摘要
目的 探讨初始可切除型胃癌肝转移(GCLM)不同治疗方式的预后情况,分析预后的影响因素.方法 采用回顾性队列研究方法.收集2010年1月至2019年12月基于真实世界数据的GCLM诊疗全国多中心回顾性队列研究数据库中 327例初始可切除型GCLM患者的临床病理资料;男267例,女60例;年龄为61(54,68)岁.根据患者具体情况分别行根治性手术联合系统治疗、姑息性手术联合系统治疗、单纯系统治疗.观察指标:(1)不同治疗方式患者临床特征情况.(2)不同治疗方式患者预后情况.(3)初始可切除型GCLM患者预后的影响因素分析.(4)根治性手术联合系统治疗和姑息性手术联合系统治疗潜在获益人群筛选.正态分布的计量资料以(x)±s表示,组间比较采用独立样本t检验.偏态分布的计量资料以M(Q1,Q3)表示,组间比较采用秩和检验.计数资料以绝对数或百分比表示,组间比较采用x2检验.采用Kaplan-Meier法计算生存率并绘制生存曲线,Log-Rank检验进行生存分析.采用COX风险比例回归模型进行单因素和多因素分析.倾向评分匹配按1∶1最近邻匹配法匹配,卡钳值为0.1.采用森林图筛选不同手术联合系统治疗的潜在获益人群.结果 (1)不同治疗方式患者临床特征情况.327例患者中,行根治性手术联合系统治疗118例,行姑息性手术联合系统治疗164例,行单纯系统治疗45例;3者吸烟、饮酒、胃原发肿瘤部位和肿瘤最大径、肝转移肿瘤部位、转移时限比较,差异均有统计学意义(P＜0.05).(2)不同治疗方式患者预后情况.327例患者的中位总生存时间为19.9个月(95％可信区间为14.9～24.9个月),1、3年总生存率分别为61.3％、32.7％.行根治性手术联合系统治疗、姑息性手术联合系统治疗、单纯系统治疗患者的1年总生存率分别为68.3％、63.1％、30.6％,3年总生存率分别为41.1％、29.9％、11.9％,3者总生存率比较,差异有统计学意义(x2=19.46,P＜0.05).进一步分析,行根治性手术联合系统治疗和单纯系统治疗患者总生存率比较,差异有统计学意义(风险比=0.40,95％可信区间为0.26～0.6 1,P＜0.05);行姑息性手术联合系统治疗和单纯系统治疗患者总生存率比较,差异有统计学意义(风险比=0.47,95％可信区间为0.32～0.71,P＜0.05).(3)初始可切除型GCLM患者预后的影响因素分析.多因素分析结果显示:胃原发肿瘤越大、肿瘤分化程度为低分化、肝转移肿瘤越大、肝转移肿瘤数目为多发是影响初始可切除型GCLM患者预后的独立危险因素(风险比=1.20,1.70,1.20,2.06,95％可信区间为1.14～1.27,1.25～2.31,1.04～1.42,1.45～2.92,P＜0.05);免疫或靶向治疗、根治性手术联合系统治疗、姑息性手术联合系统治疗是影响初始可切除型GCLM患者预后的独立保护因素(风险比=0.60,0.39,0.46,95％可信区间为0.42～0.87,0.25～0.60,0.30～0.70,P＜0.05).(4)根治性手术联合系统治疗和姑息性手术联合系统治疗潜在获益人群筛选.森林图分析结果显示:肿瘤分化程度为高-中分化、肝转移肿瘤部位为左半肝患者行根治性手术联合系统治疗总生存率均优于行姑息性手术联合系统治疗(风险比=0.21,0.42,95％可信区间为0.09～0.48,0.23～0.78,P＜0.05).结论 与行单纯系统治疗比较,行根治性手术联合系统治疗或姑息性手术联合系统治疗可以改善初始可切除型GCLM患者预后.胃原发肿瘤越大、肿瘤分化程度为低分化、肝转移肿瘤越大、肝转移肿瘤数目为多发是影响初始可切除型GCLM患者预后的独立危险因素;免疫或靶向治疗、根治性手术联合系统治疗、姑息性手术联合系统治疗是影响初始可切除型GCLM患者预后的独立保护因素.
