Abstract Background Comprehensive molecular characterization is central to the classification and management of pediatric central nervous system (CNS) tumors. However, access to advanced molecular testing remains inconsistent across institutions and geographic regions. The U.S. National Cancer Institute Childhood Cancer Data Initiative (CCDI) Molecular Characterization Initiative (MCI) was established to provide standardized, centralized molecular profiling for children and young adults with newly diagnosed cancers, including CNS tumors, to support integrated diagnosis, clinical decision-making, and research. Methods Enrollment is facilitated and clinical follow-up data are collected through the Children’s Oncology Group (COG). Tumor biospecimens undergo centralized pathology quality assurance and multi-platform molecular characterization, including paired tumor/normal exome sequencing, fusion and copy number analysis, and DNA methylation profiling. Results are returned to treating institutions for incorporation into integrated diagnoses and clinical management; and submitted to the CCDI to support research. Results Since March 2022, 5,405 patients with primary CNS tumors have enrolled in the CCDI MCI from 196 sites across the United States, Canada, Australia, and New Zealand, with an average enrollment rate of 120–130 patients per month. Patients with CNS tumors represent a diagnostically diverse cohort including greater than 100 distinct methylation classes within all CNS diagnosis categories of low-grade glial/glioneuronal tumors (35%), medulloblastoma (17%), high-grade glioma (14%), and other rarer tumor categories (34%). 13% of patients had germline cancer predisposition identified with clinical return of results. According to site-reported data from the initial 4,519 patients, final diagnosis was refined based on MCI testing results in 37.1% of cases. Molecular findings influenced patient management, with 15.3% of participants receiving therapy matched to sequencing results, either through commercially available targeted agents or therapies approved on a compassionate use basis. Follow-up data collected through APEC14B1 indicate that 6.3% of participants enrolled on a clinical trial informed by MCI testing results, including 4.0% on COG clinical trials and 2.3% on non-COG clinical trials. These findings demonstrate successful integration of molecular data into both diagnostic and therapeutic pathways. Genomic, digital pathology images and clinical data are available for research use through CCDI portals. Conclusions The CCDI MCI represents the largest prospective, international effort to deliver equitable access to comprehensive molecular profiling for pediatric CNS tumors and collect longitudinal follow-up data. This initiative has demonstrable impact on diagnostic refinement, treatment selection, and clinical trial enrollment. Continued expansion and longitudinal follow-up will enable deeper analyses linking molecular features with outcomes, supporting future advances in precision pediatric neuro-oncology.
Thomas et al. (Tue,) studied this question.
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