Total Carotid Artery Calcium Score on Standard-of-care Oncologic Computed Tomography Scans Predicts Radiation-induced Carotid Artery Disease and its Sequelae in Patients with Oropharyngeal Cancer

Introduction: Radiation therapy (RT) induced carotid artery disease (RICAD) is a significant contributor to morbidity and mortality of oropharyngeal cancer (OPC) survivors. Pre-existing carotid atherosclerosis is likely a risk factor for accelerated development of RICAD.Its evaluation prior to RT is not currently standard practice. This study aimed to utilize standard of care (SOC) oncologic pre-RT CT scans to quantify carotid calcific atherosclerosis and assess the role of carotid artery calcium score (CaACS) in predicting RICAD and its sequalae. Methods: Patients with OPC treated with RT at a tertiary center during 2016-19 were identified. SOC oncologic pre-RT CT of the neck with contrast was used to estimate CaACS utilizing the CT Cardiac package of SyngoVia (Siemens Healthcare). To separate calcified plaque from contrast, density threshold of 230 HU was used.Bilateral common and internal carotid arteries were evaluated to the C1 vertebra. Patients were split into three groups based on CaACS distribution:low (values ≤ median) as reference group,medium(values between median and 75th percentile),and high (values >75th percentile). Results: A total of 271 patients were included (mean age 61 ± 9.8, 88% male).Smoking was reported in 57%, hypertension (HTN) in 53%, dyslipidemia (DLD) in 43%, and diabetes mellitus (DM) in 14%,while 34% were on a statin prior to RT. Total median CaACS was 10.8 AU (IQR 0-140.6) with 46% having a score of 0. During a median follow up of 6.4 years (IQR 6.3-6.6), 41% developed new or worsened carotid atherosclerosis, 3.7% carotid artery stenosis >50%, 2.6% TIA or stroke, and 17% died without new or worsened carotid atherosclerosis. In a multivariate cause-specific Cox regression analysis, high CaACS was significantly associated with increased risk of the composite outcome of worsened carotid atherosclerosis, >50% stenosis, TIA or stroke (HR 2.18,95% CI[1.34-3.54]) compared to low CaACS. Hypertension was also associated with the composite outcome (2.26[1.49-3.41]) while no significant associations were noted with age, smoking, DLD, DM, or statin use. Fine-Gray analysis showed similar results. Conclusion: In our cohort of patients with OPC, high CaACS and history of HTN prior to RT, were significantly associated with development of RICAD. Quantification of carotid artery calcific atherosclerosis utilizing SOC oncologic CT imaging may assist with patient risk stratification, guide surveillance and potentially mitigate RICAD in OPC survivors.