血清甲胎蛋白作为BCLC C期肝细胞癌免疫联合靶向序贯外科治疗预后标志物的临床研究
Serum alpha-fetoprotein in predicting survival of patients with BCLC C hepatocellular carcinoma treated by salvage surgery after downstaging therapy
摘要目的:分析甲胎蛋白预测晚期肝细胞癌患者免疫联合靶向序贯外科手术生存获益的价值。方法:收集2018年12月至2021年12月解放军总医院肝胆胰外科医学部收治的免疫联合靶向序贯外科手术切除、初诊时血清甲胎蛋白阳性(>20 μg/L)的巴塞罗那临床肝癌分期(BCLC) C期肝细胞癌患者资料。入组50例患者,其中男性45例,女性5例,年龄(53.0±10.5)岁。根据免疫联合靶向治疗后患者血清甲胎蛋白是否降至正常水平分为甲胎蛋白正常组( n=27,甲胎蛋白≤20 μg/L)和对照组( n=23,甲胎蛋白>20 μg/L)。门诊复查或电话随访患者生存和复发情况。Kaplan-Meier法计算生存率,生存率比较采用log-rank检验。比较两组免疫联合靶向治疗的疗效。单因素和多因素Cox回归分析患者预后影响因素。 结果:两组均未达到中位生存期。甲胎蛋白正常组1、2年累积生存率分别为95.0%、88.2%,对照组分别为73.4%、54.1%。甲胎蛋白正常组中位无复发生存期尚未达到,对照组中位无复发生存期为11个月。甲胎蛋白正常组术后1年无复发生存率为78.1%,对照组为39.5%。甲胎蛋白正常组累积生存率和无复发生存率优于对照组,差异均有统计学意义(χ 2=7.60、8.83, P=0.006、0.003)。甲胎蛋白正常组肿瘤完全缓解、部分缓解以及病理学完全缓解均优于对照组。多因素Cox回归分析,免疫联合靶向治疗后血清甲胎蛋白>20 μg/L( HR=2.952,95% CI:1.023~8.517, P=0.045)的患者术后复发风险增加。 结论:免疫联合靶向治疗后血清甲胎蛋白降至正常可以作为BCLC C期肝细胞癌患者序贯外科治疗的预后预测指标,甲胎蛋白与患者免疫联合靶向治疗的疗效有关。
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abstractsObjective:To analyze the value of alpha-fetoprotein(AFP) in predicting survival of patients who underwent salvage surgery after tumor downstaging therapy in patients with advanced hepatocellular carcinoma.Methods:The data of 50 patients with Barcelona Clinic Liver Cancer Staging (BCLC) C hepatocellular carcinoma treated at the Faculty of Hepato-Pancreato-Biliary Surgery, Chinese PLA General Hospital from December 2018 to December 2021 were collected. There were 45 males and 5 females, with the age of (53.0±10.5) years. The patients were divided into two groups based on the serum AFP level after tumor downstaging therapy, AFP normal group ( n=27, AFP≤20 μg/L) and the control group ( n=23, AFP>20 μg/L). Patient survival and tumor recurrence were followed up by outpatient review or telephone follow-up. The survival rate was calculated by the Kaplan-Meier method and compared by the log-rank test. The efficacy of combined immunotargeted therapy were compared between the two groups. Univariate and multivariate Cox regression analysis were carried to analyse the factors influcing prognosis. Results:The median survival time was not reached in both groups. The 1-year and 2-year cumulative survival rates were 95.0% and 88.2% in the normal group and 73.4% and 54.1% in the control group, respectively. The median relapse-free survival time of the normal group was not reached, and the median relapse-free survival time of the control group was 11 months. The 1-year recurrence-free survival rate was 78.1% in the normal group and 39.5% in the control group. The cumulative survival rate and relapse-free survival rate in the normal group were significantly higher than those in the control group (χ 2=7.60, 8.83, P=0.006, 0.003). The complete response, partial response and pathological complete response of tumors in the normal group were significant better than those in the control group. Multivariate Cox regression analysis showed that patients with serum AFP >20 μg/L ( HR=2.952, 95% CI: 1.023-8.517, P=0.045) after immunotherapy combined with targeted therapy had an increased risk of postoperative recurrence. Conclusion:The reduction of serum AFP to normal after downstaging therapy could be used as a prognostic indicator of salvage surgical in patients with BCLC C hepatocellular carcinoma, and AFP was related to the efficacy of downstaging therapy in patients.
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