Title Predictors of the Extent of Carotid Atherosclerosis in Patients Treated with Radiotherapy for Nasopharyngeal Carcinoma

Objective: To determine the predictors of the extent of carotid atherosclerosis in patients treated with radiotherapy (RT) for nasopharyngeal carcinoma (NPC). Methods: The present study investigated 129 post-RT NPC patients. Carotid atherosclerotic parameters, such as carotid intima-media thickness, carotid arterial stiffness and carotid plaque burden (plaque score, the presence of plaque and $50% stenosis) were assessed using ultrasonography. The association between carotid atherosclerotic parameters and nine potential predictors, including age, gender, post-RT duration, radiation dose, chemotherapy, diabetes mellitus, hypertension, hypercholesterolemia, and smoking, were determined using multiple regression. The cutoff values of age, post-RT duration and number of cardiovascular risk factors for the presence of carotid plaque or $50% carotid stenosis were analyzed using receiver operating characteristic (ROC) curve analysis. Multiple testing was corrected using Benjamini-Hochberg false discovery rate. Results: Age, post-RT duration and number of cardiovascular risk factors were significantly associated with carotid plaque burden (corrected P value, Pcor,0.05). Age of 44.5 years (sensitivity599.2% and specificity550%, Pcor,0.01) and postRT duration of 8.5 years (sensitivity575.7% and specificity564.3%, Pcor,0.001) were the cutoff values for detecting carotid plaque, while post-RT duration of 13.5 years (sensitivity566.7% and specificity571.6%, Pcor,0.001) and 1.5 cardiovascular risk factors (sensitivity540.7% and specificity584.3%, Pcor,0.05) were the cutoff values for screening $50% carotid stenosis. OPEN ACCESS Citation: Yuan C, Wu VWC, Yip SP, Kwong DLW, Ying M (2014) Predictors of the Extent of Carotid Atherosclerosis in Patients Treated with Radiotherapy for Nasopharyngeal Carcinoma. PLoS ONE 9(12): e116284. doi:10. 1371/journal.pone. 0116284 Editor: Yingmei Feng, Katholieke Universiteit Leuven, Belgium Received: September 3, 2014 Accepted: December 8, 2014 Published: December 31, 2014 Copyright: 2014 Yuan et al. This is an openaccess article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Data Availability: The authors confirm that all data underlying the findings are fully available without restriction. All relevant data are in the paper. Funding: This research was funded by a research studentship for CY from the Hong Kong Polytechnic University (RU2R). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist. PLOS ONE | DOI:10.1371/journal.pone. 0116284 December 31, 2014 1 / 14 Conclusions: Age, post-RT duration and number of cardiovascular risk factors are significant predictors of carotid atherosclerosis in post-RT NPC patients. Post-RT NPC patients, who are at least 45 years old, with post-RT duration of 9 years or above, and/or have $2 cardiovascular risk factors, are more susceptible to carotid atherosclerosis.