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术前使用免疫检查点抑制剂对胃癌转移淋巴结癌残留影响的回顾性研究

Effect of preoperative immune checkpoint inhibitors on reducing residual lymph node metastases in patients with gastric cancer: a retrospective study

摘要:

目的:探讨术前使用免疫检查点抑制剂能否减少胃癌转移淋巴结的癌残留。方法:采用回顾性研究方法,收集2014年1月至2023年12月期间南方医科大学南方manbet官网登录 和厦门大学附属第一manbet官网登录 行术前系统治疗,且D 2根治术后病理提示原发灶退缩分级为肿瘤退缩分级(TRG)1级的胃腺癌患者,排除术前接受放疗的患者。共纳入58例患者(南方医科大学南方manbet官网登录 :46例;厦门大学附属第一manbet官网登录 :12例),根据术前用药方案的不同,分为术前单纯化疗组(36例)和术前免疫联合化疗组(22例)。两组患者的性别、年龄、体质指数、合并糖尿病、肿瘤位置、病理分型、Lauren分型、肿瘤分化程度、治疗前肿瘤原发灶浸润深度、治疗前淋巴结分期、治疗前临床分期、错配修复蛋白状态、术前治疗周期和术前治疗间隔时间比较,差异均无统计学意义(均 P>0.05)。主要观察指标为两组术后淋巴结降期情况,次要观察指标包括术后肿瘤浸润深度和淋巴结检出数目,以及影响原发灶TRG1级胃癌患者淋巴结癌残留的因素。 结果:术前免疫联合化疗组治疗后淋巴结降期显著优于术前单纯化疗组[pN0:90.9%(20/22)比61.1%(22/36);pN1:4.5%(1/22)比36.1%(13/36);pN2:4.5%(1/22)比0;pN3:0比2.8%(1/36), Z=-2.315, P=0.021]。术前免疫联合化疗组与单纯化疗组比较,术后送检淋巴结数目[(40.5±16.3)枚比(40.8±17.5)枚, t=0.076, P=0.940]和治疗后原发灶浸润深度[pT1a:50.0%(11/22)比30.6%(11/36);pT1b:13.6%(3/22)比19.4%(7/36);pT2:13.6%(3/22)比13.9%(5/36);pT3:13.6%(3/22)比25.0%(9/36);pT4a:9.1%(2/22)比11.1%(4/36), Z=-1.331, P=0.183]比较,差异均无统计学意义。单因素分析结果显示,术前治疗方案与原发灶TRG 1级胃癌患者淋巴结癌残留有关(χ 2=6.070, P=0.014)。除术前治疗方案外,另外选取治疗前肿瘤原发灶浸润深度、治疗前淋巴结分期、治疗前临床分期、术前治疗周期和术前治疗间隔时间等临床上考虑可能与淋巴结癌残留有关的因素一起纳入多因素分析,结果显示:术前联合免疫治疗是原发灶TRG 1级胃癌患者淋巴结无癌残留的独立保护因素(OR=0.147,95%CI:0.026~0.828, P=0.030)。 结论:相对术前单纯化疗,术前免疫检查点抑制联合化疗在原发灶TRG 1级胃癌患者中更好地减少了胃癌转移淋巴结的癌残留。

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abstracts:

Objective:To investigate the effect of immune checkpoint inhibitors on reducing residual lymph node metastasis in patients with gastric cancer.Methods:The cohort of this retrospective study comprised patients from Nanfang Hospital of Southern Medical University and the First Affiliated Hospital of Xiamen University who had undergone systemic treatment prior to gastrectomy with D2 lymphadenectomy and had achieved Grade 1 primary tumor regression (TRG1) from January 2014 to December 2023. After exclusion of patients who had undergone preoperative radiotherapy, data of 58 patients (Nanfang Hospital: 46; First Affiliated Hospital of Xiamen University: 12) were analyzed. These patients were allocated to preoperative chemotherapy (Chemotherapy group, N=36 cases) and preoperative immunotherapy plus chemotherapy groups (Immunotherapy group, N=22 cases). There were no significant differences between these groups in sex, age, body mass index, diabetes, tumor location, pathological type, Lauren classification, tumor differentiation, pretreatment depth of invasion by primary tumor, pretreatment lymph node stage, pretreatment clinical stage, mismatch repair protein status, number of preoperative treatment cycles, or duration of preoperative treatment (all P>0.05). The primary outcome measure was postoperative lymph node downstaging. Secondary outcomes included postoperative depth of invasion by tumor, number of lymph nodes examined, and factors affecting residual lymph node metastasis status. Results:Lymph node downstaging was achieved significantly more often in the Immunotherapy group than the Chemotherapy group (pN0: 90.9% [20/22] vs. 61.1% [22/36]; pN1: 4.5% [1/22] vs. 36.1% [13/36]; pN2: 4.5% [1/22) vs. 0; pN3: 0 vs. 2.8% [1/36], Z=-2.315, P=0.021). There were no significant difference between the two groups in number of lymph nodes examined (40.5±16.3 vs. 40.8±17.5, t=0.076, P=0.940) or postoperative depth of invasion by primary tumor (pT1a: 50.0% [11/22] vs. 30.6% [11/36]; pT1b: 13.6% [3/22] vs. 19.4% [7/36]; pT2: 13.6% [3/22] vs. 13.9% [5/36]; pT3: 13.6% [3/22] vs. 25.0% [9/36]; pT4a: 9.1% [2/22] vs. 11.1% [4/36], Z=-1.331, P=0.183). Univariate analysis revealed that both preoperative treatment regimens were associated with residual lymph node metastasis status in patients whose primary tumor regression was TRG1 (χ 2=6.070, P=0.014). Multivariate analysis incorporated the following factors: pretreatment depth of invasion by primary tumor, pretreatment lymph node stage, pretreatment clinical stage, number of preoperative treatment cycles, and preoperative treatment duration. We found that a combination of immunotherapy and chemotherapy administered preoperatively was an independent protective factor for reducing residual lymph node metastases in study patients whose primary tumor regression was TRG1 (OR=0.147, 95%CI: 0.026–0.828, P=0.030). Conclusion:Compared with preoperative chemotherapy alone, a combination of preoperative immunotherapy and chemotherapy achieved greater reduction of residual lymph node metastases in the study patients who achieved TRG1 tumor regression in their primary lesions.

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作者: 陈新华 [1] 林和新 [2] 陈粤泓 [1] 王晓东 [1] 刘超群 [3] 黄慧琳 [1] 梁华元 [1] 张惠敏 [1] 李风萍 [1] 刘浩 [1] 胡彦锋 [1] 李国新 [1] 尤俊 [2] 赵丽瑛 [4] 余江 [1]
期刊: 《中华胃肠外科杂志》2024年27卷7期 694-701页 MEDLINEISTICPKUCSCD
栏目名称: 论著
DOI: 10.3760/cma.j.cn441530-20240513-00176
发布时间: 2024-07-30
基金项目:
广东省胃肠肿瘤精准微创诊疗重点实验室 南方医科大学南方manbet官网登录 临床研究专项 北京科创医学发展基金会 Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Cancer Special Funds for Clinical Research of Nanfang Hospital of Southern Medical University Beijing Science and Technology Innovation Medical Development Foundation
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