Informatics Methods and Infrastructure Needed to Study Factors Associated with High Incidence of Pediatric Brain and Central Nervous System Tumors in Kentucky.

ABSTRACT

Pediatric brain and central nervous system tumors (PBCNSTs) are the most common solid tumors and are the leading cause of disease-related death in US children. PBCNST incidence rates in Kentucky are significantly higher than in the United States as a whole, and are even higher among Kentucky's Appalachian children. To understand and eventually eliminate such disparities, population-based research is needed to gain a thorough understanding of the epidemiology and etiology of the disease. This multi-institutional population-based retrospective cohort study is designed to identify factors associated with the high incidence of PBCNST in Kentucky, leveraging the infrastructure provided by the Kentucky Cancer Registry, its Virtual Tissue Repository (VTR), and the National Institutes of Health Gabriella Miller Kids First Data Resource Center (DRC). Spatiotemporal scan statistics have been used to explore geographic patterns of risk measured by standardized incidence ratios (SIRs) with 95% confidence intervals. The VTR is being used to collect biospecimens for the population-based cohort of PBCNST tissues that are being sequenced by Center for Data Driven Discovery in Biomedicine (D3b) at the Children's Hospital of Philadelphia (CHOP) with support from the Kids First DRC. After adjusting for demographic factors, we assess their potential relationship to environmental factors. We have identified regions in north-central and eastern Appalachian Kentucky where children experienced a significant increased risk of developing PBCNST from 1995-2017 (SIR, 1.48; 95% CI, 1.34-1.62). The VTR has been successful in the collection of a population-based cohort of 215 PBCNST specimens. Timely establishment of legal agreements for data sharing and tissue acquisition proved to be challenging which has been somewhat mitigated by the adoption of national agreement templates. Coronavirus disease 2019 (COVID-19) severely limited the generation of sequencing results due to laboratory shutdowns. However, tissue specimens processed before the shutdown indicated that punches were inferior to scrolls for generating enough quality material for DNA and RNA extraction. Informatics infrastructures that were developed have demonstrated the feasibility of our approach to generate and retrieve molecular results. Our study shows that population-based studies using historical tissue specimens are feasible and practical, but require significant investments in technical infrastructures.