Comprehensive evaluation of context dependence of the prognostic impact of MYCN amplification in neuroblastoma: A report from the International Neuroblastoma Risk Group (INRG) project
Comprehensive evaluation of context dependence of the prognostic impact of MYCN amplification in neuroblastoma: A report from the International Neuroblastoma Risk Group (INRG) project
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DOI：
10.1002/pbc.27819
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发表时间：
2019-08-01
影响因子：
3.2
通讯作者：
DuBois, Steven G.
中科院分区：
文献类型：
--
作者：
Campbell, Kevin;Shyr, Derek;DuBois, Steven G.
背景MYCN扩增（MYCN-A）是神经母细胞瘤的一个既定的不良预后因素。MYCN-A的预后影响在多大程度上取决于其他因素尚未得到充分表征。患者和方法使用国际神经母细胞瘤风险组数据库，我们构建了总生存期（OS）的考克斯模型，以获得由其他预后因素定义的亚组内MYCN-A效应的风险比。考克斯模型评估了MYCN-A的预后影响受其他协变量调节的程度。我们使用绝对风险比（HR）差异构建分类树，以确定MYCN-A具有最大差异预后效应的亚组。结果在6223例已知MYCN状态的患者中，与MYCN-A相关的OS风险比为6.3（95%置信区间5.7-7.0，P <0.001）。诊断时的年龄赋予了亚组之间MYCN-A的最大HR绝对差异（HR绝对差异16. 6; ≥ 18个月MYCN-A的HR为19. 6）。在控制其他因素后，MYCN-A仍然是OS的显著预后因素，消除了它们的预后强度。结果受MYCN状态影响最大的患者是那些
Background MYCN amplification (MYCN-A) is an established adverse prognostic factor in neuroblastoma. The extent to which the prognostic impact of MYCN-A depends on other factors has not been fully characterized. Patients and methods Using the International Neuroblastoma Risk Group database, we constructed Cox models of overall survival (OS) to obtain hazard ratios of the effect of MYCN-A within subgroups defined by other prognostic factors. Cox models assessed the degree to which the prognostic impact of MYCN-A was modulated by each other covariate. We used absolute hazard ratio (HR) differences to construct classification trees to identify subgroups with greatest differential prognostic effect of MYCN-A. Results In a cohort of 6223 patients with known MYCN status, the OS hazard ratio associated with MYCN-A was 6.3 (95% confidence interval 5.7-7.0, P < .001). Age at diagnosis conferred the largest HR absolute difference for MYCN-A between subgroups (HR absolute difference 16.6; HRs for MYCN-A of 19.6 for = 18 months). MYCN-A remained significantly prognostic of OS after controlling for other factors, abrogating their prognostic strength. Patients whose outcome was most impacted by MYCN status were those who were