Thromboprophylaxis in Portuguese Cancer Outpatients: Multicentric Real-World Evidence Study

Venous thromboembolism (VTE) affects up to 20% of cancer patients, presenting a risk four to seven times higher than that of the general population. This elevated risk is attributed to factors related to the patient, the tumour, and treatments. When deciding on primary thromboprophylaxis, these factors, along with the potential for bleeding and the impact on the patient’s quality of life, are considered. Over the years, various risk assessment models for cancer-associated thrombosis (CAT) have been developed to aid in selecting cancer outpatients for primary thromboprophylaxis and improving risk stratification and outcomes. Despite these advancements, controversies persist, and the use of primary thromboprophylaxis remains contentious despite international guidelines. Better characterization of patients undergoing thromboprophylaxis and understanding of risk factors for thrombotic and bleeding events is crucial.

A pioneering real-world evidence (RWE) study in Portugal, supported by a research grant from the Cancer and Thrombosis Study Group (GESCAT), investigated primary thromboprophylaxis in cancer outpatients. This multicentric study analysed 124 adult patients with solid tumours, evaluating the medication and duration used for thromboprophylaxis, thrombotic events (location and symptoms), bleeding events, cancer progression, and mortality. The participant group consisted primarily of elderly individuals with multiple comorbidities, balanced in gender, maintaining good performance status and body mass index, predominantly with advanced pancreatic and gastric cancers.

Thrombotic events occurred in 11%, mainly venous and symptomatic. The importance of maintaining primary thromboprophylaxis for at least six months with continuous monitoring is underscored by the observation that thrombotic events occurred around the 6th month of prophylaxis. Regarding bleeding events, they occurred in only 9%, with the majority classified as minor. Thromboprophylaxis proved effective and safe, with 81% of patients experiencing no thrombotic or bleeding events. An association was reported between known risk factors such as vascular compression, elevated D-dimer levels, and a history of VTE with the occurrence of thrombosis, showing the relationship between tumour aggression and thrombo-inflammation. These results identify a very high-risk subgroup for thrombosis, even under thromboprophylaxis, which would benefit from more personalized prophylaxis strategies.

The findings provide the first real-world data in Portugal on primary thromboprophylaxis in cancer outpatients. They support the use of primary thromboprophylaxis in medium-to-high-risk patients, as the majority did not experience VTE or bleeding events. The study highlights the need for more personalized primary thromboprophylaxis strategies, the urgency of defining optimal duration and dosage and evaluating the impact on patient's quality of life. It also emphasizes the importance of assessing adherence to international guidelines, identifying challenges in their implementation, and discovering new predictive factors for thrombosis and bleeding. Further research in cancer-associated thrombosis is crucial for optimizing prevention and improving patient quality of life.

Authors and Affiliations:

Joana Liz-Pimenta ^1 2, Valéria Tavares ^2 3 4, João Gramaça ⁵, João Rato ⁶, Maria Menezes ⁷, Mafalda Baleiras ⁸, Helena Guedes ⁹, Joana Reis ¹⁰, Catarina Guedes ¹¹, Rosa Gomes ¹, Miguel Barbosa ¹⁰, Marta Sousa ¹, Alok A Khorana ¹², Rui Medeiros ^{13 14 15 16 17}

¹ Department of Medical Oncology, Hospital Center of Trás-Os-Montes E Alto Douro, 5000-508, Vila Real, Portugal.

² Faculty of Medicine of University of Porto (FMUP), 4200-072, Porto, Portugal.

³ Molecular Oncology and Viral Pathology Group, Research Center of IPO Porto (CI-IPOP) / Pathology and Laboratory Medicine Dep., Clinical Pathology SV / RISE@CI-IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto) / Porto Comprehensive Cancer Center (Porto. CCC), 4200-072, Porto, Portugal.

⁴ ICBAS - Instituto de Ciências Biomédicas Abel Salazar, Universidade Do Porto, Porto, Portugal.

⁵ Department of Medical Oncology, Hospital Center of Barreiro Montijo, 2830-003, Barreiro, Portugal.

⁶ Department of Medical Oncology, Hospital of Luz Setúbal, 2900-722, Setúbal, Portugal.

⁷ Department of Medical Oncology, Hospital of Espírito Santo de Évora, 7000-811, Évora, Portugal.

⁸ Department of Medical Oncology, Hospital Center of Lisboa Ocidental, 1449-005, Lisbon, Portugal.

⁹ Department of Medical Oncology, Hospital Center of Vila Nova de Gaia / Espinho, 4434-502, Vila Nova de Gaia, Portugal.

¹⁰ Department of Medical Oncology, University Hospital Center of São João, 4200-319, Porto, Portugal.

¹¹ Department of Imunohemotherapy, Hospital of Senhora da Oliveira, 4835-044, Guimarães, Portugal.

¹² Department of Hematology and Medical Oncology, Taussig Cancer Institute, Cleveland Clinic Foundation, Cleveland, OH, 44106, USA.

¹³ Faculty of Medicine of University of Porto (FMUP), 4200-072, Porto, Portugal.

¹⁴ Molecular Oncology and Viral Pathology Group, Research Center of IPO Porto (CI-IPOP) / Pathology and Laboratory Medicine Dep., Clinical Pathology SV / RISE@CI-IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto) / Porto Comprehensive Cancer Center (Porto. CCC), 4200-072, Porto, Portugal. 

¹⁵ ICBAS - Instituto de Ciências Biomédicas Abel Salazar, Universidade Do Porto, Porto, Portugal.

¹⁶ Research Department, Portuguese League Against Cancer - Regional Nucleus of the North, 4200-172, Porto, Portugal.

¹⁷ Biomedical Research Center, Faculty of Health Sciences of the Fernando Pessoa University, 4249-004, Porto, Portugal.

Abstract:

Introduction: Cancer-associated thrombosis (CAT) is a significant concern among patients with malignant diseases, leading to increased mortality. While current guidelines recommend primary thromboprophylaxis for venous thromboembolism (VTE) in medium-to-high-risk outpatients, this practice remains controversial. A better understanding of primary thromboprophylaxis is crucial, yet there is a lack of Real-World Evidence (RWE) in Portugal.

Aims: This RWE study aimed to elucidate primary thromboprophylaxis practices among cancer outpatients in Portugal.

Methods: A five-year observational multicentric study in eight Portuguese health institutions enrolled 124 adult cancer outpatients under primary thromboprophylaxis for VTE. The endpoints were CAT, bleeding, cancer progression and death.

Results: High thrombotic risk tumours were prevalent, with 57% (71) of the patients presenting with pancreatic and gastric cancers. Regarding primary thromboprophylaxis, 55% (68) received Low-Molecular-Weight Heparin (LMWH). VTE was presented in 11% (14) of the patients and major bleeding in 2% (2). Vascular compression, elevated D-dimer and previous VTE were significantly associated with VTE occurrence under primary thromboprophylaxis. The Onkotev model was shown to be the best risk assessment model (RAM) in this population (p = 0.007). CAT patients exhibited a lower progression-free survival than non-CAT patients (p = 0.021), while thrombosis did not influence overall survival (p = 0.542).

Conclusion: Primary thromboprophylaxis in medium-to-high-risk cancer outpatients is a safe and effective practice in real-world settings. This study is the first Portuguese RWE on primary thromboprophylaxis, highlighting evidence for improving prophylactic strategies in this population.

Journal: Journal of Thrombosis and Thrombolysis

Link: https://link.springer.com/article/10.1007/s11239-024-02984-1