肿瘤负荷和炎症指标对接受三联治疗中晚期肝细胞癌预后的预测价值  

Predictive value of tumor burden and inflammatory indicators on the prognosis of advanced hepatocellular carcinoma treated by triple therapy

作　　者：张天佑 赵双强 张景畅 秦启明 师文楷[1] 张国坤[1] 赵永福[1] ZHANG Tianyou;ZHAO Shuangqiang;ZHANG Jingchang;QIN Qiming;SHI Wenkai;ZHANG Guokun;ZHAO Yongfu(Department of Hepatobiliary and Pancreatic Surgery,the First Affiliated Hospital of Zhengzhou University,Zhengzhou 450052,China)

机构地区：[1]郑州大学第一附属医院肝胆胰外科,河南郑州450052

出　　处：《肿瘤基础与临床》2024年第5期522-528,共7页journal of basic and clinical oncology

摘　　要：目的探究治疗前肿瘤负荷和炎症相关指标对接受经导管肝动脉化疗栓塞(TACE)、酪氨酸激酶抑制剂(TKI)及免疫检查点抑制剂(ICIs)三联治疗的中晚期肝细胞癌(HCC)患者预后的预测价值,并构建相应的预后预测模型。方法回顾性分析2020年1月至2021年12月在郑州大学第一附属医院接受TACE、TKI及ICIs三联治疗的114例中晚期HCC患者的临床资料,以疾病无进展生存时间(PFS)为主要研究终点,将患者的肿瘤负荷指标、炎症相关指标以及其他一般临床指标纳入单因素及多因素COX回归分析,筛选出患者PFS的独立危险因素。基于筛选的独立危险因素构建一种新的联合预后预测模型,通过Kaplan-Meier生存分析及受试者工作特征(ROC)曲线对比新模型与单一指标、传统分期法对患者预后的预测价值。结果通过单因素与多因素COX回归分析可知,影响接受TACE、TKI及ICIs三联治疗的中晚期HCC患者PFS的独立危险因素分别包括肿瘤负荷评分(TBS)(临界值7.96)(HR=3.421;95%CI:2.112~5.541;P<0.001)、中性粒细胞与淋巴细胞比率(NLR)(临界值3.10)(HR=2.995;95%CI:1.860~4.821;P<0.001)。ROC曲线显示,TBS和NLR对客观缓解率(ORR)的预测效能最佳,曲线下面积(AUC)分别为0.752(P<0.001)、0.700(P<0.001)。整体中位PFS为9.0个月(95%CI:7.102~10.915),Kaplan-Meier分析显示,与高TBS组相比,低TBS组(≤7.96)患者的PFS更长,中位PFS分别为13.0个月(95%CI:10.819~15.181;P<0.001)和6.0个月(95%CI:4.492~7.508;P<0.001)。而低NLR组(≤3.10)患者比高NLR组患者的中位PFS更长,分别为15.0个月(95%CI:11.426~18.574;P<0.001)和7.5个月(95%CI:6.239~8.761;P<0.001)。基于肿瘤负荷指标中TBS和炎症指标中NLR构建了TBS-NLR预后模型,以TBS≤7.96、NLR≤3.10记为0分,TBS>7.96、NLR>3.10记为1分,根据患者得分情况可分为0分、1分、2分组,即高、中、低敏感组,其中位PFS分别为16.0个月(95%CI:12.359~19.641;P<0.001)、9.0个月(95%CI:7.693~10.307;P<0.001)、Objective To explore the predictive value of pre-treatment tumor burden and inflammatory indicators on the prognosis of advanced hepatocellular carcinoma(HCC)patients receiving transcatheter arterial chemoembolization(TACE),tyrosine kinase inhibitors(TKI)and immune checkpoint inhibitors(ICIs),and to establish a model to predict the prognosis of patients.Methods The clinical data of 114 patients with advanced HCC were collected who received TACE,TKI combined ICIs in the First Affiliated Hospital of Zhengzhou University from January 2020 to December 2021.With progression-free survival(PFS)as the main end point of the study,the patients’tumor burden indicators,inflammation-related indicators and other general clinical indicators were included in univariate and multivariate COX regression analysis to screen out the independent prognostic factors of PFS.A new combined prognostic model was constructed based on screened independent predictors.Through Kaplan-Meier survival analysis and receiver operating characteristic(ROC)curve,the predictive value of the new model,single index and traditional staging method on the prognosis of patients were compared.Results Through univariate and multivariate COX analysis,the independent risk factors affecting the PFS of patients with advanced hepatocellular carcinoma receiving TACE and TKI combined ICIs were tumor burden score(TBS)(cutoff value:7.96)(HR:3.421;95%CI:2.112-5.541;P<0.001)and neutrophil-to-lymphocyte ratio(NLR)(cutoff value:3.10)(HR:2.995;95%CI:1.860-4.821;P<0.001).The ROC curve showed that TBS and NLR had the best predictive effect on objective response rate(ORR),and the area under the curve(AUC)was 0.752(P<0.001)and 0.700(P<0.001),respectively.The overall median PFS was 9.0 months(95%CI:7.102-10.915).Kaplan-Meier analysis showed that patients with low TBS(≤7.96)had longer PFS than those with high TBS,and the median PFS was 13.0 months(95%CI:10.819-15.181)and 6.0 months(95%CI:4.492-7.508)(P<0.001).Compared with the high NLR group,the median PFS in the low NLR(≤3.10

关 键 词：肝细胞癌 炎症 肿瘤负荷评分 联合治疗 预后 

分 类 号：R735.7[医药卫生—肿瘤]