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中华胸部外科电子杂志

中华胸部外科电子杂志 ›› 2021, Vol. 08 ›› Issue (04) : 247 -256. doi: 10.3877/cma.j.issn.2095-8773.2021.04.08

论著

新辅助治疗在cT2N0期食管癌患者中的临床意义：一项荟萃分析
宋佩东1, 陈东来2, 薛宇航1, 王伟1, 陈勇兵1, 桑永华1,†(), 杨文涛1   
  1. 1. 215004　苏州，苏州大学附属第二医院胸心外科
    2. 200433　上海，同济大学附属上海市肺科医院胸外科
  • 收稿日期:2021-07-02 修回日期:2021-09-13 接受日期:2021-09-15 出版日期:2021-11-28
  • 通信作者: 桑永华
  • 基金资助:
    江苏省科技厅社会发展-重点项目(BE2020653); 苏州市重点学科项目(SZXK201803); 苏州市胸部肿瘤重点实验室项目(SZS201907); 苏州市科技发展（民生科技）项目(SS2019061); 苏州大学附属第二医院学科建设托举工程项目(XKTJ-XK202004)

Clinical significance of neoadjuvant therapy in patients with cT2N0 esophageal cancer: a meta-analysis

Peidong Song1, Donglai Chen2, Yuhang Xue1, Wei Wang1, Yongbing Chen1, Yonghua Sang1,†(), Wentao Yang1   

  1. 1. Department of Thoracic Surgery, the Second Affiliated Hospital of Soochow University, Suzhou 215004, China
    2. Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University, School of Medicine, Shanghai 200433, China
  • Received:2021-07-02 Revised:2021-09-13 Accepted:2021-09-15 Published:2021-11-28
  • Corresponding author: Yonghua Sang
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引用本文：

宋佩东, 陈东来, 薛宇航, 王伟, 陈勇兵, 桑永华, 杨文涛. 新辅助治疗在cT2N0期食管癌患者中的临床意义：一项荟萃分析[J]. 中华胸部外科电子杂志, 2021, 08(04): 247-256.

Peidong Song, Donglai Chen, Yuhang Xue, Wei Wang, Yongbing Chen, Yonghua Sang, Wentao Yang. Clinical significance of neoadjuvant therapy in patients with cT2N0 esophageal cancer: a meta-analysis[J]. Chinese Journal of Thoracic Surgery(Electronic Edition), 2021, 08(04): 247-256.

目的

明确新辅助治疗在cT2N0期可切除食管癌患者中的临床意义。

方法

通过网上检索包括PubMed、Web of Science、EMBASE、the Cochrane Library、中国知网等一系列数据库，筛选符合本研究目的的真实世界研究，从中提取包括生存率、病理分期改变、切缘阳性、术后吻合口瘘等多种结局指标。通过RevMan 5.4与R version 4.0.2等数据分析软件对其进行荟萃分析。

结果

累计筛选出7项研究，共4 602例cT2N0食管癌患者纳入分析，荟萃分析表明新辅助联合手术治疗组（NS）与单纯手术组（S）在5年生存率、无复发生存率、术后吻合口瘘发生率与病理升期方面差异均无统计学意义（P>0.05）；然而两组在术中切缘阳性以及病理降期上差异均有统计学意义（P<0.05）。

结论

新辅助治疗联合手术较单纯手术并未给cT2N0食管癌患者带来明显生存获益及更高的吻合口瘘风险，也未降低病理升期风险，但应用新辅助治疗可有效降低病理分期以及术中切缘阳性的概率。推荐对于检查完善且胃镜病理提示不含高危因素的cT2N0食管癌患者可直接行手术治疗。

关键词: 新辅助治疗, 食管癌, cT2N0, 荟萃分析
Objective

To evaluate the clinical significance of NS in patients with cT2N0 resectable esophageal cancer.

Methods

Real-world studies were identified by searching databases including PubMed, Web of Science, EMBASE, Cochrane Library and China National Knowledge Infrastructure (CNKI). Data on 5-year overall survival, pathological upstaging and downstaging, margin positive rate and anastomotic leakage were extracted to assess the pros and cons of NS. The meta-analysis was performed using RevMan 5.4 and R version 4.0.2.

Results

A total of 4 602 patients from 7 real-world studies were included. The pooled results suggested that there were no significant differences in the 5-year overall survival and recurrence free survival between neoadjuvant plus surgery (NS) group and surgery alone (S) group. The pooled evidence also indicated that the NS group shared similar risk of postoperative anastomotic leakage and pathological upstaging to the S group. However, the NS group exhibited its value in pathological downstaging and reduced positive margin compared with the S group (P<0.05) .

