Molecular-guided Risk Stratification of Thyroid Nodules and Cancer

分子引导的甲状腺结节和癌症风险分层

• 批准号: 8930351
• 负责人: YURI E NIKIFOROV
• 金额: $ 28.27万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-07-01 至 2020-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8930351
• 关键词: Ablation; Address; Age; Benign; Cancer Detection; Case Study; Clinical; Clinical Trials; Cytology; Data; Diagnosis; Diagnostic; Diagnostic tests; Disease; Disease Progression; Distant Metastasis; Double-Blind Method; Epidemic; Fine needle aspiration biopsy; Gene Expression; Genes; Genetic; Genetic Markers; Genotype; Goals; Head and Neck Cancer; Health Care Costs; Image; Incidence; Individual; Indolent; Lead; Lobectomy; Malignant - descriptor; Malignant Neoplasms; Malignant neoplasm of thyroid; Molecular; Molecular Profiling; Morbidity - disease rate; Mutation; Needle biopsy procedure; Neoplasm Metastasis; Nodule; Operative Surgical Procedures; Outcome; Palpable; Papillary thyroid carcinoma; Patients; Performance; Phase; Predictive Value; Prevalence; Procedures; Prospective Studies; Radioactive Iodine; Recurrence; Reporting; Research; Resected; Resolution; Risk; Role; Sampling; Sequence Analysis; Staging; Stratification; Survival Rate; Testing; The Cancer Genome Atlas; Thyroid Diseases; Thyroid Gland; Thyroid Nodule; Thyroidectomy; Time; Tissue Sample; Tissues; Translating; Ultrasonography; Universities; base; cancer diagnosis; cancer recurrence; cancer risk; clinical practice; cost; disorder risk; experience; gene panel; high risk; medical attention; molecular marker; mortality; next generation sequencing; novel; operation; population based; prognostic; prospective; screening; standard of care; tumor

Project Summary - Project 4 Project 4 is a new project that addresses the epidemic of thyroid cancer. Well-differentiated thyroid cancer is increasing at an alarming rate. There has been a 3-fold increase in incidence of thyroid cancer in the past 3 decades. However, the mortality for these patients has remained very low (estimated to be ~2%). Therefore, performing a thyroidectomy for all patients with that thyroid cancer may not be necessary. This project addresses two major issues relevant to the thyroid cancer detection and management. Firstly, we will use next generation sequencing to develop and validate a molecular test that can more accurately distinguish between thyroid cancer and benign nodules in patients with needle biopsy results that are indeterminate. This molecular test analyses the expression and/or mutation of 62 individual genes and builds on our previous experience using a smaller panel of genes to diagnose thyroid cancer. In the second Aim, we will evaluate the ability of our molecular testing to differentiate low-risk thyroid cancers from more aggressive (high-risk) thyroid cancers. In order to accomplish this goal, we will first interrogate tissue samples obtained from patients who have undergone surgery for thyroid cancer, and then experience disease recurrence or distant metastases. Simultaneously, we will initiate a clinical trial to observe patients with small thyroid cancers. Patients with small cancers will undergo upfront molecular testing and then will be observed. A molecular profile of high-risk disease will be determined by the tumors from patients who progress during the observation period. This information will then be used to inform the second phase of the trial, which will use the molecular signature to separate patients into high-risk and low-risk disease for surgery or observation, respectively. Aim 1: To test the hypothesis that the NGS-based panel of mutational markers can reliably diagnose cancer in thyroid nodules. This Aim seeks to develop and validate a novel molecular analytic test that can accurately predict which thyroid nodules are malignant versus benign. We will develop the molecular test at the University of Pittsburgh and then validate the utility of this test in 8 other academic centers. Aim 2: To test the hypothesis that high-risk and low-risk differentiated thyroid cancers have distinct mutational profiles that can be detected in FNA samples and utilized to guide patient management. This Aim consists of two parts, the first sub-aim seeks to use molecular testing to characterize tissues derived from patients with aggressive disease (experience recurrence of cancer or develop metastases). The second sub- aim extends these data to develop and implement a prospective clinical trial that provides patients with small cancers to have observation instead of surgery. The data from this trial will validate that molecular testing can be used to stratify thyroid cancers into a low-risk subtype.

项目总结 - 项目 4 项目 4 是一个解决甲状腺癌流行问题的新项目。高分化甲状腺癌是 以惊人的速度增加。过去3年甲状腺癌发病率增加了3倍 几十年。然而，这些患者的死亡率仍然非常低（估计约为 2%）。所以， 可能没有必要对所有甲状腺癌患者进行甲状腺切除术。这个项目 解决与甲状腺癌检测和管理相关的两个主要问题。首先，我们将使用 next 世代测序来开发和验证分子测试，可以更准确地区分 甲状腺癌和良性结节患者的针吸活检结果是不确定的。这个分子 测试分析了 62 个单独基因的表达和/或突变，并建立在我们之前的经验基础上 使用较小的基因组来诊断甲状腺癌。在第二个目标中，我们将评估我们的能力 分子检测可区分低风险甲状腺癌和更具侵袭性（高风险）的甲状腺癌。在 为了实现这一目标，我们将首先询问从患有以下疾病的患者身上获得的组织样本： 接受甲状腺癌手术，然后出现疾病复发或远处转移。 同时，我们将启动一项临床试验，观察患有小型甲状腺癌的患者。体型较小的患者 癌症将接受前期分子检测，然后进行观察。高危人群的分子特征 疾病将根据观察期间进展的患者的肿瘤来确定。这 然后，信息将用于告知试验的第二阶段，该阶段将使用分子特征来 将患者分为高风险和低风险疾病，分别进行手术或观察。 目标 1：检验基于 NGS 的突变标记物组能够可靠诊断的假设 甲状腺结节中的癌症。该目标旨在开发和验证一种新颖的分子分析测试，该测试可以 准确预测哪些甲状腺结节是恶性的，哪些是良性的。我们将在 匹兹堡大学随后在其他 8 个学术中心验证了该测试的实用性。 目标 2：检验高风险和低风险分化型甲状腺癌具有不同特征的假设 可以在 FNA 样本中检测到突变谱并用于指导患者管理。这 目标由两部分组成，第一个子目标旨在利用分子测试来表征来自 患有侵袭性疾病的患者（癌症复发或发生转移）。第二个子 目标扩展这些数据来开发和实施一项前瞻性临床试验，为患者提供小 癌症以观察代替手术。该试验的数据将验证分子测试可以 用于将甲状腺癌分层为低风险亚型。