PD-1单抗联合铂类 + 替吉奥化疗用于局部进展期胃癌新辅助治疗近期效果研究

A Study on the Latest Results of Neoadjuvant Chemotherapy for Locally Advanced Gastric Cancer Utilising PD-1 Monoclonal Antibody in Combination with Platinum Antineoplastic Agent and Tegafur Chemotherapy

摘要: 目的：探讨程序性细胞死亡受体1 (programmed death receptor 1, PD-1)药物联合铂类 + 替吉奥用于局部进展期胃癌新辅助治疗的有效性与安全性。方法：回顾性分析安徽医科大学第二附属医院2018年至2023年3月收治的53例接受术前新辅助治疗的局部进展期胃腺癌患者(cT3-4aNxM0)的临床资料。依据是否使用PD-1，分为对照组与观察组，对照组(n = 28)应用铂类(奥沙利铂/洛铂/顺铂) + 替吉奥方案，观察组(n = 25)在对照组基础上加用PD-1抑制剂(卡瑞利珠单抗12例/信迪利单抗13例)，比较两组患者3周期术前化疗后临床疗效、药物不良反应，对于行D2标准根治术患者，比较其临床特点：R0切除率、肿瘤退缩分级、主要病理缓解(major pathologic response, MPR)率等。再通过单因素及多因素回归分析探索影响MPR的危险因素。结果：观察组肿瘤客观缓解率优于对照组，两组疾病控制率、CEA/CA199降低值无明显差异。药物不良反应方面，观察组反应性皮肤毛细血管增生症(reactive cutaneous capillary endothelial proliferation, RCCEP)/药物性皮疹、肝肾功能损伤方面高于对照组，以I~II度为主。观察组组内比较，卡瑞利珠单抗组RCCEP/药物性皮疹高于信迪利单抗组，余无差异。手术病人中，观察组MPR高于对照组，TRG分级、肿块长径、手术时间、淋巴结转移、脉管癌栓侵犯情况低于对照组；R0切除率、pCR等无统计学差异。PD-1的使用是MPR的保护因素。结论：PD-1单抗与铂类 + 替吉奥联用于局部进展期胃癌术前新辅助治疗，较单纯化疗可有效降低肿瘤退缩分级，提高MPR，近期疗效更佳。但需及时关注药物毒副反应。

Abstract: Objective: To investigate the efficacy and safety of programmed cell death receptor1 (PD-1) mono-clonal antibody combined with platinum antineoplastic agent + tegafur for neoadjuvant chemo-therapy of locally advanced gastric cancer. Methods: Clinical data of 53 patients with locally ad-vanced gastric cancer adenocarcinoma (cT3-4aNxM0) who received preoperative neoadjuvant chemotherapy from 2018 to March 2023 at the Second Affiliated Hospital of Anhui Medical Univer-sity were retrospectively analyzed. Based on whether PD-1 was used or not, they were divided into the control group and the observation group. The control group (n = 28) was treated with platinum (oxaliplatin/lobaplatin/cisplatin) + tegafur regimen, and the observation group (n = 25) was treat-ed with the addition of a PD-1 inhibitor (Carelizumab in 12 cases/Sintilimab in 13 cases) on top of the control group. All of them were treated with 3 cycles of preoperative chemotherapy. The clinical efficacy and adverse reactions of the two groups were compared. The clinical characteristics of pa-tients who underwent D2 standard radical surgery were compared: R0 resection rate, tumor re-gression grade, major pathologic response (MPR) rate, etc. The risk factors affecting MPR were then explored by univariate and multivariate regression analysis. Results: The objective remission rate of the observation group was better than that of the control group, and there was no significant dif-ference between the two groups in terms of disease control rate and CEA/ CA199 reduction value. Regarding adverse events, the observation group was higher than the control group in terms of re-active cutaneous-capillary endothelial proliferation/drug eruption and hepatic and renal function impairment, predominantly of I~II degree. As for intra-group comparison, RCCEP/eruption was higher in the carelizumab group than in the sintilimab group, and there was no difference in the rest. Among the surgical patients, MPR was higher in the observation group than in the control group, and TRG grade, mass length diameter, operation time, lymph node metastasis, and vascular cancer thrombus invasion were lower than those in the control group; the differences in R0 resec-tion rate and pCR were not statistically significant. The use of PD-1 was a protective factor for MPR. Conclusion: PD-1 monoclonal antibody combined with chemotherapy for preoperative neoadjuvant treatment of locally advanced gastric cancer can effectively reduce tumor regression grade and im-prove MPR than chemotherapy alone, with better recent efficacy. However, timely attention should be paid to the drug toxicity.