Venous thromboembolism (VTE) is a well-established complication in cancer patients, with a 4- to 7-fold higher risk compared to noncancer patients . Anticoagulant treatment is crucial for managing acute VTE, but it poses a risk of bleeding, ranging from trivial to life-threatening. Patients with brain cancer face an elevated VTE risk. Treating them with anticoagulants is challenging due to the potential for intracranial hemorrhage (ICH), which may offset benefits .
The unique risk profile of patients with brain cancer has led to their exclusion or underrepresentation in VTE treatment trials, resulting in limited data on managing VTE in this specific population. The Registro Informatizado de Enfermedad TromboEmbólica (RIETE, NCT02832245) is an international registry tracking patients with acute VTE, aiming to collect data on clinical characteristics, treatment, and outcomes .
An analysis within the RIETE study focuses on patients with VTE and brain cancer, aiming to: I) provide insights into a substantial sample of this specific group; II) compare VTE outcomes in patients with active brain cancer, those with active nonbrain cancer, and those without cancer; III) offer information on the clinical course of VTE in patients with different types of active brain cancer, such as glioblastoma or other malignant brain cancers .
In this article, we summarize the key points of the analysis.
The study methods
The study enrolled consecutive patients with acute, symptomatic, objectively confirmed VTE from the RIETE Registry, spanning March 2001 to September 2022. Patients were categorized into three groups: I) those with active brain cancer, II) those with active nonbrain cancer, III) those without active cancer. Exclusion criteria included participants in blind medication trials and those not providing consent. Active cancer was defined within three months of incident VTE, including metastatic cancer or ongoing cancer therapy.
Treatment decisions were based on each hospital’s clinical practice, lacking standardization. The primary outcome was ICH at three months post-VTE diagnosis, with secondary outcomes including recurrent VTE, major bleeding, fatal ICH, fatal VTE, and death. ICH was confirmed by neuroimaging, major bleeding was clinically assessed, and VTE events were objectively confirmed. Baseline data, therapeutic strategies, and dosing of anticoagulant treatments were collected. Data quality control measures were implemented through regular monitoring, queries, and periodic visits to participating hospitals by contract research organizations.
The study findings indicate that individuals with active brain cancer are at an elevated risk of experiencing ICH and fatal ICH during anticoagulant treatment, surpassing the risks observed in patients with nonbrain cancer or those without cancer. Notably, the risk of ICH and fatal bleeding remains consistently high over time in patients with brain cancer following VTE, whereas the risk of fatal VTE peaks initially and stabilizes. Although the risks of recurrent VTE and major bleeding are similar in patients with active brain and nonbrain cancer, they are higher than in patients without cancer. Among various types of brain cancer, glioblastoma patients exhibit the highest risks of ICH, major bleeding, and VTE recurrences.
It is noteworthy that the absolute risk of ICH in patients with brain tumors is significantly higher than in those without or with nonbrain cancer. The occurrence of major bleeding in brain cancer patients is predominantly intracranial, emphasizing the inherent risk of ICH in this population. Interestingly, there is an observed higher incidence of subtherapeutic doses of anticoagulants and vena cava filter insertion in brain cancer patients compared to other groups, possibly due to the perceived heightened risk of ICH.
While the reported rate of ICH in brain cancer patients is lower than in some previous studies, potential discrepancies may stem from differences in study design and follow-up duration. In this study, the 3-month follow-up period revealed major bleeds occurring predominantly during anticoagulant treatment.
Regarding recurrent VTE and fatal pulmonary embolism, the rates were similar in patients with brain and nonbrain cancer, suggesting comparable risks. However, limited data on recurrent VTE in brain cancer patients are available.
In patients with brain cancer, rates of ICH and fatal ICH during anticoagulant treatment increase over time, while fatal PE rates are higher initially and stabilize. This distinctive pattern is not observed in patients without cancer or with nonbrain cancer. Consequently, the study suggests the need for further investigation into anticoagulation regimens, such as early dose reduction in brain cancer patients, and explores the potential benefits of direct oral anticoagulants (DOACs).
Differentiating between types of brain cancer, the study identifies varying risks of major bleeding and ICH, with glioblastoma patients exhibiting the worst prognosis in terms of recurrent VTE and bleeding complications. Although small sample sizes limit definitive conclusions, these findings hold particular relevance due to the prevalence of glioblastoma among primary brain cancers.
Despite some limitations inherent in registry-based research, such as variability in anticoagulation regimens and potential underestimation of event frequencies, the study’s large sample size and consistency with previous literature support the reliability of its results.
In conclusion, individuals with brain cancer and VTE face substantial risks of ICH and fatal ICH, complicating anticoagulation decisions and underscoring the imperative need for further research to evaluate diverse treatment strategies for this specific population.
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