Division of Oncology, Children's Hospital of Philadelphia and Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania.
Pediatr Blood Cancer. 2014 Apr;61(4):627-35. doi: 10.1002/pbc.24777. Epub 2013 Sep 13.
Neuroblastoma in older children and adolescents has a distinctive, indolent phenotype, but little is known about the clinical and biological characteristics that distinguish this rare subgroup. Our goal was to determine if an optimal age cut-off exists that defines indolent disease and if accepted prognostic factors and treatment approaches are applicable to older children.
Using data from the International Neuroblastoma Risk Group, among patients ≥18 months old (n = 4,027), monthly age cut-offs were tested to determine the effect of age on survival. The prognostic effect of baseline characteristics and autologous hematopoietic cell transplant (AHCT) for advanced disease was assessed within two age cohorts; ≥5 to <10 years (n = 730) and ≥10 years (n = 200).
Older age was prognostic of poor survival, with outcome gradually worsening with increasing age at diagnosis, without statistical evidence for an optimal age cut-off beyond 18 months. Among patients ≥5 years, factors significantly prognostic of lower event-free survival (EFS) and overall survival (OS) in multivariable analyses were INSS stage 4, MYCN amplification and unfavorable INPC histology classification. Among stage 4 patients, AHCT provided a significant EFS and OS benefit. Following relapse, patients in both older cohorts had prolonged OS compared to those ≥18 months to <5 years (P < 0.0001).
Despite indolent disease and infrequent MYCN amplification, older children with advanced disease have poor survival, without evidence for a specific age cut-off. Our data suggest that AHCT may provide a survival benefit in older children with advanced disease. Novel therapeutic approaches are required to more effectively treat these patients.
大龄儿童和青少年的神经母细胞瘤具有独特的、惰性的表型，但对于区分这一罕见亚组的临床和生物学特征知之甚少。我们的目标是确定是否存在最佳的年龄截止值来定义惰性疾病，以及是否可以将已接受的预后因素和治疗方法应用于大龄儿童。
利用国际神经母细胞瘤风险组的数据，在年龄≥18 个月的患者中（n=4027），逐月测试年龄截止值，以确定年龄对生存的影响。在两个年龄组内评估基线特征和自体造血细胞移植（AHCT）对晚期疾病的预后影响：≥5 至<10 岁（n=730）和≥10 岁（n=200）。
年龄较大是生存不良的预后因素，随着诊断时年龄的增加，预后逐渐恶化，但在 18 个月之后，没有统计学证据表明存在最佳的年龄截止值。在≥5 岁的患者中，多变量分析显示，INSS 分期 4、MYCN 扩增和不良 INPC 组织学分类是与较低无事件生存率（EFS）和总生存率（OS）显著相关的因素。在 4 期患者中，AHCT 提供了 EFS 和 OS 的显著获益。复发后，与≥18 个月至<5 岁的患者相比，两个年龄组的患者 OS 均延长（P<0.0001）。
尽管疾病呈惰性且 MYCN 扩增不常见，但患有晚期疾病的大龄儿童生存不良，没有证据表明存在特定的年龄截止值。我们的数据表明，AHCT 可能为患有晚期疾病的大龄儿童提供生存获益。需要新的治疗方法来更有效地治疗这些患者。
