首页|存活肿瘤细胞比例在初始不可切除肝细胞癌患者转化序贯外科治疗预后评估中的应用

存活肿瘤细胞比例在初始不可切除肝细胞癌患者转化序贯外科治疗预后评估中的应用

Value of the ratio of viable tumor cells in the prognostic evaluation for patients with unresectable hepatocellular carcinoma undergoing sequential surgery after conversional therapy

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目的 探讨存活肿瘤细胞比例(RVTCs)在初始不可切除肝细胞癌(HCC)患者转化序贯外科治疗预后评估中的作用.方法 回顾性分析2019年6月至2022年6月解放军总医院肝胆胰外科医学部收治的80例初始不可切除HCC患者的临床资料,其中男性70例,女性10例,年龄(54.5± 10.9)岁.患者接受以程序性死亡蛋白1(PD-1)抗体联合酪氨酸激酶抑制剂(TKI)为基础的转化序贯外科治疗,计算术后病理标本中的RVTCs,并依据RVTCs情况分组考察其对预后的影响.通过病历系统、门诊系统数据调阅和电话随访患者术后的生存情况.使用受试者工作特征(ROC)曲线分析RVTCs与患者无复发生存时间的关系,探讨RVTCs的最佳临界值.采用Kaplan-Meier法进行生存分析,生存率比较采用log-rank检验.使用logistic多元回归分析预后的影响因素.结果 17例患者的肿瘤切除病理标本未发现存活的肿瘤细胞,即RVTCs为0,获得完全病理学反应(CPR),依据病理结果是否为CPR,将80例患者分为CPR组(n=17)和非CPR组(n=63),CPR组术后无复发生存时间和总生存时间均优于非CPR组,差异具有统计学意义(均P<0.05).RVTCs预测初始不可切除HCC患者术后1、2、3年无复发生存时间的ROC曲线下面积分别为0.850、0.880和0.788,RVTCs的截断值均为15%,因而确定其最佳临界值为15%,并以此将80例患者分为RVTCs>15%组(n=37)和RVTCs≤15%组(n=43),RVTCs≤15%组患者的无复发生存时间和总生存时间均优于RVTCs>15%组,差异具有统计学意义(均P<0.05).logistic多元回归分析结果显示,伴乙型肝炎病毒感染(OR=8.114,95%CI:1.343~49.044,P=0.023)、术前改良实体肿瘤疗效评价标准评估为完全缓解或部分缓解(OR=4.423,95%CI:0.976~20.050,P=0.042)、术前甲胎蛋白 ≤20 μg/L(OR=5.939,95%CI:1.576~22.383,P=0.008)的初始不可切除HCC患者,手术切除病理标本达到RVTCs≤15%的概率高.结论 对于接受PD-1抗体联合TKI转化序贯外科治疗的初始不可切除HCC患者,RVTCs可作为预测预后的标志物,其与患者的无复发生存时间和总生存时间相关.
Objective To evaluate the prognostic value of the ratio of viable tumor cells(RVTCs)in patients with initially unresectable hepatocellular carcinoma(HCC)treated with sequential surgery after immunotherapy combined with targeted therapy.Methods Clinical data of 80 patients with initially unre-sectable HCC undergoing sequential surgery after immunotherapy combined with targeted therapy in the Fac-ulty of Hepato-Pancreato-Biliary Surgery,the First Medical Center of Chinese PLA General Hospital from June 2019 to June 2022 were retrospectively analyzed,including 70 males and 10 females,aged(54.5± 10.9)years old.Patients underwent sequential surgery after conversional therapy based on programmed death-1 antibody combined with tyrosine kinase inhibitor.RVTCs in postoperative pathological specimens were calculated.The postoperative treatment and survival of patients were followed up by medical record system,outpatient system data and telephone review.The receiver operating characteristic(ROC)curve was used to analyze the relationship between RVTCs and recurrence-free survival(RFS)and its best cut-off value.The Kaplan-Meier method was used for survival analysis,and the survival rates were compared using log-rank test.Multivariate logistic regression analysis was used to analyze the influencing factors of progno-sis.Results No viable tumor cells were found in the tumor specimens of 17 patients,which indicated that the RVTCs was 0 and complete pathological response(CPR)was achieved.According to postoperative pathology,patients were divided into the CPR group(n=17)and non-CPR group(n=63).The postopera-tive RFS and overall survival(OS)in the CPR group were better than those in the non-CPR group(both P<0.05).The area under the ROC curve of RVTCs for predicting the 1-,2-,and 3-year RFS with initially unresectable HCC was 0.850,0.880,and 0.788,respectively.The cut-off values of RVTCs were all 15%,so the best cut-off value of RVTCS was set up as 15%.Patients were then divided into the RVTCs>15%group(n=37)and RVTCs≤15%group(n=43).The RFS and OS of patients with RVTCs≤15%were better than those in patients with RVTCs>15%(both P<0.05).Multivariate logistic regression analysis showed that patients with hepatitis B virus infection(OR=8.114,95%CI:1.343-49.044,P=0.023),defined as compelete response or partial response based on preoperative modified respond evaluation criteria in solid tumors(OR=4.423,95%CI:0.976-20.050,P=0.042),and preoperative alpha-fetoprotein ≤20 μg/L(OR=5.939,95%CI:1.576-22.383,P=0.008)were risk factors for RVTCs≤15%in surgi-cal specimens.Conclusion RVTCs can be used as a prognostic marker in patients with initially unresect-able HCC undergoing sequential surgery after immunotherapy combined with targeted therapy,which is correlated with the RFS and OS of patients.

Carcinoma,hepatocellularImmunotherapyTargeted therapyHepatectomyPathological response

李俊锋、袁静、张雯雯、王湛博、李雪瑞、刘哲、万涛、胡丙洋、曹俊宁、卢实春

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解放军总医院第一医学中心肝胆胰外科医学部,北京 100853

解放军总医院病理科,北京 100853

南开大学医学院,天津 300071

青岛大学附属医院器官移植中心,青岛 266003

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癌,肝细胞 免疫治疗 靶向治疗 肝切除术 病理学反应

2024

中华肝胆外科杂志
中华医学会

中华肝胆外科杂志

CSTPCD北大核心
影响因子:1.846
ISSN:1007-8118
年,卷(期):2024.30(4)
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