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June 13, 2023; 100 (24) Research Article

Clinical and Demographic Characteristics, Mechanisms, and Outcomes in Patients With Acute Ischemic Stroke and Newly Diagnosed or Known Active Cancer

View ORCID ProfileGianluca Costamagna, Andreas Hottinger, Haralampos Milionis, Dimitris Lambrou, View ORCID ProfileAlexander Salerno, Davide Strambo, Françoise Livio, Babak Benjamin Navi, Patrik Michel
First published April 24, 2023, DOI: https://doi.org/10.1212/WNL.0000000000207341
Gianluca Costamagna
From the Stroke Center (G.C., D.L., A.S., D.S., P.M.), Neurology Service, Department of Clinical Neurosciences, L. Lundin & Family Brain Tumor Research Center (A.H.), Services of Neurology and Oncology, and Service of Clinical Pharmacology (F.L.), Lausanne University Hospital and University of Lausanne, Switzerland; Dino Ferrari Centre (G.C.), Department of Pathophysiology and Transplantation (DEPT), University of Milan, Italy; 1st Department of Internal Medicine (H.M.), University of Ioannina, Medical School, Greece; Feil Family Brain and Mind Research Institute and Department of Neurology (B.B.N.), Weill Cornell Medicine; and Department of Neurology (B.B.N.), Memorial Sloan Kettering Cancer Center, New York, NY.
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  • ORCID record for Gianluca Costamagna
Andreas Hottinger
From the Stroke Center (G.C., D.L., A.S., D.S., P.M.), Neurology Service, Department of Clinical Neurosciences, L. Lundin & Family Brain Tumor Research Center (A.H.), Services of Neurology and Oncology, and Service of Clinical Pharmacology (F.L.), Lausanne University Hospital and University of Lausanne, Switzerland; Dino Ferrari Centre (G.C.), Department of Pathophysiology and Transplantation (DEPT), University of Milan, Italy; 1st Department of Internal Medicine (H.M.), University of Ioannina, Medical School, Greece; Feil Family Brain and Mind Research Institute and Department of Neurology (B.B.N.), Weill Cornell Medicine; and Department of Neurology (B.B.N.), Memorial Sloan Kettering Cancer Center, New York, NY.
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Haralampos Milionis
From the Stroke Center (G.C., D.L., A.S., D.S., P.M.), Neurology Service, Department of Clinical Neurosciences, L. Lundin & Family Brain Tumor Research Center (A.H.), Services of Neurology and Oncology, and Service of Clinical Pharmacology (F.L.), Lausanne University Hospital and University of Lausanne, Switzerland; Dino Ferrari Centre (G.C.), Department of Pathophysiology and Transplantation (DEPT), University of Milan, Italy; 1st Department of Internal Medicine (H.M.), University of Ioannina, Medical School, Greece; Feil Family Brain and Mind Research Institute and Department of Neurology (B.B.N.), Weill Cornell Medicine; and Department of Neurology (B.B.N.), Memorial Sloan Kettering Cancer Center, New York, NY.
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Dimitris Lambrou
From the Stroke Center (G.C., D.L., A.S., D.S., P.M.), Neurology Service, Department of Clinical Neurosciences, L. Lundin & Family Brain Tumor Research Center (A.H.), Services of Neurology and Oncology, and Service of Clinical Pharmacology (F.L.), Lausanne University Hospital and University of Lausanne, Switzerland; Dino Ferrari Centre (G.C.), Department of Pathophysiology and Transplantation (DEPT), University of Milan, Italy; 1st Department of Internal Medicine (H.M.), University of Ioannina, Medical School, Greece; Feil Family Brain and Mind Research Institute and Department of Neurology (B.B.N.), Weill Cornell Medicine; and Department of Neurology (B.B.N.), Memorial Sloan Kettering Cancer Center, New York, NY.
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Alexander Salerno
