PD-1抑制剂联合SOX化疗方案治疗局部进展期胃腺癌患者的近期疗效及影响因素

doi:10.3760/cma.j.cn441417-20241118-10016

摘要/Abstract

摘要：

目的　探讨程序性死亡蛋白-1（programmed death protein-1，PD-1）抑制剂联合奥沙利铂+替吉奥（SOX）化疗方案在局部进展期胃腺癌新辅助治疗中的近期疗效及其影响因素。方法　选取2022年5月至2024年5月西安市第三医院收治的128例局部进展期胃腺癌患者进行随机对照试验。采用随机数字表法将其分为对照组和研究组，各64例。对照组采用SOX化疗方案治疗，研究组采用PD-1抑制剂联合SOX化疗方案治疗。两组患者均按照计划完成3个周期的化疗。比较两组近期临床疗效、年龄、性别、肿瘤长径、肿瘤部位、TNM分期、病理类型、分化程度、胆汁酸水平、中性粒细胞与淋巴细胞计数比值（NLR）、程序性死亡受体配体1（programmed cell death ligand 1，PD-L1）表达。统计两组患者治疗期间不良反应发生情况，采用logistic回归分析影响局部进展期胃腺癌患者应用PD-1抑制剂联合SOX化疗方案治疗近期疗效的影响因素。采用χ2检验和t检验进行统计分析。结果　研究组近期疗效高于对照组［75.00%（48/64）比57.81%（37/48）］，差异有统计学意义（P<0.05）。两组年龄、性别、肿瘤部位、病理类型、分化程度比较，差异均无统计学意义（均P>0.05）。研究组肿瘤长径<6 cm、TNM分期为Ⅱ期、PD-L1表达≥1%的患者占比分别为78.13%（50/64）、68.75%（44/64）、76.56%（49/64），高于对照组的51.56%（33/64）、28.13%（18/64）、48.44%（31/64），而胆汁酸水平、NLR≥3.7的患者占比分别为（4.64±1.42）μmol/L、23.44%（15/64），明显低于对照的的（5.87±1.78）μmol/L、68.75%（44/64），差异均有统计学意义（均P<0.05）。治疗期间，研究组发生恶心4例，呕吐5例，食欲减退7例；对照组发生恶心6例，呕吐4例，食欲减退8例；差异无统计学意义（χ2=0.160，P>0.05）。logistic回归分析结果显示，肿瘤长径<6 cm、TNM分期Ⅱ期、低胆汁酸水平、NLR≥3.7、PD-L1表达≥1%均是局部进展期胃腺癌患者应用PD-1抑制剂联合SOX化疗方案治疗近期疗效的保护因素（均P<0.05）。结论　PD-1抑制剂联合SOX化疗方案治疗局部进展期胃腺癌患者近期疗效较好，其中PD-L1表达≥1%、肿瘤长径<6 cm以及TNM分期为Ⅱ期是影响临床疗效的保护因素。临床上应基于这些因素选择适合的治疗方案。

关键词: 进展期胃腺癌, , , 程序性死亡蛋白-1, , , 奥沙利铂, , , 替吉奥, , , 疗效

Abstract:

Objective　To investigate the short-term efficacy of programmed death protein-1 (PD-1) inhibitor combined with oxaliplatin + tiggio (SOX) chemotherapy regimen in the neoadjuvant treatment of patients with locally advanced gastric adenocarcinoma and its influencing factors. Methods　One hundred and twenty-eight patients with locally advanced gastric adenocarcinoma treated at Xi'an Third Hospital from May 2022 to May 2024 were selected for the randomized controlled trial, and were divided into a control group and a study group by the random number table method, with 64 cases in each group. The control group took the SOX chemotherapy regimen, while the study group PD-1 inhibitor and the SOX chemotherapy regimen; both groups completed three cycles of chemotherapy. The short-term clinical efficacies, age, gender, maximum tumor diameters, tumor sites, TNM stages, pathological types, degrees of differentiation, bile acid levels, neutrophil to lymphocyte count ratios (NLR), and expressions of programmed death receptor ligand 1 (PD-L1) were compared between the two groups. The occurrences of adverse reactions during the treatment in the two groups were analyzed. The logistic regression analysis was used to assess the factors influencing the short-term efficacy of PD-1 inhibitor combined with the SOX chemotherapy regimen for the patients with locally advanced gastric adenocarcinoma. χ² and t tests were used for the statistical analysis. Results　The short-term efficacy in the study group was higher than that in the control group [75.00% (48/64) vs. 57.81% (37/64)], with a statistical difference (P<0.05); There were no statistical differences in age, gender, tumor site, pathological type, and differentiation degree between the two groups (all P>0.05). The proportions of the patients with a maximum tumor diameter <6 cm, TNM stage Ⅱ, and PD-L1 expression ≥1% in the study group were higher than those in the control group [78.13% (50/64) vs. 51.56% (33/64), 68.75% (44/64) vs. 28.13% (18/64), and 76.56% (49/64) vs. 48.44% (31/64)], and the bile acid level and proportion of the patients with NLR≥3.7 were lower [(4.64±1.42) μmol/L vs. (5.87±1.78) μmol/L and 23.44% (15/64) vs. 68.75% (44/64)], with statistical differences (all P<0.05). During the treatment, there were 4 cases of nausea, 5 cases of vomiting, and 7 cases of anorexia in the study group; there were 6 cases of nausea, 4 cases of vomiting, and 8 cases of anorexia in the control group; there was no statistical differences (χ²=0.160, P>0.05). The logistic regression analysis showed that maximum tumor diameter <6 cm, TNM stage Ⅱ, low bile acid level, NLR≥3.7, and PD-L1 expression ≥1% were all protective factors for the short-term efficacy of PD-1 inhibitor combined with SOX chemotherapy regimen for the patients with locally advanced gastric adenocarcinoma (all P<0.05). Conclusions　PD-1 inhibitor combined with SOX chemotherapy regimen for patients with locally advanced gastric adenocarcinoma has good short-term efficacy. PD-L1 expression ≥1%, the maximum tumor diameter < 6 cm, and TNM stage Ⅱ are protective factors of clinical efficacy. The appropriate treatment regimen should be selected clinically based on these factors.

