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).