Managing Cancer-Associated Stroke

Globally, around 15% of cancer patients have a concomitant cerebrovascular disease, mostly ischaemic stroke, either as the first manifestation or preceding cancer diagnosis. Several cancer-specific mechanisms have been proposed, including direct tumour effects, hypercoagulable state by overexpressing procoagulant factors, cancer-related mucin production, non-bacterial thrombotic endocarditis, or because of anti-neoplastic treatments.¹ Studies have attempted to elucidate which cancer types conveyed a higher risk of ischaemic stroke occurrence, with urogenital, breast, and gastrointestinal being the most common types. On the other hand, melanoma, renal cell carcinoma, and brain metastasis have a higher tendency for bleeding and haemorrhagic stroke.²

Since the average lifespan is increasing, the incidence of cancer-associated ischemic stroke may increase owing to progress in cancer treatment, adding to the fact that patients with active malignancy are usually excluded from major clinical trials, acute stroke management remains a challenge. Although current guidelines state that systemic malignancy is not an absolute contraindication for intravenous thrombolysis (IVT) if life expectancy is >6 months and contraindications such as systemic bleeding, recent surgery, or coagulopathy do not coexist, concerns rise especially in gastrointestinal and intra-axial primary or metastatic brain tumours, regarded as high risk for bleeding complications.

A recent study from a comprehensive stroke centre including 79 patients with active malignancy, including mostly urogenital, and breast cancer patients, showed that IVT seems to be safe in these patients. Although bleeding was reported in this study, it was not associated with a higher risk for stroke treatment-related systemic or intracranial bleeding. Some report an increased risk of intracranial bleeding after recanalization therapy due to mechanisms such as disseminated intravascular coagulation or compromised synthesis of coagulation factors in the liver in case of primary liver tumour or metastases. Furthermore, IVT seems less safe in melanoma metastasis and haematological tumours as they are associated with a higher risk of symptomatic intracerebral haemorrhages.^3-4

In a recent systematic review on mechanical thrombectomy (MT) of large vessel occlusion due to cancer-related cerebral embolism including 37 patients, 67.5% underwent MT alone, while 32.5% received MT combined with IVT. Successful reperfusion was achieved in 89.1% of cases, with 59.4% reaching complete recanalization. Moreover, functional independence was observed in 29.7% of patients, highlighting the potential benefits of MT in this subset of patients.⁵

In conclusion, managing strokes in cancer patients is tricky, with concerns about bleeding risks. However, recent findings suggest that treatments like thrombolysis and thrombectomy could be safe and beneficial in most patients, offering hope for improved outcomes in this challenging patient population.

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References:

1. Costamagna G, Navi BB, Beyeler M, Hottinger AF, Alberio L, Michel P. Ischemic Stroke in Cancer: Mechanisms, Biomarkers, and Implications for Treatment. Semin Thromb Hemost. 2023 Jul 28.
2. Dearborn JL, Urrutia VC and Zeiler SR. Stroke and cancer: a complicated relationship. J Neurol Transl Neurosci 2014; 2: 1039
3. Chae WH, Vössing A, Li Y, Deuschl C, Milles LS, Kühne Escolà J, Hüsing A, Darkwah Oppong M, Dammann P, Glas M, Forsting M, Kleinschnitz C, Köhrmann M, Frank B. Treatment of acute ischemic stroke in patients with active malignancy: insight from a comprehensive stroke center. Ther Adv Neurol Disord. 2023 Oct 31;16:17562864231207508.
4. Schrag M, Kirshner H. Management of Intracerebral Hemorrhage: JACC Focus Seminar. J Am Coll Cardiol. 2020 Apr 21;75(15):1819-1831.
5. Toruno M, Al-Janabi O, Karaman I, Ghozy S, Senol YC, Kobeissi H, Kadirvel R, Ashdown B, Kallmes DF. Mechanical thrombectomy for the treatment of large vessel occlusion due to cancer-related cerebral embolism: A systematic review. Interv Neuroradiol. 2024 Feb 8:15910199241230356.