食管癌新辅助放化疗后手术时机选择的系统评价与Meta分析  

Timing of surgery for esophageal cancer patients after neoadjuvant chemoradiotherapy:A systematic review and meta-analysis

作　　者：何枫 帖红涛[2] 郎伟思[1] 罗骏[2] 陈丹[2] 吴庆琛[2] 杨龙[1] HE Feng;TIE Hongtao;LANGWeisi;LUO Jun;CHEN Dan;WU Qingchen;YANG Long(Department of Cardiothoracic Surgery,The Fifth Peopled Hospital of Chongqing,Chongqing,400062,P.R.China;Department of Cardiothoracic Surgery,The First Affiliated Hospital of Chongqing Medical University,Chongqing,400016,P.R.China)

机构地区：[1]重庆市第五人民医院胸心外科,重庆400062 [2]重庆医科大学附属第一医院胸心外科,重庆400016

出　　处：《中国胸心血管外科临床杂志》2019年第11期1125-1135,共11页Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

摘　　要：目的研究新辅助放化疗(neoadjuvant chemoradiotherapy,nCRT)和食管癌切除术之间时间间隔(简称为时间间隔)对食管癌临床结局的影响。方法计算机检索PubMed和EMbase数据库,检索时间为建库至2018年3月。随机效应模型用于所有Meta分析,而不考虑异质性。Meta分析采用RevMan5.3软件进行。文献的主要结局为手术死亡率、吻合口瘘发生率及生存情况,次要结局为病理完全缓解率、R0切除率、切缘阳性率。结果共17个研究含18 173例患者纳入本研究。其中,原始研究13个包含2 950例患者,基于数据库研究4个含15 223例患者。相关性分析发现时间间隔与手术死亡率呈显著正相关(Spearman系数0.360,P=0.027)。剂量-效应Meta分析发现nCRT后存在一个相对较佳的手术时间窗。进一步对主要结局不同时间截点(较短与较长时间间隔分界点)分析发现:(1)时间截点在30~70 d内时,较短时间间隔均可降低手术死亡风险[7~8周:RR=0.67,95%CI(0.55,0.81),P<0.05;30~46 d:RR=0.63,95%CI(0.47,0.85),P<0.05;60~70 d:RR=0.64,95%CI(0.48,0.85),P<0.05];(2)时间截点在30~46 d内时,较短时间间隔可以降低吻合口瘘发生风险[RR=0.39,95%CI(0.21,0.72),P<0.05];时间截点在7~8周时,较短时间间隔对吻合口瘘发生风险的影响处于临界状态[RR=0.73,95%CI(0.52,1.03),P>0.05];(3)当时间截点在7~8周内时,较长时间间隔会显著增加远期死亡风险[HR=1.17,95%CI(1.00,1.36),P<0.05]。对次要结局分析发现,时间截点在56~60 d时,较短时间间隔可以显著降低切缘阳性率[RR=0.53,95%CI(0.38,0.75),P<0.05]。结论在一定时间截点内,尽可能缩短时间间隔可以降低手术死亡率、吻合口瘘发生率、远期死亡风险及切缘阳性率。建议食管癌切除术应该在患者体能恢复后尽早进行,不超过7~8周最佳,支持目前研究推荐的nCRT后3~8周内。Objective To investigate the effect of the interval between neoadjuvant chemoradiotherapy(nCRT and surgery on the clinical outcome of esophageal cancer. Methods PubMed and EMbase databases from inception to March 2018 were retrieved by computer. A random-effect model was used for all meta-analyses irrespective of heterogeneity. The meta-analysis was performed by RevMan5.3 software. The primary outcomes were operative mortality,incidence of anastomotic leakage, and overall survival;secondary outcomes were pathologic complete remission rate, R0 resection rate, and positive resection margin rate. Results A total of 17 studies with 18 173 patients were included.Among them, 13 were original studies with 2 950 patients, and 4 were database-based studies with a total of 15 223 patients. The results showed a significant positive correlation between the interval and operative mortality(Spearman coefficient=0.360, P=0.027). Dose-response meta-analysis revealed that there was a relatively better time window for surgery after nCRT. Further analysis for primary outcomes at different time cut-offs found the following results:(1) when the time cut-off point within 30-70 days, the shorter interval was associated with a reduced operative mortality(7-8 weeks:RR=0.67, 95% CI 0.55-0.81, P<0.05;30-46 days: RR=0.63, 95%CI 0.47-0.85, P<0.05;60-70 days: RR=0.64, 95%CI 0.48-0.85,P<0.05);(2) when the time cut-off point within 30-46 days, the shorter interval correlated with a reduced incidence of anastomotic leakage(RR=0.39, 95%CI 0.21-0.72, P<0.05);when the time cut-off point within 7-8 weeks, the shorter interval could achieve a critical-level effect of reducing the incidence of anastomotic leakage(RR=0.73, 95%CI 0.52-1.03,P>0.05);(3) when the time cut-off point within 7-8 weeks, increased interval significantly was associated with the poor overall survival(HR=1.17, 95% CI 1.00-1.36, P<0.05). Secondary outcomes found that the shorter interval could significantly reduce the positive resection margin rate(RR=0.53, 95% CI 0.38-0.75, P<0.05

关 键 词：食管癌 新辅助放化疗 手术切除 时间间隔 系统评价/META分析 

分 类 号：R73[医药卫生—肿瘤]