Risk-stratified staging in paediatric hepatoblastoma: a unified analysis from the Children's Hepatic tumors International Collaboration.
Risk-stratified staging in paediatric hepatoblastoma: a unified analysis from the Children's Hepatic tumors International Collaboration.
复制标题
DOI：
10.1016/s1470-2045(16)30598-8
复制
发表时间：
2017-01
期刊：
影响因子：
--
通讯作者：
Czauderna P
中科院分区：
文献类型：
--
作者：
Meyers RL;Maibach R;Hiyama E;Häberle B;Krailo M;Rangaswami A;Aronson DC;Malogolowkin MH;Perilongo G;von Schweinitz D;Ansari M;Lopez-Terrada D;Tanaka Y;Alaggio R;Leuschner I;Hishiki T;Schmid I;Watanabe K;Yoshimura K;Feng Y;Rinaldi E;Saraceno D;Derosa M;Czauderna P
在儿科肝母细胞瘤试验中，由于患者数量少和四个主要试验组使用多种不同的分期系统，对治疗结果的比较评估受到阻碍。为了应对这一挑战，我们成立了一个全球联盟，即儿童肝脏肿瘤国际合作组织（CHIC），旨在为这种罕见癌症的分期和风险分层创造一种共同的方法。CHIC指导委员会由四个主要合作试验小组（国际儿童肝脏肿瘤战略小组、儿童肿瘤小组、德国儿科肿瘤和血液学学会以及日本儿科肝脏肿瘤研究组）的领导组成，创建了一个共享的国际数据库，其中包括25年来在8个多中心肝母细胞瘤试验中治疗的1605名儿童的综合数据。初步分析发现对预后影响最大的诊断因素为疾病前处理程度（预处理程度）组；3岁以下、3 - 7岁、8岁以上；α胎蛋白（AFP）浓度为100 ng/mL及以下和101 ~ 1000 ng/mL；而其解释因素包括转移性疾病(M)、所有肝静脉的大血管累及(V)或门脉分叉(P)、肝外肿瘤(E)、多灶性肿瘤(F)和自发破裂(R)。我们根据已确定的预后因素定义了五个临床相关的支柱组：托普I/II、托普III、托普IV、转移性疾病和诊断时AFP浓度为100 ng/mL或更低。然后，我们将额外的因素带入分层向后消除多变量分析，并使用结果创建一个新的国际分期系统。在每个骨干组中，我们确定了最能预测该组结果的一系列因素。然后使用自举过程对候选模型进行鲁棒性检验。使用临床建立的第I、II、III和IV组作为我们的研究对象，我们基于5年无事件生存期和临床适用性创建了风险分层树。我们定义并采用了四个风险组：极低、低、中、高。我们已经创建了一个统一的全球方法来对患有肝母细胞瘤的儿童进行风险分层，该方法基于严格的统计调查，据我们所知，这是迄今为止为这种罕见的儿科肿瘤收集的最大数据集。这一成果为进一步的合作和前瞻性的国际合作研究提供了结构框架，例如儿科肝脏国际肿瘤试验（PHITT）。欧洲儿童和青少年癌症研究网络，由欧盟委员会框架计划7资助（资助号261474）；由肝母细胞瘤基金会资助的儿童肿瘤小组CureSearch基金；日本医学研究机构创新癌症控制实践研究和促进新药和医疗器械开发临床试验项目；和瑞士癌症研究基金。
Comparative assessment of treatment results in paediatric hepatoblastoma trials has been hampered by small patient numbers and the use of multiple disparate staging systems by the four major trial groups. To address this challenge, we formed a global coalition, the Children’s Hepatic tumors International Collaboration (CHIC), with the aim of creating a common approach to staging and risk stratification in this rare cancer. The CHIC steering committee—consisting of leadership from the four major cooperative trial groups (the International Childhood Liver Tumours Strategy Group, Children’s Oncology Group, the German Society for Paediatric Oncology and Haematology, and the Japanese Study Group for Paediatric Liver Tumours)—created a shared international database that includes comprehensive data from 1605 children treated in eight multicentre hepatoblastoma trials over 25 years. Diagnostic factors found to be most prognostic on initial analysis were PRETreatment EXTent of disease (PRETEXT) group; age younger than 3 years, 3–7 years, and 8 years or older; α fetoprotein (AFP) concentration of 100 ng/mL or lower and 101–1000 ng/mL; and the PRETEXT annotation factors metastatic disease (M), macrovascular involvement of all hepatic veins (V) or portal bifurcation (P), contiguous extrahepatic tumour (E), multifocal tumour (F), and spontaneous rupture (R). We defined five clinically relevant backbone groups on the basis of established prognostic factors: PRETEXT I/II, PRETEXT III, PRETEXT IV, metastatic disease, and AFP concentration of 100 ng/mL or lower at diagnosis. We then carried the additional factors into a hierarchical backwards elimination multivariable analysis and used the results to create a new international staging system. Within each backbone group, we identified constellations of factors that were most predictive of outcome in that group. The robustness of candidate models was then interrogated using the bootstrapping procedure. Using the clinically established PRETEXT groups I, II, III, and IV as our stems, we created risk stratification trees based on 5 year event-free survival and clinical applicability. We defined and adopted four risk groups: very low, low, intermediate, and high. We have created a unified global approach to risk stratification in children with hepatoblastoma on the basis of rigorous statistical interrogation of what is, to the best of our knowledge, the largest dataset ever assembled for this rare paediatric tumour. This achievement provides the structural framework for further collaboration and prospective international cooperative study, such as the Paediatric Hepatic International Tumour Trial (PHITT). European Network for Cancer Research in Children and Adolescents, funded through the Framework Program 7 of the European Commission (grant number 261474); Children’s Oncology Group CureSearch grant contributed by the Hepatoblastoma Foundation; Practical Research for Innovative Cancer Control and Project Promoting Clinical Trials for Development of New Drugs and Medical Devices, Japan Agency for Medical Research; and Swiss Cancer Research grant.