Cancer-associated thrombosis management is incredibly challenging because of the high risk of recurrence and severe bleeding associated with anticoagulant therapies. In addition, multiple peculiar variables exist in patients with cancer. For example, cancer type, cancer treatment, and patient-specific characteristics influence the risk of thrombosis and complicate anticoagulant treatment decision-making [1].
Many clinical practice guidelines are available for the management of CAT. However, several critical decisions are still based on low-level evidence, especially for those categories of under-represented patients in clinical trials [2]. For example, very little information is available for patients with temporary or sustained chronic thrombocytopenia, or those who receive targeted therapies, antiangiogenics, or immunotherapy, or for patients with severe kidney failure [2].
Real-world evidence studies and cancer registries are emerging tools that could improve clinical practice.
Registries available on VTE and cancer
The RIETE registry is the largest registry for venous thromboembolism (VTE) globally, comprising over 82,000 patients. However, it is not specific to CAT, meaning that it doesn’t consider cancer-specific variables that can impact VTE risk [3].
It is known that specific mutations can increase the risk of VTE, such as ALK mutation in non-small-cell lung cancer, which is associated with a risk increase of 30–47% [4]. In addition, chemotherapy can modify the risk of VTE depending on the drug used, with cisplatin being the drug correlated with the highest risk of thrombosis [5].
To further complicate decision making, each variable interacts with the others, modifying the VTE risk. For this reason, it is important to gather specific and detailed information on the risk of VTE in patients with cancer.
A few cancer focused thrombosis registries exist, but most of them include patients with only some types of VTE or have a short follow-up.
GARFIELD-VTE is an international, multicenter, observational, and prospective study of patients with newly diagnosed VTE. It enrolled more than 10,000 patients with deep vein thrombosis (DVT) and pulmonary embolism (PE) in 28 countries worldwide. One of the objectives was an analysis of a subgroup of patients with cancer [6].
PERCEIVE is a large prospective, non-interventional cancer registry designed to record thromboembolic and cardiovascular events in patients with a new breast, colon, and rectum, pancreas, lung, prostate, or ovary cancer diagnosis. It includes patients recruited from North America, Europe, and Asia and followed for 11 years (https://www.perceiveregistry.org/).
The international registry on recurrent VTE in anticoagulated patients with cancer aims at exploring different antithrombotic regimens and new VTE despite anticoagulation. It enrolled patients from 10 countries followed until death or for a maximum of 3 months. However, one of its limitations is the short follow-up period [7].
The cancer-VTE registry is a cross-sectional Japanese cohort study based on a multicenter, prospective clinical registry. It enrolled patients with colorectal, lung, stomach, breast, gynecological or pancreatic cancer, and it has a follow-up period of 1 year. However, one of its limitations is the lack of representation of all cancer types [8].
The TESEO registry
The TESEO registry was launched by the Cancer and Thrombosis Section of the Spanish Society of Medical Oncology (SEOM) to provide prospective real-life information on CAT, including special situations, rare conditions, and areas not represented by clinical trials [9].
It is an ongoing epidemiological, prospective, non-interventional, multicenter study in cancer patients with a newly diagnosed thromboembolism.
The main objective of the registry is to provide epidemiological and clinical data on CAT, while the secondary objectives are to:
- determine factors related to recurrent thrombosis and bleeding risk,
- provide knowledge on CAT management in patients underrepresented in clinical trials,
- collect information in new areas of interest and new specific oncological contexts (like new therapies or certain molecular cancer varieties) [2].
The information gathered by the TESEO registry will be useful for expanding our knowledge on CAT and construct predicting models for recurrent thrombosis and bleeding.
Patients are recruited prospectively and consecutively to avoid selection bias, and eligibility criteria include:
- age above 18 years,
- histologically confirmed diagnosis of malignancy,
- radiological confirmed symptomatic or incidental thromboembolism in the previous month or up to two years after cancer diagnosis [2].
Patients are treated following the local practice and will be followed for a minimum of 5 years or until death.
Two integrated and independent prospective registries will be carried out. The first registry includes regular CAT seen in a general population of patients with cancer. The second includes CAT registered in special situations like:
- patients with temporary or chronic thrombocytopenia
- patients with a high bleeding risk due to cancer type or antitumor treatment
- patients who receive new non-cytostatic treatments
- patients with kidney failure [2]
The main outcomes of interest include:
- recurrent VTE,
- major bleeding and clinically relevant non-major bleeding,
- arterial thromboembolism,
- prevalence of thromboembolism by type of cancer or treatment,
- side effects of anticoagulant therapies,
- causa of death, tumor progression, and survival,
- the therapeutic algorithm used in special situations [2].
