儿童肝母细胞瘤预后影响因素分析

Analysis of prognostic factors in children with hepatoblastoma

目的探讨儿童肝母细胞瘤(hepatoblastoma,HB)的预后影响因素。方法回顾性分析2011年1月至2019年1月首诊于上海儿童医学中心普外科的120例HB患儿的临床资料,记录患儿年龄、性别、PRETEXT分期、病理类型、远处转移、血清甲胎蛋白(alpha fetoprotein,AFP)水平、乳酸脱氢酶与白蛋白比值(lactate dehydrogenase to albumin ratio,LAR)水平、治疗方案及治疗后随访结果。根据上海儿童医学中心危险度分层标准,分为标准危险组(n=39)和高度危险组(n=81),并采用不同的化疗方案。采用单因素分析和多因素分析方法分析影响儿童HB无事件生存期和总体生存期的危险因素。结果120例患儿中,男性73例,女性47例;发病中位年龄为16个月,3岁以内患儿103例,3岁以上患儿17例;伴远处转移为20例,不伴远处转移为100例;血清AFP≤100 ng/mL为2例,AFP>100 ng/mL为118例;LAR≤31.6为92例,LAR>31.6为28例。随访中位时间为29.0(10.3,62.8)个月,患儿5年无事件生存率(event-free survival,EFS)和5年总体生存率(overall survival,OS)分别为79.8%±4.1%和84.9%±3.7%。多因素回归分析表明,影响HB患儿预后独立危险因素包括年龄(EFS:HR=1.029,95%CI 1.015~1.042;OS:HR=1.030,95%CI 1.014~1.046)、AFP≤100 ng/mL(EFS:HR=18.10,95%CI 3.20~102.53;OS:HR=19.82,95%CI 3.26~120.56)、伴远处转移(EFS:HR=3.13,95%CI 1.07~9.20;OS:HR=4.36,95%CI 1.22~15.60)以及LAR>31.6(EFS:HR=5.77,95%CI 1.89~17.66;OS:HR=7.69,95%CI 1.91~31.02),均P<0.05。结论HB患儿发病年龄增加、肿瘤远处转移、AFP≤100 ng/mL、LAR>31.6是影响HB预后独立危险因素,LAR值可作为一种新的判断儿童HB预后的生物标志物。

Objective To explore the prognostic factors of children with hepatoblastoma.Methods A retrospective analysis was performed on 120 children with hepatoblastoma who were newly diagnosed in Shanghai Children’s Medical Center from January 2011 to January 2019.The age,gender,PRETEXT stage,pathological type,distant metastasis,serum AFP at admission,therapy protocols and follow-up were recorded.According to the Shanghai Children’s Medical Center risk stratification,all patients were divided into standard(n=39)and high-risk groups(n=81)and received different chemotherapy protocols.Univariate and multivariate analysis were used to study the risk factors involving event-free survival and overall survival in children with hepatoblastoma.Results Among the 120 cases,73 cases were male and 47 cases were female;the median age of onset was 16 months,103 cases were under 3 years old,and 17 cases were over 3 years old.There were 20 cases with distant metastasis and 100 cases without distant metastasis.There were 2 cases with serum AFP≤100 ng/mL and 118 cases with AFP>100 ng/mL.There were 92 cases with preoperative LAR(lactate dehydrogenase to albumin ratio)≤31.6 and 28 cases with LAR>31.6.The follow-up time was 29.0(10.3,62.8)months,and the 5-year event-free survival(EFS)and 5-year overall survival(OS)rates were 79.8%±4.1%and 84.9%±3.7%,respectively.Multivariate regression analysis showed that independent prognostic factors for children with hepatoblastoma included age(HR=1.029,95%CI 1.015-1.042 for EFS;HR=1.030,95%CI 1.014-1.046 for OS),AFP≤100 ng/mL at admission(HR=18.10,95%CI 3.20-102.53 for EFS;HR=19.82,95%CI 3.26-120.56 for OS),with distant metastasis(HR=3.13,95%CI 1.07-9.20 for EFS;HR=4.36,95%CI 1.22-15.60 for OS)and LAR>31.6(HR=5.77,95%CI 1.89-17.66 for EFS;HR=7.69,95%CI 1.91-31.02 for OS),all P<0.05.Conclusion Age,distant metastasis,AFP≤100 ng/mL at admission,and LAR>31.6 were independent risk factors involving the prognosis of patients with hepatoblastoma,and LAR can be used as a new prognostic biomarker for children with hepatoblastoma.