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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 4700 subjects, over 1500 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 1000 tumors and germline material are currently available with data generation for > 5000 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.

For pediatric patients with high‐grade gliomas, standard‐of‐care treatment includes surgery, chemotherapy, and radiation therapy; however, most patients ultimately succumb to their disease. With advances in genomic characterization of pediatric high‐grade gliomas, the use of targeted therapies in combination with current treatment modalities offer the potential to improve survival in this patient population. In this report, we present the case of a 3‐year‐old girl with glioblastoma who continues to experience an exceptional and durable response (>2 years) to the poly (ADP‐ribose) polymerase (PARP) inhibitor olaparib. Our patient presented with persistent and progressive seizure activity that upon workup was the result of a large heterogeneously enhancing, mixed cystic and solid mass in the left frontal‐parietal‐temporal region. Histopathologic analysis of resected tumor tissue confirmed the diagnosis of glioblastoma, and comprehensive genomic profiling demonstrated absence of any BRAF or H3F3A mutations. Genomic profiling, however, did reveal a probable germline heterozygous BRCA2 Lys3326Ter (K3226*) nonsense variant. After debulking surgery, the patient received standard‐of‐care treatment with radiation and temozolomide. Nine months later the PARP inhibitor olaparib was administered in combination with temozolomide for 16 cycles. This regimen was well tolerated by the patient and serial imaging showed reduction in tumor size. Since completion of the regimen, the patient remains neurologically intact with no evidence of tumor recurrence. To our knowledge, this represents the first case of a pediatric glioblastoma that maintains a durable response to a therapeutic strategy that included the PARP inhibitor olaparib and more generally highlights the potential clinical utility of incorporating these agents into the treatment of pediatric high‐grade gliomas. Key Points: Germline mutations detected in pediatric gliomas may represent a cancer predisposition syndrome.Integrating molecular testing into routine clinical care for pediatric patients with glioma is critical to identify therapeutic targets and patients with a cancer predisposition syndrome.Patients with glioma with defects in DNA repair pathway components (e.g., BRCA1/2) may show increased responsiveness to poly (ADP‐ribose) polymerase (PARP) inhibitors.Combining PARP inhibitors with temozolomide (standard‐of‐care treatment) revealed no adverse events or toxicities over the course of 18 months. This article reports the first case of a pediatric glioblastoma that maintained a durable response to a therapeutic strategy that included the PARP inhibitor olaparib, highlighting the potential clinical utility of incorporating these agents into the treatment of pediatric high‐grade gliomas. [ABSTRACT FROM AUTHOR]

Embryonal tumors (ET) of the central nervous system (CNS) in children encompass a wide clinical spectrum of aggressive malignancies. Until recently, the overlapping morphological features of these lesions posed a diagnostic challenge and undermined discovery of optimal treatment strategies. However, with the advances in genomic technology and the outpouring of biological data over the last decade, clear insights into the molecular heterogeneity of these tumors are now well delineated. The major subtypes of ETs of the CNS in children include medulloblastoma, atypical teratoid rhabdoid tumor (ATRT), and embryonal tumors with multilayered rosettes (ETMR), which are now biologically and clinically characterized as different entities. These important developments have paved the way for treatments guided by risk stratification as well as novel targeted therapies in efforts to improve survival and reduce treatment burden. [ABSTRACT FROM AUTHOR]