Randomized Controlled Trial

. 2024 Nov 26;103(10):e210027.

doi: 10.1212/WNL.0000000000210027. Epub 2024 Oct 31.

Diagnosis of Incident Cancer After Cryptogenic Stroke: An Exploratory Analysis of the ARCADIA Randomized Trial

Babak B Navi¹, Cenai Zhang¹, Benjamin R Miller¹, Anokhi Pawar¹, Mary Cushman¹, Scott E Kasner¹, David Tirschwell¹, W T Longstreth¹, Richard Kronmal¹, Jordan Elm¹, Richard M Zweifler¹, Joseph Tarsia¹, Joseph P Broderick¹, David J Gladstone¹, Morin Beyeler¹, Hooman Kamel¹, Mitchell S V Elkind¹, Christopher Streib¹

Affiliations

Affiliation

¹ From the Clinical and Translational Neuroscience Unit (B.B.N., C.Z., A.P., M.B., H.K.), Feil Family Brain and Mind Research Institute and Department of Neurology, Weill Cornell Medicine, New York; Department of Neurology (B.B.N.), Memorial Sloan Kettering Cancer Center, New York, NY; Department of Neurology (B.R.M., C.S.), University of Minnesota, Minneapolis; Division of Hematology and Oncology (M.C.), Department of Medicine, University of Vermont Larner College of Medicine, Burlington; Department of Neurology (S.E.K.), University of Pennsylvania School of Medicine, Philadelphia; Department of Neurology (D.T., W.L.), Department of Epidemiology (W.L.), and Department of Biostatistics (R.K.), University of Washington, Seattle; Department of Biostatistics (J.E.), Medical University of South Carolina, Charleston; Ochsner Neuroscience Institute (R.M.Z., J.T.), Ochsner Health, New Orleans, LA; Department of Neurology and Rehabilitation Medicine (J.P.B.), University of Cincinnati College of Medicine, OH; Sunnybrook Research Institute (D.J.G.), Hurvitz Brain Sciences Program, Sunnybrook Health Sciences Centre, and Division of Neurology (D.J.G.), Department of Medicine, University of Toronto, Ontario, Canada; Department of Neurology (M.B.), Inselspital, Bern University Hospital and University of Bern, Switzerland; and Department of Neurology (M.S.V.E.), Vagelos College of Physicians and Surgeons, and Department of Epidemiology (M.S.V.E.), Mailman School of Public Health, Columbia University, New York, NY.

PMID: 39481070
PMCID: PMC11527484 (available on 2025-11-26)
DOI: 10.1212/WNL.0000000000210027

Randomized Controlled Trial

Diagnosis of Incident Cancer After Cryptogenic Stroke: An Exploratory Analysis of the ARCADIA Randomized Trial

Babak B Navi et al. Neurology. 2024.

. 2024 Nov 26;103(10):e210027.

doi: 10.1212/WNL.0000000000210027. Epub 2024 Oct 31.

Authors

Affiliation

¹ From the Clinical and Translational Neuroscience Unit (B.B.N., C.Z., A.P., M.B., H.K.), Feil Family Brain and Mind Research Institute and Department of Neurology, Weill Cornell Medicine, New York; Department of Neurology (B.B.N.), Memorial Sloan Kettering Cancer Center, New York, NY; Department of Neurology (B.R.M., C.S.), University of Minnesota, Minneapolis; Division of Hematology and Oncology (M.C.), Department of Medicine, University of Vermont Larner College of Medicine, Burlington; Department of Neurology (S.E.K.), University of Pennsylvania School of Medicine, Philadelphia; Department of Neurology (D.T., W.L.), Department of Epidemiology (W.L.), and Department of Biostatistics (R.K.), University of Washington, Seattle; Department of Biostatistics (J.E.), Medical University of South Carolina, Charleston; Ochsner Neuroscience Institute (R.M.Z., J.T.), Ochsner Health, New Orleans, LA; Department of Neurology and Rehabilitation Medicine (J.P.B.), University of Cincinnati College of Medicine, OH; Sunnybrook Research Institute (D.J.G.), Hurvitz Brain Sciences Program, Sunnybrook Health Sciences Centre, and Division of Neurology (D.J.G.), Department of Medicine, University of Toronto, Ontario, Canada; Department of Neurology (M.B.), Inselspital, Bern University Hospital and University of Bern, Switzerland; and Department of Neurology (M.S.V.E.), Vagelos College of Physicians and Surgeons, and Department of Epidemiology (M.S.V.E.), Mailman School of Public Health, Columbia University, New York, NY.

PMID: 39481070
PMCID: PMC11527484 (available on 2025-11-26)
DOI: 10.1212/WNL.0000000000210027

Abstract

Objectives: The objective of this study was to estimate the incidence, timing, and type of new cancer diagnosis among patients with cryptogenic stroke.

