Introduction: The prevalence of comorbid cancer is higher in patients with ischaemic stroke than in the general population, and recent studies have attempted to clarify the relationship between the two. We observed that the evidence for the impact of comorbid cancer on post-stroke clinical outcomes was not established and aimed to investigate it among patients with new-onset acute ischaemic stroke. Methods: We evaluated 13,345 patients with acute ischaemic stroke who were functionally independent before onset (modified Rankin Scale [mRS] score of 0–2) and admitted to one of the seven stroke centres in Fukuoka, Japan, between June 2007 and September 2019. A total of 13,047 patients were included in the analyses after excluding those with missing potential confounders (n = 13) or loss to follow-up (n = 298). Comorbid cancer was diagnosed based on previous history or newly identified cancer during hospitalisation for the index stroke. Multivariable-adjusted Poisson regression analyses were conducted to assess the association of comorbid cancer with post-stroke outcomes: clinically assessed poor functional outcomes (mRS score, 3–6), functional dependency (mRS score, 3–5), and mortality (mRS score, 6) at 3 months after stroke onset. Results: Of 13,047 patients (aged 71.1 ± 12.3 years, 62.8% men) with acute ischaemic stroke, 2,027 (15.6%) had comorbid cancer. Among those with no cancer, 24.0% recorded poor functional outcomes; with non-active cancer, 30.7%; and with active cancer, 46.1%. The risk ratios (95% confidence interval) for poor functional outcome at 3 months increased with active cancer (1.50 [1.37–1.65] vs. no cancer) and recently diagnosed cancer (7 months–4 years: 1.43 [1.28–1.59], ≤6 months: 1.53 [1.36–1.72]) after adjusting for potential confounders. These associations were observed for both 3-month functional dependency and mortality. No significant heterogeneity was observed in these associations across sex, nutritional status, inflammatory status, or coagulation status, except for age and stroke severity. The strongest association with 3-month poor functional outcome was observed for pancreatic cancer, followed by gallbladder and biliary tract, liver, and colon cancers. Conclusions: Comorbid cancer is likely to be independently associated with unfavourable outcomes in patients with acute ischaemic stroke.

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