By Christian Boehme
Twitter: @chris7ianb
Ischemic Stroke in Cancer
Vojtech Novotny from Oslo, Norway chaired this exciting session in the afternoon.
Jamie Verhoeven (Nijmegen, Netherlands) sparked off the session with a talk about Stroke in the young and cancer. She highlighted the facts that the highest risk of stroke is in the first 6 months after diagnosis and in stage IV cancer. The absolute risk of cancer in stroke is higher in older patients but the relative risk is higher in young patients (compared to the general population). The risk increase is age- and time dependent with the highest risk in the first years after stroke in young patients. The shared unpublished data from a Dutch cohort showed that in roughly 1700 stroke patients aged 18-49 years, 1.0% of these had a cancer diagnosis between 1 year pre- and post-stroke. Jamie also highlighted the “3-territory sign” on imaging as a red flag for a possible cancer-related stroke which made an underlying cancer 6-times more likely than AF as stroke etiology. Predictors of occult cancer in stroke patients are older age, smoking, cryptogenic etiology, multiple vascular territories affected, lower hemoglobin, and higher CRP, fibrinogen and D-dimer levels. Evidence regarding cancer screening in stroke patients is still lacking, but may be beneficial in selected (young) stroke patients with the aforementioned characteristics.
Matthias Endres (Berlin, Germany) did a presentation on clonal hematopoeisis as a novel stroke risk factor. Clonal hematopoiesis (CH) is associated with a higher risk of stroke, especially in hemorrhagic and small-vessel-disease ischemic stroke. In a prospective study (PROSCIS-B), 17% of stroke patients with clonal hematopoiesis had vascular endpoints after 3 years, predominantly recurrent stroke and vascular death. Vascular risk increased with clone size and number of mutations with the most prevalent being DNMT3A, TET2 and ASXL1. The clone size is primarily a function of the mutation-specific clonal fitness and not age per se. Furthermore, TET2- and PPM1D-mutations have a strong association with recurrent vascular events and death, whereas DNMT3A obviously is a more benign phenotype. Matthias also pointed out that there are stroke-specific subtype differences in the prevalence of CH, with large artery atherosclerosis being the predominant etiology in case a CH is detected.
Next, Babak Navi from Weill Cornell University, New York talked about mechanisms of stroke in cancer patients. There are lots of hematological biomarkers in cancer-related ischemic stroke, of those D-dimer and P-selectin having the most pronounced increase. Also, he reported research of more frequent circulating microemboli detected in transcranial ultrasound in cancer-related ischemic stroke. Babak showed his personal diagnostic approach to cancer-related ischemic stroke. He includes brain-MRI with and without contrast, as well as CTA of head and neck, d-dimer, lipid profile and HbA1c. Furthermore ,he pointed out the importance of cardiac imaging including TEE (with remark to valvular “thickening” which might be indicative for non-bacterial thrombotic endocarditis (NBTE). Finally, he includes lower extremity ultrasound in case of R-L shunt, TCD monitoring for microemboli and cardiac rhythm monitoring for at least 2 weeks. In conclusion, cancer is associated with a marked increase of ischemic stroke especially around the time of diagnosis, stroke mechanisms in cancer patients seem to be often unique and related to neoplastic or treatment properties, and very important, 50% of cancer-related strokes are considered cryptogenic, whereby many might be due to NBTE, which produces platelet-rich emboli.
Gianluca Costamagna (Lausanne, Switzerland) elaborated on prognostic factors in cancer-related stroke in a great talk. He defined prognosis of disability to be mainly driven by metastatic cancer and the use of revascularization. He pointed out that, based on available evidence, thrombolysis and thrombectomy are considered to be safe in cancer patients with an exemption to brain tumors. Prognostic factors for mortality include venous thromboembolism, metastatic cancer, the use of revascularization procedures, the 3-territory sign in imaging, as well as high D-dimer levels and very important, the restart or initiation of cancer treatment. Prognostic factors of stroke recurrence are adenocarcinoma subtypes, high D-dimer levels and use of dOACS, hence the use of dOACS and antithrombotic therapies requires more research and there is – until now – not sufficient evidence to draw final conclusions.
In a question from the audience, Gianluca points out the striking underresearch of cancer-related hemorrhagic stroke.
Last but not least, Nilufer Yesilot (Istanbul, Türkiye) gave an update on stroke prevention in cancer patients. She pointed out, that registries of cancer-related stroke patients showed no difference in odds for recurrent stroke, recurrent thromboembolism or death between antiplatelet and anticoagulant therapy regimes. As mentioned before, retrieved emboli from EVT showed to be platelet-rich, possibly indicating a benefit of antiplatelet therapy in this population. Additionally, research reports a 20% annual risk of bleeding undermining a possible benefit of antiplatelet therapy but evidence to date shows equipoise. Furthermore, dOACS might be comparable to LMWH therapy and are subject to further research. Of note, and probably most important, it should be the central goal to reduce cancer activity to fight further thromboembolic events. Finally, Nilufer reports results from a meta-analysis by Cereda et al. which showed equal risk of stroke and major bleeding in cancer patients with AF amounting at 5.2%. DOACS reduced the incidence of ischemic stroke by 27% and reduced major bleeding events by 42% compared to warfarin.