Methods: We used data from the ARCADIA trial, which enrolled patients with cryptogenic stroke and atrial cardiopathy. Participants were prospectively followed, and serious adverse events were assessed every 3 months or sooner if investigators were alerted between visits to an event. Kaplan-Meier statistics were used to estimate the cumulative incidence of a cancer diagnosis within the first year after randomization.

Results: Among 878 participants without baseline history of cancer, 13 (1.5%) were diagnosed with incident cancer in the year after randomization, comprising 12 solid cancers (3 prostate, 2 breast, 2 gastrointestinal, and 5 other primary sites) and 1 hematologic cancer (non-Hodgkin lymphoma). The cumulative incidences of a cancer diagnosis were 0% at 3 months, 0.6% (95% CI 0.2%-1.5%) at 6 months, and 2.0% (95 CI 1.1%-3.4%) at 1 year. The median time from index stroke to cancer diagnosis was 261 days (interquartile range 183-358).

Discussion: In a multicenter cryptogenic stroke cohort with prospective follow-up, the 1-year cumulative incidence of a cancer diagnosis was 2%. This rate may be an underestimation because of the clinical trial population and exclusion of cancers diagnosed immediately after stroke.

Trial registration information: ClinicalTrials.gov Identifier: NCT03192215. Registered June 20, 2017. First patient enrolled February 1, 2018.

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Conflict of interest statement

B.B. Navi discloses receiving consulting fees for serving on an adjudication committee for MindRhythm Inc. C. Zhang, B. Miller, A. Pawar, and M. Cushman report no disclosures relevant to the manuscript. S.E. Kasner discloses receiving grant funding from Diamedica, Bayer, Bristol Myers Squibb, Genentech, and WL Gore, consulting fees for serving on a DSMB for AstraZeneca and an adjudication committee for NovoNordisk, and royalties from UpToDate. D.L. Tirschwell, W.T. Longstreth Jr, R.A. Kronmal, J. Elm, R.M. Zweifler, and J. Tarsia report no disclosures relevant to the manuscript. J.P. Broderick reports receiving multiple research awards from the National Institutes of Neurological Disorders and Stroke (NINDS), receiving study medication and monetary support from Novo Nordisk for temperature monitoring and after-hour enrollment for the ongoing NINDS-funded FASTEST trial, and receiving monies for educational and research funds for the University of Cincinnati Department of Neurology and Rehabilitation Medicine from Genentech (for his role on the Executive Committee of the TIMELESS trial), Roche, BrainsGate Ltd., Basking Biosciences, and the Pharmacy and Therapeutics Committee of Kroger Prescriptions Plans Inc., as a voting member of the committee. D.J. Gladstone reports no disclosures relevant to the manuscript. M. Beyeler reports grant support from the University of Bern, Switzerland. H. Kamel reports no disclosures relevant to the manuscript. M.S.V. Elkind discloses receiving salary as an employee of the American Heart Association and royalties for chapters on cryptogenic stroke in UpToDate. C. Streib reports no disclosures relevant to the manuscript. Go to Neurology.org/N for full disclosures.

References

1. Navi BB, Reiner AS, Kamel H, et al. . Association between incident cancer and subsequent stroke. Ann Neurol. 2015;77(2):291-300. doi:10.1002/ana.24325 - DOI - PMC - PubMed
1. Lun R, Roy DC, Hao Y, et al. . Incidence of stroke in the first year after diagnosis of cancer: a systematic review and meta-analysis. Front Neurol. 2022;13:966190. doi:10.3389/fneur.2022.966190 - DOI - PMC - PubMed
1. Navi BB, Iadecola C. Ischemic stroke in cancer patients: a review of an underappreciated pathology. Ann Neurol. 2018;83(5):873-883. doi:10.1002/ana.25227 - DOI - PMC - PubMed
1. Navi BB, Reiner AS, Kamel H, et al. . Risk of arterial thromboembolism in patients with cancer. J Am Coll Cardiol. 2017;70(8):926-938. doi:10.1016/j.jacc.2017.06.047 - DOI - PMC - PubMed
1. Navi BB, Reiner AS, Kamel H, et al. . Arterial thromboembolic events preceding the diagnosis of cancer in older persons. Blood. 2019;133(8):781-789. doi:10.1182/blood-2018-06-860874 - DOI - PMC - PubMed

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Diagnosis of Incident Cancer After Cryptogenic Stroke: An Exploratory Analysis of the ARCADIA Randomized Trial

Affiliation

Diagnosis of Incident Cancer After Cryptogenic Stroke: An Exploratory Analysis of the ARCADIA Randomized Trial

Authors

Affiliation

Abstract

Conflict of interest statement

References

Publication types

MeSH terms

Associated data

Grants and funding

LinkOut - more resources

Full Text Sources

Medical