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中华结直肠疾病电子杂志 ›› 2022, Vol. 11 ›› Issue (01) : 44 -53. doi: 10.3877/cma.j.issn.2095-3224.2022.01.007

论著

新辅助治疗反应对局部进展期直肠癌患者预后的影响
刘恩瑞1, 关旭1, 魏然1, 姜争1, 刘正1, 陈瑛罡2,(), 王锡山1,()   
  1. 1. 100021 北京,国家癌症中心/国家肿瘤临床医学研究中心/中国医学科学院北京协和医学院肿瘤医院结直肠外科
    2. 518116 国家癌症中心/国家肿瘤临床医学研究中心/中国医学科学院北京协和医学院肿瘤医院深圳医院胃肠外科
  • 收稿日期:2021-12-26 出版日期:2022-02-25
  • 通信作者: 陈瑛罡, 王锡山
  • 基金资助:
    中国医学科学院创新基金(CIFMS)(2016-I2M-1-001); 深圳市‘医疗卫生三名工程’(SZSM201911012)

The prognostic impact of neoadjuvant therapy response on survival in patients with locally advanced rectal cancer

Enrui Liu1, Xu Guan1, Ran Wei1, Zheng Jiang1, Zheng Liu1, Yinggang Chen2,(), Xishan Wang1,()   

  1. 1. Department of Colorectal Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Bejing 100021, China
    2. Department of Gastrointestinal Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen 518116, China
  • Received:2021-12-26 Published:2022-02-25
  • Corresponding author: Yinggang Chen, Xishan Wang
引用本文:

刘恩瑞, 关旭, 魏然, 姜争, 刘正, 陈瑛罡, 王锡山. 新辅助治疗反应对局部进展期直肠癌患者预后的影响[J/OL]. 中华结直肠疾病电子杂志, 2022, 11(01): 44-53.

Enrui Liu, Xu Guan, Ran Wei, Zheng Jiang, Zheng Liu, Yinggang Chen, Xishan Wang. The prognostic impact of neoadjuvant therapy response on survival in patients with locally advanced rectal cancer[J/OL]. Chinese Journal of Colorectal Diseases(Electronic Edition), 2022, 11(01): 44-53.

目的

探究新辅助治疗反应对局部进展期直肠癌患者远期预后的影响。

方法

回顾性收集中国医学科学院肿瘤医院218例接受术前新辅助放化疗的局部进展期直肠癌患者(LARC)的临床病理资料。根据Dowrak/R?del肿瘤退缩分级(TRG)标准将患者分为治疗反应良好(TRG3~4)和治疗反应不佳(TRG0~2)。采用Cox风险比例回归单因素和多因素分析确定无病生存(disease-free survival,DFS)和肿瘤总生存(overall survival,OS)影响因素。采用Kaplan-Meier法绘制生存曲线并利用Log-rank检验比较肿瘤生存差异。

结果

本研究纳入患者218例,其中治疗反应良好126例,治疗反应不佳92例。单因素和多因素Cox回归分析确定新辅助治疗反应不佳是DFS(HR=3.85,95%CI:1.40~10.60;P=0.009)和OS(HR=3.81,95%CI:1.02~14.20;P=0.046)的独立危险因素。5年DFS分别为反应良好93.46%,反应不佳65.04%(χ2=28.23,P<0.001);5年OS分别为反应良好95.38%,反应不佳78.99%(χ2=18.51,P<0.001)。

结论

新辅助治疗反应是LARC患者DFS和OS的独立预后因素;良好的治疗反应预示着更好的肿瘤学预后,为进一步的临床研究风险分层提供了理论基础。

Objective

To explore the prognostic impact of neoadjuvant therapy response on survival in patients with locally advanced rectal cancer.

Methods

The clinicopathological data of 218 patients with locally advanced rectal cancer (LARC) who received preoperative neoadjuvant chemoradiotherapy in Cancer Hospital of Chinese Academy of Medical Sciences were retrospectively collected. Patients were divided into good response (TRG3~4) and poor response (TRG0~2) based on Dowrak/R?del tumor regression grade (TRG) criteria. Cox proportional regression univariate and multivariate analyses were performed to identify the influence factors for disease-free survival (DFS) and overall survival (OS). Kaplan-Meier method was used to plot the survival curve and the Log-rank test was used to compare the differences in tumor survival.

Results

A total of 218 patients were enrolled in this study, including 126 patients with good treatment responses and 92 patients with poor treatment responses. Univariate and multivariate Cox regression analysis identified that poor response to neoadjuvant therapy was an independent risk factor for DFS (HR=3.85, 95%CI: 1.40~10.60; P=0.009) and OS (HR=3.81, 95%CI: 1.02~14.20; P=0.046). 5-year DFS was 93.46% in the good response group and 65.04% in the poor response group (χ2=28.23, P<0.001); and 5-year OS were 95.38% in the good response group and 78.99% in the poor response group (χ2=18.51, P<0.001).

Conclusion

Neoadjuvant therapy response was an independent prognostic factor for DFS and OS in locally advanced rectal cancer patients, and good response predicts better oncology prognosis. This study provides a theoretical basis for further clinical research on risk stratification.

