Lu T T, Gao Y H, Zhang G, Zhang H Y, Liu Y, Chen Z D, Xi H Q
Chinese People's Liberation Army Medical School, Beijing 100853, China.
Department of General Surgery, First Medical Center, Chinese People's Liberation Army General Hospital, Beijing 100853, China.
Zhonghua Wai Ke Za Zhi. 2025 Feb 1;63(2):136-146. doi: 10.3760/cma.j.cn112139-20240612-00292.
To explore the efficacy and factors affecting the treatment of gastric cancer liver metastasis (GCLM) with immune checkpoint inhibitors (ICI). 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 ((IQR)) 60(14) years (range: 18 to 86 years). Patients were divided into an ICI treatment group (=142) and a non-ICI treatment group (=446) based on whether they received ICI therapy. Clinical and pathological data between the two groups were compared using the test or Mann-Whitney 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. 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 >0.05). The results of Cox multivariate analysis after PSM showed that cN2-3 stage (=1.348, 95%: 1.091 to 1.665, =0.006) and peritoneal metastasis (=1.877, 95%:1.360 to 2.590, <0.01) were independent risk factors for survival in GCLM patients; radical surgery (=0.391, 95%: 0.305 to 0.501, <0.01), immunotherapy (=0.630, 95%: 0.503 to 0.788, <0.01), and deficient DNA mismatch repair (dMMR) or combined positive score (CPS)≥5 (=0.454, 95%: 0.320 to 0.644, <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:=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 <0.05). 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.
探讨免疫检查点抑制剂（ICI）治疗胃癌肝转移（GCLM）的疗效及影响因素。这是一项回顾性队列研究。回顾性收集了2018年1月至2022年12月在解放军总医院第一医学中心普通外科接受治疗的588例GCLM患者的临床和病理资料。其中男性491例，女性97例，年龄（四分位间距）为60（14）岁（范围：18至86岁）。根据患者是否接受ICI治疗，将其分为ICI治疗组（n = 142）和非ICI治疗组（n = 446）。两组间的临床和病理资料采用t检验或Mann-Whitney U检验进行比较。以cT分期、cN分期、手术治疗、靶向治疗和生物标志物作为协变量，采用1∶1最近邻匹配法和卡尺值为0.2进行倾向评分匹配（PSM）。使用Cox比例风险回归模型进行单因素和多因素分析，通过向前逐步回归选择相关变量。采用Kaplan-Meier法绘制生存曲线，使用Log-rank检验比较组间差异。通过森林图进行亚组分析，以确定ICI的潜在受益人群。PSM后，每组纳入114例患者，两组间基线数据无统计学差异（均P>0.05）。PSM后Cox多因素分析结果显示，cN2-3期（HR = 1.348，95%CI：1.091至1.665，P = 0.006）和腹膜转移（HR = 1.877，95%CI：1.360至2.590，P<0.01）是GCLM患者生存的独立危险因素；根治性手术（HR = 0.391，95%CI：0.305至0.501，P<0.01）、免疫治疗（HR = 0.630，95%CI：0.503至0.788，P<0.01）以及DNA错配修复缺陷（dMMR）或联合阳性评分（CPS）≥5（HR = 0.454，95%CI：0.320至0.644，P<0.01）是GCLM患者生存的独立保护因素。PSM后，非免疫治疗组的总生存期为12.4（13.0）个月，免疫治疗组为17.6（17.8）个月（Log-rank检验：P = 0.029）。亚组分析显示，女性患者、原发肿瘤位于胃上部的患者、cN2-3期患者、有1处肝转移的患者、同时性肝转移的患者、接受靶向治疗的患者以及dMMR或CPS≥5的患者更有可能从ICI治疗中获益（均P<0.05）。ICI可延长GCLM患者的总生存期。女性患者、原发肿瘤位于胃上部的患者、cN2-3期患者、有1处肝转移的患者、同时性肝转移的患者、接受靶向治疗的患者以及dMMR或CPS≥5的患者更有可能从ICI治疗中获益。
