中性粒细胞/淋巴细胞比值对TACE联合微波消融治疗中期肝细胞癌患者预后的预测价值

Neutrophil/lymphocyte ratio vs.TACE combined with microwave ablation for intermediate hepatocellular carcinoma Predictive value of patient prognosis

目的本研究分析肝动脉灌注化疗栓塞术(TACE)联合微波消融(MWA)治疗中期肝细胞癌(HCC)患者治疗前、后中性粒细胞/淋巴细胞比值(NLR)的变化,及其与患者预后的关系,探讨NLR对HCC患者预后的预测价值。方法本研究回顾性分析2014年9月-2018年12月期间盐城市第三人民医院行TACE联合MWA治疗的中期HCC患者。确定NLR值;使用Xtile软件计算TACE前NLR和MWA后的最佳cut-off值;采用Kaplan-Meier生存分析法和Log-rank秩和检验比较患者PFS的差异;采用单因素和多因素COX比例风险回归模型分析探索PFS相关独立预后因子。结果1)中位随访时间29.8(95%CI:20.2-39.4)个月,总体的中位PFS时间为18.3(95%CI:14.7-22.9)个月。2)通过Xtile软件计算出TACE前NLR和MWA后NLR cut-off值分别为3和2.4。3)TACE前NLR分组患者之间临床资料比较:高NLR组患者肝硬化的比例(25/31 vs.21/40,P=0.029)、肿瘤数目>3的比例(17/31 vs.5/40,P<0.001)、超出up-to-7标准(10/31 vs.2/40,P=0.003)的比例及肿瘤直径大小(P=0.015)均显著高于低NLR组患者。4)TACE前、MWA后高NLR组、低NLR组及NLR升高组和NLR降低组PFS比较:NLR降低组的1、2年PFS率为96.7%,48.0%,而NLR上升组的1、2年PFS率为53.7%、28.9%。NLR降低组和NLR升高组中位PFS分别为21.4(95%CI:11.7-31.1)月和12.3(95%CI:7.2-17.3)月,NLR降低组显著高于NLR升高组(P=0.009)。治疗前高NLR组、低NLR组(20.5,95%CI:16.8-24.3 vs.17.0,95%CI:10.0-24.0;P=0.485)及治疗后高NLR组、低NLR组(18.2,95%CI:13.3-23.1 vs.21.0,95%CI:1.7-40.2;P=0.109)的PFS无明显差异。5)TACE前高、低NLR组及NLR升高、降低组患者疗效评价:TACE前低NLR组1、3、6月的ORR均显著高于高NLR组(P分别为0.0004,和0.001)。NLR降低组的治疗后6月ORR显著高于NLR升高组(P=0.026),预后因子分析:NLR上升(HR=2.659,95%CI:1.369-5.165,P=0.004)和AST>40 U/L(HR=1.981,95%CI:1.060-3.703,P=0.032)是中期HCC患者的独立不良预后因子。结论NLR对中期HCC行TCAE联合MWA的患者有较好的预测价值,尤其监测治疗前后NLR的动态变化比治疗前、后NLR值,能更准确的判断预后。

Objective This study was to analyze the changes of neutrophil/lymphocyte ratio(NLR)before and after hepatic arterial infusion chemoembolization(TACE)combined with microwave ablation(MWA)in the treatment of patients with intermediate hepatocellular carcinoma(HCC)and its relationship with patient prognosis,and to explore the predictive value of NLR in the prognosis of HCC patients.Methods This study retrospectively analyzed the HCC patients who received TACE combined with MWA in Yancheng Third People's Hospital from September 2014 to December 2018.Determine the NLR value;Xtile software was used to calculate the optimal cut-off values before TACE and after MWA.Kaplan-Meier survival analysis and Log-rank rank sum test were used to compare the differences in PFS.Univariate and multivariate COX proportional hazard regression models were used to explore independent prognostic factors associated with PFS.Results 1)The median follow-up time was 29.8(95%CI:20.2-39.4)months,and the overall median PFS time was 18.3(95%CI:14.7-22.9)months.2)The cut-off values of NLR before TACE and NLR after MWA were calculated by Xtile software to be 3 and 2.4 respectively.3)Comparison of clinical data among patients in NLR group before TACE:The proportion of patients in the high NLR group with cirrhosis(25/31 vs.21/40,P=0.029),the proportion of patients with tumor numbers>3(17/31 vs.5/40,P<0.001),and the proportion exceeding the up-to-7 criteria(10/31 vs.2/40,P=0.003),and tumor diameter(P=0.015)were significantly higher than those in low NLR group.4)PFS comparison between high NLR group,low NLR group,increased NLR group and decreased NLR group before TACE and after MWA:PFS rates at 1 and 2 years were 96.7% and 48.0% in the NLR decreasing group,while PFS rates at 1 and 2 years were 53.7% and 28.9% in the NLR increasing group.The median PFS of the NLR decreased group and the NLR increased group were 21.4(95%CI:11.7-31.1)months and 12.3(95%CI:7.2-17.3)months,respectively,and the NLR decreased group was significantly higher than the NLR increased group(P=0.009).Before treatment,high NLR group and low NLR group(20.5,95%CI:16.8-24.3 vs.17.0,95%CI:10.0-24.0;P=0.485)and high NLR group and low NLR group after treatment(18.2,95%CI:13.3-23.1 vs.21.0,95%CI:1.7-40.2;P=0.109)had no significant difference in PFS.5)Efficacy evaluation of patients in the high and low NLR groups and the increased and decreased NLR groups before TACE:the ORR of the low NLR group at 1,3 and 6 months before TACE was significantly higher than that of the high NLR group(P 0.0004 and 0.001,respectively).6 months after treatment,the ORR of the NLR decreased group was significantly higher than that of the NLR increased group(P=0.026).Prognostic factor analysis:NLR increased(HR=2.659,95%CI:1.369-5.165,P=0.004)and AST>40 U/L(HR=1.981,95%CI:1.060-3.703,P=0.032)was an independent poor prognostic factor for patients with mid-stage HCC.Conclusion NLR has a better predictive value for patients receiving TCAE combined with MWA in the middle stage of HCC.In particular,monitoring the dynamic changes of NLR before and after treatment can more accurately judge the prognosis than NLR values before and after treatment.