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Cancer patients with acute ischemic stroke (AIS) are high-risk for recurrent thromboembolic events (RTE). Currently, no risk stratification model exists to predict RTE in this population. We tested the hypothesis that the Khorana score, a validated risk model for predicting venous thromboembolism in cancer patients, can effectively classify RTE risk in cancer patients with AIS. We retrospectively identified adults with active solid or hematological cancer diagnosed with AIS at a tertiary-care cancer center from 2005 to 2010. The Khorana score at the time of index stroke was calculated. The primary outcome was arterial or venous RTE. Cox regression was used to evaluate the association of the Khorana score and its individual components with RTE. Harrell’s c-statistic was used to calculate the score’s discriminatory ability. Among 263 AIS patients, median survival was 84 days (IQR 24–149 days) and 90 (34%) had RTE. The median Khorana score was 2 (IQR 1–2, range 0–5). Cumulative rate of RTE was 28% among patients who scored 0, 36% with scores of 1–2, and 32% with scores of 3–6. The overall Khorana score was marginally associated with RTE (HR, 1.14; 95% CI, 1.02–1.28). Of its individual components, only leukocytosis was associated with RTE (HR adjusted for other components, 1.45; 95% CI 1.11–1.90). The score’s c-statistic for predicting RTE was 0.57. In this study, the Khorana score had poor discriminatory ability for predicting RTE in cancer patients with AIS. Future research is needed to identify better methods for predicting RTE in this high-risk population.

Introduction: Anticoagulants are often used in cancer patients with acute ischemic stroke (AIS) because of concerns for hypercoagulability. However, cancer patients are also prone to bleeding. No prospective study has compared different antithrombotic strategies in this population. We aimed to perform the first randomized trial comparing anticoagulation to antiplatelet therapy in cancer patients with AIS. Methods: We conducted a pilot multicenter randomized trial in adult patients with active systemic cancer and MRI-confirmed AIS. Patients were randomized to subcutaneous enoxaparin (1 mg/kg twice daily) or oral aspirin (81 mg daily) for 6 months. Antithrombotic therapy beyond 6 months was dictated by treating clinicians. Exclusion criteria included clear indications for anticoagulant (e.g., DVT) or antiplatelet (e.g., recent stents) therapy, high-risk conditions for bleeding, symptomatic carotid stenosis, and severe hematologic derangements. Patients were followed at clinical visits at 1, 3, and 6 months and by chart review from 6 months to 1 year. The primary outcome was feasibility, defined as an enrollment rate among eligible patients for which the lower bound of the 95% confidence interval (CI) exceeds 30%. Secondary feasibility outcomes included patient dropout and crossover rates. Results: In this interim analysis, 469 patients with cancer and stroke were screened from January 2013 to April 2016 and 49 (10.4%) were eligible. Frequent exclusionary reasons were clear indications for anticoagulation (n=128) and inactive cancer (n=83). We enrolled 20 of the 49 eligible patients, equating to an enrollment rate of 41% (95% CI 27-55%). Enrollment failures primarily occurred because of patient aversion to injections (n=11), patient or physician preference for anticoagulation (n=9), and patient aversion to trial participation (n=7). Thus far, there have been no dropouts but 6 patients crossed over from the enoxaparin arm to the aspirin arm. Major bleeding occurred in 3 patients in the aspirin arm and 1 in the enoxaparin arm; no patients had intracranial hemorrhage. Conclusion: A randomized trial comparing anticoagulation to antiplatelet therapy in cancer patients with AIS may be feasible and safe, particularly with an oral anticoagulant.

Introduction: Cancer patients who develop acute ischemic stroke (AIS) are at high risk for recurrent thromboembolism. No risk stratification model exists to predict recurrent events in this population. The Khorana score is a validated risk score for predicting venous thromboembolism in newly diagnosed cancer patients. Hypothesis: The Khorana score can effectively classify the risk of recurrent thromboembolism (RTE) in cancer patients with AIS. Methods: We retrospectively identified all adults with active systemic cancer diagnosed with AIS by MRI at a tertiary-care cancer center from 2005 through 2009. Two neurologists independently reviewed all available medical records through July 31, 2012. The Khorana score at the time of index stroke was calculated for each patient. Points were assigned for specific cancer sites (2 points for very high-risk sites: stomach or pancreas; 1 point for high-risk sites: lung, lymphoma, gynecologic, bladder, testicular, or renal), platelet count ≥350,000/mcL, hemoglobin Results: Among 263 study patients, 90 (34%) were diagnosed with RTE, including 36 (14%) with recurrent AIS. The median Khorana score was 2 (IQR 1-2, range 0-5). None of the individual components of the score were independently associated with RTE, although there was a nonsignificant trend for high-risk cancer sites (OR 1.56, 95% CI 0.88-2.77). The rate of RTE was 28% among patients with a score of 0, 36% among patients with a score of 1-2, and 32% among patients with a score of 3-6. The c-statistic was 0.52 (95% CI 0.45-0.58) for predicting RTE and 0.49 (95% CI 0.38-0.59) for predicting recurrent AIS. Discussion: The Khorana score has poor discriminatory ability for predicting RTE in cancer patients with AIS, probably because these patients represent an especially high-risk group. Future research is needed to identify better methods for predicting RTE in this high-risk population.

This randomized clinical trial compares anticoagulation vs antiplatelet therapy in patients with cancer and acute ischemic stroke.

Introduction: Cancer patients can develop hypercoagulability, leading to stroke. The pathophysiology of cancer-mediated hypercoagulability, however, is poorly understood and biomarkers associated with stroke in cancer patients are uncertain. Methods: We performed a pilot cross-sectional study at a tertiary-care cancer center to evaluate potential hematological biomarkers of stroke in cancer patients. From October 2013 through May 2014, we prospectively identified 15 inpatients with active systemic cancer and acute ischemic stroke and 15 inpatients with active systemic cancer and no stroke. Using collected plasma, we compared six potential biomarkers of stroke, selected in advance based on expert opinion and prior data, which included markers of coagulation (thrombin-antithrombin complex and D-dimer), platelet function (P-selectin), and endothelial activation state (sICAM-1, vICAM-1, and thrombomodulin). We used the Wilcoxon rank-sum test to compare biomarker levels between groups. Results: Each group comprised 14 patients with solid cancer and one patient with hematological cancer. All patients in the cancer and stroke group had stage 4 disease, while only 60% of the cancer and no stroke group had stage 4 disease. Age and demographics were similar between groups. Median levels of thrombin-antithrombin complex, D-dimer, P-selectin, sICAM-1, and vICAM-1 were significantly increased in cancer patients with stroke, but thrombomodulin was not (Table). Our results were substantially unchanged in a sensitivity analysis limited to patients with only stage 4 cancer. Conclusion: These preliminary data suggest that thrombin-antithrombin complex, D-dimer, P-selectin, sICAM-1, and vICAM-1 could serve as the focus of future prospective studies to elucidate the potential predictive, diagnostic, or etiologic role of hematological biomarkers for stroke in the cancer population.