Measuring Perceptions of Utility of Clinical Genome Sequencing: Instrument Testing and Validation

项目摘要 通过这项临床测序证据生成研究（CSER 2）， 多样性项目，我们将完成一项试验（得克萨斯州KidsCanSeq研究）比较结果 在儿科癌症患者中进行靶向癌症面板测序与基因组规模测试的对比 在不同的临床环境中。我们将比较靶向癌症小组和整个生殖系 对1100例儿童癌症患者进行外显子组测序（WES）， FFPE肿瘤样品的转录组测序和拷贝数阵列，用于以下子组： 高危肿瘤患者（n=360）。我们将在成功完成CSER的基础上再接再厉 BASIC 3外显子组测序试验（包括60%的西班牙裔和非洲裔美国人） 来自一个大型学术中心的患者）在这项大型多机构研究中， 来自德克萨斯州五个不同医疗机构的更多样化的患者人群。的 试验将由经验丰富的多PI团队领导，包括Plon博士（医学遗传学家），Parsons （儿科肿瘤学家）和McGuire（伦理学家和卫生政策专家）。我们将评估临床 通过测量诊断性和/或可操作的生殖系的频率来利用这些测试， 肿瘤发现和对治疗决策的影响（目标1）。我们将首先比较 一级亲属进行家族基因检测，并推荐按种族进行癌症监测， 种族和临床环境（目标2）。我们将描述感知效用（临床，心理， 和务实）通过调查和采访父母和参与儿科肿瘤学家 （n=40）（目标3）。与我们的儿科癌症利益相关者合作，包括倡导者，BASIC 3 研究父母和国家组织，我们将创造和评估文化的使用， 包括英文和西班牙文录像在内的敏感教育材料， 基因组测试报告和咨询材料，并将比较面对面与远程医疗 外显子组结果披露（Aim 4）。最后，我们将提供数据，以指导未来的应用 临床基因组学通过三个创新的试点项目，重点是卫生经济学，决策 支持癌症监测和全基因组测序（目标5）。Baylor College of 医学，得克萨斯州儿童医院和我们在全州的合作机构是理想的 适合进行本研究，并在基于以下内容的CSER 2联盟活动中发挥领导作用 我们长期的儿科肿瘤学和癌症遗传学专业知识， CLIA认证的临床生殖细胞和癌症基因组诊断测试，以及 在基因组学和健康差异研究的伦理和社会影响方面的奖学金。

PROJECT SUMMARY 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.