Preliminary results of TESEO
Between July 2018 and December 2019, 939 patients with VTE have been recruited. Among these, the highest incidence tumors were colorectal (21.4%), non-small-cell lung (19.2%), and breast (11,1%) [10].
71.5% of patients had an active tumor or stage IV at the moment of VTE event, even though cancer type influences VTE distribution based on TNM stage [10].
50.3% of VTE were unsuspected, but of these, only 57.1% were asymptomatic. Most events were grade 2 and 3 (43.2% and 52.2%, respectively). PE occurred in 60.8% of patients, and in 21.0% of patients was accompanied by DVT [10].
VTE location depends on the type of neoplasm. For example, portal vein thrombosis occurred predominantly in colorectal, pancreatic, hepatocellular, and biliary tumors, while caterer-related VTE in colorectal, breast, and gastric cancer [10].
Tumors with the highest rate of recurrent thrombosis were non-small cell lung, colorectal and pancreatic cancer and the median time of recurrence was 1.7 months. The time of recurrence varies with the cancer stage, being 0.8 months for stages I–III and 2 months for stage IV [10].
To learn more insights from the TESEO registry, subscribe for our upcoming webinar “Clinical insights in CAT to include COVID‐19,” when Prof Andrez Munoz will share the latest results. It is free, and an application has been made to the UEMS EACCME® for CME accreditation.
References
1. Prandoni P, Lensing AW, Piccioli A, et al. Recurrent venous thromboembolism and bleeding complications during anticoagulant treatment in patients with cancer and venous thrombosis. Blood. 2002;100(10):3484-3488. doi:10.1182/blood-2002-01-0108
2. Muñoz-Langa J, Jimenez-Fonseca P, Carmona-Bayonas A, et al. Rationale, design and methodology of TESEO study: a registry of thrombosis and neoplasia of SEOM (Spanish Society of Medical Oncology). Clin Transl Oncol. 2021;23(4):799-811. doi:10.1007/s12094-020-02472-x
3. Bikdeli B, Jimenez D, Hawkins M, et al. Rationale, Design and Methodology of the Computerized Registry of Patients with Venous Thromboembolism (RIETE). Thromb Haemost. 2018;118(1):214-224. doi:10.1160/TH17-07-0511
4. Zugazagoitia J, Biosca M, Oliveira J, et al. Incidence, predictors and prognostic significance of thromboembolic disease in patients with advanced ALK-rearranged non-small cell lung cancer. Eur Respir J. 2018;51(5):1702431. Published 2018 May 3. doi:10.1183/13993003.02431-2017
5. Moore RA, Adel N, Riedel E, et al. High incidence of thromboembolic events in patients treated with cisplatin-based chemotherapy: a large retrospective analysis. J Clin Oncol. 2011;29(25):3466-3473. doi:10.1200/JCO.2011.35.5669
6. Weitz JI, Haas S, Ageno W, et al. Global Anticoagulant Registry in the Field – Venous Thromboembolism (GARFIELD-VTE). Rationale and design. Thromb Haemost. 2016;116(6):1172-1179. doi:10.1160/TH16-04-0335
7. Schulman S, Zondag M, Linkins L, et al. Recurrent venous thromboembolism in anticoagulated patients with cancer: management and short-term prognosis. J Thromb Haemost. 2015;13(6):1010-1018. doi:10.1111/jth.12955
8. Ohashi Y, Ikeda M, Kunitoh H, et al. Venous thromboembolism in patients with cancer: design and rationale of a multicentre, prospective registry (Cancer-VTE Registry). BMJ Open. 2018;8(5):e018910. Published 2018 May 30. doi:10.1136/bmjopen-2017-018910
9. Muñoz Martín AJ, Jiménez-Fonseca P, Carmona-Bayonas A, et al. TESEO, cancer-associated thrombosis registry from the Spanish Society of Medical Oncology (SEOM). Clin Transl Oncol. 2020;22(8):1423-1424. doi:10.1007/s12094-019-02265-x
10. Carmona-Bayonas A, Gómez D, Martínez de Castro E, et al. A snapshot of cancer-associated thromboembolic disease in 2018-2019: First data from the TESEO prospective registry. Eur J Intern Med. 2020;78:41-49. doi:10.1016/j.ejim.2020.05.031