A combined clinical and biological risk classification improves prediction of outcome in hepatoblastoma patients
A combined clinical and biological risk classification improves prediction of outcome in hepatoblastoma patients
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DOI：
10.1016/j.ejca.2020.09.026
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发表时间：
2020-12-01
影响因子：
8.4
通讯作者：
Kappler, Roland
中科院分区：
文献类型：
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作者：
Cairo, Stefano;Armengol, Carolina;Kappler, Roland
目的：肝母细胞瘤（HB）患者的分层是基于诊断时获得的临床和影像学特征。我们的目标是将生物标志物整合到一个工具中，准确地预测HB患者的生存率。方法：我们回顾性分析了174例HB患者的四种生物标志物的存在，并通过与总生存率（OS）和无事件生存率（EFS）的相关性来探讨其预后潜力。CTNNB 1、NFE 2L 2和TERT的突变分别在135例（78%）、10例（6%）和10例（6%）患者中发现，并且在63例（36%）患者中发现了16个基因签名的不利C2亚型。与C1-患者相比，C2-患者有更频繁的转移性疾病、更高的甲胎蛋白水平、非胎儿组织学和显著更差的3年OS（68% vs 95%）和EFS（63% vs 87%）。携带NFE 2L 2突变的患者的3年OS（57%对88%）显著低于NFE 2L 2野生型患者，并且更可能发生血管浸润性生长和非胎儿组织学。TERT突变几乎只在老年患者中发现，而CTNNB 1突变与任何临床特征或结果无关。在多变量分析中，C2亚型仍然是预后不良的重要预测因子，OS和EFS的风险比分别为6.202和3.611。当添加到儿童肝肿瘤国际协作风险分层，C2亚型的存在确定了一组高风险的患者与一个非常差的outcome.Conclusion：我们提出了一个新的分层系统的基础上结合临床因素和16个基因的签名，这可能有利于风险适应性管理HB患者。(C)2020作者（S）爱思唯尔有限公司出版
Aim: Stratification of hepatoblastoma (HB) patients is based on clinical and imaging characteristics obtained at the time of diagnosis. We aim to integrate biomarkers into a tool that accurately predicts survival of HB patients.Methods: We retrospectively analysed 174 HB patients for the presence of four biomarkers and explored their prognostic potential by correlating with overall survival (OS) and event-free survival (EFS).Results: Mutations of CTNNB1, NFE2L2 and TERT were found in 135 (78%), 10 (6%) and 10 (6%) patients, respectively, and the adverse C2 subtype of the 16-gene signature in 63 (36%) patients. C2-patients had more frequent metastatic disease, higher alpha-fetoprotein levels, non-fetal histology and significantly worse 3-year OS (68% versus 95%) and EFS (63% versus 87%) than C1-patients. Patients carrying a NFE2L2 mutation had a significantly worse 3-year OS (57% versus 88%) than NFE2L2 wild-type patients and were more likely to have vessel invasive growth and non-fetal histology. TERT mutations were almost exclusively found in older patients, whereas CTNNB1 mutations showed no association with any clinical feature or outcome. In a multivariable analysis, the C2 subtype remained a significant predictor of poor outcome with hazard ratios of 6.202 and 3.611 for OS and EFS, respectively. When added to the Children's Hepatic tumors International Collaboration risk stratification, the presence of the C2 subtype identified a group of high-risk patients with a very poor outcome.Conclusion: We propose a new stratification system based on the combination of clinical factors and the 16-gene signature, which may facilitate a risk-adapted management of HB patients. (C) 2020 The Author(s). Published by Elsevier Ltd.