Ischemic stroke in cancer patients: A review of an underappreciated pathology

Abstract

Currently 1 in 10 patients with ischemic stroke have comorbid cancer, and this frequency is expected to increase with continued advances in cancer therapeutics prolonging median survival. Well known for its association with venous thrombosis, cancer has recently emerged as a significant risk factor for arterial thromboembolism, including stroke; however, the underlying mechanisms are uncertain. In addition, the optimal strategies to prevent and acutely treat stroke in cancer patients are yet to be established. This review summarizes the current evidence on ischemic stroke risk, biomarkers, pathophysiology, treatments, and prognosis in cancer patients, emphasizing knowledge gaps and the potential strategies to address them. Ann Neurol 2018;83:873-883.

Figure 1

Potential reasons for cancer patients’ increased risk of ischemic stroke. Diagram depicting the possible underlying explanations for cancer patients’ heightened stroke risk. These include: (a) biological factors, such as cancer-mediated hypercoagulability, adverse effects of cancer treatments, and increased psychological stress after cancer diagnosis; (b) diagnosis-related factors, such as detection bias from heightened surveillance and underutilization or frequent interruption of antithrombotics because of bleeding concerns; and (c) shared risk factors, such as atrial fibrillation, obesity, and tobacco use. Most likely multiples factors are at play, some of which may be synergistic.

Figure 2

Hypothesized line graph of cancer patients’ suspected risk of ischemic stroke over time. Based on the totality of current evidence, we hypothesize a U-point curve whereby risks are increased immediately before and in the year after cancer diagnosis when cancer-mediated hypercoagulability is generally at its peak, followed by a reduction or normalization in stroke risk for several years among those whose cancers are cured or put into long-term remission, followed again years later by progressively increasing risk due to the long-term effects of cancer treatments, particularly radiation vasculopathy.