切换至 "中华医学电子期刊资源库"

中华妇幼临床医学杂志(电子版) ›› 2019, Vol. 15 ›› Issue (04) : 373 -381. doi: 10.3877/cma.j.issn.1673-5250.2019.04.004

所属专题: 文献

论著

儿童肝母细胞瘤疗效及预后分析
孙静静1, 郭霞1, 饶艳琼1, 代依灵1, 田钰1, 高举1,()   
  1. 1. 四川大学华西第二医院儿科、出生缺陷与相关妇儿疾病教育部重点实验室,成都 610041
  • 收稿日期:2019-01-24 修回日期:2019-07-11 出版日期:2019-08-01
  • 通信作者: 高举

Therapeutic efficacy and prognosis of childhood hepatoblastoma: retrospective analysis of 23 cases in a single center

Jingjing Sun1, Xia Guo1, Yanqiong Rao1, Yiling Dai1, Yu Tian1, Ju Gao1,()   

  1. 1. Department of Pediatrics, Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
  • Received:2019-01-24 Revised:2019-07-11 Published:2019-08-01
  • Corresponding author: Ju Gao
  • About author:
    Corresponding author: Gao Ju, Email:
  • Supported by:
    National Natural Science Foundation of China for Youth(81600122)
引用本文:

孙静静, 郭霞, 饶艳琼, 代依灵, 田钰, 高举. 儿童肝母细胞瘤疗效及预后分析[J]. 中华妇幼临床医学杂志(电子版), 2019, 15(04): 373-381.

Jingjing Sun, Xia Guo, Yanqiong Rao, Yiling Dai, Yu Tian, Ju Gao. Therapeutic efficacy and prognosis of childhood hepatoblastoma: retrospective analysis of 23 cases in a single center[J]. Chinese Journal of Obstetrics & Gynecology and Pediatrics(Electronic Edition), 2019, 15(04): 373-381.

目的

探讨儿童肝母细胞瘤(HB)患儿的临床特征、疗效、生存情况、预后相关危险因素及其临床诊治。

方法

选择2010年1月至2017年9月,于四川大学华西第二医院儿童血液肿瘤科收治的23例新发HB患儿为研究对象。采用回顾性分析方法,收集其临床病例资料,包括患儿确诊时年龄、性别、首发临床表现、组织病理学类型、治疗前病变范围(PRETEXT)分期、术后儿童肿瘤协作组(COG)分期等临床资料,以及治疗方案、疗效、预后、化疗相关不良反应等。对本组HB患儿的生存分析,如2年总体生存(OS)率、无事件生存(EFS)率,采用Kaplan-Meier法,不同临床特征患儿的生存曲线比较采用log-rank检验。HB患儿接受不同化疗方案治疗的不良反应率比较,采用Fisher确切概率法。本研究遵循的程序符合2013年修订的《世界医学协会赫尔辛基宣言》要求。

结果

①本组23例HB患儿确诊时的中位年龄为25.9个月(2.3~155.0个月);男性患儿为12例,女性为11例;腹部肿块为最常见首发临床表现(56.5%,13/23)。其完全缓解(CR)率为65.2%(15/23),部分缓解(PR)率为8.7%(2/23),死亡为5例(21.7%)。②对23例患儿的中位随访时间为21.5个月(7.5~81.4个月),其2年EFS率、OS率分别为60.1%和75.0%。HB患儿预后影响因素的单因素分析结果显示,HB累及血管患儿的2年EFS率为38.9%,显著低于未累及者的81.8%,二者比较,差异有统计学意义(χ2=4.293,P=0.038)。HB患儿PRETEXT分期为Ⅳ期者,其2年EFS率为33.3%,显著低于PRETEXT分期为Ⅰ~Ⅲ期者的70.6%,二者比较,差异有统计学意义(χ2=5.258,P=0.022)。肺转移HB患儿的2年EFS率、OS率分别为20.0%、30.0%,均显著低于无肺转移者的71.4%、85.7%,二者分别比较,差异均有统计学意义(χ2=5.491,P=0.015;χ2=7.773,P=0.005)。手术后接受3个疗程化疗,血清甲胎蛋白(AFP)值未恢复正常患儿的2年EFS率、OS率分别为27.2%、37.7%,显著低于手术后接受≤3个疗程化疗即恢复正常者的91.7%、100.0%,二者比较,差异亦均有统计学意义(χ2=9.837,P=0.002;χ2=8.682,P=0.003)。③严重血液学毒性反应为本组HB患儿最常见化疗相关不良反应,尤其是采取包含多柔比星的联合化疗方案者更严重。本组术后接受化疗的22例HB患儿中,接受联合化疗方案包含多柔比星的14例患儿的3级以上血液学毒性反应、轻度转氨酶升高发生率分别为100.0%(14/14)、64.3%(9/14),显著高于未包含多柔比星患儿的37.8%(3/8)、0(0/8),二者分别比较,差异均有统计学意义(P=0.002,P=0.006)。

