Impact of Chemotherapy on Venous Thromboembolism in Cervical Cancer: Systematic Meta-Analysis Observational Studies
Abstract
Objective: Cervical cancer is associated with an increased risk of venous thromboembolism (VTE), which may be further aggravated by chemotherapy. This study aimed to assess the impact of chemotherapy on VTE incidence in patients with cervical cancer. Methods: A systematic review was conducted according to PRISMA 2020 guidelines. PubMed, the Cochrane Library, and EMBASE were searched from inception to October 2024 for observational studies reporting VTE incidence in cervical cancer patients receiving chemotherapy. Studies including women with cervical cancer treated with chemotherapy and reporting VTE outcomes were eligible, while studies evaluating radiotherapy or surgery alone were excluded. Results: Three observational studies involving 2,292 patients met the inclusion criteria. Pooled analysis showed that chemotherapy significantly increased VTE risk (RR 2.83; 95% CI: 2.05–3.90; p < 0.001), with low statistical heterogeneity. The reported incidence of chemotherapy-associated VTE ranged from 10.0% to 18.7%. Conclusion: Chemotherapy is associated with a nearly threefold increased risk of VTE in cervical cancer patients. These findings support routine VTE risk stratification prior to chemotherapy and consideration of individualized thromboprophylaxis. Further prospective studies are needed to define optimal prevention strategies.
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References
Sung H, Ferlay J, Siegel RL. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA: A Cancer Journal for Clinicians. 2021;71(3):209–49.
Small W Jr, Bacon MA, Bajaj A. Cervical cancer: A global health crisis. Cancer. 2017;123(13):2404–12.
Cohen PA, Jhingran A, Oaknin A, Denny L. Cervical cancer. Lancet. 2019;393(10167):169–82.
Khorana AA, Francis CW, Culakova E, Kuderer NM, Lyman GH. Thromboembolism is a leading cause of death in cancer patients receiving outpatient chemotherapy. Journal of Thrombosis and Haemostasis. 2007;5(3):632–4.
Abdol Razak NB, Jones G, Bhandari M, Berndt MC, Metharom P. Cancer-associated thrombosis: an overview of mechanisms, risk factors, and treatment. Cancers. 2018;10(10):380.
Abu Saadeh F, Norris L, O’Toole S. Venous thromboembolism in ovarian cancer: incidence, risk factors and impact on survival. European Journal of Obstetrics, Gynecology, and Reproductive Biology. 2013;170(1):214–8.
Fotopoulou C, duBois A, Karavas AN. Incidence of venous thromboembolism in patients with ovarian cancer undergoing platinum/paclitaxel-containing first-line chemotherapy: an exploratory analysis by the Arbeitsgemeinschaft Gynaekologische Onkologie Ovarian Cancer Study Group. Journal of Clinical Oncology. 2008;26(16):2683–9.
Ay C, Pabinger I, Cohen AT. Cancer-associated venous thromboembolism: burden, mechanisms, and management. Thrombosis and Haemostasis. 2017;117(2):219–30.
Khorana AA, Mackman N, Falanga A. Cancer-associated venous thromboembolism. Nature Reviews Disease Primers. 2022;8(1):11.
Horsted F, West J, Grainge MJ. Risk of venous thromboembolism in patients with cancer: a systematic review and meta-analysis. PLoS Medicine. 2012;9(7):e1001275.
Matsuo K, Moeini A, Machida H. Significance of venous thromboembolism in women with cervical cancer. Gynecologic Oncology. 2016;142(3):405–12.
Levitan N, Dowlati A, Remick SC. Rates of initial and recurrent thromboembolic disease among patients with malignancy versus those without malignancy. Medicine. 1999;78(5):285–91.
Heit JA, Silverstein MD, Mohr DN, Petterson TM, O’Fallon WM, Melton LJ 3rd. Risk factors for deep vein thrombosis and pulmonary embolism: a population-based case-control study. Archives of Internal Medicine. 2000;160(6):809–15.
Verso M, Agnelli G. Venous thromboembolism associated with long-term use of central venous catheters in cancer patients. Journal of Clinical Oncology. 2003;21(19):3665–75.
