Reducing false positives during interpretations of ultrasound examinations for breast cancer screening

 描述(申请人提供)：每年筛查早期发现乳腺癌是一种被广泛接受的做法，但在美国仍然存在争议，因为归因于“收益”和“成本”都被不断地审查。一个主要的担忧是大量的假阳性解释和大量的良性活检正在进行。在美国，每年大约有500万名女性被召回进行诊断检查，但只有大约每20人中就有一人被发现患有癌症。目前对未发现高危女性的做法包括全场数字乳房X光摄影(FFDM)和数字乳房断层摄影(DBT)。这两种方法都需要电离辐射，在检测浸润性癌症方面并不是最佳的灵敏度，特别是在乳房致密的女性中，约占所有筛查女性的40%-45%。全乳房超声(WBUS)，无论是手持还是自动，不需要辐射暴露，对发现早期浸润性癌症明显更敏感，但在今天的实践中，也会导致更高的假阳性率(~1.5倍)。尽管我们多次尝试降低所有医疗模式的召回率，但基本上都失败了。许多问题可能源于这样一个事实，即没有对口译放射科医生的参考信息(例如，对于阴性病例或“第二意见”，“CAD”)会提高他/她对什么是“不能回忆”的信心。欧洲人通过在达成共识的情况下进行双重阅读来解决假阳性问题，这会导致两名读者中的一人最初获得阳性分数的回忆考试减少约50%。越大 单个阅读器的假阳性率越大，观察者间的变异性越大，降低的幅度就越大。然而，这种做法在美国操作上并不可行。因此，我们建议评估一种简单、经济、改进的方法是否会在超声检查的解释过程中影响放射科医生。为了测试我们的概念，我们建议最初执行两种模式的完全平衡的回溯性观察者研究，在该研究中，经验丰富的放射科医生将解释在临床上实际召回的致密乳房(密度BIRAD 3或4，更有可能被召回)女性的WBUS检查(确诊的癌症为阳性和阴性)。在第二阅读模式中，解释放射科医生将被给予独立的第二意见结果，这些结果来自于“低回忆”放射科医生。到目前为止，这种类型的可能的干预还没有被调查过，很容易证明这种方法是“经济有效的”(专业努力)，并可能导致WBUS召回率的显著降低，同时保持癌症的检测率。因此，我们建议回顾检验这一假设，即在这种方法下，筛查超声检查被召回的可能性在统计学上显著降低，因此也不太可能被建议接受良性活检，而无论口译放射科医生的潜在表现水平如何。我们的主要假设是，这种方法将导致召回率至少降低20%，而在癌症检测方面没有(或最坏情况下是最小的)损失。

 DESCRIPTION (provided by applicant): Annual screening for the early detection of breast cancer is a widely accepted practice, but it remains controversial in the United States in that both the attributable "benefit" and "cost" are continually scrutinized. One primary concern is the high number of false positive interpretations and the large number of benign biopsies being performed. There are approximately five million women being recalled for diagnostic workup in the United States each year and only approximately one in 20 are found to have cancer. Current practices for women not known to be at high risk include full field digital mammography (FFDM) and digital breast tomosynthesis (DBT). Both practices require ionizing radiation and are not optimal in terms of sensitivity for detecting invasive cancers, particularly in women with dense breasts constituting approximately 40%-45% of all screened women. Whole breast ultrasound (WBUS), whether hand held or automated, does not require radiation exposure and is significantly more sensitive to finding early invasive cancers, but also results, in today's practie, in even a higher false positive rate (~1.5X). Despite many attempts to reduce recall rates of all modalities, we have largely failed. Much of the problem may stem from the fact that there is no reference information to the interpreting radiologist (e.g., "CAD" for negative cases or a "second opinion") that would raise his/her confidence in what "not to recall". The Europeans address false positives by practicing double reading with consensus that results in approximately a 50% reduction in recalling examinations initially scored positive by one of the two readers. The larger the single reader false positive rate is and the larger the inter- observer variability, the largerthe reduction. However, this practice is not operationally feasible in the United States. Therefore, we propose to assess if a simple, cost effective, modified approach would affect radiologists during interpretations of ultrasound examinations. To test our concept, we propose to initially perform a two mode fully balanced retrospective observer study in which experienced radiologists will interpret WBUS examinations of women with dense breasts (density BIRADS 3 or 4 who are more likely to be recalled) that had been actually recalled in the clinic (positive an negative for verified cancers). In a second reading mode, the interpreting radiologists will be given independent second opinion results from "low recalling" radiologists. To date, this type of a possible intervention has not been investigated and it is easy to demonstrate that this approach is "cost effective" (professional effort) and could lead to a significant reduction in WBUS recall rates while maintaining cancer detection rates. Hence, we propose to retrospectively test the hypothesis that under this approach screening ultrasound examinations will be statistically significantly less likely to be recalled and thereby also less likely to be recommended to undergo benign biopsies, regardless of the underlying performance levels of the interpreting radiologists in question. Our primary hypothesis is that this approach, will resul in at least a 20% reduction in recall rates with no (or at worst a minimal) loss in cancer detection.