结论

本组儿童HB的临床特征、组织病理学类型与国内外相关临床报道结果基本一致。HB患儿肺转移及手术后接受3个疗程化疗,血清AFP值未恢复正常水平,与该病的不良预后密切相关。

Objective

To explore the clinical and pathological features, therapeutic efficacy, survival, related risk factors of prognosis and clinical diagnosis and treatments of children with hepatoblastoma (HB).

Methods

A total of 23 cases of newly diagnosed HB children in Department of Pediatric Hematology and Oncology, West China Second University Hospital, Sichuan University, from January 2010 to September 2017, were enrolled in this study and selected as research subjects. The clinical data regarding age at diagnosis, gender, clinical manifestations, histopathological types, staging of pre-treatment extent of disease (PRETEXT) and divided group by Children′s Oncology Group (COG) of United States after operation, and clinical protocols, therapeutic effect, prognosis and chemotherapy-related adverse reactions and so on were retrospectively analyzed. Kaplan-Meier method was used for survival analysis of childhood HB, such as rates of 2-year overall survival (OS) and 2-year event-free survival (EFS), and log-rank test was employed for comparisons of OS and EFS curves between HB children with different clinical features. The incidences of adverse reactions between children treated with different chemotherapy regimens were compared by Fisher exact probability method. This study was in line with the requirements of World Medical Association Declaration of Helsinki revised in 2013.

Results

①The median age of 23 cases of children with HB at diagnosis was 25.9 months (2.3-155.0 months). There were 12 boys and 11 girls. Clinically, abdominal mass was the most frequent presenting manifestations, identified in 56.5% (13/23) of HB children. Rates of complete remission (CR) and partial remission (PR) were 65.2% (15/23) and 8.7% (2/23), respectively at the end of chemotherapy, and 5 cases (21.7%) died. ②With median follow-up time of 21.5 months (7.5-81.4 months), the rates of 2-year EFS and 2-year OS among the 23 cases of HB children were 60.1% and 75.0%, respectively. Univariate analysis revealed that the 2-year EFS rate was 38.9% in children with vascular involvement of HB, which was significantly lower than 81.8% in children without vascular involvement of HB, and the difference was statistically significant (χ2=4.293, P=0.038). The 2-year EFS rate of children with stage Ⅳ in PRETEXT stage was 33.3%, which was also significantly lower than 70.6% in children with stage Ⅰ-Ⅲ in PRETEXT stage, and the difference was statistically significant (χ2=5.258, P=0.022). The rates of 2-year EFS and OS in children with lung metastasis were 20.0% and 30.0%, respectively, which were statistically lower than those of 71.4% and 85.7%, respectively in children without lung metastasis, and both the differences were statistically significant (χ2=5.491, P=0.015; χ2=7.773, P=0.005). The rates of 2-year EFS and OS in children with failure of serum alpha-fetoprotein (AFP) normalization after 3 courses of postoperative chemotherapy were 27.2% and 37.7%, respectively, which were statistically lower than those of 91.7% and 100.0%, respectively in children with normalization in AFP after ≤ 3 courses of postoperative chemotherapy, and both the differences were statistically significant (χ2=9.837, P=0.015; χ2=8.682, P=0.003). ③Severe hematological toxicity was the most common chemotherapy associated adverse reaction, particularly in children who received the treatment of doxorubicin-based combination chemotherapy. Among the 22 cases of HB children who who received chemotherapy, the incidences of hematologic toxicity in grade 3 or higher and mild transaminase elevation in 14 children receiving doxorubicin-based combination chemotherapy were 100.0% (14/14) and 64.3% (9/14), respectively, which were significantly higher than those of 37.8% (3/8) and 0 (0/8) in children who did not receive doxorubicin in the chemotherapy regimen, and both the differences were statistically significant (P=0.002, P=0.006).

