Cancer and Stroke

Learning objectives

Cancer as a risk for stroke Different mechanisms

Introduction

• The relationship between stroke and cancer is complex
• Cancers can cause stroke indeed Stroke may be the presenting feature
• High risk - adenocarcinoma or those with widespread metastases
• Cancer is 2nd leading cause of death and stroke 4th in the USA
• Occult cancer may be an important missed diagnosis in cryptogenic stroke.

Cancers causing stroke

• Lung cancer
• Prostate cancer
• primary brain tumours
• Haematological malignancies
• Pancreatic cancer
• Gynaecological

Cancers with haemorrhagic metastases

• Melanoma, Renal, thyroid cancer
• germ cell tumours

Aetiologies

Tumour compression on vascular supply – arterial/venous/capillary Procoagulant effect of malignancy Procoagulant effect of treatments Leukostasis Cardioemboli from marantic endocarditis Radiation vasculopathy from head and neck cancers Coexisting risk factors : hypertension, hyperlipidemia, diabetes, atrial fibrillation and tobacco use

Possible mechanism: see See paper

Mechanism	Causal factor	Associated tumours	Stroke Characteristics
Hypercoagulability	Adenocarcinomas especially; secrete mucin; tumours activate coagulation cascade; release pro-coagulant cytokines	Adenocarcinoma of breast, lung, prostate, etc. Also brain, kidney or hematologic malignancies	Embolic appearing infarcts, end vessels
Venous-to-arterial embolism	PFO, right-to-left shunt	Uncertain, likely similar to tumours of hypercoagulable state	Embolic appearing
Non bacterial thrombotic endocarditis	Sterile vegetations, clumps of platelets and fibrin develop on aortic valve	Adenocarcinoma is most common	Multiple widely distributed small and large strokes
Direct tumour compression of vessel	Tumour growth and resultant oedema compresses major intracranial vessel	Glioblastoma multiforme, metastasis to brain	Large vessel, MCA common
Tumour embolism	Rare- cardiac tumour causes embolization of malignant cells	Atrial or aortic valve myxoma, metastatic tumours to heart	Embolic appearing
Hyperviscocity	Rare-“Thickened” blood causes hypoviscious obstruction of small end vessels	Polycythemia vera, multiple myeloma, Waldenstrom’s Macroglobulinemia, leptomeningeal carcinomatosis	Small end-vessels strokes
Angioinvasive/infiltrative	Rare-Hematologic malignancies infiltrate blood vessel wall, causing irregularities that predispose to arterial embolism	B-cell lymphoma	Multiple vascular territory infarcts
Post –radiation vasculopathy	Radiation after head and neck cancer causes vasculopathy leading to accelerated atherosclerosis, predisposing to vessel wall irregularities and embolism	Squamous cell carcinoma, other head and neck tumours	Embolic stroke from the affected carotid
Chemotherapy associated	Unknown	Associated with as cisplatin, methotrexate, L-aspariginase, thalidomide, lenalidomide, and bevacizumab	Varied

Clinical

• Ischaemic stroke syndromes
• Haemorrhagic stroke syndromes
• Strokes in cancer patients may be subclinical
• DVT often a sign of hypercoagulability

Marantic endocarditis

• This is a nonbacterial thrombotic endocarditis where there are found to be vegetations consisting of an amorphous mixture of fibrin and platelets onto heart valves on previously undamaged heart valves (most often aortic and mitral) in the absence of a bloodstream bacterial infection.
• It is a rare condition often associated with hypercoagulable states or advanced malignancy such as adenocarcinomas.
• The diagnosis is made by Echocardiography showing evidence of vegetations.
• It may be a cause of cardioembolic stroke. Management is focused on managing the underlying cause.

Investigations

• FBC, U&E, ESR, TFTs, CRP, ECG
• CT scan +/- contrast
• MRI +/- Gadolinium
• 12 lead ECG
• Echo and TOE if marantic endocarditis suspected
• Tumour staging

Differentials

• Prothrombotic conditions
• Vasculitis

Management

• Ensure good VTE prophylaxis as high risk with immobility + cancer
• Close liaison with oncology and haematology with shared care planing
• Depends very much on the state of the patient, the advancement of their malignancy and their best interest.
• LMWH is usually the treatment with a confirmed coagulopathy or a marantic endocarditis

References and further reading

• Stroke and Cancer- A Complicated Relationship. J Neurol Transl Neurosci. 2014; 2(1): 1039.
• Ischemic stroke in cancer patients: A review of an underappreciated pathology. Ann Neurol 2018;83:873–883

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