RESUMEN
Abstract Objects: Radiotherapy (RT) serves as the most effective treatment for Nasopharyngeal Carcinoma (NPC) and can cause carotid stenosis. The aim of this study is to assess the impact of RT on carotid stenosis in NPC patients, as well as to explore the risk factors for significant carotid stenosis. Methods: Studies reporting the carotid stenosis in NPC patients who underwent RT were found on PubMed, Embase and Web of Science. Outcomes of our interest included incidence of overall/significant stenosis, Common Carotid Artery (CCA) stenosis, External Carotid Artery (ECA) stenosis, Internal Carotid Artery (ICA) stenosis, and risk factors for significant carotid stenosis. Results: Sixteen studies met the inclusion criteria and were included in this meta-analysis. Pooled estimate showed that RT was associated with a significantly higher incidence of overall stenosis (Risk Ratio [RR = 3.53], 95% CI: 2.32-5.37; p < 0.001) and significant stenosis (RR = 7.06, 95% CI: 3.61-13.79; p < 0.001) as compared with controls. Moreover, patients treated with RT had a significantly higher risk of stenosis in CCA (RR = 6.87, 95% CI: 4.08-11.58; p < 0.001), ICA (RR = 3.43, 95% CI: 1.35-8.73; p= 0.010), ECA (RR = 9.37, 95% CI: 2.06-42.68; p = 0.004), and ECA/ICA (RR = 2.18, 95% CI: 1.52-3.13; p < 0.001). Meta-analysis indicated that age (RR = 1.46, 95% CI: 1.05-2.04; p = 0.024), smoking habit (RR = 1.20, 95% CI: 1.02-2.78; p = 0.045) and time interval from radiotherapy (RR = 1.56, 95% CI: 1.07-2.28; p = 0.02) were independent predictors of significant carotid stenosis. Conclusion: Our results suggested that RT increased the risk of carotid stenosis in patients with NPC. Prevention and control measurements should be made for older NPC patients with longer interval from RT, especially those with smoking habit. Level of evidence: 3.
RESUMEN
Abstract Purpose: To evaluate the toxicity of Erbitux as well as its biosimilar APZ001 antibody (APZ001) in pre-clinical animal models including mice, rabbits and cynomolgus monkeys. Methods: We performed analysis of normal behavior activity, autonomic and non-autonomic nervous functions, nervous-muscle functions, nervous excitability and sensorimotor functions on CD-1 mice. Subsequently, we studied that effects of APZ001 and Erbitux on respiratory system, cardiovascular system and kidney in Cynomolgus monkey models and performed local tolerance experiments on New Zealand rabbits. Results: The comparisons between APZ001 and Erbitux showed no significant differences in mice autonomic nervous system, nervous muscle functions, non-autonomic nervous functions, nervous excitability and sensorimotor functions between treated and untreated group (p>0.05). APZ001 and Erbitux showed negative effect on CD-1 mice in the present of pentobarbital sodium anesthesia (p>0.05). Single administrations of high, medium or low doses of APZ001 did not lead to monkey urine volume alterations (p>0.05). In human tissues, APZ001 and Erbitux showed positive signals in endocardium, lung type II alveolar epithelial cell and surrounding vessels, but showed negative results in kidney and liver tissues. No hemolysis phenomenon and serious side-effects in vessels and muscles were observed in rabbits when administrated with APZ001 and Erbitux respectively. Conclusion: The safety comparisons between APZ001 antibody and Erbitux showed that these two antibodies showed highly similarities in mice, rabbits and cynomolgus monkey animal models in consideration of pharmaceutical effects, indicating APZ001 might be a suitable substitute for Erbitux.