Conclusions

The children with HB collected in this study share similar clinical and pathological features as reported previously. Lung metastasis and failure of serum AFP normalization after 3 courses of postoperative chemotherapy are risk factors intimately associated with adverse clinical outcomes of HB children.

表1 本组23例HB患儿的临床资料分析[例数(%)]
图8 手术后接受3个疗程化疗,血清AFP值未恢复正常与手术后接受≤3个疗程化疗即恢复正常的HB患儿的OS曲线
表2 HB患儿预后影响因素的单因素分析
表3 接受不同方案化疗HB患儿不良反应发生情况比较[例数(%)]
[1]
Howlader N, Noone AM, Krapcho M, et al. Age-adjusted and age-specific SEER cancer incidence rates review, 1975-2014, National Cancer Institute. Bethesda[DB/OL]. (2018-04-02) [2019-03-02].

URL    
[2]
Litten JB, Tomlinson GE. Liver tumors in children[J]. Oncologist, 2008, 13(7): 812-820.
[3]
Allan BJ, Parikh PP, Diaz S, et al. Predictors of survival and incidence of hepatoblastoma in the paediatric population[J]. HPB (Oxford), 2013, 15(10): 741-746.
[4]
Hung GY, Lin LY, Yu TY, et al. Hepatoblastoma incidence in Taiwan: a population-based study[J]. J Chin Med Assoc, 2018, 81(6): 541-547.
[5]
Ikeda H, Nakamura Y. Trends in incidence of childhood malignant solid tumors in Japan: estimation based on hospital-based registration[J]. J Pediatr Surg, 2015, 50(9): 1506-1512.
[6]
Exelby PR, Filler RM, Grosfeld JL. Liver tumors in children in the particular reference to hepatoblastoma and hepatocellular carcinoma: American Academy of Pediatrics Surgical Section Survey--1974[J]. J Pediatr Surg, 1975, 10(3): 329-337.
[7]
de Camargo B, de Oliveira Ferreira JM, de Souza Reis R, et al. Socioeconomic status and the incidence of non-central nervous system childhood embryonic tumours in Brazil[J]. BMC Cancer, 2011, 11: 160.
[8]
Towbin AJ, Meyers RL, Woodley H, et al. 2017 PRETEXT: radiologic staging system for primary hepatic malignancies of childhood revised for the Paediatric Hepatic International Tumour Trial (PHITT)[J]. Pediatr Radiol, 2018, 48(4): 536-554.
[9]
Roebuck DJ, Aronson D, Clapuyt P, et al. 2005 PRETEXT: a revised staging system for primary malignant liver tumours of childhood developed by the SIOPEL group[J]. Pediatr Radiol, 2007, 37(2): 123-132; quiz 249-250.
[10]
中国抗癌协会小儿肿瘤专业委员会,中华医学会小儿外科分会肿瘤专业组. 儿童肝母细胞瘤多学科诊疗专家共识(CCCG-HB-2016)[J]. 中华小儿外科杂志,2017, 38(10): 733-739.
[11]
Czauderna P, Lopez-Terrada D, Hiyama E, et al. Hepatoblastoma state of the art: pathology, genetics, risk stratification, and chemotherapy[J]. Curr Opin Pediatr, 2014, 26(1): 19-28.
[12]
