Objective: To explore the efficacy and factors affecting the treatment of gastric cancer liver metastasis (GCLM) with immune checkpoint inhibitors (ICI). Methods: This is a retrospective cohort study. Clinical and pathological data of 588 patients with GCLM treated at the Department of General Surgery, First Medical Center, People's Liberation Army General Hospital, from January 2018 to December 2022 were retrospectively collected. There were 491 males and 97 females, aged (M(IQR)) 60(14) years (range: 18 to 86 years). Patients were divided into an ICI treatment group (n=142) and a non-ICI treatment group (n=446) based on whether they received ICI therapy. Clinical and pathological data between the two groups were compared using the χ2 test or Mann-Whitney U test. Propensity score matching (PSM) was performed with cT stage, cN stage, surgical treatment, targeted therapy, and biomarkers as covariates, using a 1∶1 nearest neighbor matching method with a caliper value of 0.2. Univariate and multivariate analyses were conducted using Cox proportional hazards regression models, with relevant variables selected through forward stepwise regression. Survival curves were plotted using the Kaplan-Meier method, and group differences were compared using the Log-rank test. Subgroup analysis was conducted to identify potential beneficiary populations for ICI through forest plots. Results: After PSM, 114 patients were included in each group, and there were no statistically significant differences in the baseline data between the two groups (all P>0.05). The results of Cox multivariate analysis after PSM showed that cN2-3 stage (HR=1.348, 95%CI: 1.091 to 1.665, P=0.006) and peritoneal metastasis (HR=1.877, 95%CI:1.360 to 2.590, P<0.01) were independent risk factors for survival in GCLM patients; radical surgery (HR=0.391, 95%CI: 0.305 to 0.501, P<0.01), immunotherapy (HR=0.630, 95%CI: 0.503 to 0.788, P<0.01), and deficient DNA mismatch repair (dMMR) or combined positive score (CPS)≥5 (HR=0.454, 95%CI: 0.320 to 0.644, P<0.01) were independent protective factors for survival in GCLM patients. After PSM, the overall survival was 12.4 (13.0) months in the non-immunotherapy group and 17.6 (17.8) months in the immunotherapy group (Log-rank test:P=0.029). Subgroup analysis showed that female patients, those with primary tumors located in the upper stomach, cN2-3 stage, one liver metastasis, synchronous liver metastasis, receiving targeted therapy, and those with dMMR or CPS≥5 were more likely to benefit from ICI therapy (all P<0.05). Conclusions: ICI prolongs overall survival in GCLM patients. Female patients, those with primary tumors located in the upper stomach, cN2-3 stage, one liver metastasis, synchronous liver metastasis, receiving targeted therapy, and those with dMMR or CPS≥5 are more likely to benefit from ICI therapy.
目的： 探讨免疫检查点抑制剂（ICI）治疗胃癌肝转移（GCLM）的效果和影响因素。 方法： 本研究为回顾性队列研究。回顾性收集2018年1月至2022年12月解放军总医院第一医学中心普通外科医学部收治的588例GCLM患者的临床和病理学资料。男性491例，女性97例，年龄［M（IQR）］60（14）岁（范围：18~86岁）。根据患者是否接受ICI治疗将其分为免疫治疗组（n=142）和非免疫治疗组（n=446）。采用χ2检验、Mann-Whitney U检验等比较两组临床和病理学资料的差异。以cT分期、cN分期、手术治疗、靶向治疗和生物标志物为协变量进行倾向性评分匹配（PSM），按1∶1最邻近匹配法进行匹配，卡钳值取0.2。采用Cox风险比例回归模型进行单因素、多因素分析，通过逐步回归前进法筛选相关变量。采用Kaplan-Meier法绘制生存曲线，通过Log-rank检验比较组间差异。采用亚组分析绘制森林图并筛选ICI的潜在获益人群。 结果： PSM后，两组各纳入114例患者，组间基线资料的差异均无统计学意义（P值均>0.05）。PSM后Cox多因素分析结果显示，cN2~3期（HR=1.348，95%CI：1.091~1.665，P=0.006）及腹膜转移（HR=1.877，95%CI：1.360~2.590，P<0.01）是影响GCLM患者生存的独立危险因素；根治性手术（HR=0.391，95%CI：0.305~0.501，P<0.01）、免疫治疗（HR=0.630，95%CI：0.503~0.788，P<0.01）及DNA错配修复蛋白表达缺失（dMMR）或联合阳性评分（CPS）≥5分（HR=0.454，95%CI：0.320~0.644，P<0.01）是影响GCLM患者生存的独立保护因素。PSM后，非免疫治疗组与免疫治疗组总体生存时间分别为12.4（13.0）个月与17.6（17.8）个月（Log-rank检验：P=0.029）。亚组分析结果显示，女性、原发灶肿瘤位于上部、cN2~3期、1个肝脏转移灶、同时性肝转移、接受靶向治疗及dMMR或CPS≥5分的患者可从ICI治疗中获益（P值均<0.05）。 结论： ICI 可延长GCLM患者的总体生存时间，女性、胃上部癌、cN2~3期、1个肝脏转移灶、同时性肝转移、接受靶向治疗、dMMR或CPS≥5分的患者更可能从ICI治疗中获益。.