From the Stroke Center (G.C., D.L., A.S., D.S., P.M.), Neurology Service, Department of Clinical Neurosciences, L. Lundin & Family Brain Tumor Research Center (A.H.), Services of Neurology and Oncology, and Service of Clinical Pharmacology (F.L.), Lausanne University Hospital and University of Lausanne, Switzerland; Dino Ferrari Centre (G.C.), Department of Pathophysiology and Transplantation (DEPT), University of Milan, Italy; 1st Department of Internal Medicine (H.M.), University of Ioannina, Medical School, Greece; Feil Family Brain and Mind Research Institute and Department of Neurology (B.B.N.), Weill Cornell Medicine; and Department of Neurology (B.B.N.), Memorial Sloan Kettering Cancer Center, New York, NY.
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Davide Strambo
From the Stroke Center (G.C., D.L., A.S., D.S., P.M.), Neurology Service, Department of Clinical Neurosciences, L. Lundin & Family Brain Tumor Research Center (A.H.), Services of Neurology and Oncology, and Service of Clinical Pharmacology (F.L.), Lausanne University Hospital and University of Lausanne, Switzerland; Dino Ferrari Centre (G.C.), Department of Pathophysiology and Transplantation (DEPT), University of Milan, Italy; 1st Department of Internal Medicine (H.M.), University of Ioannina, Medical School, Greece; Feil Family Brain and Mind Research Institute and Department of Neurology (B.B.N.), Weill Cornell Medicine; and Department of Neurology (B.B.N.), Memorial Sloan Kettering Cancer Center, New York, NY.
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Françoise Livio
From the Stroke Center (G.C., D.L., A.S., D.S., P.M.), Neurology Service, Department of Clinical Neurosciences, L. Lundin & Family Brain Tumor Research Center (A.H.), Services of Neurology and Oncology, and Service of Clinical Pharmacology (F.L.), Lausanne University Hospital and University of Lausanne, Switzerland; Dino Ferrari Centre (G.C.), Department of Pathophysiology and Transplantation (DEPT), University of Milan, Italy; 1st Department of Internal Medicine (H.M.), University of Ioannina, Medical School, Greece; Feil Family Brain and Mind Research Institute and Department of Neurology (B.B.N.), Weill Cornell Medicine; and Department of Neurology (B.B.N.), Memorial Sloan Kettering Cancer Center, New York, NY.
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Babak Benjamin Navi
From the Stroke Center (G.C., D.L., A.S., D.S., P.M.), Neurology Service, Department of Clinical Neurosciences, L. Lundin & Family Brain Tumor Research Center (A.H.), Services of Neurology and Oncology, and Service of Clinical Pharmacology (F.L.), Lausanne University Hospital and University of Lausanne, Switzerland; Dino Ferrari Centre (G.C.), Department of Pathophysiology and Transplantation (DEPT), University of Milan, Italy; 1st Department of Internal Medicine (H.M.), University of Ioannina, Medical School, Greece; Feil Family Brain and Mind Research Institute and Department of Neurology (B.B.N.), Weill Cornell Medicine; and Department of Neurology (B.B.N.), Memorial Sloan Kettering Cancer Center, New York, NY.
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Patrik Michel
From the Stroke Center (G.C., D.L., A.S., D.S., P.M.), Neurology Service, Department of Clinical Neurosciences, L. Lundin & Family Brain Tumor Research Center (A.H.), Services of Neurology and Oncology, and Service of Clinical Pharmacology (F.L.), Lausanne University Hospital and University of Lausanne, Switzerland; Dino Ferrari Centre (G.C.), Department of Pathophysiology and Transplantation (DEPT), University of Milan, Italy; 1st Department of Internal Medicine (H.M.), University of Ioannina, Medical School, Greece; Feil Family Brain and Mind Research Institute and Department of Neurology (B.B.N.), Weill Cornell Medicine; and Department of Neurology (B.B.N.), Memorial Sloan Kettering Cancer Center, New York, NY.
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Clinical and Demographic Characteristics, Mechanisms, and Outcomes in Patients With Acute Ischemic Stroke and Newly Diagnosed or Known Active Cancer
Gianluca Costamagna, Andreas Hottinger, Haralampos Milionis, Dimitris Lambrou, Alexander Salerno, Davide Strambo, Françoise Livio, Babak Benjamin Navi, Patrik Michel
Neurology Jun 2023, 100 (24) e2477-e2489; DOI: 10.1212/WNL.0000000000207341

