Abstract

Tumor mutational burden (TMB) has been studied across numerous cancer types as a means of risk stratification. To examine the prognostic relevance of TMB to pediatric central nervous system (CNS) tumors, we conducted a retrospective analysis of patients at Albany Medical Center diagnosed from 2012 to present. Patients were <21 at diagnosis, had a primary CNS tumor and available genomic data. Forty-seven patients were included – 22 low-grade gliomas, 10 high-grade gliomas, 5 medulloblastomas, 3 ependymomas, 2 choroid plexus carcinomas, and 5 other CNS tumors, with a median follow up of 36 months, median age at diagnosis 10 (1–19), and 47% female. Median TMB was 1 mutation per megabase (mut/mb); range 0–6. Nine patients did not have available TMB data. Twenty-seven patients had driver mutations and other alterations implicated in cancer development including, including BRAF-KIAA1549 fusion (n=6), NF1 loss (n=5), FGFR1 amplification (n=4), TP53 inactivation (n=4), BRAF V600E mutation (n=3), and H3F3A K28M mutation (n=3). Patients with low TMB (<3 muts/mb; n=24) versus high TMB (≥3 muts/mb; n=14) had a survival of 87% versus 71%, respectively, at last follow-up. Of note, all but one patient in the low TMB cohort had localized disease at diagnosis versus three in the high TMB cohort. High TMB was more prevalent in high- (45%, 9/20) versus low-grade histologies (22%, 4/18). Patients with BRAF alterations had LGGs and low TMB (0–1 muts/mb) with all patients surviving at last follow up. Of the eight deaths observed (median 18 months from diagnosis) TMB was high in 4, low in 3, and unknown in 1; all had high-grade histology. Although limited, our data suggests higher TMB may be associated with worse outcome. This analysis will be expanded via a multi-institutional review of TMB and genomic alterations in pediatric CNS patients to better identify high-risk patients requiring alternative treatment strategies.

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