Kumar SV, Lupo PJ, Pompeii LA, et al. Maternal residential proximity to major roadways and pediatric embryonal tumors in offspring[J]. Int J Environ Res Public Health, 2018, 15(3): E505.
[13]
Turcotte LM, Georgieff MK, Ross JA, et al. Neonatal medical exposures and characteristics of low birth weight hepatoblastoma cases: a report from the Children′s Oncology Group[J]. Pediatr Blood Cancer, 2014, 61(11): 2018-2023.
[14]
Czauderna P, Lopez-Terrada D, Hiyama E, et al. Hepatoblastoma state of the art: pathology, genetics, risk stratification, and chemotherapy[J]. Curr Opin Pediatr, 2014, 26(1): 19-28.
[15]
Zsiros J, Brugieres L, Brock P, et al. Dose-dense cisplatin-based chemotherapy and surgery for children with high-risk hepatoblastoma (SIOPEL-4): a prospective, single-arm, feasibility study[J]. Lancet Oncol, 2013, 14(9): 834-842.
[16]
Hiyama E, Hishiki T, Watanabe K, et al. Resectability and tumor response after preoperative chemotherapy in hepatoblastoma treated by the Japanese Study Group for Pediatric Liver Tumor (JPLT)-2 protocol[J]. J Pediatr Surg, 2016, 51(12): 2053-2057.
[17]
Kremer N, Walther AE, Tiao GM. Management of hepatoblastoma: an update[J]. Curr Opin Pediatr, 2014, 26(3): 362-369.
[18]
Perilongo G, Shafford E, Maibach R, et al. Risk-adapted treatment for childhood hepatoblastoma, final report of the second study of the International Society of Paediatric Oncology: SIOPEL 2[J]. Eur J Cancer, 2004, 40(3): 411-421.
[19]
Meyers RL, Maibach R, Hiyama E, et al. Risk-stratified staging in paediatric hepatoblastoma: a unified analysis from the Children′s Hepatic tumors International Collaboration[J]. Lancet Oncol, 2017, 18(1): 122-131.
[20]
Qiao GL, Li L, Cheng W, et al. Predictors of survival after resection of children with hepatoblastoma: a single Asian center experience[J]. Eur J Surg Oncol, 2014, 40(11): 1533-1539.
[21]
张伟令,张谊,黄东生,等. 102例儿童肝母细胞瘤的治疗及预后分析[J]. 中国小儿血液与肿瘤杂志,2015, 20(6): 289-292.
[22]
王天怡,潘慈,汤静燕,等. 儿童肝母细胞瘤74例随访研究[J]. 中华儿科杂志,2017, 55(5): 364-368.
[23]
姚东亚,罗源,盛光耀. 儿童肝母细胞瘤36例预后分析[J]. 临床儿科杂志,2017, 35(2): 121-124.
[24]
陆正华,杨静薇,邵静波,等. 小儿肝母细胞瘤24例的临床特点及预后因素分析[J]. 中国小儿血液与肿瘤杂志,2015, 20(2): 79-82.
[25]
汤梦婕,袁晓军,谈珍,等. 多学科综合治疗47例儿童肝母细胞瘤的疗效评估[J]. 中华实用儿科临床杂志,2016, 31(15): 1175-1179.
[26]
易优,张谊,张伟令,等. 晚期儿童肝母细胞瘤的预后分析[J]. 中国小儿血液与肿瘤杂志,2014, 19(6): 303-307.
[27]
Shi Y, Commander SJ, Masand PM, et al. Vascular invasion is a prognostic indicator in hepatoblastoma[J]. J Pediatr Surg, 2017, 52(6): 956-961.
[28]
Erginel B, Gun Soysal F, Keskin E, et al. Pulmonary metastasectomy in pediatric patients[J]. World J Surg Oncol, 2016, 14(1): 27.