表1 局部进展期直肠癌新辅助放化疗后反应良好和反应不佳患者临床病理资料[例(%)]
变量 总数(n=218) 反应不佳(n=92) 反应良好(n=126) χ2 P
性别 0.908 0.341

79(36.2) 30(32.6) 49(38.9)

139(63.8) 62(67.4) 77(61.1)
年龄(岁) 3.537 0.060

<60

131(60.1) 62(67.4) 69(54.8)

≥60

87(39.9) 30(32.6) 57(45.2)
BMI(kg/m2 0 1.000

<24

109(50.0) 46(50.0) 63(50.0)

≥24

109(50.0) 46(50.0) 63(50.0)
糖尿病 0.610 0.435

196(89.9) 81(88.0) 115(91.3)

22(10.1) 11(12.0) 11(8.7)
高血压 0.10 0.921

158(72.5) 67(72.8) 91(72.2)

60(27.5) 25(27.2) 35(27.8)
肿瘤家族史 0.690 0.406

174(79.8) 71(77.2) 103(81.7)

44(20.2) 21(22.8) 23(18.3)
吸烟 0.005 0.945

125(57.3) 53(57.6) 72(57.1)

93(42.7) 39(42.4) 54(42.9)
饮酒 0.026 0.864

136(62.4) 58(63.0) 78(61.9)

82(37.6) 34(37.0) 48(38.1)
CEA(ng/mL) 1.165 0.280

正常

130(59.6) 51(55.4) 79(62.7)

异常

88(40.4) 41(44.6) 47(37.3)
CA 19-9(U/mL) 1.114 0.291

正常

171(78.4) 69(75.0) 102(81.0)

异常

47(21.6) 23(25.0) 24(19.0)
术前cT分期 3.091 0.079

3

184(84.4) 73(79.3) 111(88.1)

4

34(15.6) 19(20.7) 15(11.9)
术前cN分期 3.678 0.055

0

36(16.5) 10(10.9) 26(20.6)

1~2

182(83.5) 82(89.1) 100(79.4)
术后pT分期 75.367 <0.001

0

49(22.5) 0(0) 49(38.9)

1~2

68(31.2) 20(21.7) 48(38.1)

3~4

101(46.3) 72(78.3) 29(23.0)
术后pN分期 15.506 <0.001

0

150(68.8) 50(54.3) 100(79.4)

1~2

68(31.2) 42(45.7) 26(20.6)
淋巴结检出数(个) 1.374 0.241

≥12

142(65.1) 64(69.6) 78(61.9)

<12

76(34.9) 28(30.4) 48(38.1)
肿瘤直径(cm) 15.065 <0.001

≤3

168(77.1) 59(64.1) 109(86.5)

>3

50(22.9) 33(35.9) 17(13.5)
肿瘤分化 53.662 <0.001

高-中分化

92(42.2) 54(58.7) 38(30.2)

低分化

34(15.6) 25(27.2) 9(7.1)

未知*

92(42.2) 13(14.1) 79(62.7)
脉管侵犯 7.249 0.007

200(91.7) 79(85.9) 121(96.0)

18(8.3) 13(14.1) 5(4.0)
神经侵犯 21.896 <0.001

187(85.8) 67(72.8) 120(95.2)

31(14.2) 25(27.2) 6(4.8)
术前放疗 0.029 0.865

短程

65(29.8) 28(30.4) 37(29.4)

长程

153(70.2) 64(69.6) 89(70.6)
术前化疗 0.001 0.981

卡培他滨单药

140(64.2) 59(64.1) 81(64.3)

奥沙利铂+卡培他滨

78(35.8) 33(35.9) 45(35.7)
术后化疗 3.353 0.067

120(55.0) 44(47.8) 76(60.3)

98(45.0) 48(52.2) 50(39.7)
表2 局部进展期直肠癌患者无病生存率影响因素的单因素和多因素Cox风险比例回归分析
表3 局部进展期直肠癌患者总生存率影响因素的单因素和多因素Cox风险比例回归分析
图1 局部进展期直肠癌新辅助治疗后不同反应对无病生存率和总体生存率的影响。1A:无病生存率;1B:总体生存率
图2 局部进展期直肠癌术前放疗方案对无病生存率和总体生存率的影响。2A:短程放疗组不同治疗反应对无病生存率影响;2B:长程放疗组不同治疗反应对无病生存率影响;2C:短程放疗组不同治疗反应对总体生存率影响;2D:长程放疗组不同治疗反应对总体生存率影响
图3 局部进展期直肠癌术前化疗方案对无病生存率和总体生存率的影响。3A:卡培他滨单药化疗组不同治疗反应对无病生存率的影响;3B:奥沙利铂联合卡培他滨化疗组不同治疗反应对无病生存率的影响;3C:卡培他滨单药化疗组不同治疗反应对总体生存率的影响;3D:奥沙利铂联合卡培他滨化疗组不同治疗反应对总体生存率的影响
图4 局部进展期直肠癌术后化疗对总体生存和无病生存的影响。4A:卡培他滨单药化疗组不同治疗反应对无病生存率的影响;4B:奥沙利铂联合卡培他滨化疗组不同治疗反应对无病生存率的影响;4C:卡培他滨单药化疗组不同治疗反应对总体生存率的影响;4D:奥沙利铂联合卡培他滨化疗组不同治疗反应对总体生存率的影响
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