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).