Abstract
Objective To investigate the prognosis of patients with initially resectable gastric cancer liver metastasis(GCLM)who were treated by different modalities,and analyze the influenc-ing factors for prognosis of patients.Methods The retrospective cohort study was conducted.The clinicopathological data of 327 patients with initially resectable GCLM who were included in the data-base of a nationwide multicenter retrospective cohort study on GCLM based on real-world data from January 2010 to December 2019 were collected.There were 267 males and 60 females,aged 61(54,68)years.According to the specific situations of patients,treatment modalities included radical sur-gery combined with systemic treatment,palliative surgery combined with systemic treatment,and systemic treatment alone.Observation indicators:(1)clinical characteristics of patients who were treated by different modalities;(2)prognostic outcomes of patients who were treated by different modalities;(3)analysis of influencing factors for prognosis of patients with initially resectable GCLM;(4)screening of potential beneficiaries in patients who were treated by radical surgery plus systemic treatment and patients who were treated by palliative surgery plus systemic treatment.Measurement data with normal distribution were represented as Mean±SD,and comparison between groups was conducted using the independent sample t test.Measurement data with skewed distribution were represented as M(Q1,Q3),and comparison between groups was conducted using the rank sum test.Count data were described as absolute numbers or percentages,and comparison between groups was conducted using the chi-square test.The Kaplan-Meier method was used to calculate survival rate and draw survival curve,and Log-Rank test was used for survival analysis.Univariate and multi-variate analyses were conducted using the COX proportional hazard regression model.The propensity score matching was employed by the 1∶1 nearest neighbor matching method with a caliper value of 0.1.The forest plots were utilized to evaluate potential benefits of diverse surgical combined with systemic treatments within the population.Results(1)Clinical characteristics of patients who were treated by different modalities.Of 327 patients,there were 118 cases undergoing radical surgery plus systemic treatment,164 cases undergoing palliative surgery plus systemic treatment,and 45 cases undergoing systemic treatment alone.There were significant differences in smoking,drinking,site of primary gastric tumor,diameter of primary gastric tumor,site of liver metastasis,and metastatic interval among the three groups of patients(P＜0.05).(2)Prognostic outcomes of patients who were treated by different modalities.The median overall survival time of the 327 pati-ents was 19.9 months(95％confidence interval as 14.9-24.9 months),with 1-,3-year overall survival rate of 61.3％,32.7％,respectively.The 1-year overall survival rates of patients undergoing radical surgery plus systemic treatment,palliative surgery plus systemic treatment and systemic treatment alone were 68.3％,63.1％,30.6％,and the 3-year overall survival rates were 41.1％,29.9％,11.9％,showing a significant difference in overall survival rate among the three groups of patients(x2=19.46,P＜0.05).Results of further analysis showed that there was a significant difference in over-all survival rate between patients undergoing radical surgery plus systemic treatment and patients undergoing systemic treatment alone(hazard ratio=0.40,95％confidence interval as 0.26-0.61,P＜0.05),between patients undergoing palliative surgery plus systemic treatment and patients under-going systemic treatment alone(hazard ratio=0.47,95％confidence interval as 0.32-0.71,P＜0.05).(3)Analysis of influencing factors for prognosis of patients with initially resectable GCLM.Results of multivariate analysis showed that the larger primary gastric tumor,poorly differentiated tumor,larger liver metastasis,multiple hepatic metastases were independent risk factors for prognosis of patients with initially resectable GCLM(hazard ratio=1.20,1.70,1.20,2.06,95％confidence interval as 1.14-1.27,1.25-2.31,1.04-1.42,1.45-2.92,P＜0.05)and immunotherapy or targeted therapy,the treatment modality of radical or palliative surgery plus systemic therapy were independent protec-tive factors for prognosis of patients with initially resectable GCLM(hazard ratio=0.60,0.39,0.46,95％confidence interval as 0.42-0.87,0.25-0.60,0.30-0.70,P＜0.05).(4)Screening of potentinal ben-eficiaries in patients who were treated by radical surgery plus systemic treatment and patients who were treated by palliative surgery plus systemic treatment.Results of forest plots analysis showed that for patients with high-moderate differentiated GCLM and patients with liver metastasis located in the left liver,the overall survival rate of patients undergoing radical surgery plus systemic treat-ment was better than patients undergoing palliative surgery plus systemic treatment(hazard ratio=0.21,0.42,95％confidence interval as 0.09-0.48,0.23-0.78,P＜0.05).Conclusions Compared to sys-temic therapy alone,both radical and palliative surgery plus systemic therapy can improve the pro-gnosis of patients with initially resectable GCLM.The larger primary gastric tumor,poorly differen-tiated tumor,larger liver metastasis,multiple hepatic metastases are independent risk factors for prognosis of patients with initial resectable GCLM and immunotherapy or targeted therapy,the treatment modality of radical or palliative surgery plus systemic therapy are independent protec-tive factors for prognosis of patients with initially resectable GCLM.
基金项目
国家自然科学基金(81972790)
军队后勤科研项目(145BHQ090003000X08)
军队装备综合研究项目(LB2022B020200-QZ)
NETL
NSTL
万方数据