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中华普通外科学文献(电子版)

中华普通外科学文献(电子版) ›› 2021, Vol. 15 ›› Issue (06) : 472 -480. doi: 10.3877/cma.j.issn.1674-0793.2021.06.016

循证医学

全程新辅助治疗与标准治疗对局部进展期直肠癌疗效的Meta分析
高瞻鹏1, 姬哲1, 董胜利1,†()   
  1. 1. 030001　太原，山西医科大学第二医院普外科
  • 收稿日期:2021-07-21 出版日期:2021-12-01
  • 通信作者: 董胜利

Meta-analysis of the efficacy of total neoadjuvant therapy versus standard treatment in locally advanced rectal cancer

Zhanpeng Gao1, Zhe Ji1, Shengli Dong1,†()   

  1. 1. Department of General Surgery, the Second Hospital of Shanxi Medical University, Taiyuan 030001, China
  • Received:2021-07-21 Published:2021-12-01
  • Corresponding author: Shengli Dong
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引用本文：

高瞻鹏, 姬哲, 董胜利. 全程新辅助治疗与标准治疗对局部进展期直肠癌疗效的Meta分析[J]. 中华普通外科学文献(电子版), 2021, 15(06): 472-480.

Zhanpeng Gao, Zhe Ji, Shengli Dong. Meta-analysis of the efficacy of total neoadjuvant therapy versus standard treatment in locally advanced rectal cancer[J]. Chinese Archives of General Surgery(Electronic Edition), 2021, 15(06): 472-480.

目的

对全程新辅助治疗（TNT）在局部进展期直肠癌治疗中的疗效进行Meta分析，以期对临床治疗决策提供参考依据。

方法

通过检索中国知网、万方数据、Cochrane Library、PubMed、Embase数据库，收集从2003年1月至2021年1月所有对比TNT与标准治疗（将新辅助同步放化疗/术前短程放疗+全直肠系膜切除术+术后辅助化疗模式统称为标准治疗）的文献，试验组为TNT，对照组为标准治疗。筛选出合格的文献进行质量评估，并提取相关的数据和资料，采用RevMan 5.4软件进行Meta分析。

结果

共纳入14篇文献3 352例患者，包括试验组1 688例，对照组1 664例。与对照组相比，试验组病理完全缓解（pCR）率更高（OR=1.87，95% CI：1.56~2.25，P<0.001），R0切除率更高（OR=1.37，95% CI：1.07~1.76，P=0.01），无病生存期（DFS）（HR=0.85，95% CI：0.74~0.98，P=0.02）与总生存期（OS）（HR=0.73，95% CI：0.62~0.85，P<0.001）更优；两组肿瘤降期、3~4级不良事件、保肛率、总并发症发生率、吻合口漏和切口感染发生率比较，差异均无统计学意义。

结论

对于局部进展期直肠癌患者，TNT尽管与标准治疗相比未显著改善OS和DFS，但明显提高了肿瘤的pCR率和R0切除率，是安全可行的。

关键词: 直肠肿瘤, 肿瘤辅助疗法, 化学疗法，辅助, Meta分析
Objective

A Meta-analysis is conducted on the efficacy of total neoadjuvant therapy (TNT) in the treatment of locally advanced rectal cancer, in order to provide reference for clinical treatment decision-making.

Methods

By searching CNKI, Wanfang Data, Cochrane Library, PubMed and Embase databases from January 2003 to January 2021, all literatures comparing TNT with standard treatment (neoadjuvant chemoradiotherapy/preoperative short-course radiotherapy + total mesorectum excision + postoperative adjuvant chemotherapy collectively referred to as standard treatment) were collected. The trial group was TNT, and the control group was standard treatment. Qualified literatures were selected and literature quality was evaluated, relevant data and materials were extracted for Meta-analysis with RevMan 5.4 software.

Results

A total of 3 352 patients in 14 literatures were included. There were 1 688 cases in the trial group and 1 664 cases in the control group. Compared to the control group, the rate of pathological complete response (pCR) in the trial group was higher (OR=1.87, 95% CI: 1.56-2.25, P<0.001), R0 resection rate was higher (OR=1.37, 95% CI: 1.07-1.76, P=0.01), disease-free survival (DFS) (HR=0.85, 95% CI: 0.74-0.98; P=0.02) and overall survival (OS) (HR=0.73, 95% CI: 0.62-0.85; P<0.001) were better. There were no significant differences in tumor descending stage, grade 3-4 adverse events, anus preserving rate, overall complications of operation, anastomotic fistula and incision infection between the two groups.

Conclusion

For patients with locally advanced rectal cancer, although TNT can’t significantly improve OS and DFS, it significantly improved the pCR rate and R0 resection rate, which is safe and feasible.