Conclusion

This study indicates that NS is not significantly associated with better long-term survival and higher probability of anastomotic leakage or pathological upstaging compared with S, but NS exhibits significant advantages in pathological downstaging as well as margin positive rate. It is recommended that upfront surgery should be considered for patients receiving thorough preoperative examinations whose gastroscopy-based pathology reports reveal no major risk factors.

Key words: Neoadjuvant therapy, Esophageal cancer, cT2N0, Meta-analysis
表1 文献特征表
序号 作者（年份） 地区 病例时间范围 研究类型 样本量（人） 病理类型（%） 随访时间（月） 数据来源 新辅助治疗策略 AJCC分期版本 NOS评分 新辅助后最终病理分期（%）
新辅助联合组 单纯手术组 腺癌 鳞癌 <T2N0 T2N0 >T2N0
1 Zhang等，2012[15] 美国 1989—2009 回顾性研究 55 14 78.3 21.7 未报道 约翰霍普金斯医院 5-FU+铂类+放射 第6版 8 10.9 0 89.1
2 Markar等，2015[16] 欧洲地区 2000—2010 回顾性研究 70 285 48.2 51.8 平均54 多个中心 化疗或放化疗结合 第7版 9 32.9 31.4 35.7
3 Capovilla等，2021[12] 意大利 1990—2019 回顾性研究 38 191 41.9 58.1 中位30 帕多瓦大学 放化疗结合 第8版 8 47.4 23.7 28.9
4 Rhodin等，2021[17] 美国 2004—2015 回顾性研究 1226 1177 80.8 19.2 未报道 NCDB 化疗或放化疗结合 未报道 8 未报道 未报道 未报道
5 Crabtree等，2013[18] 美国 2002—2011 回顾性研究 270 482 未报道 未报道 未报道 STS 化疗或放化疗结合 第7版 8 31.1 30.8 38.1
6 Dolan等，2016[19] 美国 1999—2011 回顾性研究 11 16 92.6 7.4 平均48 俄勒冈健康与科学大学 5-FU+铂类+放射 第7版 8 54.5 9.2 36.3
7 ECSGPC，2019[20] 欧美地区 2002—2012 回顾性研究 268 499 87.7 12.3 中位30 多个中心 化疗或放化疗结合 第7版 9 45.1 20.9 34.0
表2 纳入文献偏倚风险评估
纳入研究 随机方法 分配隐藏 盲法 不完整资料偏倚 选择性报告偏倚 利益冲突
Zhang等，2012[15] L U H L L L
Markar等，2015[16] U U H L U L
Capovilla等，2021[12] L U L L L L
Rhodin等，2020[17] L U L H U L
Crabtree等，2013[18] L U H H L L
Dolan等，2016[19] U U H L L L
ECSGPC，2018[20] L U L H U L
图1 文章纳入筛选流程
图2 新辅助治疗联合手术组与单纯手术组的（A）5年生存率和（B）无复发生存率森林图
表3 新辅助联合手术治疗与单纯手术治疗对于病理降期影响的亚组分析
参数 研究数量（N＝6） 关联检验 异质性检验
OR 95%CI P I2（%） P
发表年份            
  ≥2016（近5年） 3 1.44 1.10~1.89 <0.01 84 <0.01
  <2016 3 1.51 1.14~2.00 <0.01 48 0.15
地区            
  美国 3 1.26 0.92~1.73 0.15 5 0.35
  欧洲或欧美地区 3 1.52 1.19~1.95 <0.01 85 <0.01
病理类型            
  腺癌 — 1.91 1.56~5.49 0.04 77 0.13
  鳞癌 — 2.11 1.19~3.72 0.01 78 0.03
AJCC分期版本            
  6 1 3.80 0.95~15.14 0.06 — —
  7 4 1.34 1.08~1.66 <0.01 5 0.37
  8 1 5.03 2.38~10.64 <0.01 — —
图3 应用新辅助联合治疗对于（A）病理分期下降、（B）病理分期上升、（C）术中切缘阳性发生概率及（D）术后吻合口瘘发生概率的影响森林图
图4 应用新辅助联合治疗对于（A）5年生存率、（B）无复发生存率、（C）病理分期下降、（D）切缘阳性发生概率及（E）病理分期上升的影响敏感性分析
图5 应用新辅助联合治疗对于（A）病理分期下降、（B）病理分期上升、（C）吻合口瘘事件及（D）切缘阳性事件的发表偏倚漏斗图
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