Clinical Assessment and Targeted Imaging to Characterize High-Risk Atherosclerotic Cardiovascular Disease of Survivors in SJLIFE

Survivors of childhood cancer experience substantially increased risk of ischemic heart disease and stroke compared to the general population. This excess risk is largely driven by cancer therapy exposures such as chest or neck radiation and platinum-based chemotherapy. However, most evidence-based ASCVD screening and prevention guidelines are derived from populations aged 40 years or older without cancer therapy exposure, leaving younger survivors inadequately risk stratified.

This study leverages the St. Jude Lifetime Cohort (SJLIFE) to conduct enhanced cardiovascular phenotyping among survivors at treatment-related risk for ASCVD. Participants undergo coronary artery calcium (CAC) scoring using low-dose non-contrast ECG-gated CT, bilateral carotid ultrasound to assess carotid stenosis and intima-media thickness, blood-based measurement of lipoprotein(a), and noninvasive vascular function testing including pulse wave velocity, augmentation index, and arterial elasticity. A cohort of community control participants enrolled in SJLIFE undergoes identical testing.

The primary objectives are to determine the prevalence of abnormal CAC and carotid stenosis among at-risk survivors and to compare findings with community controls. Secondary objectives include characterization of lipoprotein(a) levels and assessment of ASCVD markers among survivors exposed solely to platinum chemotherapy.

The study uses a cross-sectional design with prospective longitudinal follow-up through ongoing participation in SJLIFE. Results are intended to inform future survivor-specific screening approaches and interventional trials.

Inclusion criteria

• SJLIFE Survivor or Control

• Age ≥18 years
• Enrolled in the St. Jude Lifetime Cohort (SJLIFE)
• Participant or legal guardian/representative is able and willing to give informed consent.

SJLIFE Survivor only

• Participant has been treated with at least one of the following cancer therapies:

platinum chemotherapy, neck radiation exposure of at least 1000 centigray (cGy), or chest radiation exposure of at least 1000 cGy (with potential exposure to the heart).

Exclusion criteria

SJLIFE Survivor or Control

• Previous stroke or intervention for severe carotid arterial disease including carotid endarterectomy or carotid angioplasty and stent placement.
• Previous myocardial infarction or intervention for severe cardiovascular disease including Coronary Artery Bypass Graft (CABG), coronary stent placement or coronary angioplasty.
• History of aortic valve replacement
• Inability or unwillingness of research participant or legal guardian/representative to give written informed consent.

Control Only

• First degree relative of SJLIFE Survivor
• History of cancer