MRI Imaging and Genetic Signatures to Manage Prostate Cancer Overdiagnosis

描述（由申请人提供）：我们建议研究主动监测（AS）的候选患者，以识别区分惰性前列腺癌和侵袭性前列腺癌的影像学和基因表达特征，并更好地了解潜在的进展机制。我们将应用新的MRI技术(1)定量多参数MRI （MP-MRI）结果来定义前列腺内的“栖息地”；（ii）指导前列腺活检确定MP-MRI定义的病变，并确定与栖息地的组织病理学关联；（iii）开发基于高通量成像特征分析的签名（放射组学）；（iv）将活检寡核苷酸基因表达特征联系起来，以告知与成像特征相关的分子特征（放射基因组学）；(v)建立包括临床、组织病理学、影像学特征和基因表达特征的进展模型（转化为治疗）。一项针对前列腺癌患者的II期AS试验旨在每年获得MP-MRI、前列腺组织和生物体液，以与MP-MRI结果和主要进展终点相关。我们提出的技术有可能更好地识别惰性与侵袭性疾病，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期临床试验中，评估接受MP-MRI评估和定向前列腺活检的男性AS的总体进展率和时间分布。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。分子表征获得的mp - mri定向前列腺活检，开发惰性前列腺癌与侵袭性前列腺癌的基因表达特征，并将此信息与放射组学衍生的特征联系起来。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，从而减少不必要的活检率。

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.