MRI Radiomic Signatures of DCIS to Optimize Treatment

摘要/项目总结：本研究的目的是确定乳腺MRI放射组学特征是否 可用于优化导管原位癌（DCIS）（乳腺癌的最早形式）的治疗 诊断。尽管DCIS的生存率接近100%，但人们担心其管理通常 导致过度治疗，使每年诊断的50，000名美国妇女中的许多人遭受不必要的治疗。 焦虑和发病率。绝大多数DCIS是在无症状的女性中发现的， 在乳房X线照相术上识别钙化，并使用有限的组织病理学来表征钙化。 不幸的是，传统的影像学和病理学还没有被证明是可靠的区分低与高风险 DCIS。具体而言，在诊断时尚不清楚哪种形式的DCIS将升级为侵袭性疾病或具有 治疗后同侧乳房复发（IBR）。这种有限的风险分层部分是由于 整个DCIS病变的取样和不能解释瘤周微环境特征。这 导致多达一半的妇女接受不必要的手术、放射治疗和药物治疗。 诊断为DCIS。乳腺MRI是一种常见且容易进行的检查，能够最好地描述DCIS的范围， 评估肿瘤和肿瘤周围的异质性植根于生物学特征，如血管生成，使其成为一个 放射组学检测的一个有吸引力的选择，以改善DCIS风险评估。乳腺定量成像 华盛顿大学的实验室已经表明，定量MRI特征与DCIS等级相关， 复发的分子标志物（Oncotype DX DCIS评分）和IBR。计算生物标志物成像 宾夕法尼亚大学的一个研究小组开创了乳腺MRI放射组学表型分析的先河， 乳腺癌的测量与基因组特征和复发相关。统计中心 布朗大学的科学部拥有放射组学、机器学习和统计分析方面的专业知识， 来自ECOG-ACRIN的影像学试验。在这项合作应用中，我们假设乳腺MRI放射组学 DCIS的特征将导致不同的表型，这些表型是预后的，并且可以与 临床、分子和病理标志物，以优化DCIS治疗。为了验证这个假设，我们将 创建一个包含1400多个MRI的多机构数据库，包括来自ECOG-ACRIN E4112试验的检查， 具有策划的结果（例如，侵袭的升级、DCIS评分和IBR）。利用一种新颖的方法， 协调多中心数据（嵌套战斗放射性特征标准化），我们将发现和验证 MRI放射组学表型，并评估这些表型与侵袭性升级，Oncotype DX DCIS评分以及5年和10年IBR。最后，我们将确定这些表型是否整合到 现有的临床预后指标（例如，范奈斯预后指数）可以提供更精确的估计 IBR。如果成功，这项研究将帮助临床医生降低低风险患者的DCIS治疗，并解决 重要的公共卫生目标：减少乳腺癌过度治疗。

Abstract/Project Summary: The purpose of this study is to determine whether breast MRI radiomic features can be utilized to optimize treatment of ductal carcinoma in situ (DCIS), the earliest form of breast cancer diagnosed. Although DCIS survival rates approach 100%, there is concern that its management generally results in overtreatment, exposing many of the 50,000 U.S. women diagnosed each year to unnecessary anxiety and morbidity. The vast majority of DCIS is detected in asymptomatic women in whom suspicious calcifications are identified on mammography and characterized using limited tissue histopathology. Unfortunately, conventional imaging and pathology have not proven reliable for distinguishing low vs. high-risk DCIS. Specifically, it is unclear at diagnosis which forms of DCIS will upstage to invasive disease or have an ipsilateral breast recurrence (IBR) after treatment. This limited risk-stratification is due in part to inadequate sampling of the entire DCIS lesion and an inability to account for peritumoral microenvironment features. This results in unnecessary surgery, radiation therapy, and medical therapy for as many as half of women diagnosed with DCIS. Breast MRI is commonly and easily performed, able to best depict DCIS span, and can assess tumor and peritumoral heterogeneity rooted in biological features such as angiogenesis, making it an appealing choice for a radiomics assay to improve DCIS risk assessments. The Quantitative Breast Imaging Lab at the University of Washington has shown that quantitative MRI features are associated with DCIS grade, a molecular marker of recurrence (Oncotype DX DCIS Score), and IBR. The Computational Biomarker Imaging Group at the University of Pennsylvania has pioneered breast MRI radiomic phenotyping and shown radiomic measures of breast cancers correlate with genomic features and recurrence. The Center for Statistical Sciences at Brown University has expertise with radiomics, machine learning, and statistical analyses for imaging trials from ECOG-ACRIN. In this collaborative application, we hypothesize that breast MRI radiomic signatures of DCIS will result in distinct phenotypes that are prognostic and can be integrated with clinical, molecular, and pathologic markers to optimize DCIS treatment. To test this hypothesis, we will create a multi-institutional database of over 1400 MRIs, including exams from the ECOG-ACRIN E4112 trial, with curated outcomes (e.g., upstage to invasion, DCIS Score, and IBR). Leveraging a novel approach to harmonize multicenter data (nested-Combat radiomic feature standardization), we will discover and validate MRI radiomic phenotypes and assess those phenotypes’ associations with invasive upstaging, Oncotype DX DCIS Score, and 5- and 10-year IBR. Finally, we will determine whether integration of these phenotypes into existing clinical prognostic indices (e.g., Van Nuys Prognostic Index) can provide more precise estimates of IBR. If successful, this study will help clinicians de-escalate DCIS therapy in low-risk patients and address an important public health goal: decreasing breast cancer overtreatment.