Methods:
We conducted a multi-institutional retrospective analysis of all
pediatric patients <21 years with a primary diagnosis of a CNS
tumor, who had available histopathology data from 2008 to 2021 at 4
upstate New York hospitals. Institutional Review Board approval was
obtained from each respective institution; only de-identified data were
shared across institutions. Tumors were classified based on molecular
genetics and clinical features. DMs were determined based on Catalogue
Of Somatic Mutations In Cancer (COSMIC) database Tier 1 genes (genes
that are definitively implicated in cancer
development).10 Using COSMIC, the following mutations
were identified in our subset of patients as DMs: TP53inactivation, BRAF-KIAA1549 fusion, FGFR1 amplification,BRAF V600E mutation, NF1 loss and H3F3A K28Mmutation. Patient demographics, clinical history, tumor histopathology
and genomics, treatments, and outcomes were obtained from the electronic
medical record (EMR). Specific genomic alterations and TMB were
identified using FoundationOne sequencing.
The prespecified primary analysis of this study was to compare TMB with
survival outcomes. High TMB (≥3 mut/Mb) and low TMB (<3
mut/Mb) were stratified based on patient TMB distribution in our study
and also based on prior literature.11 Time to
progression (TTP) was defined as the days from date of diagnosis to
first clinical documentation of progression. Time to death (TTD) was
defined as the days from date of diagnosis to date of death. A cutoff
date of July 1, 2021, was used for survival calculations. Secondarily,
we sought to further characterize the genomics of pediatric patients
with CNS tumors.
Frequencies, means, medians and confidence intervals were used to
describe the patients, treatments, and genomics. Univariable
cox-regression analyses were conducted to assess the relationship
between patient/tumor characteristics and survival. Variables with
p<0.05 on univariable analysis were included in a
multi-variable cox-regression model. All analyses were performed via
SPSS Statistics, Version 28.0.1.1 (IBM Corp., Armonk, NY).