Venous thromboembolism during neoadjuvant chemotherapy for ovarian cancer.

To determine the incidence of venous thromboembolism in patients with advanced epithelial ovarian cancer undergoing neoadjuvant chemotherapy in UK gynecological cancer centers. Secondary outcomes included incidence and timing of venous thromboembolism since cancer presentation, impact on cancer treatment, and mortality. All UK gynecological cancer centers were invited to participate in this multi-center retrospective audit through the British Gynecological Cancer Society. Data were captured on all patients undergoing neoadjuvant chemotherapy for International Federation of Gynecology and Obstetrics (FIGO) stage III/IV epithelial ovarian cancer within a 12-month period during 2021-2022. Patients on anticoagulation prior to cancer presentation were excluded. Patients who were diagnosed with venous thromboembolism between cancer presentation and commencing neoadjuvant chemotherapy were also excluded from our analysis of venous thromboembolism rates from neoadjuvant chemotherapy. Fourteen UK gynecological cancer centers returned data on 660 eligible patients. The median age was 67 years (range 34-96). In total, 131/660 (19.8%) patients were diagnosed with venous thromboembolism from cancer presentation until discharge following cytoreductive surgery. Between commencing neoadjuvant chemotherapy and post-operative discharge, 65/594 (10.9%) patients developed venous thromboembolism (median 11.3%, IQR 5.9-11.3); 55/594 (9.3%) during neoadjuvant chemotherapy, 10/594 (1.7%) during post-operative admission. There was no significant difference across centers (p=0.47). Of these 65 patients, 44 (68%) were diagnosed with pulmonary embolism and 30 (46%) with deep-vein thrombosis (nine had both), including in major abdominal/pelvic vessels, with 36 (55%) presenting symptomatically and 29 (45%) diagnosed incidentally on imaging. Venous thromboembolism resulted in mortality (n=3/65, 5%), and delays/changes/cancelation of treatment (n=18/65, 28%). Across a large, representative sample of UK gynecological cancer centers, one in five patients undergoing neoadjuvant chemotherapy were diagnosed with a potentially preventable venous thromboembolism, including one in nine diagnosed after commencing chemotherapy. This led to adverse clinical consequences for one third, including delay to oncological treatment and mortality. This high venous thromboembolism rate justifies the consideration of thromboprophylaxis in this patient group.

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Competing interests: MT declares research funding from Thrombosis UK and Anthos, has received speaker fees from Bayer, Sanofi and Anthos, served on advisory boards for Ablynx, Sanofi and Bayer, consultancy for Bayer and Anthos, and is the senior author for the British Society of Haematology Guideline - Cancer-associated venous thrombosis in adults (second edition). SO and RM acknowledge funding outside this work from the Rosetrees trust. RM declares research funding from Barts Charity, the Eve Appeal, NHS Innovation Accelerator, British Gynaecological Cancer Society, GSK and Yorkshire Cancer Research outside this work, an honorarium for grant review from Israel National Institute for Health Policy Research and honoraria for advisory board membership from Astrazeneca, MSD, EGL, GSK. RM is the Topic Advisor for the NICE Guideline [GID-NG10225] -- Ovarian cancer: identifying and managing familial and genetic risk. NeR is supported by a NES/CSO Postdoctoral Clinical Lectureship Scheme – PCL/23/03 from the Chief Scientist Office Scotland. The other authors declare no conflicts of interest.