Aurora Semerano, MD
European Stroke Organisation Conference
May 4-6, 2022
Among other themes, this year ESOC has represented a unique opportunity to discuss cancer-related stroke in a dedicated Scientific Session titled “Stroke, thrombosis and cancer,” chaired by Blanca Fuentes (Spain) and Leo Bonati (Switzerland).
Indeed, cancer is recently emerging as a risk factor for arterial thromboembolism, including stroke. Among ischemic stroke patients, comorbid cancer is a devastating condition associated with increased stroke severity, disability, and mortality. Importantly, the optimal strategies to prevent and acutely treat stroke in cancer patients are yet to be established, with high recurrence rates despite antithrombotic therapies, and there are currently limited resources to assist stroke clinicians in the specific management of cancer patients.
Nicolas Martinez-Majander (Finland) provided a solid introduction to the topic. Epidemiologically, 10% of newly-diagnosed ischemic stroke patients might also have comorbid cancer. Specific cancer types (namely, lung, pancreatic and colorectal cancers) seem to have higher association with ischemic stroke, while other common cancer types (including breast, urogenital and prostate cancers) have been recently reported too. No international guidelines include a recommendation on whether to search for an underlying cancer in the first place in a stroke patient; however, clinical features (weight loss, fatigue, smoking), laboratory data (persistently elevated markers of coagulation, anemia, elevated CRP and/or ESR), stroke subtype (ESUS), and neuroimaging pattern (multiple DWI lesions in multiple arterial territories) may help in suspecting an underlying cancer.
Konstantin Stark (Germany) went deep into mechanisms of cancer-related hypercoagulability. Several pathways are involved, including release of tissue factor, cancer cell-derived microvesicles, platelet and endothelial activation, unbalance of procoagulant/fibrinolysis factors, release of neutrophil extracellular traps that promote thrombo-inflammation, and production of cytokines. They result in a procoagulant/proinflammatory environment and represent possible targets to address potential future preventive therapies. Finally, Clonal Hematopoiesis of Indeterminate Potential (CHIP) is mentioned as a new risk factor at the crossroads between aging, cardiovascular disease, and cancer.
Scott Kasner (USA) talked about the complex relationship and causality among cancer, stroke, and cancer treatments. Different treatments (including radiotherapy, different lines of chemotherapy, cancer supportive treatment with growth factors, new strategies such as CAR T therapy) were specifically reviewed. Whereas the topic remains difficult to study, with many confounders, some potential mechanisms of cancer treatment-related stroke have been identified, including direct vascular injury, accelerated atherosclerosis, cardiotoxicity, hypercoagulability, and cytokine release. Whereas the strength of the association and optimal antithrombotic treatments are unclear, aggressive control of vascular risk factors is recommended.
Babak Navi (USA) shared implications about biomarkers of cancer-related hypercoagulability. Blood markers of coagulation, platelet activity, endothelial dysfunction are increased in cancer-related stroke compared to matched controls, indicating that the underlying hypercoagulable state leading to these events is complex and multifactorial. These biomarkers also are associated with risk of poor outcomes, and thus may be useful prognostic tools. Although not specific, D-dimer is probably the most robust and powerful marker for cancer-related stroke in terms of risk, mechanisms, and prognosis. It has been recently found that D-dimer strongly correlates with CA125 levels, a mucinous tumor marker, providing evidence that cancer activity drives cancer-related hypercoagulability, hence aggressive tackling cancer activity should be a priority.
Oh Young Bang (South Korea) concluded the session by discussing optimal anti-thrombotic treatments in patients with stroke and comorbid cancer. Considerations for the development and the choice of the best strategy for each patient should include the etiologic mechanisms of stroke (not all strokes in cancer patients are cancer-related), the molecular mechanisms for coagulopathy, and patient compliance. At the research level, strategies addressing specific pathways with limited implications on hemostasis (i.e., NETosis) appear promising. No specific guidelines exist so far. Retrospective studies are available about anticoagulation in cancer-associated stroke, but they show conflicting results. Two randomized clinical trials (ENCHASE and TEACH2) are ongoing to evaluate NOACs for the treatment of coagulopathy in active cancer and acute stroke.