The management of cancer-associated venous thrombosis (CAT) is particularly challenging because of a high risk of major bleeding and recurrent venous thrombosis compared with the non-cancer population. However, in the last 20 years, thrombosis prophylaxis in cancer patients improved quite a lot. Clinicians learned the most relevant risk factors for cancer patients and have access to validated risk assessment models, randomized trials, and guidelines.
Still, a gap exists that can jeopardize treatment for cancer patients. Several reports have revealed treatment patterns for CAT that are not consistent with contemporary guideline recommendations, including both underuse and inappropriate choice of anticoagulant agents [1,2]. In addition, oncologists seem to be less aware of guidelines and risk scores [3].
Prof Pabinger, during her presentation at the 10th ICTHIC, said in this regard: “It is like playing bubble soccer; the thrombosis community is in one bubble, and the oncologist is in another one. We don’t understand each other.”
The use of risk assessment and anticoagulation prophylaxis
A survey published in 2020 among oncologists assessed current practice patterns surrounding venous thromboembolism (VTE) in the USA. The results showed that almost 70% of oncologist specialists do not know about the Khorana risk score (the first risk scored validated in 2008) [3,4].
Of the 24 participants who responded to the survey, only 38% reported “usually” discussing VTE risk with their patients, and 58% reported “never” using validated VTE risk assessment scores in clinical practice.
Most clinicians reported no or scarce familiarity with the Khorana score (67% “not at all” familiar, 17% “a little bit” familiar), and 67% reported no familiarity with the International Society on Thrombosis and Haemostasis (ISTH) recommendations [3].
A Clinical Practice Assessment
Another recent survey, presented at the ISTH 2020 Congress survey, assessed attitudes and barriers in CAT treatment among cardiologists, hematologists, and oncologists. The results indicate a substantial lack of knowledge regarding the existence of designated cancer thrombosis guidelines, despite these being available for over a decade [5].
Although 79% of responders manage 1–5 patients with CAT per week, the analysis showed that physicians had poor knowledge of low-molecular-weight heparin (LWMH) and direct oral anticoagulants (DOACs) clinical trial data in CAT and the risk of bleeding. Most importantly, the majority had difficulty selecting appropriate anticoagulant treatment for patients with CAT; only 21% of participants felt confident in selecting the appropriate anticoagulant strategy [5].
A Nationwide Survey among Danish Oncologists
A Nationwide Survey among Danish Oncologists aimed to describe contemporary CAT management in Danish oncology departments and identified, once again, knowledge gaps and inconsistencies between guidelines and clinical practice. The survey was open from 30 November 2018 to 31 January 2019; it collected answers from 156 physicians employed at oncology departments in Denmark based on their common practice [6].
The participants covered a broad range of oncology subspecialties; the most represented were lung cancer (19.0%, n=27), gastrointestinal cancer (19.0%, n=27), and breast cancer (18.3%, n=26). Even though CAT was often treated and followed up in oncology departments, a substantial proportion of physicians were unaware of designated cancer thrombosis guidelines [6].
In total, 98.6% (n=140) and 62.7% (n=89) of responders stated that deep vein thrombosis (DVT) and pulmonary embolism (PE) were treated in the oncology department, respectively. Regarding PE, 35.9% (n=51) responded that they only treat patients if they are hemodynamically stable; patients not hemodynamically stable were reported to be most treated at the cardiology department (86.3%, n=44) [6].
A total of 11.3% (n=16) of the participants reported that the department did not have clinical practice guidelines for the management of CAT, and 36.6% (n=52) that they did not know.
The great majority of responders (80.7% %, n=113, for DVT and 94.3%, n=132, for PE) do not use the diagnostic score to assess the risk of venous thrombosis. In addition, LMWH was the most frequently used anticoagulant as first-line treatment for CAT (98.6%, n=138 of responders). DOACs and vitamin K antagonists are used as second-line treatment (where the patient either does not tolerate or accept first-line treatment) by 36.4% and 12.1% of the responders, respectively. However, approximately half of the responders do not know which treatment to use as second-line treatment [6]. Most guidelines and the Danish guideline recommend using DOACs as first-line treatment now [7-9].
