Background: The natural history of pediatric patients with metastasis of primary brain tumors within and outside the central nervous system is poorly understood, as too are possible clinical correlates with outcome. Correspondingly, the aim of this study was to interrogate a national database to characterize this diagnosis and its clinical course in pediatric patients. Methods: The U.S. National Cancer Database (NCDB) was interrogated between the years 2005–2016 for all patients aged 18 years and younger with a primary brain tumor diagnosis, as well as evidence of disease metastasis at initial diagnosis. Data were summarized and overall survival (OS) was modeled using Kaplan–Meier and Cox regression analyses. Results: Out of a total of 8615 pediatric brain tumor patients, 356 (4%) had evidence of metastasis at initial diagnosis. Compared to patients without metastasis, patients with metastasis were statistically younger, more often male, and less likely to have private health insurance (allp< 0.050). With respect to clinical characteristics, the primary tumors of patients with metastasis were statistically more likely to be located in the cerebellum; be of higher histologic grading, with a higher proportion of medulloblastoma diagnoses and lower proportion of malignant glioma and pilocytic astrocytoma diagnoses; and were more likely to be treated by subtotal surgical resection, chemotherapy and radiation therapy (allp< 0.050) when compared to patients without metastasis. Five-year OS for those with metastasis was significantly lower than those without (48% vs. 75%,p< 0.001), with the median overall survival for patients with metastasis being 53 months (95% CI 29–86). Multivariate analysis indicated that a shorter OS was independently associated with the primary diagnoses of malignant glioma (HR 27.7,p= 0.020) and Atypical Teratoid/Rhabdoid Tumor (ATRT, HR 41.1,p= 0.041) and with WHO grades 3 (HR 20.1,p= 0.012) and 4 (HR 11.5,p< 0.001). Longer OS was significantly and independently associated with surgery (HR 0.49,p< 0.001), chemotherapy (HR 0.53,p= 0.041), and radiation therapy (HR 0.57,p= 0.026). Conclusions: Although uncommon, pediatric brain tumors with evidence of metastasis at initial diagnosis will present with a distinct socioeconomic and clinical profile compared to patients without metastasis. Multiple predictors are independently associated with overall prognosis, and understanding these features should be validated in prospective efforts to identify vulnerable patients earlier in order to maximize the impact of treatment.
背景：目前对儿童原发性脑肿瘤在中枢神经系统内外转移的自然病程及其与预后的潜在临床相关性了解甚少。因此，本研究旨在通过分析国家数据库，以明确此类患儿的确诊特征及其临床病程。方法：检索美国国家癌症数据库（NCDB）2005年至2016年间所有18岁及以下原发性脑肿瘤患者数据，筛选初诊时即存在转移证据的病例。采用描述性统计总结数据，并运用Kaplan-Meier法和Cox回归模型分析总生存期（OS）。结果：在8615例儿童脑肿瘤患者中，356例（4%）初诊时存在转移证据。与无转移患者相比，转移患者年龄更小、男性比例更高、拥有私人医疗保险的比例更低（均p<0.050）。临床特征方面：转移患者的原发肿瘤更常位于小脑；组织学分级更高，髓母细胞瘤占比更高而恶性胶质瘤与毛细胞型星形细胞瘤占比更低；更常接受次全手术切除、化疗及放疗（均p<0.050）。转移患者5年总生存率显著低于无转移患者（48% vs. 75%，p<0.001），中位总生存期为53个月（95% CI 29-86）。多变量分析显示：恶性胶质瘤（HR 27.7，p=0.020）与非典型畸胎样/横纹肌样瘤（ATRT，HR 41.1，p=0.041）的原发诊断，以及WHO 3级（HR 20.1，p=0.012）和4级（HR 11.5，p<0.001）与较短总生存期独立相关；而手术（HR 0.49，p<0.001）、化疗（HR 0.53，p=0.041）和放疗（HR 0.57，p=0.026）与较长总生存期显著独立相关。结论：虽然发生率较低，但初诊即存在转移证据的儿童脑肿瘤患者具有区别于无转移患者的独特社会经济与临床特征。多种预测因子与总体预后独立相关，未来需通过前瞻性研究验证这些特征，以早期识别高危患者，从而最大化治疗效果。
Characterizing the Natural History of Pediatric Brain Tumors Presenting with Metastasis
肿瘤(癌症)患者之家