Venous thromboembolism (VTE) is a significant concern for patients with active cancer undergoing systemic therapy, with an increased risk of both VTE occurrence and recurrence. Over the years, advances in understanding cancer-associated thrombosis (CAT) and the development of risk assessment tools have improved our ability to identify those at high risk. However, a critical need remains to examine the associations of various factors with CAT, such as race and ethnicity, cancer subtype, and systemic therapy regimens, particularly over time as treatment landscapes have evolved.
Prior large cohort studies reported a higher incidence of CAT over time, but introducing new systemic therapies, including immunotherapy and targeted therapy, has prompted further investigation into VTE risk compared to traditional chemotherapy [1,2]. Moreover, recent analyses have highlighted disparities in CAT incidence and risk among patients of different races and ethnicities [3,4].
The Cohort Study in US Veterans
To address these gaps, a longitudinal cohort analysis was conducted using integrated data from the US Department of Veterans Affairs (VA) national healthcare system [5]. The analysis included 434,203 US patients with both solid tumors and hematologic neoplasms over 16 years. The aim was to characterize the incidence, associated factors, and outcomes of CAT among patients with cancer in the US [5].
The study specifically examined the trends of VTE incidence over time. It explored the relationships between cancer type, treatment, race and ethnicity, US region, and other relevant factors with the occurrence of CAT and overall survival in this diverse patient population [5].
The overall incidence of CAT at 12 months was 4.5%, with yearly trends ranging from 4.2% to 4.7%. In contrast with other large population studies, the incidence of CAT in this analysis remained largely stable over time [1,2]. This difference might be attributed to variations in cancer type compositions, average age, and the predominance of male patients in the cohort. The study used a rigorous outcome algorithm, including radiology reports in addition to ICD codes, to accurately capture and interpret CAT trends over time [5].
The risk of CAT was most strongly associated with cancer type and stage, with up to a 6-fold difference observed between different cancer subtypes. Systemic treatment, particularly chemotherapy-based and immunotherapy-based regimens, was also linked to a higher risk of CAT [5].
Interestingly, after adjusting for various patient, cancer, and treatment-related variables, the study found a 20% higher risk of CAT among non-Hispanic Black patients and a 20% lower risk among Asian or Pacific Islander patients compared with non-Hispanic White patients. However, differences in risk remained between different cancer types. These findings suggest that patient-specific and treatment-specific factors are critical in assessing CAT risk and should be considered in future VTE risk stratification models [5].
The study also revealed novel patterns among patients with hematologic neoplasms, with a higher incidence of VTE observed in patients with aggressive leukemias and lymphomas than indolent ones. Additionally, chemotherapy-based and immunotherapy-based regimens were associated with a higher risk of VTE than targeted agents or endocrine therapy alone [5]. In a previous article, we overviewed immune checkpoint inhibitors and cancer-associated thrombosis.
Finally, when comparing adjusted rates of CAT among patients of different races and ethnicities, non-Hispanic Black patients were found to have a significantly higher risk of CAT compared to non-Hispanic White patients, even after accounting for socioeconomic and other patient-related and cancer-related factors. However, these differences in risk among races and ethnicities were not associated with worse outcomes, as Hispanic patients and Asian or Pacific Islander patients had improved survival outcomes compared to non-Hispanic White patients [5].
Limitations and conclusions
The study acknowledges several limitations, such as underestimating the incidence of VTE, the predominantly older male study population, and the inability to include certain potential risk factors. Despite these limitations, the findings highlight the importance of considering additional epidemiologic factors in future VTE risk stratification models [5].
Overall, this study provides valuable insights into the incidence and risk factors of CAT in cancer patients, emphasizing the need for personalized approaches to manage and prevent VTE in this population.
Also, the findings from this study can help optimize treatment strategies and prognostic assessment for cancer patients at risk of CAT, ultimately improving patient outcomes and quality of care.
References
- Mulder FI, Horváth-Puhó E, van Es N, et al. Venous thromboembolism in cancer patients: a population-based cohort study. Blood. 2021;137(14):1959–1969. doi:10.1182/blood.2020007338
- Mahajan A, Brunson A, Adesina O, Keegan THM, Wun T. The incidence of cancer-associated thrombosis is increasing over time. Blood Adv. 2022;6(1):307–320. doi:10.1182/bloodadvances.2021005590
- Datta T, Brunson A, Mahajan A, Keegan T, Wun T. Racial disparities in cancer-associated thrombosis. Blood Adv. 2022;6(10):3167–3177. doi:10.1182/bloodadvances.2021006209
- da Costa WL Jr, Guffey D, Oluyomi A, et al. Patterns of venous thromboembolism risk, treatment, and outcomes among patients with cancer from uninsured and vulnerable populations. Am J Hematol. 2022;97(8):1044–1054. doi:10.1002/ajh.26623
- Martens KL, Li A, La J, et al. Epidemiology of cancer-associated venous thromboembolism in patients with solid and hematologic neoplasms in the Veterans Affairs health care system. JAMA Netw Open. 2023;6(6):e2317945. doi:10.1001/jamanetworkopen.2023.17945