Introduction:
Pediatric central nervous system (CNS) tumors are the leading cause of
pediatric cancer mortality.1 Historically, pediatric
CNS tumors were characterized by tumor location and histologic features.
With advances in next-generation sequencing, these data may better
inform tumor diagnosis and clinical decision
making.1,2
Tumor mutational burden (TMB) is the total number of mutations per
megabase (mut/Mb) in a tumor’s genetic coding region.3Driver mutations (DM) are specific mutations that are thought to enable
oncogenicity.4 TMB and DMs have been studied across
numerous cancer types as a means of risk
stratification.5 High TMB has been associated with
poor outcomes in adult diffuse glioma patients.6Multiple types of high TMB tumors have demonstrated improved responses
to immunotherapy.7 More research is needed, especially
in pediatric populations, to identify ways in which TMB and DMs may be
used as prognostic and therapeutic determinants.8
Patel et al. were among the first investigators to analyze TMB and DMs
in a large cohort of pediatric brain tumors patients. They provided
evidence that a high TMB subsets exists in pediatric brain tumor
patients and demonstrated a clear relationship between TMB and certain
types of DMs. For example, low TMB tumors had a higher incidence ofBRAF alterations, whereas high TMB tumors had a higher incidence
of TP53 mutations.9
The aim of this study is to identify specific patient and genomic
variables that may be associated with outcomes in pediatric brain
tumors. Specifically, we aim to determine the prognostic relevance of
TMB and identify potential populations that may benefit from the
addition of immunotherapy agents, including immune checkpoint inhibitors
(ICI).