Department of Pediatric Oncology and Hematology, University of Cologne, Cologne, Germany.
Department of Experimental Pediatric Oncology, University of Cologne, Cologne, Germany.
Pediatr Blood Cancer. 2021 Aug;68(8):e29038. doi: 10.1002/pbc.29038. Epub 2021 Apr 7.
The survival of children with stage 4(M) neuroblastoma without MYCN amplification and below the age of 18 months is considered better than the still dismal outcome of older high-risk neuroblastoma patients. This study analyzes the impact of clinical and molecular characteristics on the long-term outcome.
Clinical presentation, survival, and recurrence patterns of patients enrolled onto trials NB90, NB97, and NB2004 were retrospectively analyzed. Gene expression signatures based on RNA microarrays (TH10) were investigated if tumor material was available.
Between 1990 and 2015, 177 patients with stage 4(M) MYCN nonamplified neuroblastoma aged less than 18 months at diagnosis were eligible. After a median follow-up of 9.7 years (IQR 5.0, 13.4), the proportions of 10-year event-free survival (EFS) and overall survival (OS) were 73% (95% confidence interval [CI] 67-79%) and 86% (95% CI 80-92%), respectively. Of the 27 neuroblastoma recurrences, 44% occurred in more than one site. Four additional patients presented histologically mature ganglioneuroma at recurrence. Six patients developed a secondary malignancy. The secondary 5-year EFS and OS of the 27 patients with neuroblastoma recurrence were 44% and 59%, respectively. TH10 gene expression signature was not prognostically predictive in the investigated subcohort.
The outcome of patients with stage 4(M) neuroblastoma aged less than 18 months is favorable when treated with high-risk or otherwise intensive therapy. The development of secondary malignancies and the potential of maturation to ganglioneuroma call for a controlled stepwise reduction of treatment intensity.
对于未扩增 MYCN 且年龄小于 18 个月的 4 期（M）神经母细胞瘤患儿，其生存率被认为优于年龄较大的高危神经母细胞瘤患者仍然较差的结局。本研究分析了临床和分子特征对长期结果的影响。
回顾性分析了参加 NB90、NB97 和 NB2004 试验的患者的临床表现、生存和复发模式。如果有肿瘤标本，还研究了基于 RNA 微阵列（TH10）的基因表达特征。
1990 年至 2015 年，共有 177 例诊断时年龄小于 18 个月且未扩增 MYCN 的 4 期（M）神经母细胞瘤患儿符合条件。中位随访 9.7 年（IQR 5.0，13.4）后，10 年无事件生存率（EFS）和总生存率（OS）的比例分别为 73%（95%CI 67-79%）和 86%（95%CI 80-92%）。27 例神经母细胞瘤复发中有 44%发生在多个部位。另外 4 例在复发时出现组织学成熟的节细胞神经瘤。6 例发生继发性恶性肿瘤。27 例神经母细胞瘤复发患者的继发性 5 年 EFS 和 OS 分别为 44%和 59%。在研究的亚组中，TH10 基因表达特征未显示出预后预测价值。
对于接受高危或其他强化治疗的年龄小于 18 个月的 4 期（M）神经母细胞瘤患者，其预后良好。继发性恶性肿瘤的发生和向节细胞神经瘤成熟的可能性需要控制逐步降低治疗强度。
