The Children’s Brain Tumor Network (CBTN) - Accelerating Research in Pediatric Central Nervous System Tumors through Collaboration and Open Science

Abstract

Pediatric brain tumors are the leading cause of cancer-related death in children in the United States and contribute a disproportionate number of potential years of life lost compared to adult cancers. Moreover, survivors frequently suffer long-term side effects, including secondary cancers. The Children's Brain Tumor Network (CBTN) is a multi-institutional international clinical research consortium created to advance therapeutic development through the collection and rapid distribution of biospecimens and data via open-science research platforms for real-time access and use by the global research community. The CBTN's 32 member institutions utilize a shared regulatory governance architecture at the Children's Hospital of Philadelphia to accelerate and maximize the use of biospecimens and data. As of August 2022, CBTN has enrolled over 4,700 subjects, over 1,500 parents, and collected over 65,000 biospecimen aliquots for research. Additionally, over 80 preclinical models have been developed from collected tumors. Multi-omic data for over 1,000 tumors and germline material is currently available with data generation for > 5,000 samples underway. To our knowledge, CBTN provides the largest open-access pediatric brain tumor multi-omic dataset annotated with longitudinal clinical and outcome data, imaging, associated biospecimens, child-parent genomic pedigrees, and in vivo and in vitro preclinical models. Empowered by NIH-supported platforms such as the Kids First Data Resource and the Childhood Cancer Data Initiative, the CBTN continues to expand the resources needed for scientists to accelerate translational impact for improved outcomes and quality of life for children with brain and spinal cord tumors.

Automated Tumor Segmentation and Brain Tissue Extraction from Multiparametric MRI of Pediatric Brain Tumors: A Multi-Institutional Study

“…Our retrospective study was compliant with the HIPAA and obtained approval from the IRB of the Children's Hospital of Philadelphia (CHOP) through Children's Brain Tumor Network (CBTN) Protocol. MRI exams were collected from the subjects enrolled onto the CBTN, which is a biorepository (cbtn.org 21 ) that allows for the collection of specimens, longitudinal clinical and imaging data, and sharing of de-identified samples and data for future research. From this dataset, multi-parametric MRI scans of n = 273 patients with histologically confirmed pediatric brain tumors were selected.…”

Pioneering models of pediatric brain tumors

“…Considering the rarity of each tumor type as a nature of pediatric brain tumors, integrative and collaborative efforts, together with such available clinical models are necessary to develop novel and effective treatment. As an example, CBTN has established more than 80 preclinical models and the largest multiomic dataset derived from patient tumors and those models [152] , which will lead to thorough biological understanding of each tumor. In these contexts, such robust tumor models established so far and addition of novel ones will continue to contribute to the accelerated discovery of effective therapeutics for pediatric brain tumor patients.…”

ALT in Pediatric High-Grade Gliomas Can Occur withoutATRXMutation and is Enriched in Patients with Pathogenic Germline MMR Variants

“…Tumor DNA was obtained from the Children’s Brain Tumor Network 34 from individuals consented on the institutional review board approved CBTN protocol. C-circle analysis (CCA), which is a highly accurate read-out of ALT 36 , was performed on tumor samples and controls as described previously 10 .…”

“…Paired tumor and normal WGS BAMs (N = 940) from previously sequenced pediatric brain tumors were obtained by data access request to the Children's Brain Tumor Network (CBTN) 34 . The BAMs were used as paired inputs to TelomereHunter 16 , which was run using default parameters to estimate telomere content.…”