Immune checkpoint inhibitors (ICI) have revolutionized cancer treatment and are now approved for various types of cancer. The most common side effects of ICI are immune-related adverse events which can affect any organ or system in the body. Recently, concerns have also risen about cardiovascular effects of ICI. Retrospective studies showed an 4-5 times increased risk of developing an arterial thromboembolic event.
The mechanisms driving the ICI-associated risks of arterial thromboembolic events such as myocardial infarction and stroke, are unclear. Since the risk of a thromboembolism appears to be increased already during the first months after initiation of ICI, immune-related hypercoagulability or (autoimmune) antiphospholipid antibodies may play a role, but data to support this are lacking. The longer-term risk of arterial thromboembolism may be predominantly driven by (accelerated) atherosclerosis, a chronic low-grade inflammatory disease of the larger arteries. Therefore, this study evaluates the effect of ICI on progression of coronary non-calcifid plaque volume by using computed tomography angiography (CCTA).
Patients with confirmed diagnosis of the following tumor types, any stage: esophageal, gastric or junction cancer, colorectal cancer, non-small cell lung carcinoma, melanoma, renal cell carcinoma
Prior to start of new therapy (i.e. immune checkpoint inhibitor, chemotherapy or follow-up in case of esophageal cancer)
Age ≥ 50 years
ICI therapy in previous 12 months
Suspected or confirmed viral, fungal, or bacterial infectious disease
Use of immunosuppressive therapy prior to ICI start
Estimated glomerular filtration rate (eGFR) <30 mL/min/1.73m2
Adult male or female subjects are eligible for study participation if they have a confirmed cancer diagnosis
Cohort
Prospective
Coronary computed tomography angiography (CCTA) at baseline
Diagnostic testDetailed imaging of coronary arteries
Coronary computed tomography angiography (CCTA) after 1 year
Diagnostic testDetailed imaging of coronary arteries
Non-calcified coronary plaque volume (difference between baseline and follow-up CT)
Plaque characteristics (differences between baseline and follow-up)
Difference in plaque characteristics (i.e. fat attenuation index)
Differences in plasma biomarkers (pro-inflammatory markers) between baseline and follow-up
Immune cell composition, T cell composition, IL-1b, IL-6, NLRP3, IL-17, TNF-a, IFN-y
Incidence of Arterial thromboembolic event
Incidence of Arterial Thromboembolic events, defined as major cardiovascular events (MACE), including nonfatal ischemic stroke, nonfatal myocardial infarction and cardiovascular death
Venous thromboembolism
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Hanneke W. M. van Laarhoven
Lead sponsor
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Sponsor institution
Amsterdam UMC
Collaborator
