邝玉慧 徐方飚 赵哲 梁家琦 陈欣菊

中圖分类号 R735.7 文献标志码 A 文章编号 1001-0408（2021）08-0996-08

DOI 10.6039/j.issn.1001-0408.2021.08.17

摘 要 目的：系统评价复方斑蝥胶囊联合不同放化疗方案治疗原发性肝癌（PHC）的有效性和安全性，旨在为临床用药提供循证参考。方法：计算机检索中国生物医学文献数据库、中国知网、万方数据、维普网、PubMed、Embase、Cochrane图书馆等，检索时限均为各数据库建库起至2020年9月，收集复方斑蝥胶囊联合不同放化疗方案（试验组）对比不同放化疗方案（对照组）的随机对照试验（RCT）、队列研究。筛选文献、提取资料后，采用Cochrane系统评价员手册5.1.0推荐的偏倚风险评估工具对RCT进行质量评价;采用纽卡斯尔-渥太华量表对队列研究进行质量评价;采用Rev Man 5.3软件进行Meta分析，采用TSA 0.9.5.10 Beta软件进行试验序贯分析，采用GRADE Profiler 3.6.1证据等级质量评价工具对RCT和队列研究进行证据质量等级评价。结果：共纳入15项RCT，共计1 148例患者。Meta分析结果显示，试验组患者的治疗有效率显示高于对照组[RR=0.80，95%CI（0.73，0.88），P<0.000 01];按化疗方案不同进行亚组分析的结果显示，试验组联合肝动脉化疗栓塞术（TACE）介入治疗方案、三维适形放疗方案患者的治疗有效率均显著高于对照组（P<0.05）。试验组患者的生存率显著高于对照组[RR=0.81，95%CI（0.74，0.89），P<0.000 1];按生存时间不同进行亚组分析的结果显示，试验组患者1年、2年、3年生存率均显著高于对照组（P<0.05）。试验组患者骨髓抑制发生率显著低于对照组，自然杀伤细胞计数、T细胞亚群计数均显著高于对照组（P<0.05）;而两组患者甲胎蛋白含量、肝功能指标比较，差异均无统计学意义（P>0.05）。试验序贯分析结果显示，复方斑蝥胶囊联合TACE介入治疗的治疗有效率更优的证据确切。GRADE评价结果显示，治疗有效率的证据等级为中级，生存率及骨髓抑制发生率的证据等级为低级，其余指标均为极低级。结论：复方斑蝥胶囊联合不同放化疗方案用于PHC的疗效显著且安全性较好，尤以联合TACE介入治疗的疗效最佳，且治疗有效率的证据等级为中级。

关键词 复方斑蝥胶囊;原发性肝癌;疗效;安全性;Meta分析;试验序贯分析;GRADE评价

Meta-analysis and Trial Sequential Analysis of Effectiveness and Safety of Compound Banmao Capsules Combined with Different Chemoradiotherapy in the Treatment of Primary Hepatic Carcinoma

KUANG Yuhui1，XU Fangbiao1，ZHAO Zhe2，LIANG Jiaqi3，CHEN Xinju4（1. First School of Clinical Medicine， Henan University of TCM， Zhengzhou 450046， China; 2. Second School of Clinical Medicine， Henan University of TCM， Zhengzhou 450046， China; 3. Dept. of Hepatic Disease， Beijing TCM Hospital Affiliated to Capital Medical University， Beijing 100010， China; 4. First Ward of Spleen， Stomach， Liver and Gall， the First Affiliated Hospital of Henan University of TCM， Zhengzhou 450002， China）

ABSTRACT   OBJECTIVE： To systematically evaluate the efficacy and safety of Compound banmao capsules combined with different chemoradiotherapy in the treatment of primary hepatic carcinoma （PHC）. METHODS： Retrieved from CBM， CNKI， Wanfang database， VIP， PubMed， Embase and Cochrane Library during the inception to Sept. 2020， randomized controlled trial （RCTs）， cohort study about Compound banmao capsules combined with different chemoradiotherapy plans （trial group） versus different chemoradiotherapy plans （control group） were collected. After literature screening and data extraction， the quality of included RCTs were evaluated with bias risk evaluation tool recommended by Cochrane system evaluator mannual 5.1.0. Newcastle Ottawa scale was used to evaluate the quality of cohort studies; Rev Man 5.3 software was used for Meta-analysis; TSA 0.9.5.10 Beta software was used for  trail sequential analysis， and GRADE Profiler 3.6.1 software was used for evidence quality evaluation of RCT and cohort studies. RESULTS： A total of 15 RCTs were included， involving  1 148 patients. Meta-analysis showed that effective rate of trial group was significantly higher than that of control group [RR=0.80，95%CI（0.73，0.88），P<0.000 01]. The results of subgroup analysis according to different chemotherapy plan showed that the effective rate of trial group combined with TACE and three dimensional conformal radiotherapy were significantly higher than control group （P<0.05）. The survival rate of trial group was significantly higher than control group [RR=0.81， 95%CI（0.74， 0.89）， P<0.000 1]; the results of subgroup analysis according to different survival time showed that 1-year， 2-year and 3-year survival rates of trial group were significantly higher than control group （P<0.05）. The incidence of myelosuppression in trial group was significantly lower than control group， and the natural killer cell count and T cell count of trial group were significantly higher than control group （P<0.05）. There was no statistical significance in AFP content and liver function index between 2 groups （P>0.05）. Trial sequential analysis showed that there was definite evidence for better effective rate of Compound banmao capsules combined with TACE. GRADE evaluation results showed that the evidence level of effective rate was intermediate， the evidence level of survival rate and incidence of myelosuppression was low， and other indicators were very low. CONCLUSIONS： Compound banmao capsules combined with different chemoradiotherapy in the treatment of PHC has significant efficacy and good safety， especially in combination with TACE， and the evidence level of effective rate is intermediate.

KEYWORDS   Compound banmao capsules; Primary hepatic carcinoma; Efficacy; Safety; Meta-analysis; Trial sequential analysis; GRADE evaluation

原发性肝癌（PHC）是常见的消化道恶性肿瘤，据2018年美国癌症协会统计，肝癌是全球第六大常见的肿瘤，近10年来发病率呈逐年上升的趋势，其死亡率居全球恶性肿瘤第4位，每年新发病例约84万例、死亡约78万例[1]。……