MRI Imaging and Genetic Signatures to Manage Prostate Cancer Overdiagnosis

MRI 成像和基因特征管理前列腺癌过度诊断

• 批准号: 8785593
• 负责人: Alan Pollack
• 金额: $ 66.75万
• 依托单位: UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-08-01 至 2019-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8785593
• 关键词: Age; Algorithms; Biological Preservation; Biopsy; Cancer Patient; Characteristics; Clinical; Clinical Trials; Collaborations; Data; Development; Diffusion; Disease; Early treatment; Gene Expression Profile; Gene Expression Profiling; Genes; Genetic; Habitats; Histology; Image; Indolent; Lesion; Life Expectancy; Magnetic Resonance Imaging; Malignant Neoplasms; Malignant neoplasm of prostate; Modeling; Molecular; Molecular Abnormality; Multiparametric Analysis; Neoplasm Metastasis; Oligonucleotides; Outcome; Patient Monitoring; Patients; Pattern; Phase; Phase II Clinical Trials; Population; Prostate; Prostatectomy; Quality of life; Radiation therapy; Radical Prostatectomy; Radiogenomics; Recommendation; Reporting; Risk; Sampling; Techniques; Testing; Time; Tissues; Tumor Tissue; Ultrasonography; base; cancer cell; chromosome 22 supernumerary marker; density; design; high risk; high throughput analysis; men; novel; prognostic; prospective; public health relevance; tumor

DESCRIPTION (provided by applicant): We propose to study patients who are candidates for active surveillance (AS) to identify imaging and gene expression signatures that distinguish indolent from aggressive prostate cancer and to better understand the mechanisms underlying progression. We will apply novel MRI techniques (i) for quantitative multiparametric MRI (MP-MRI) findings to define "habitats" within the prostate; (ii) to guide prostate biopsies to MP-MRI defined lesions and determine histopathologic associations with habitats; (iii) to develop signatures based on high throughput analysis of imaging features (radiomics); (iv) to relate biopsy oligonucleotide gene expression signatures to inform on the molecular characteristics associated with imaging signatures (radiogenomics); and (v) develop models of progression (conversion to treatment) that incorporate clinical, histopathologic, imaging signatures and gene expression signatures. A Phase II AS trial of prostate cancer patients is designed to acquire MP-MRI, prostate tissue and biofluids at yearly intervals to relate to MP-MRI results and the primary endpoint of progression. The techniques that we propose have the potential to better identify indolent versus aggressive disease, thereby reducing the effects of overdiagnosis. The Specific Aims are: Aim 1. To assess the overall rate and temporal distribution of progression in men undergoing MP-MRI assessments and directed prostate biopsies for AS in a prospective Phase II trial. Aim 2. To establish MP-MRI habitats and use radiomics analysis of MP-MRI features to develop signatures related to adverse histopathologic parameters and patient progression. Aim 3. To molecularly characterize the MP-MRI-directed prostate biopsies obtained, develop a gene expression signature of indolent versus aggressive prostate cancers, and relate this information to the radiomics-derived signatures. We propose that quantitative MP-MRI parameters will be representative of histopathologic and molecular parameters and be an important adjunct to defining risk of progression and, consequently, reduce the rate of unnecessary biopsies.

描述（由申请人提供）：我们建议研究主动监测（AS）候选者的患者，以确定区分惰性前列腺癌和侵袭性前列腺癌的影像和基因表达特征，并更好地了解进展的机制。我们将应用新型 MRI 技术 (i) 进行定量多参数 MRI (MP-MRI) 结果来定义前列腺内的“栖息地”； (ii) 引导前列腺活检找到 MP-MRI 定义的病变并确定与栖息地的组织病理学关联； (iii) 基于成像特征的高通量分析（放射组学）开发特征； (iv) 将活检寡核苷酸基因表达特征联系起来，以了解与成像特征相关的分子特征（放射基因组学）； (v) 开发包含临床、组织病理学、成像特征和基因表达特征的进展模型（转化为治疗）。针对前列腺癌患者的 II 期 AS 试验旨在每年采集 MP-MRI、前列腺组织和生物液，以与 MP-MRI 结果和进展的主要终点相关。我们提出的技术有可能更好地识别惰性疾病与侵袭性疾病，从而减少过度诊断的影响。具体目标是： 目标 1. 在一项前瞻性 II 期试验中，评估接受 MP-MRI 评估和针对 AS 的定向前列腺活检的男性进展的总体速率和时间分布。目标 2. 建立 MP-MRI 栖息地并使用 MP-MRI 特征的放射组学分析来开发与不良组织病理学参数和患者进展相关的特征。目标 3. 对获得的 MP-MRI 指导的前列腺活检进行分子表征，开发惰性前列腺癌与侵袭性前列腺癌的基因表达特征，并将该信息与放射组学衍生的特征相关联。我们建议定量 MP-MRI 参数将代表组织病理学和分子参数，并成为确定进展风险的重要辅助手段，从而降低不必要的活检率。