In the study, treatment duration seemed wrongly influenced by subtype of venous thrombosis, and thromboprophylaxis among hospitalized patients was substantially underused [6]. Danish guidelines recommend a similar duration of anticoagulant treatment for CAT for every subtype of venous thrombosis [9]. This study’s findings show that the management of patients with PE is more often following guidelines than DVT management [6].
Physicians were more likely to provide extended anticoagulation for patients with PE (77.7%) compared with patients with DVT (58.3%). In addition, 77.7% (n=108) responded that patients with active cancer and PE are treated while they have active cancer, and 20.1% (n=28) responded they are treated for six months. Instead, for patients with new-onset DVT, 58.3% (n=81) responded that patients are treated while cancer is ongoing, 36.0% (n=50) for 6 months, and 3.6% (n=5) for 3 months [6].
If patients experience recurrent VTE while treated with LMWH, 70.3% (n=97) of the participants responded that the treatment choice in the department was to increase the dosage of LMWH. Only 10.9% (n=15) reported other treatment choices, including continuing current treatment, dividing the current dose into two, and seeking specialist advice [6].
For immobilized patients with active cancer, almost half of the participants (44.6%) responded that thromboprophylaxis was only offered in exceptional cases [6].
Conclusion
All these studies indicate that still, a knowledge gap exists among oncologists about CAT management and treatment, despite national and international guidelines.
Increasing the dialogue between oncologists and experts in the thrombosis field is fundamental to raise awareness among oncologists by sharing information with them. In addition, it is of utmost importance to share information with clinicians that do not have an interest or real knowledge about CAT.
References
- Mahé I, Puget H, Buzzi JC, et al. Adherence to treatment guidelines for cancer-associated thrombosis: a French hospital-based cohort study. Support Care Cancer. 2016;24(8):3369-3377.
- Matzdorff A, Ledig B, Stuecker M, Riess H. Practice Patterns for Prophylaxis and Treatment of Venous Thromboembolism in German Cancer Patients. Oncol Res Treat. 2016;39(4):194-201.
- Martin KA, Molsberry R, Khan SS, Linder JA, Cameron KA, Benson A 3rd. Preventing venous thromboembolism in oncology practice: Use of risk assessment and anticoagulation prophylaxis. Res Pract Thromb Haemost. 2020;4(7):1211-1215
- 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):4902-4907
- Spyropoulos J, Padbury C. Uncovering Clinical Gaps in Treatment of Cancer-Associated Thrombosis: A Clinical Practice Assessment [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/uncovering-clinical-gaps-in-treatment-of-cancer-associated-thrombosis-a-clinical-practice-assessment/. Accessed June 22, 2021
- Højen AA, Overvad TF, Nybo M, et al. Management of Cancer-Associated Venous Thrombosis: A Nationwide Survey among Danish Oncologists. TH Open. 2021;5(2):e188-e194. Published 2021 Jun 16.
- Streiff MB, Holmstrom B, Angelini D, et al. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines), Cancer-Associated Venous Thromboembolic Disease. Version 1.2020. April 16, 2020. www.nccn.org/professionals/physician_gls/pdf/vte.pdf.
- Key NS, Khorana AA, Kuderer NM, et al. Venous thromboembolism prophylaxis and treatment in patients with cancer: ASCO clinical practice guideline update. J Clin Oncol. 2020;38:496-520
- Rasmussen MS, Dorff MH, Holt MI, Grove EL, Hvas AM. Cancer Og Venøs Tromboembolisme. Retningslinje Fra Dansk Selskab for Trombose Og Hæmostase Og Dansk Selskab for Klinisk Onkologi Accessed 2021 at: https://dsth.dk/pdf/CAT_2020.pdf