Carotid Artery Stenosis and Ischemic Cerebrovascular Events After Radiotherapy in Patients With Head and Neck Cancer (RT-CASinHNC)

The study had a cross-sectional design and included 907 patients with HNC involving the oral cavity, pharynx, larynx, nasal cavity, or salivary glands. The study was approved by the Chulabhorn Institutional Ethics Committee for Human Research (approval number 048/2565). All patients underwent radiotherapy to the head and neck region between February 2011 and June 2022 with or without surgical resection and were investigated by computed tomography (CT) before and after radiotherapy. Patients with lymphoma and those with previous treatment for CAS or radiotherapy for other diseases were excluded. We obtained information on patient background factors, tumor characteristics, and treatment from the medical records. Risk factors for atherosclerosis, including hypertension, dyslipidemia, diabetes mellitus, coronary artery disease, peripheral arterial disease, and cigarette smoking, were identified. Baseline laboratory data, including hemoglobin A1C, fasting blood sugar, lipid profile, serum creatinine level, and estimated glomerular filtration rate, were obtained, as was information on treatment, including antiplatelet agents, statins, angiotensin-converting enzyme inhibitors (ACEIs), calcium channel blockers (CCBs), and anticoagulants. The type and stage of HNC, indication for radiotherapy, type of radiotherapy, total cumulative dose, and number of courses were also recorded. Unfortunately, the laboratory data were incomplete in many cases, so could not be subjected to statistical analysis. Follow-up was continued until loss to follow-up, death, or the end of 2023, whichever came first. Moreover, full written informed consent was obtained from the patient for publication of this article. Confidentiality of the data was secured by assigning of a code for each patient record. Images were analyzed to determine the timing of development of CAS, identify significant (>50%) CAS using the North American Symptomatic Carotid Endarterectomy Trial criteria, and calculate the total plaque score (TPS) and wall thickness. The carotid vessels were divided into the common carotid artery (CCA), carotid bulb, internal carotid artery (ICA), and external carotid artery (ECA). The bulb was defined as the portion of the artery 1 cm caudally to 1 cm cranially from the point where the CCA divided into the ICA and ECA. The right and left carotid artery systems were each divided into the following five segments: proximal CCA (≥20 mm proximal to bulb), distal CCA (<20 mm proximal to bulb), carotid bulb, ICA. and ECA. Each segment was graded as follows: 0, normal or no detectable plaque; 1, plaque occupying <30% of vessel diameter; 2, plaque occupying 30%-49% of vessel diameter; 3, plaque occupying 50%-69% of vessel diameter; 4, plaque occupying 70%-99% of vessel diameter; and 5, 100% occlusion of vessel diameter by plaque. The carotid plaque score was obtained for each patient by summing the scores obtained for the five arterial segments in both carotid arteries. Wall thickness and degree of CAS were measured in the five segments of the carotid artery at baseline and during follow-up. Differences in these values were calculated. CT was performed at least twice. The initial CT scan was performed within 2 months before initiation of radiotherapy and follow-up CT was performed 1 month after completing radiotherapy. In cases with multiple follow-up CT scans, the last scan was used to evaluate post-radiation change. The 1-year follow-up CT scan was also examined. All baseline and follow-up measurements were made by a vascular surgeon who was blinded to the clinical data.