Key words: Advanced gastric adenocarcinoma, , Programmed death protein-1, , Oxaliplatin, , Teggio, , Curative effect

李菲杜静孙力蔡成. PD-1抑制剂联合SOX化疗方案治疗局部进展期胃腺癌患者的近期疗效及影响因素 [J]. 国际医药卫生导报, 2025, 31(10): 1660-1664.

Li Fei, Du Jing, Sun Li, Cai Cheng.

Short-term efficacy of PD-1 inhibitor combined with SOX chemotherapy regimen for patients with locally advanced gastric adenocarcinoma and its influencing factors [J]. International Medicine and Health Guidance News, 2025, 31(10): 1660-1664.

参考文献

[1]Margalit O, Yu S, Shacham-Shmueli E, et al. Correction to: Benefit for single-agent adjuvant chemotherapy in elderly patients with locally advanced gastric adenocarcinoma [J]. J Cancer Res Clin Oncol, 2022, 148(7): 1709. DOI: 10.1007/s00432-022-04062-6.

[2]中国抗癌协会胃癌专业委员会,梁寒,徐惠绵. 2024版CACA胃癌整合诊治指南(精简版)[J].中国肿瘤临床,2024,51(13):650-657. DOI:10.12354/j.issn.1000-8179.2024. 20240882.

[3]焦福智,陈雅蕊,姬薇,等. PD-1抑制剂联合化疗一线新辅助治疗局部进展期胃腺癌的近期疗效及安全性评估[J].中国药物警戒,2023,20(3):301-305. DOI:10.19803/j.1672-8629.20220594.

[4]王涛,张璐璐,杜书祥,等. PD-1抑制剂联合SOX新辅助治疗局部进展期胃腺癌的近期疗效及安全性分析[J].肿瘤,2023,43(8):635-645. DOI:10.3781/j.issn.1000-7431. 2023.2207-0481.

[5]尹玉平,张鹏,蔡明,等. PD-1抑制剂联合SOX化疗方案在进展期胃食管结合部腺癌新辅助治疗中的疗效及安全性初探[J].腹部外科,2021,34(3):199-202,210. DOI:10.3969/j.issn.1003-5591.2021.03.007.

[6]中华医学会肿瘤学分会,中华医学会杂志社.中华医学会胃癌临床诊疗指南(2021版)[J].中华医学杂志,2022,102(16):1169-1189. DOI:10.3760/cma.j.cn112137- 20220127-00197.

[7]Endo S, Nishikawa K, Ikenaga M, et al. Prognostic factors for cytology-positive gastric cancer: a multicenter retrospective analysis [J]. Int J Clin Oncol, 2021, 26(5): 858-866. DOI: 10.1007/s10147-021-01873-4.

[8]Wainberg ZA, Kang YK, Lee KW, et al. Bemarituzumab as first-line treatment for locally advanced or metastatic gastric/gastroesophageal junction adenocarcinoma: final analysis of the randomized phase 2 FIGHT trial [J]. Gastric Cancer, 2024, 27(3): 558-570. DOI: 10.1007/s10120-024-01466-w.

[9]陈芳,关玉峰,杨文婷,等.胃底腺型腺癌二例临床病理分析[J].海南医学, 2022, 33(17): 2207-2211. DOI: 10.3969/j.issn.1003-6350.2022.17.008.

[10]中华人民共和国国家卫生健康委员会医政医管局.胃癌诊疗指南(2022年版)[J].中华消化外科杂志,2022,21(9):1137-1164. DOI:10.3760/cma.j.cn115610-20220726- 00432.

[11]王子铭,张浩文.化疗联合PD1免疫检查点抑制剂新辅助治疗局部进展期SiewertⅡ/Ⅲ型食管胃结合部腺癌后行根治性手术的安全性及效果分析[J].临床外科杂志, 2023, 31(12):1137-1140.

[12]田青怡,德吉央宗,张丽娜,等.新辅助免疫治疗联合化疗联合或不联合其他疗法治疗可切除局部进展期胃癌或胃食管结合部癌疗效和安全性的Meta分析[J].中国肿瘤临床与康复,2024,31(1):17-29. DOI:10.13455/j.cnki.cjcor.113494-20231205-0189.

[13]户军燕,邱作栋,周宁,等.曲妥珠单抗联合SOX方案治疗进展期胃癌的效果及对患者血清肿瘤标志物水平的影响[J].实用癌症杂志,2024,39(1):122-125. DOI:10.3969/j.issn.1001-5930.2024.01.030.

[14]王向阳. PD-1抑制剂联合SOX方案治疗晚期胃癌患者的疗效及对外周血T淋巴细胞亚群水平的影响[J].宁夏医学杂志,2024,46(6):461-464. DOI:10.13621/j.1001-5949. 2024.06.0461.

[15]刘璐,姜成毅,王莹,等. PD-1抑制剂联合化疗对进展期胃癌的近期疗效及影响因素 [J].中国老年学杂志, 2024, 44 (12): 2844-2847.

[16]蒋纪祥,陆斌,张军峰,等. PD-1抑制剂联合化疗对进展期胃癌患者的近期疗效及相关因素分析[J].中国医学创新,2023,20(18):5-9. DOI:10.3969/j.issn.1674-4985. 2023.18.002.