早期肿瘤退缩和肿瘤反应深度对HER-2阴性晚期胃癌患者疗效与预后的影响

Effects of Early Tumor Shrinkage and Depth of Response on the Efficacy and Prognosis of Patients with HER-2-Negative Advanced Gastric Cancer

目的探讨早期肿瘤退缩(ETS)和肿瘤反应深度(DpR)对阿帕替尼联合多西他赛治疗人表皮生长因子受体2(HER-2)阴性晚期胃癌患者疗效与预后的影响。方法回顾性分析安徽省宿州市立医院2018年1月至2020年1月收治的82例HER-2阴性晚期胃癌患者的临床资料,依据患者的生存状况分为进展生存组(A组,31例)、无进展生存组(B组,35例)、死亡组(C组,16例),比较3组的人口学特征和临床资料。采用Logistic多因素回归分析HER-2阴性晚期胃癌患者疗效与预后的相关因素,采用Pearson相关性分析ETS和DpR与各危险因素的相关性,采用受试者工作特征曲线(ROC)评估ETS和DpR对阿帕替尼联合多西他赛治疗HER-2阴性晚期胃癌患者疗效与预后的预测价值。结果3组患者人口学特征、临床资料比较,差异均有统计学意义(P<0.05)。C组患者年龄≥60岁、饮酒史、家族史、TNMⅣ期、胃体部和胃幽门部肿瘤、肿瘤直径>3.5 cm、阳性淋巴结比率(LNR)<0.16%、合并并发症、美国东部肿瘤协作组(ECOG)评分为1分、疗效为病变进展、ETS<15%、DpR缩小<15%、化疗时长≤12周、中性粒细胞减少分级为G0(中性粒细胞<1.5×109/L)的占比均显著高于A组和B组,且A组上述指标显著高于B组(P<0.05);与A组和B组比较,C组患者术中出血量较多、术后血钾平均值较低、术后首次下床时间较长,且A组上述指标较B组差异显著(P<0.05)。Logistic多因素回归分析结果显示,年龄≥60岁[OR=2.94,95%CI(2.492,4.095),P=0.031],TNMⅣ期[OR=3.673,95%CI(2.017,4.812),P=0.001],胃体部和胃幽门部肿瘤[OR=3.012,95%CI(2.684,4.348),P=0.018],肿瘤直径>3.5 cm[OR=2.301,95%CI(2.485,4.128),P=0.028],LNR<0.16%[OR=2.012,95%CI(2.783,3.573),P=0.023],ETS<15%[OR=1.793,95%CI(2.846,3.965),P=0.017],DpR缩小<15%[OR=1.782,95%CI(3.283,4.174),P=0.004],化疗时长≤12周[OR=2.942,95%CI(1.742,4.970),P=0.000]为HER-2阴性晚期胃癌患者疗效与预后不良的危险因素。Pearson相关性分析结果显示,ETS与年龄≥60岁、TNMⅣ期、胃体部和胃幽门部肿瘤、肿瘤直径>3.5 cm、LNR<0.16%呈负相关(r=-0.741,-0.324,-0.536,-0.974,-0.445,P<0.05),与DpR缩小<15%、化疗时长≤12周呈正相关(r=0.791,0.354,P<0.05);DpR缩小与年龄≥60岁、TNMⅣ期、胃体部和胃幽门部肿瘤、肿瘤直径>3.5 cm呈负相关(r=-0.837,-0.987,-0.044,-0.097,P<0.05);与LNR<0.16%、ETS<15%、化疗时长≤12周呈正相关(r=0.512,0.275,0.791,P<0.05)。预测阿帕替尼联合多西他赛治疗HER-2阴性晚期胃癌患者疗效与预后中,ETS的灵敏度、特异性和ROC曲线下与坐标轴围成的面积(AUC)分别为90.74%,87.03%,0.83,DpR分别为96.29%,94.44%,0.87,ETS+DpR分别为98.14%,96.29%,0.93;ETS+DpR的灵敏度、特异性和AUC均优于单用ETS或DpR。结论ETS和DpR均为阿帕替尼联合多西他赛治疗HER-2阴性晚期胃癌患者疗效与预后的危险因素,且ETS和DpR水平与各危险因素均相关,二者单独及联合预测HER-2阴性晚期胃癌患者的疗效与预后均有较高价值。

