血清血管内皮生长因子对肝动脉化疗栓塞单独/联合靶免治疗在中晚期肝癌临床疗效中的评估价值

The Value of Serum VEGF in Evaluating the Clinical Efficacy of TACE Alone or Combined with Target Immunotherapy in Advanced Hepatocellular Carcinoma

背景 中晚期肝癌治疗面临挑战,寻求有效评估及改善疗法成为研究重点,其中肝动脉化疗栓塞(TACE)结合免疫疗法显示出潜力,但需进一步验证其疗效与患者预后的生物标志物。目的 探讨血清血管内皮生长因子(VEGF)对TACE单独/联合靶免治疗在中晚期肝癌临床疗效中的评估价值。方法 收集2021年1月—2022年7月在河北医科大学第三医院住院的113例初治中晚期肝癌患者,按治疗方案分为TACE组(n=66)、TACE联合靶向治疗组(n=22)、TACE联合靶免治疗组(n=25),于治疗前后分别进行VEGF、甲胎蛋白(AFP)、异常凝血酶原(PIVKA-Ⅱ)等肿瘤标志物检测。根据改良的实体瘤反应评估标准(mRECIST)于治疗3、6、12个月后进行随访以评价中晚期肝癌临床疗效,分析患者的疾病缓解率(ORR)和疾病控制率(DCR);采用Kaplan-Meier法计算中位无进展生存期(PFS)并绘制生存曲线。应用受试者工作特征(ROC)曲线分析血清VEGF及相关联合血清肿瘤标志物对中晚期肝癌临床疗效的预测价值。结果 TACE组、TACE联合靶向治疗组及TACE联合靶免治疗组随访12个月的ORR分别为17.14%(6/35)、33.33%(4/12)、54.55%(6/11),DCR分别为28.57%(10/35)、41.67%(5/12)、72.73%(8/11),治疗12个月的TACE联合靶免治疗组的ORR和DCR高于TACE组(P<0.05)。TACE联合靶免治疗组中位PFS(15.039个月)高于TACE组(8.757个月)和TACE联合靶向治疗组(9.680个月)(P<0.05)。TACE联合靶免治疗组随访12个月行TACE次数低于TACE组和TACE联合靶向治疗组(P<0.05)。TACE联合靶向治疗组和TACE联合靶免治疗组治疗前后血清VEGF差值高于TACE组(P<0.05)。治疗前后血清VEGF差值预测中晚期肝癌临床疗效的ROC曲线下面积(AUC)为0.748(P<0.001),灵敏度和特异度分别为0.909、0.629。血清VEGF联合PIVKA-Ⅱ、VEGF联合AFP、VEGF联合AFP及PIVKA-Ⅱ预测中晚期肝癌临床疗效的AUC分别为0.781、0.869、0.872(P<0.001)。结论 TACE联合靶免治疗能提高中晚期肝癌患者的疗效,延长患者PFS。患者血清VEGF可作为临床疗效评估的生物学指标。

Background The treatment of intermediate and advanced-stage hepatocellular carcinoma poses significant challenges,prompting a research focus on the effective evaluation and enhancement of therapies.Transarterial chemoembolization(TACE)combined with immunotherapy has exhibited potential,however,there is a need for further validation of its efficacy and the identification of biomarkers that can predict patient prognosis.Objective To explore the clinical value of serum vascular endothelial growth factor(VEGF)in evaluating the clinical efficacy of TACE alone or combined with target immunotherapy in advanced hepatocellular carcinoma.Methods The clinical data of 113 newly diagnosed patients with advanced hepatocellular carcinoma were hospitalized in the Third Hospital of Hebei Medical University from January 2021 to July 2022 were analyzed.According to the treatment regimen,the patients were divided into TACE group(n=66),TACE combined targeting group(n=22),and TACE combined with target immunity group(n=25).Tumor markers such as VEGF,alpha fetoprotein(AFP),and protein induced by vitamin K antagonist-Ⅱ(PIVKA-Ⅱ)were detected before and after treatment.According to the modified response evaluation criteria in solid tumors(mRECIST),patients were followed up for 3,6,and 12 months after treatment to evaluate the clinical efficacy of advanced hepatocellular carcinoma.The objective response rate(ORR)and disease control rate(DCR)of the patients were analyzed.The median progression free survival(PFS)was calculated by the Kaplan-Meier and the survival curve was drawn.The receiver operating characteristic(ROC)curve was used to analyze the predictive value of serum VEGF and related combined serum tumor markers for the clinical efficacy of advanced hepatocellular carcinoma.Results The ORRs of the TACE group,TACE combined targeting group and TACE combined target immunity group were after 12 months of follow-up were 17.14%(6/35),33.33%(4/12),and 54.55%(6/11),respectively,and the DCRs were 28.57%(10/35),41.67%(5/12),and 72.73%(8/11),respectively.The ORR and DCR of the TACE combined target immunity group after 12 months of treatment were significantly higher than those of the TACE group,with statistically significant differences(P<0.05).The median PFS of TACE combined with target immunity group(15.039 months)was better than that of TACE group(8.757 months)and TACE combined targeting group(9.680 months)(P<0.05).The frequency of TACE in TACE combined with target immunity group after 12 months of follow-up was significantly less than that in TACE groupand TACE combined targeting group(P<0.05).The difference of serum VEGF before and after treatment in TACE combined targeting group and TACE combined target immunity group was significantly higher than that in TACE group,and the difference was statistically significant(P<0.05).The AUC of the difference in serum VEGF before and after treatment for predicting the clinical efficacy of advanced hepatocellular carcinoma was 0.748(P<0.001),and the sensitivity and specificity were 0.909 and 0.629,respectively.The AUCs of serum VEGF combined with PIVKA-Ⅱ,VEGF combined with AFP,and VEGF combined with AFP and PIVKA-Ⅱfor predicting the clinical efficacy of advanced hepatocellular carcinoma were 0.781,0.869,and 0.872,respectively(P<0.001).Conclusion TACE combined with targeted immunotherapy can improve the efficacy of patients with advanced hepatocellular carcinoma and prolong the PFS of patients.Serum VEGF in patients can be used as a biological indicator for evaluating clinical efficacy.