Through this Clinical Sequencing Evidence-Generating Research (CSER2) with Enhanced Diversity project we will complete a trial (The Texas KidsCanSeq Study) comparing the results of targeted cancer panel sequencing versus genome-scale testing in pediatric cancer patients across diverse clinical settings. We will compare the targeted cancer panel to germline whole exome sequencing (WES) of unselected childhood cancer patients (n=1100) and WES, transcriptome sequencing and copy number array of FFPE tumor samples for the subset of patients with high-risk tumors (n=360). We will build on our success completing the CSER program BASIC3 exome sequencing trial (which included 60% Hispanic and African-American patients from a single large academic center) in this large multi-institutional study of an even more diverse patient population from five heterogeneous healthcare settings across Texas. The trial will be led by an experienced multi-PI team of Drs. Plon (medical geneticist), Parsons (pediatric oncologist) and McGuire (ethicist and health policy expert). We will assess clinical utility of these tests by measuring the frequency of diagnostic and/or actionable germline and tumor findings and the effect on treatment decisions (Aim 1). We will compare uptake by first degree relatives for familial genetic testing and recommended cancer surveillance by race, ethnicity and clinical settings (Aim 2). We will describe perceived utility (clinical, psychological, and pragmatic) by surveying and interviewing parents and participating pediatric oncologists (n=40) (Aim 3). Working with our pediatric cancer stakeholders, including advocates, BASIC3 study parents, and national organizations, we will create and evaluate the use of culturally sensitive educational materials, including videos in English and Spanish, improved integrated genomic test reports and counseling materials, and will compare in-person versus telemedicine exome results disclosure (Aim 4). Finally, we will provide data to guide future application of clinical genomics through three innovative pilot projects focused on health economics, decision support for cancer surveillance and whole genome sequencing (Aim 5). Baylor College of Medicine, Texas Children?s Hospital, and our partner institutions across the state are ideally suited to conduct this study and play leadership roles in CSER2 consortium activities based on our longstanding pediatric oncology and cancer genetics expertise, extensive experience in CLIA-certified clinical germline and cancer genomic diagnostic testing, and a track record of scholarship in ethical and social implications of genomics and health disparities research.

Public Health Relevance

This study is designed to determine the relative clinical, pragmatic and psychological utility of more focused panel testing versus genome-scale testing including exome and RNA sequencing of both blood and tumor samples with regard to improving the care of childhood cancer patients and their at-risk family members. We will explore this innovative topology of utility for parents and physicians across the highly diverse patient populations and health care settings in Texas.

Agency
National Institute of Health (NIH)
Institute
National Human Genome Research Institute (NHGRI)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01HG006485-06
Application #
9540074
Study Section
Special Emphasis Panel (ZHG1)
Program Officer
Hindorff, Lucia
Project Start
2011-12-05
Project End
2021-05-31
Budget Start
2018-06-01
Budget End
2019-05-31
Support Year
6
Fiscal Year
2018
Total Cost
Indirect Cost
Name
Baylor College of Medicine
Department
Genetics
Type
Schools of Medicine
DUNS #
051113330
City
Houston
State
TX
Country
United States
Zip Code
77030
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Amendola, Laura M; Robinson, Jill O; Hart, Ragan et al. (2018) Why Patients Decline Genomic Sequencing Studies: Experiences from the CSER Consortium. J Genet Couns 27:1220-1227
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Gutierrez, Amanda M; Robinson, Jill O; Statham, Emily E et al. (2017) Portero versus portador: Spanish interpretation of genomic terminology during whole exome sequencing results disclosure. Per Med 14:503-514
Mody, Rajen J; Prensner, John R; Everett, Jessica et al. (2017) Precision medicine in pediatric oncology: Lessons learned and next steps. Pediatr Blood Cancer 64:

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