Characterizing the Natural History of Pediatric Brain Tumors Presenting with Metastasis

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.

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.

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 (all p < 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 (all p < 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).

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.