRØM KAHR eT Al.

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Section: Eoc Patients (%) Asupporting

confidence: 82%

Section: Discussionmentioning

confidence: 98%

The timing of venous thromboembolism in ovarian cancer patients: A nationwide Danish cohort study

Kahr

Christiansen

Riddersholm

et al. 2021

Journal of Thrombosis and Haemostasis

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“…Only a few studies have reported an incidence of VTE in women with ovarian cancer, ranging from 1.2% -39.3% [7,[16][17][18]22]. In our study, incidence of VTE in women with ovarian cancer was lower than in previous studies, supporting a lower incidence of VTE in Asian patients than in the Western population (Table 1) [35].…”

Section: Discussionsupporting

confidence: 69%

Incidence and risk of venous thromboembolism according to primary treatment in women with ovarian cancer: A retrospective cohort study

et al. 2021

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Objective This study aimed to investigate incidence and risk for venous thromboembolism (VTE) according to primary treatment in women with ovarian cancer. Methods We selected 26,863 women newly diagnosed with ovarian cancer between 2009 and 2018 from the Korean Health Insurance Review and Assessment Service databases. During the total follow-up period and the first six months after initiation of primary treatments, incidence and risk of VTE were evaluated according to primary treatment as no treatment, surgery, radiotherapy, or chemotherapy. Results The mean follow-up period was 1285.5±6 days. The VTE incidence was highest in women who underwent chemotherapy (306 per 10,000 women). Among women who underwent surgery, VTE was highest in surgery with neoadjuvant chemotherapy (536 per 10,000 women), followed by surgery with adjuvant chemotherapy (360 per 10,000 women) and surgery alone (132 per 10,000 women). During the first 12 months, monthly incidence of VTE decreased. Compared with women with no treatment, risk of VTE significantly increased in women undergoing chemotherapy (HR 1.297; 95% CI, 1.08–1.557; P = 0.005) during the total follow-up period and decreased in women undergoing surgery (HR 0.557; 95% CI, 0.401–0.775; P<0.001) and radiotherapy (HR 0.289; 95% CI, 0.119–0.701; P = 0.006) during the first six months. Among women who underwent surgery, VTE risk significantly increased in surgery with neoadjuvant chemotherapy (HR 4.848; 95% CI, 1.86–12.632; P = 0.001) followed by surgery with adjuvant chemotherapy (HR 2.807; 95% CI, 1.757–4.485; P<0.001) compared with surgery alone during the total follow-up period and in surgery with neoadjuvant chemotherapy (HR 4.223; 95% CI, 1.37–13.022; P = 0.012) during the first six months. Conclusions In this large Korean cohort study, incidence and risk of VTE were highest in women with ovarian cancer who underwent chemotherapy and surgery with neoadjuvant chemotherapy as a primary cancer treatment. Incidence of VTE decreased over time.

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“…Ovarian cancers are associated with a very high rate of venous thromboembolism (VTE) with cumulative incidence rates of 20% in the first year following diagnosis, depending on tumour histological subtype [1,2]. Thrombosis is a common complication of chemotherapy and occurs in 11-12.5% of ovarian cancer patients undergoing chemotherapy treatment [3,4].…”

Section: Introductionmentioning

confidence: 99%

Procoagulant activity in high grade serous ovarian cancer patients following neoadjuvant chemotherapy-The role of the activated protein C pathway

Ward

Saadeh

O’Toole

et al. 2021

Thrombosis Research

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Introduction: Ovarian cancer patients are at high risk of thrombosis particularly during chemotherapy treatment however the mechanism is not understood. The aim of this study is to investigate the role of the activated protein C (aPC) pathway in the procoagulant activity observed in ovarian cancer patients undergoing neoadjuvant chemotherapy. Patients and methods: Thrombin generation was determined before and after addition of thrombomodulin (TM) in high grade serous ovarian cancer (HGSOC) patients treated with neoadjuvant chemotherapy (n = 29) compared with HGSOC patients who were chemo naïve (n = 23) and patients with benign tumours (n = 29). Plasma expression of proteins from the aPC pathway was analysed. mRNA expression was determined in endothelial (EA.hy926) and ovarian (OAW42) cell lines following addition of carboplatin and paclitaxel. Results: Lower levels of ETP (p < 0.007; p < 0.003) and peak thrombin (p < 0.0008; p < 0.0018) were found in the neoadjuvant group compared with both chemo naïve and benign groups. Following addition of TM, ETP (p < 0.0005) and peak thrombin (p < 0.0049) were higher in the neoadjuvant group compared with the benign controls indicating an increase in aPC resistance. Increased TM and lower levels of protein S were found in the neoadjuvant group compared with benign controls (p < 0.05; p < 0.003). Factor V levels were increased in the neoadjuvant group compared with the chemo naïve group (p < 0.05). Carboplatin and paclitaxel altered the expression of EPCR and thrombomodulin in OAW42 cells with a modest effect on EA.hy926 cells. Conclusion: Chemotherapy induced procoagulant activity in HGSOC is associated with an alteration in expression of key members of the aPC pathway. This acquired aPC resistance may explain the procoagulant phenotype associated with ovarian cancer patients undergoing chemotherapy.

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Venous thromboembolism in epithelial ovarian cancer. A prospective cohort study

Cited by 17 publications

References 36 publications

The timing of venous thromboembolism in ovarian cancer patients: A nationwide Danish cohort study

The timing of venous thromboembolism in ovarian cancer patients: A nationwide Danish cohort study

Incidence and risk of venous thromboembolism according to primary treatment in women with ovarian cancer: A retrospective cohort study

Procoagulant activity in high grade serous ovarian cancer patients following neoadjuvant chemotherapy-The role of the activated protein C pathway

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