Pediatric brain and spinal cord tumors are collectively the second most common malignancy in children after leukemia, representing the leading disease-related cause of death in children [@doi:10.1093/neuonc/noz150]. Five-year survival rates vary widely across different histologic and molecular classifications of brain tumors. For example, most high-grade gliomas carry a universally fatal prognosis, while children with pilocytic astrocytoma have an estimated 10-year survival rate of 92% [@doi:10.1093/neuonc/now207]. Recent estimates suggest that children and adolescents aged 0-19 with brain tumors in the United States lose an average 47,631 years of life [@doi:10.1002/cam4.410].
The low survival rates for some pediatric tumors are multifactorial, explained partly by our lack of comprehensive understanding of ever-evolving brain tumor molecular subtypes, difficulty drugging these tumors, and shortage of drugs specifically labeled for pediatric malignancies. Historically, fatal inoperable brain tumors, such as diffuse intrinsic pontine gliomas (DIPGs), were not routinely biopsied due to perceived biopsy risks and the paucity of therapeutic options. Thus, combined with rare incidences of pediatric tumors in the first place, limited availability of tissue for developing patient-derived cell lines and mouse models has hindered research.
To address these barriers, multiple national and international consortia have collaborated to uniformly collect clinically-annotated surgical biosamples and associated germline materials through both observational and interventional clinical trials. The Pediatric Brain Tumor Atlas (PBTA) initiative established in 2018 by the Children's Brain Tumor Network (CBTN, cbtn.org)[@doi:10.1016/j.neo.2022.100846] and the Pacific Pediatric Neuro-Oncology Consortium (PNOC, pnoc.us) built upon 12 years of enrollment, sample collection, and clinical followup across over 30 institutions. Just as cooperation accelerates specimens and data sharing, collaboration among computational researchers, bench scientists, clinicians, and pathologists is critical for rigorous genomic analysis.
Although there has been significant progress elucidating genomic bases of pediatric brain tumor formation and progression, translating therapeutic agents to phase II or III clinical trials and subsequent FDA approvals have not kept pace. Within the last 20 years, the FDA has approved only seven targeted agents for treating pediatric brain tumors [@url:https://www.fda.gov/about-fda/oncology-center-excellence/pediatric-oncology-drug-approvals]. This is partly due to pharmaceutical company priorities, posing challenges for researchers to obtain therapeutic agents for pediatric clinical trials. Critically, since August 2020, an amendment to the Pediatric Research Equity Act called the "Research to Accelerate Cures and Equity (RACE) for Children Act" mandates that all new adult oncology drugs also be tested in children when the molecular target exists in a childhood cancer. The RACE Act, coupled with genomics advances to identify putative molecular targets in pediatric cancers, will accelerate identification of previously-overlooked but effective therapeutic options for pediatric diseases.
We anticipated that a model of open collaboration would enhance the PBTA's value and provide a framework for ongoing analysis of pediatric brain tumor datasets. Leveraging diverse scientific and analytical expertise, we established the OpenPBTA, which employs an open science model with features such as analytical code review [@doi:10.1093/aje/kwab092; @doi:10.7287/peerj.preprints.3210v1] and continuous integration [@doi:10.1038/nbt.3780; @doi:10.7287/peerj.preprints.3210v1], thereby ensuring reproducibility throughout the project's lifetime. Through OpenPBTA, we present a comprehensive, collaborative, open genomic analysis of 1,074 tumors and 22 cell lines, comprised of 58 distinct brain tumor histologies from 943 patients. The data and containerized infrastructure of OpenPBTA have already supported discovery and translational research studies [@doi:10.1016/j.celrep.2021.108917; @doi:10.1158/1078-0432.CCR-22-0803; @doi:10.1136/jitc-2021-004450; @doi:10.1093/neuonc/noac278], are actively integrated into PNOC molecular tumor board decision-making, and have provided a foundational layer for the Childhood Cancer Data Initiative's (CCDI) recently-established pediatric Molecular Targets Platform (https://moleculartargets.ccdi.cancer.gov/). We anticipate OpenPBTA will continue to be invaluable to the pediatric oncology community.