Objective To investigate the effects of early tumor shrinkage(ETS)and depth of response(DpR)on the efficacy and prognosis of apatinib combined with docetaxel in the treatment of patients with human epidermal growth factor receptor 2(HER-2)negative advanced gastric cancer.Methods The clinical data of 82 patients with HER-2 negative advanced gastric cancer admitted to the Suzhou Municipal Hospital from January 2018 to January 2020 was analyzed retrospectively.The patients were divided into the progressive survival group(group A,31 cases),progression-free survival group(group B,35 cases)and death group(group C,16 cases)according to the survival condition.The demographic characteristics and clinical data of the three groups were compared.The Logistic multivariate regression analysis was used to analyze the related factors of the efficacy and prognosis of patients with HER-2 negative advanced gastric cancer.The Pearson correlation analysis was used to analyze the correlation of ETS and DpR with various risk factors.The receiver operating characteristic(ROC)curve was used to evaluate the predictive value of ETS and DpR on the efficacy and prognosis of apatinib combined with docetaxel in the treatment of patients with HER-2 negative advanced gastric cancer.Results There were significant differences in demographic characteristics and clinical data among the three groups(P<0.05).The proportions of patients′age≥60 years,history of alcohol intake,family history,TNM stageⅣ,tumors of gastric body and gastric pylorus,tumor diameter>3.5 cm,positive lymph node ratio(LNR)<0.16%,with comorbidities,Eastern Cooperative Oncology Group(ECOG)score of 1 point,disease progression(PD)as the efficacy,ETS<15%,DpR reduction<15%,chemotherapy duration≤12 weeks and neutropenia graded G0(the number of neutrophils<1.5×109/L)in group C were significantly higher than those in group A and group B,and the above indexes in group A were significantly higher than those in group B(P<0.05).Compared with the patients in group A and group B,those in group C had more intraoperative bleeding,lower average postoperative blood potassium and longer time to get out of bed for the first time after operation,and the above indexes in group A were significantly different from those in group B(P<0.05).Logistic multivariate regression analysis showed that age≥60 years[OR=2.94,95%CI(2.492,4.095),P=0.031],TNM stageⅣ[OR=3.673,95%CI(2.017,4.812),P=0.001],tumors of gastric body and gastric pylorus[OR=3.012,95%CI(2.684,4.348),P=0.018],tumor diameter>3.5 cm[OR=2.301,95%CI(2.485,4.128),P=0.028],LNR<0.16%[OR=2.012,95%CI(2.783,3.573),P=0.023],ETS<15%[OR=1.793,95%CI(2.846,3.965),P=0.017],DpR reduction<15%[OR=1.782,95%CI(3.283,4.174),P=0.004],chemotherapy duration≤12 weeks[OR=2.942,95%CI(1.742,4.970),P=0.000]were risk factors for the efficacy and poor prognosis of patients with HER-2 negative advanced gastric cancer.Pearson correlation analysis showed that ETS was negatively correlated with age≥60 years,TNM stageⅣ,tumors of gastric body and gastric pylorus,tumor diameter>3.5 cm and LNR<0.16%(r=-0.741,-0.324,-0.536,-0.974,-0.445,P<0.05),while ETS was positively correlated with DpR reduction<15%and chemotherapy duration≤12 weeks(r=0.791,0.354,P<0.05).DpR reduction was negatively correlated with age≥60 years,TNM stageⅣ,tumors of gastric body and gastric pylorus and tumor diameter>3.5 cm(r=-0.837,-0.987,-0.044,-0.097,P<0.05),while DpR reduction was positively correlated with LNR<0.16%,ETS<15%and chemotherapy duration≤12 weeks(r=0.512,0.275,0.791,P<0.05).In predicting the efficacy and prognosis of apatinib combined with docetaxel in the treatment of the patients with HER-2 negative advanced gastric cancer,the sensitivity,specificity and the the area under the ROC curve(AUC)of ETS were 90.74%,87.03%,0.83,the above indexes of DpR were 96.29%,94.44%,0.87,and the above indexes of ETS+DpR were 98.14%,96.29%,0.93.The sensitivity,specificity and AUC of ETS+DpR were better than those of ETS or DpR alone.Conclusion ETS and DpR are risk factors for the efficacy and prognosis of apatinib combined with docetaxel in the treatment of patients with HER-2 negative advanced gastric cancer,and the levels of ETS and DpR are related to each risk factor.ETS and DpR alone and in combination have high value in predicting the efficacy and prognosis of patients with HER-2 negative advanced gastric cancer.