不同药物干预方案对131I辅助治疗甲状腺癌患者唾液腺功能保护作用的网状Meta分析

背景　131I辅助治疗甲状腺癌可显著提高患者生存率，但由此引起的唾液腺损伤严重影响患者生存质量。目前对于防治唾液腺损伤的药物有多种，但缺乏药物疗效之间的比较，因此进行网状Meta分析至关重要。目的　采用网状Meta分析方法评价不同药物干预方案对131I辅助治疗甲状腺癌患者唾液腺功能的保护作用。方法　计算机检索Cochrane Central Register of Controlled Trials、Web of Science、PubMed、EMBase、维普网、中国知网、万方数据知识服务平台、中国生物医学文献服务系统建库至2021年1月发表的不同药物干预方案对131I辅助治疗甲状腺癌患者唾液腺功能保护作用的随机对照试验或非随机对照试验。由两名研究者筛选文献，提取研究资料；使用Cochrane Handbook 5.10偏倚风险评估工具和MINORS评价文献质量，Stata 16.0软件进行一致性检验、发表偏倚分析和图形绘制，OpenBUGS 3.2.3软件进行网状Meta分析。结果　共纳入11篇文献，涉及7种药物干预方案，分别为氨磷汀、维生素C、氨磷汀+维生素C、柠檬酸、维生素E、硒、丙硫氧嘧啶。网状Meta分析结果显示，对腮腺排泌分数（EF）的防护作用氨磷汀+维生素C、氨磷汀高于柠檬酸和丙硫氧嘧啶，氨磷汀高于常规治疗（P<0.05）；累积排序概率图下面积（SUCRA）排序：氨磷汀+维生素C>氨磷汀>维生素C>常规治疗>维生素E>硒>柠檬酸>丙硫氧嘧啶。对颌下腺EF的防护作用维生素E、氨磷汀+维生素C、氨磷汀、常规治疗高于丙硫氧嘧啶（P<0.05）；SUCRA排序：维生素E>氨磷汀+维生素C>氨磷汀>硒>维生素C>柠檬酸>常规治疗>丙硫氧嘧啶。腮腺EF和颌下腺EF的漏斗图对称性良好。结论　氨磷汀+维生素C可能是防护131I辅助治疗甲状腺癌患者腮腺排泌功能的最佳干预方案，维生素E可能是防护131I辅助治疗甲状腺癌患者颌下腺排泌功能的最佳干预方案，氨磷汀+维生素C次之；但因网状Meta分析的局限性，仍需谨慎对待此结果，建议进行更多高质量、大样本的临床研究进一步验证。

Different Medications for Preventing 131I-induced Salivary Gland Damage in Thyroid Cancer Patients：a Network Meta-analysis

Background　Although 131I adjunctive therapy can significantly improve the survival rate of patients with thyroid cancer，its induced salivary gland damage seriously affects the quality of life. Currently，there are a variety of drugs for the prevention and treatment of 131I-induced salivary gland damage，but it needs to conduct a network Meta-analysis to fill the gap of comparison of these medications. Objective　To perform a network Meta-analysis of different medications for preventing 131I-induced salivary gland damage in thyroid cancer patients. Methods　Randomized controlled trials（RCTs） or non-RCTs about different medications for preventing 131I-induced salivary gland damage in thyroid cancer patients were searched in databases of Cochrane Central Register of Controlled Trials，Web of Science，PubMed，and EMBase，VIP，CNKI，Wanfang Data and SinoMed from inception to January 2021. Literature screening and data extraction were performed by two researchers，separately. The literature quality was evaluated using the risk of bias assessment tool in the Cochrane Handbook for Systematic Reviews of Interventions（Version 5.1.0） and MINORS. Consistency test，publication bias analysis and graph drawing were carried out using Stata 16.0. OpenBUGS 3.2.3 was used for network Meta-analysis. Results　A total of 11 articles were included，involving 7 intervention schemes：amifostine，vitamin C，amifostine with vitamin C，citric acid，vitamin E，selenium and propylthiouracil. Network Meta-analysis revealed that in terms of preventing 131I-induced loss of salivary excretion fraction in the parotid gland，amifostine with vitamin C was superior to citric acid and propylthiouracil，so was amifostine（P<0.05）. Amifostine was also superior to the regular treatment（P<0.05）. The SUCRA score for the schemes in preventing 131I-induced loss of salivary excretion fraction in the parotid gland ranked from highest to lowest was：amifostine with vitamin C> amifostine > vitamin C>regular treatment > vitamin E> selenium >citric acid > propylthiouracil. In terms of preventing 131I-induced loss of salivary excretion fraction in the submandibular gland，propylthiouracil was inferior to vitamin E，amphostine with vitamin C，amphostine and regular treatment（P<0.05）. The SUCRA score for the schemes in preventing 131I-induced loss of salivary excretion fraction in the submandibular gland ranked from highest to lowest was：vitamin E>amphostine with vitamin C> amphostine>selenium> vitamin C> citric acid> regular treatment > propylthiouracil. The funnel plot of comparing different medications for preventing 131I-induced loss of salivary excretion fraction in the parotid gland or submandibular gland was obviously symmetrical. Conclusion　Amphostine with vitamin C may be the best intervention for preventing 131I-induced loss of salivary excretion fraction in the parotid gland. And vitamin E may be the best scheme for preventing 131I-induced loss of salivary excretion fraction in the submandibular gland，followed by amphostine with vitamin C. Due to limitations of this study，these results should be taken with caution，which still need to be verified by more large-sample，high-quality clinical studies.