MRI Imaging and Genetic Signatures to Manage Prostate Cancer Overdiagnosis

描述(由申请者提供)：我们建议对积极监测(AS)的候选患者进行研究，以确定区分惰性前列腺癌和侵袭性前列腺癌的成像和基因表达特征，并更好地了解进展的机制。我们将应用新的磁共振成像技术(I)定量多参数磁共振成像(MP-MRI)结果来定义前列腺内的“栖息地”；(Ii)引导前列腺活检以MP-MRI定义的病变并确定与栖息地的组织病理学关联；(Iii)基于对成像特征的高通量分析来开发签名(放射组学)；(Iv)将活检寡核苷酸基因表达签名与成像签名相关联(放射基因组学)；以及(V)建立融合临床、组织病理学、成像签名和基因表达签名的进展模型(转化为治疗)。前列腺癌患者的第二阶段AS试验旨在每年收集MP-MRI、前列腺组织和生物液，以与MP-MRI的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和侵袭性疾病，从而减少过度诊断的影响。具体目标是：目的1.评估接受MP-MRI评估并在前瞻性II期试验中对AS进行定向前列腺活检的男性的总体进展率和时间分布。目的2.建立MP-MRI环境，并利用MP-MRI特征的放射组学分析，开发与不良组织病理学参数和患者进展相关的征象。目的3.对MP-MRI引导的前列腺癌活检标本进行分子表征，建立惰性前列腺癌和侵袭性前列腺癌的基因表达特征，并将该信息与放射组学的特征相关联。我们认为，定量的MP-MRI参数将代表组织病理学和分子参数，并作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。

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.