Berthold Frank, Ernst Angela, Ackermann Sandra, Bartenhagen Christoph, Christiansen Holger, Hero Barbara, Rosswog Carolina, von Schweinitz Dietrich, Klingebiel Thomas, Schmid Irene, Simon Thorsten, Fischer Matthias
Department of Pediatric Oncology and Hematology, University of Cologne, Kerpener Str. 62, 50924 Cologne, Germany.
Institute of Medical Statistics and Computational Biology, Medical Faculty, University of Cologne, 50924 Cologne, Germany.
Cancers (Basel). 2021 Aug 28;13(17):4360. doi: 10.3390/cancers13174360.
To identify variables predicting outcome in neuroblastoma patients assigned to the high-risk group solely by the presence of oncogene amplification (MNA).
Clinical characteristics, genomic information, and outcome of 190 patients solely assigned to high-risk neuroblastoma by MNA were analyzed and compared to 205 patients with stage 4 neuroblastoma aged ≥18 months with MNA (control group).
Event-free survival (EFS) and overall survival (OS) at 10 years were 47% (95%-CI 39-54%) and 56% (95%-CI 49-63%), respectively, which was significantly better than EFS and OS of the control group (EFS 25%, 95%-CI 18-31%, < 0.001; OS 32% 95%-CI 25-39%, < 0.001). The presence of /p53-pathway gene alterations was associated with impaired 10-year EFS and OS (19% vs. 55%, and 19% vs. 67%, respectively; both < 0.001). In time-dependent multivariable analyses, alterations of RAS-/p53-pathway genes and the extent of the best primary tumor resection were the only independent prognostic variables for OS ( < 0.001 and = 0.011, respectively).
Neuroblastoma patients attributed to high risk solely by amplification have generally a more favorable outcome. Mutations of genes of the RAS and/or p53 pathways and incomplete resection are the main risk factors predicting poor outcome.
确定仅通过癌基因扩增（MNA）被归为高危组的神经母细胞瘤患者的预后预测变量。
分析了190例仅因MNA被归为高危神经母细胞瘤患者的临床特征、基因组信息和预后，并与205例年龄≥18个月的4期伴有MNA的神经母细胞瘤患者（对照组）进行比较。
10年无事件生存率（EFS）和总生存率（OS）分别为47%（95%置信区间39 - 54%）和56%（95%置信区间49 - 63%），显著优于对照组的EFS和OS（EFS 25%，95%置信区间18 - 31%，P < 0.001；OS 32%，95%置信区间25 - 39%，P < 0.001）。/p53通路基因改变与10年EFS和OS受损相关（分别为19%对55%，以及19%对67%；均P < 0.001）。在时间依赖性多变量分析中，RAS - /p53通路基因改变和最佳原发肿瘤切除范围是OS的仅有的独立预后变量（分别为P < 0.001和P = 0.011）。
仅通过MNA被归为高危的神经母细胞瘤患者总体预后更有利。RAS和/或p53通路基因的突变以及不完全切除是预测不良预后的主要危险因素。
