Circulating Tumor DNA Sequencing of Pediatric Solid and Brain Tumor Patients: An Institutional Feasibility Study

Authors

Ross Mangum
Jacquelyn Reuther
Koel Sen Baksi
Ilavarasi Gandhi
Ryan C Zabriskie
Alva Recinos
Robin Raesz-Martinez
Frank Y Lin
Samara L Potter
Andrew C Sher
Stephen F Kralik
Carrie A Mohila
Murali M Chintagumpala
Donna Muzny
Jianhong Hu
Richard A Gibbs
Kevin E Fisher
Juan Carlos Bernini
Jonathan Gill
Timothy C Griffin
Gail E Tomlinson
Kelly L Vallance
Sharon E Plon
Angshumoy Roy
D Williams Parsons

Publication Date

1-1-2023

Journal

Pediatric Hematology and Oncology

DOI

10.1080/08880018.2023.2228837

PMID

37366551

PMCID

PMC10592361

PubMedCentral® Posted Date

6-27-2024

PubMedCentral® Full Text Version

Author MSS

Published Open-Access

yes

Keywords

Humans, Child, Circulating Tumor DNA, Feasibility Studies, Biomarkers, Tumor, High-Throughput Nucleotide Sequencing, Brain Neoplasms, Mutation, circulating tumor DNA, cell-free DNA, liquid biopsy, precision oncology, Central Nervous System Tumors

Abstract

The potential of circulating tumor DNA (ctDNA) analysis to serve as a real-time "liquid biopsy" for children with central nervous system (CNS) and non-CNS solid tumors remains to be fully elucidated. We conducted a study to investigate the feasibility and potential clinical utility of ctDNA sequencing in pediatric patients enrolled on an institutional clinical genomics trial. A total of 240 patients had tumor DNA profiling performed during the study period. Plasma samples were collected at study enrollment from 217 patients and then longitudinally from a subset of patients. Successful cell-free DNA extraction and quantification occurred in 216 of 217 (99.5%) of these initial samples. Twenty-four patients were identified whose tumors harbored 30 unique variants that were potentially detectable on a commercially-available ctDNA panel. Twenty of these 30 mutations (67%) were successfully detected by next-generation sequencing in the ctDNA from at least one plasma sample. The rate of ctDNA mutation detection was higher in patients with non-CNS solid tumors (7/9, 78%) compared to those with CNS tumors (9/15, 60%). A higher ctDNA mutation detection rate was also observed in patients with metastatic disease (9/10, 90%) compared to non-metastatic disease (7/14, 50%), although tumor-specific variants were detected in a few patients in the absence of radiographic evidence of disease. This study illustrates the feasibility of incorporating longitudinal ctDNA analysis into the management of relapsed or refractory patients with childhood CNS or non-CNS solid tumors.