Contrast Enhanced Mammography (CEM) to Reduce Biopsy Rates for Less Than Highly Suspicious Breast Abnormalities: a Prospective Study

摘要 关于当前乳腺癌检测和诊断的主要关注点是大量的良性肿瘤。 正在进行活检。在美国，放射科医生每年都会召回超过500万名女性， 诊断检查和进行超过一百万次乳腺活检，只有不到四分之一的人被诊断为 癌新的BI-RADS 4子集评估类别4A/B/C为以下方面提供了新的定制方法： 在不同的情况下，基于“风险”的决定。在该分类方案中，评定为4A的病变具有 恶性肿瘤的预期概率大于2%，最高可达10%，被评定为4 B的患者的概率为 恶性肿瘤超过10%，高达50%。最近发表的评价阳性预测值（PPV 3）的文献 美国放射学会（ACR）国家乳腺X线检查中收集的125，447项诊断检查 数据库（NMD）显示，88%的活检是在BI-RADS 4A和4 B病变上进行的。因此，在本发明中， 有机会确定新的方法来更准确地对这些低概率病变进行更好的分类， 以改善PPV 3，并减少每年数十万妇女的实际良性结果的活检。 我们相信，一个操作简单，成本效益，对比增强乳腺X线检查（CEM），执行 在病人的诊断评估，将是最好的方法，以提高准确性的放射科医生的 决定是否需要对乳腺X线摄影、断层合成（DBT）或US分类为4A或4 B的病变进行活检。 CEM使用碘造影剂和低KeV和高KeV乳房X线摄影图像来增强对比度 直接覆盖乳房X线照片的乳房图，从而提供解剖学和动力学信息， 类似于MRI。我们在一项初步的临床试验中发现，放射科医生的真阳性率较高， CEM活检建议的假阳性率高于DBT和US。验证这些 初步研究结果，我们建议前瞻性和顺序进行CEM的1855同意妇女与BI- 乳腺X线摄影、DBT或US检测到RADS 4A或4 B病变。专业放射科医生将提供BI- 单独使用DBT，然后使用US，最后使用CEM对每个病变进行RADS评级。病理学已知， 基于研究设计，以最大限度地减少放射科医生的潜在偏倚，我们计划估计NPV水平 的基于CEM的建议（总体和常规确认活检的病例中 建议），并证明它是足够高的，同时导致实质性减少活检 良性病变的建议。我们的主要期望是， 活检良性病变将显着下降（~20%），而保持高NPV（>95%）之间的 初步建议。使用前瞻性收集的验证案例子集，我们将进行多- 阅片人（MRMC）研究，以评估放射科医师之间CEM效应的异质性，获得可推广的结果， 并通过病变特征阐明补充的特定CEM性能。

Abstract A primary concern regarding current breast cancer detection and diagnosis is the large number of benign biopsies being performed. Annually in the United States, radiologists recall over five million women for diagnostic workup and perform over one million breast biopsies, with fewer than one in four diagnosed as cancer. The new BI-RADS 4 subset assessment categories of 4A/B/C enables new tailored approaches for “risk” based decisions in different subsets of cases. In this classification scheme, lesions rated as 4A have an expected probability of malignancy more than 2% and up to 10% and those rated as 4B have a probability of malignancy more than 10% and up to 50%. A recent publication evaluating the positive predictive value (PPV3) for 125,447 diagnostic exams collected in the American College of Radiology (ACR) National Mammography Database (NMD) demonstrated that 88% of biopsies were performed on BI-RADS 4A and 4B lesions. Thus, opportunity exists to identify novel ways to better classify these low probability lesions more accurately in order to improve PPV3 and reduce biopsy of actually benign findings for hundreds of thousands of women annually. We believe that an operationally simple, cost effective, contrast enhanced mammogram (CEM), performed during the patient's diagnostic evaluation, would be the best approach to improve accuracy of radiologists' decisions for need to biopsy lesions classified with mammography, tomosynthesis (DBT) or US as 4A or 4B. CEM uses iodine contrast with dual low and high KeV mammogram images to create a contrast enhancement map of the breast that directly overlays the mammogram, thus providing anatomic and kinetic information, similar to MRI. We found in a preliminary clinical trial that radiologists had higher true-positive rates and lower false-positive rates for biopsy recommendation with CEM than when using DBT and US. To validate those initial findings, we propose to prospectively and sequentially perform CEM on 1855 consenting women with BI- RADS 4A or 4B lesions detected on mammography, DBT or US. Prospectively radiologists will provide BI- RADS ratings for every lesion using DBT alone, then with US and finally with CEM. With pathology known and based on the study design to minimize case by radiologist potential biases, we plan to estimate the NPV level of CEM-based recommendations (overall and within the cases with conventionally confirmed biopsy recommendation) and demonstrate that it is sufficiently high, while leading to substantial reduction in biopsy recommendations for actually benign lesions. Our primary expectation is that the number of recommendations to biopsy benign lesions will decrease significantly (~20%), while maintaining high NPV (>95%) among the initial recommendations. Using a subset of prospectively collected verified cases we will conduct a multi- reader (MRMC) study to assess heterogeneity of CEM effects across radiologists, obtain generalizable results, and elucidate supplemental specific CEM performance by lesion characteristics.