[29]
Eisenhauer E, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid tumours: Revised RECIST guideline (version 1.1)[J]. Eur J Cancer, 2009, 45(2): 228-247.
[30]
O′Neill AF, Towbin AJ, Krailo MD, et al. Characterization of pulmonary metastases in children with hepatoblastoma treated on children′s oncology group protocol AHEP0731 (the treatment of children with all stages of hepatoblastoma): a report from the children′s oncology group[J]. J Clin Oncol, 2017, 35(30): 3465-3473.
[31]
Koh KN, Park M, Kim BE, et al. Prognostic implications of serum alpha-fetoprotein response during treatment of hepatoblastoma[J]. Pediatr Blood Cancer, 2011, 57(4): 554-560.
[32]
De Ioris M, Brugieres L, Zimmermann A, et al. Hepatoblastoma with a low serum alpha-fetoprotein level at diagnosis: the SIOPEL group experience[J]. Eur J Cancer, 2008, 44(4): 545-550.
[1] 张璇, 马宇童, 苗玉倩, 张云, 吴士文, 党晓楚, 陈颖颖, 钟兆明, 王雪娟, 胡淼, 孙岩峰, 马秀珠, 吕发勤, 寇海燕. 超声对Duchenne肌营养不良儿童膈肌功能的评价[J]. 中华医学超声杂志(电子版), 2023, 20(10): 1068-1073.
[2] 张宝富, 俞劲, 叶菁菁, 俞建根, 马晓辉, 刘喜旺. 先天性原发隔异位型肺静脉异位引流的超声心动图诊断[J]. 中华医学超声杂志(电子版), 2023, 20(10): 1074-1080.
[3] 韩丹, 王婷, 肖欢, 朱丽容, 陈镜宇, 唐毅. 超声造影与增强CT对儿童肝脏良恶性病变诊断价值的对比分析[J]. 中华医学超声杂志(电子版), 2023, 20(09): 939-944.
[4] 刘婷婷, 林妍冰, 汪珊, 陈幕荣, 唐子鉴, 代东伶, 夏焙. 超声衰减参数成像评价儿童代谢相关脂肪性肝病的价值[J]. 中华医学超声杂志(电子版), 2023, 20(08): 787-794.
[5] 周钰菡, 肖欢, 唐毅, 杨春江, 周娟, 朱丽容, 徐娟, 牟芳婷. 超声对儿童髋关节暂时性滑膜炎的诊断价值[J]. 中华医学超声杂志(电子版), 2023, 20(08): 795-800.
[6] 应康, 杨璨莹, 刘凤珍, 陈丽丽, 刘燕娜. 左心室心肌应变对无症状重度主动脉瓣狭窄患者的预后评估价值[J]. 中华医学超声杂志(电子版), 2023, 20(06): 581-587.
[7] 杨倩, 李翠芳, 张婉秋. 原发性肝癌自发性破裂出血急诊TACE术后的近远期预后及影响因素分析[J]. 中华普外科手术学杂志(电子版), 2024, 18(01): 33-36.
[8] 栗艳松, 冯会敏, 刘明超, 刘泽鹏, 姜秋霞. STIP1在三阴性乳腺癌组织中的表达及临床意义研究[J]. 中华普外科手术学杂志(电子版), 2024, 18(01): 52-56.
[9] 马伟强, 马斌林, 吴中语, 张莹. microRNA在三阴性乳腺癌进展中发挥的作用[J]. 中华普外科手术学杂志(电子版), 2024, 18(01): 111-114.
[10] 钟广俊, 刘春华, 朱万森, 徐晓雷, 王兆军. MRI联合不同扫描序列在胃癌术前分期诊断及化疗效果和预后的评估[J]. 中华消化病与影像杂志(电子版), 2023, 13(06): 378-382.
[11] 李永胜, 孙家和, 郭书伟, 卢义康, 刘洪洲. 高龄结直肠癌患者根治术后短期并发症及其影响因素[J]. 中华临床医师杂志(电子版), 2023, 17(9): 962-967.
[12] 刘笑笑, 张小杉, 刘群, 马岚, 段莎莎, 施依璐, 张敏洁, 王雅晳. 中国学龄前儿童先天性心脏病流行病学研究进展[J]. 中华临床医师杂志(电子版), 2023, 17(9): 1021-1024.
[13] 王军, 刘鲲鹏, 姚兰, 张华, 魏越, 索利斌, 陈骏, 苗成利, 罗成华. 腹膜后肿瘤切除术中大量输血患者的麻醉管理特点与分析[J]. 中华临床医师杂志(电子版), 2023, 17(08): 844-849.
[14] 索利斌, 刘鲲鹏, 姚兰, 张华, 魏越, 王军, 陈骏, 苗成利, 罗成华. 原发性腹膜后副神经节瘤切除术麻醉管理的特点和分析[J]. 中华临床医师杂志(电子版), 2023, 17(07): 771-776.
[15] 李静, 张玲玲, 邢伟. 兴趣诱导理念用于小儿手术麻醉诱导前的价值及其对家属满意度的影响[J]. 中华临床医师杂志(电子版), 2023, 17(07): 812-817.
阅读次数
全文


摘要