The Role of Coronary Artery Calcium Score to Assess Risk of Cardiovascular Disease in Irradiated Esophageal Cancer Patients

Abstract

Coronary artery calcium (CAC) score is an important predictive imaging marker of cardiovascular disease (CVD). While studies have found positive association between CAC score and cardiac toxicity in irradiated lung and breast cancer patients, there are no studies assessing CAC scores in esophageal cancer (EC). While a cardiac-gated CT is required for standard Agatston CAC score, visual assessment of CAC via ordinal scoring on non-gated CT has shown good concordance with Agatston score. In this study, we sought to examine whether visual assessment of CAC, measured on standard of care, non-contrast chest CT, predicts the development of adverse cardiovascular events (ACVE) in irradiated EC patients. This is a single institution retrospective study of EC patients treated with RT from 2010-2021. We included patients with available PET/CT at diagnosis or chest CT simulation scan without contrast, and excluded those with history of percutaneous coronary intervention, coronary bypass surgery, or prior thoracic RT. Pre-treatment characteristics, clinical factors, and grade ≥ 3 (G3+) adverse cardiovascular events (ACVE) (CTCAEv5.0) were evaluated. Visual assessment of CAC was performed using ordinal method (CAC scored from 0 to 12), by a thoracic radiologist. Fine and Gray regression was used to compute hazard ratios for time to first ACVE. Univariate analyses using Cox proportional hazards were used for overall survival (OS). ACVEs were recorded from start of oncologic treatment and OS calculated after completion of RT. A total of 118 patients were analyzed with a median follow-up of 16 months. Median age was 67 years, 65% male, 43% white, 59% with EC of distal esophagus, and 59% had squamous cell carcinoma. Median mean heart dose was 21.93 Gy (range 0.15-36.94). 24% developed G3+ ACVEs: atrial fibrillation 9%, stroke 6%, heart failure 4%, pulmonary embolism 4%, pericardial effusion 3%, myocardial infarction 2%, heart block 2%, and cardiac death 1%. On univariate analyses, CAC >1 vs. CAC ≤ 1 trended towards increased risk of ACVE (HR = 1.95, 95% CI = 0.89-4.26; p = 0.094), however it is not predictive of OS (HR = 1.31, 95% CI = 0.75-2.30; p = 0.343). Proportion of patients with ACVEs was greater in CAC>1 group (Table). When compared to patients with CAC ≤ 1, those with CAC >1 were older (median age 62 vs 72 years, p = 0.0015), less likely to be never smokers (38% vs 30%, p = 0.0437), and more likely to have hypertension (43% vs 64%, p = 0.0197), and hyperlipidemia (30% vs 47%, p = 0.0557). This is the first study to investigate the relationship between CAC score and ACVEs in EC. While the study was underpowered (likely due to low rates of recorded ACVEs), to detect a significant association between CAC score and ACVEs, there was a trend towards increased risk of ACVEs in patients with a CAC score >1 by visual ordinal scoring. Further prospective evaluation with a larger cohort is warranted.