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Abstract

Background and Objectives Patients with a new diagnosis of cancer carry an increased risk of acute ischemic stroke (AIS), and this risk varies depending on age, cancer type, stage, and time from diagnosis. Whether patients with AIS with a new diagnosis of neoplasm represent a distinct subset from those with a previously known active malignancy remains unclear. We aimed to estimate the rate of stroke in patients with newly diagnosed cancer (NC) and previously known active cancer (KC) and to compare the demographic and clinical features, stroke mechanisms, and long-term outcomes between groups.

Methods Using 2003–2021 data from the Acute STroke Registry and Analysis of Lausanne registry, we compared patients with KC with patients with NC (cancer identified during AIS hospitalization or within the following 12 months). Patients with inactive and no history of cancer were excluded. Outcomes were the modified Rankin scale (mRS) score at 3 months and mortality and recurrent stroke at 12 months. We used multivariable regression analyses to compare outcomes between groups while adjusting for important prognostic variables.

Results Among 6,686 patients with AIS, 362 (5.4%) had active cancer (AC), including 102 (1.5%) with NC. Gastrointestinal and genitourinary cancers were the most frequent cancer types. Among all patients with AC, 152 (42.5%) AISs were classified as cancer related, with nearly half of these cases attributed to hypercoagulability. In multivariable analysis, patients with NC had less prestroke disability (adjusted odds ratio [aOR] 0.62, 95% CI 0.44–0.86) and fewer prior stroke/transient ischemic attack events (aOR 0.43, 95% CI 0.21–0.88) than patients with KC. Three-month mRS scores were similar between cancer groups (aOR 1.27, 95% CI 0.65–2.49) and were predominantly driven by the presence of newly diagnosed brain metastases (aOR 7.22, 95% CI 1.49–43.17) and metastatic cancer (aOR 2.19, 95% CI 1.22–3.97). At 12 months, mortality risk was higher in patients with NC vs patients with KC (hazard ratio [HR] 2.11, 95% CI 1.38–3.21), while recurrent stroke risk was similar between groups (adjusted HR 1.27, 95% CI 0.67–2.43).

Discussion In a comprehensive institutional registry spanning nearly 2 decades, 5.4% of patients with AIS had AC, a quarter of which were diagnosed during or within 12 months after the index stroke hospitalization. Patients with NC had less disability and prior cerebrovascular disease, but a higher 1-year risk of subsequent death than patients with KC.

Glossary

AC=
active cancer;
aHR=
adjusted hazard ratio;
AIS=
acute ischemic stroke;
aOR=
adjusted odds ratio;
ASTRAL=
Acute STroke Registry and Analysis of Lausanne;
ESUS=
embolic stroke of undetermined source;
EVT=
endovascular thrombectomy;
HRA=
Human Rights Act;
HRO=
Human Research Ordinance;
IQR=
interquartile range;
IVT=
IV thrombolysis;
KC=
known active cancer;
MDS=
myelodysplastic syndrome;
mRS=
modified Rankin scale;
NC=
newly diagnosed cancer;
NIHSS=
NIH Stroke Scale;
PFO=
patent foramen ovale;
TOAST=
Trial of Org 10172 in Acute Stroke Treatment

Footnotes

  • Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

  • Submitted and externally peer reviewed. The handling editor was Editor-in-Chief José Merino, MD, MPhil, FAAN.

  • Received November 8, 2022.
  • Accepted in final form March 9, 2023.
  • © 2023 American Academy of Neurology
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