Cancer-related stroke: When to suspect and how to treat?

Author: Dr Nicolas Martinez-Majander

Affiliation: Clinical Neurosciences, Department of Neurology, University of Helsinki and Department of Neurology, Helsinki University Hospital, Finland

According to Word Health Organization (WHO), noncommunicable diseases, such as cardiovascular diseases, cancer, and chronic obstructive pulmonary disease account for 80% of deaths in the European Region. Particularly, diseases of the circulatory system (e.g. stroke) are the most important cause of premature death in Europe, accounting for nearly 50% of the total.

Up to 10% of ischemic stroke patients have also comorbid cancer.¹ Potential mechanisms between cancer and ischemic stroke are still partially unclear, but include abnormalities in the coagulation system, in platelets, and in fibrinolytic pathways, as well as endothelium dysfunction and abnormalities in turbulence in abnormal blood vessels. Cancer can also lead to marantic (non-bacterial) endocarditis, anemia, mechanical compression of critical vessels, tumor embolism, and cerebral venous thrombosis.^2,3 Importantly, active cancer can contribute to early neurological deterioration, higher in-hospital post-stroke mortality, and substantial short-term risk of stroke recurrence and other thromboembolic events.^4,5,6

Cancers related to smoking are particularly associated with increased risk of stroke, but other malignancies such as lymphoma and central nervous system cancer, could be also associated with stroke.^7,8 In patients with stroke of unknown cause you should particularly be aware of  lung, pancreatic, breast, stomach and colon cancers, as these are most likely to be associated with stroke.

Regarding to stroke etiologic subtype, cryptogenic strokes especially in elderly patients, perhaps with an embolic pattern (brain imaging might show multiple lesions in multiple arterial territories), should raise the suspicion of occult cancer as a possible underlying etiology. ⁹

What about hemorrhagic strokes? In a registry-based study of 208 patients with intracerebral or subarachnoidal hemorrhages, 68% had solid tumors, while 16% had primary brain tumors and 16% hematopoietic tumors. Of all the patients in this study, up to 44% had a known primary or metastatic brain tumor at the time of hemorrhage.  Overall, patients had less frequently conventional risk factors such as hypertension, and the prognosis was quite poor – but still comparable to intracranial hemorrhage in general population.¹⁰ The Danish study by Anderssen et al reported that as with ischemic stroke, the most frequent cancer types associated with hemorrhagic stroke are also smoking-related.⁸

When treating patients with cancer-related ischemic stroke, the most frequent question concerns optimal antithrombotic therapy in the future. An excellent review by Navi et al summarizes the scarce data on the topic so far.³ Although anticoagulation, especially low-molecular-weight heparins and more recently NOACs have been recommended for secondary prevention, the data so far comes mainly from venous thromboembolism trials.¹¹ Navi et al also showed in their TEACH trial pilot that in 20 patients with active cancer-related ischemic stroke randomized either to enoxaparin or aspirin, there were no difference in the relevant outcomes (major bleeding, thromboembolic events, and survival).¹² Still, only few studies have addressed the issue of superiority of e.g. direct oral anticoagulant compared to antiplatelets and large prospective randomized trials are needed.

In conclusion, the association between active cancer and stroke should be kept in mind, especially in cryptogenic stroke with embolic pattern. However, further studies on optimal antithrombotic treatment strategies in cancer-related stroke are still needed.

 

References:

1. Navi BB, Reiner AS, Kamel H, et al. Association between incident cancer and subsequent stroke. Ann Neurol 2015;77:291–300.
2. Lip GY, Chin BS, Blann AD. Cancer and the prothrombotic state. Lancet Oncol 2002;3:27-34.
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4. Nam KW, Kim CK, Kim TJ, An SJ, Oh K, Mo H, et al. Predictors of 30-day mortality and the risk of recurrent systemic thromboembolism in cancer patients suffering acute ischemic stroke. PLoS One 2017;12:e0172793.
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