Key words: Rectal neoplasms, Neoadjuvant therapy, Chemotherapy, adjuvant, Meta-analysis
图1 文献筛选流程图
表1 NOS量表评价非随机对照研究
非RCT研究 选择 可比性 暴露
作者 病例的定义 病例的代表性 对照的选择 对照的定义 病例和对照的可比性 暴露的评估方法 病例和对照的调查方法是否相同 无应答率
Bhatti √ √ √ √ √ √ √ -
Cercek √ √ √ √ √ √ √ -
Cui √ √ √ √ √ √ √ -
Liang √ √ √ √ √ √ √ -
Zhai √ √ √ √ √ √ √ -
图2 纳入研究的偏倚风险评价结果
表2 纳入文献的基本特征
第一作者 年份 研究类型 新辅助资料方案 例数 临床T分期 临床N分期 肿瘤至肛缘距离[例(%) ] 中位随访时间 结局指示
T3-4 [例(%)] N+ [例(%)] <5 5-10 >10 (月)
Femandez-Martos 2010 随机对照研究 XELOX x 4→CRT→Sx 试验56 25(44.6) NR       69 ①②③④ ⑤⑥⑦⑧ ⑨
      CRT→Sx→XELOX 对照52 15(22.8) NR        
Marechal 2012 随机对照研究 FOLFOXx 2→CRT→Sx 试验28 27(96.0) 26(93.0) 11(39.3) 13(46.4) 4(14.3) NR ①②⑥⑧ ⑨⑩
      CRT→Sx 对照29 26(89.0) 25(86.0) 13(44.8) 9(31.0) 7(24.1)  
杨翠颜 2015 随机对照研究 CRT+XELOX x 1→Sx 试验40 40(100.0) 28(70.0)   NR   29 ①⑧⑨
      CRT→Sx 对照40 40(100.0) 24(60.0)       27
Bujko 2016 随机对照研究 SCRT→FOLFOX x 3→Sx 试验261 261(100.0) NR 148(56.7) 106(40.6) 7(2.7) 35 ①②③④ ⑥⑧
      CRT→Sx 对照254 254(100.0) NR 138(54.3) 99(39.0) 16(6.3)  
李雷蕾 2017 随机对照研究 CRT+FOLFOX4 x 4→Sx→FOLFOX4 x 4 试验40 40(100.0) 25(62.5) 14(35.0) 26(65.0) NR 30 ①②④ ⑤⑨
      CRT→Sx→ FOLFOX 4 x 8 对照40 40(100.0) 29(72.5) 19(47.5) 21(52.5) NR  
Moor 2017 随机对照研究 CRT→5FU x 3→Sx 试验25 25(100.0) 25(100)   NR   NR ①②⑧⑨
      CRT→Sx 对照24 23(95.8) 22(91.7)        
Kim 2018 随机对照研究 CRT一XELOX x2→Sx 试验53 53(100.0) 49(92.5)   NR   26 ①②⑤ ⑥⑦
      CRT→Sx 对照55 55(100.0) 51(92.7)        
Conroy 2020 随机对照研究 FOLFIRINOX x 6→CRT→Sx→ FOLFOX x 6 试验231 231(100.0) 206(89.2) 87(37.7) 114(49.3) 30(13.0) 46.5 ①③④⑥
      CRT→Sx→FOLFOX x 12 对照230 230(100.0) 207(90.0) 83(36.1) 118(51.3) 29(12.6)  
Bahadoer 2021 随机对照研究 SCRT→XELOX x 6/FOLFOX x 9→Sx 试验462 448(97.0) 420(90.9) 103(22.4) 180(39.1) 32(6.9) 54 ①②③ ④⑥
      CRT→Sx→CT x 6m 对照450 436(6.9) 415(92.2) 114(25.8) 148(33.6) 21(4.8)  
Bhatti 2015 回顾性研究 CAPOX x4→CRT→Sx 试验93 82(88.2) 84(90.3) 65(69.9) 28(30.1)   45 ①②③④
      CRT→Sx 对照61 57(93.4) 46(75.4) 47(77.0) 14(23.0)    
Cercek 2018 回顾性研究 FOLFOX/CAPOX/FLOX x 4m→CRT→Sx 试验308 287(93.2) 265(86.0) 102(33.1) 143(46.4) 63(20.5) 23 ①
      CRT→Sx 对照320 297(92.8) 226(70.6) 98(30.6) 175(54.7) 47(14.7) 40
Liang 2019 回顾性研究 CRT→CAP/CAPOX/FOLFOX→Sx 试验76 76(100.0) 62(81.2) 47(61.8) 29(31.2) NR 31 ①②③④ ⑦⑧⑨
      CRT→Sx 对照80 80(100.0) 68(85.0) 43(53.8) 37(46.2) NR  
Zhai 2020 回顾性研究 CapOX x 1→CRT→ CapOX x 2→Sx 试验79 73(92.4) 73(92.4) 43(54.4) 29(36.7) 7(6.9) NR ①②⑤⑦ ⑧⑨⑩
      CRT→Sx 对照55 52(94.5) 52(94.5) 28(50.9) 21(38.2) 6(10.9)  
Cui 2020 回顾性研究 CRT→XELOX x 2→Sx 试验83 83(100.0) 83(100.0)   NR   NR ①⑤⑦⑧ ⑨⑩
      CRT→Sx 对照61 61(100.0) 61(100.0)        
图3 两组患者病理完全缓解（pCR）率的Meta分析森林图
图4 两组患者R0切除率的Meta分析森林图
图5 两组患者无病生存期（DFS）的Meta分析森林图
图6 两组患者总生存期（OS）的Meta分析森林图
图7 两组患者肿瘤降期的Meta分析森林图
图8 两组患者3~4级不良事件发生率的Meta分析森林图
图9 两组患者保肛率的Meta分析森林图
图10 两组患者手术总体并发症的Meta分析森林图
图11 两组患者吻合口漏的Meta分析森林图
图12 两组患者切口感染的Meta分析森林图
图13 两组患者病理完全缓解（pCR）率的Meta分析漏斗图
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