Moore RA, Adel N, Riedel E. High incidence of thromboembolic events in patients treated with cisplatin-based chemotherapy: a large retrospective analysis. Journal of Clinical Oncology. 2011;29(25):3466–73.
Falanga A, Russo L, Milesi V, Vignoli A. Mechanisms and risk factors of thrombosis in cancer. Critical Reviews in Oncology/Hematology. 2017;118:79–83.
Sørensen HT, Mellemkjaer L, Olsen JH, Baron JA. Prognosis of cancers associated with venous thromboembolism. New England Journal of Medicine. 2000;343(25):1846–50.
Clarke-Pearson DL, Olt GJ. Thromboembolism in patients with gynecologic malignancy. Obstetrics and Gynecology Clinics of North America. 1994;21(1):103–10.
Khorana AA, Kuderer NM, Culakova E, Lyman GH, Francis CW. Development and validation of a predictive model for chemotherapy-associated thrombosis. Blood. 2008;111(10):4902–7.
Carrier M, Abou-Nassar K, Mallick R. Apixaban to prevent venous thromboembolism in patients with cancer. New England Journal of Medicine. 2019;380(8):711–9.
Khorana AA, Soff GA, Kakkar AK. Rivaroxaban for thromboprophylaxis in high-risk ambulatory patients with cancer. New England Journal of Medicine. 2019;380(8):720–8.
Mulder FI, Bosch FTM, van Es N. Primary thromboprophylaxis in ambulatory cancer patients: where do we stand? Cancers. 2020;12(2):367.
Page MJ, McKenzie JE, Bossuyt PM. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021;372:n71.
Chen YS, Park JY, Hong MK. Incidence and risk factors of VTE in patients with cervical cancer using the Korean national health insurance data. Scientific Reports. 2021;11(1):8927.
Zhao H, Peng Y, Lv M, Shi Y, Zhang S. Incidence and risk factors of perioperative venous thromboembolism in patients with cervical cancer. Mol Clin Oncol. 2022 Jun;16(6):108.
Geddings JE, Mackman N. Tumor-derived tissue factor-positive microparticles and venous thrombosis in cancer patients. Blood. 2013;122(11):1873–80.
Gadducci A, Cosio S, Spirito N, Genazzani AR. The perioperative management of patients with gynecological cancer undergoing major surgery: a debated clinical challenge. Critical Reviews in Oncology/Hematology. 2010;73(2):126–40.
Rodriguez AO, Wun T, Chew H, Zhou H, Harvey D, White RH. Venous thromboembolism in ovarian cancer. Gynecologic Oncology. 2007;105(2):428–32.
Barber EL, Clarke-Pearson DL. Prevention of venous thromboembolism in gynecologic oncology surgery. Gynecologic Oncology. 2017;144(2):420–7.
Prandoni P, Lensing AW, Piccioli A. Recurrent venous thromboembolism and bleeding complications during anticoagulant treatment in patients with cancer and venous thrombosis. Blood. 2002;100(10):3484–8.
Lyman GH, Carrier M, Ay C. American Society of Hematology 2021 guidelines for management of venous thromboembolism: prevention and treatment in patients with cancer. Blood Advances. 2021;5(4):927–74.
Streiff MB, Holmstrom B, Angelini D. NCCN Guidelines Insights: Cancer-Associated Venous Thromboembolic Disease, Version 2.2018. Journal of the National Comprehensive Cancer Network. 2018;16(11):1289–303.
Kim JY, Jung KW, Park S. The incidence of venous thromboembolism in cervical cancer: a nationwide population-based study. Medicine. 2012;91(4):196–203.
Farge D, Frere C, Connors JM. 2022 international clinical practice guidelines for the treatment and prophylaxis of venous thromboembolism in patients with cancer, including patients with COVID-19. Lancet Oncology. 2022;23(7):e334–47.
Mandala M, Falanga A, Roila F. Management of venous thromboembolism in cancer patients: ESMO Clinical Practice Guidelines. Annals of Oncology. 2011;22(Suppl 6):vi85–92.
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