Prospective randomized comparison of digital breast tomosynthesis plus synthesized images versus standard full-field digital mammography (TOSYMA)

数字乳腺断层合成加合成图像与标准全视野数字乳腺 X 线摄影 (TOSYMA) 的前瞻性随机比较

• 批准号: 286538777
• 负责人: Professor Dr. Walter Heindel
• 金额: --
• 依托单位: Klinik für Radiologie
• 依托单位国家: 德国
• 项目类别: Clinical Trials
• 财政年份: 2016
• 资助国家: 德国
• 起止时间: 2015-12-31 至 2022-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/286538777?language=en
• 关键词: Prospective; randomized; comparison; digital; breast

The randomised controlled TOSYMA study examines the hypothesis that the combination of Digital Breast Tomosynthesis (DBT) and synthesised 2D mammograms leads to a clinically relevant increase in the screening detection rate of invasive breast cancer compared to the standard, digital 2D mammography.However, the expected increase in cancer detection caused by DBT could also be due to overdiagnosis. For this reason, it is important to assess whether the use of DBT not only increases cancer detection but also reduces the occurrence of interval cancers.To balance the potential benefit of DBT in terms of raised cancer detection against the potential for overdiagnosis, two primary endpoints have been defined in the study protocol: the detection rate of invasive breast cancers and the cumulative 24-month incidence of invasive interval cancers. A hierarchical test procedure will be applied to account for multiplicity, evaluating the detection rate in the first and the interval cancer rate in the second place of the sequence of hierarchically ordered hypotheses. The pre-defined order of hypotheses corresponds to the natural hierarchy in the medical context: the issue of a reduction in the interval cancer rate is only raised in the case of increased cancer detection. According to the pre-defined order of hypotheses and the primary objective of the study in the planning phase, the initial sample size calculation was based solely on the first primary endpoint (detection rate). However, as the investigation of interval cancers to assess the impact of potential overdiagnosis caused by tomosynthesis has gained increasing national and international attention, it seems most important to achieve a reasonable statistical power for the evaluation of both primary endpoints. This requires an increase of the initially calculated sample size of 80,000 to 120,000 women.The revised sample size calculation takes into account both, the detection rate and the interval cancer rate. It was carried out without knowledge of the data from the currently recruiting TOSYMA study, i.e. all planning assumptions are based on external data that do not belong to ongoing study. The assumptions regarding the first primary endpoint - on which the initial calculation was based - have been updated and revised in accordance with data that became accessible in the meantime. The multiple significance level of 5% is still maintained.The intended sample size increase offers the unique potential to evaluate both primary hypotheses and may help to provide currently universally lacking insights into the effectiveness of breast cancer detection with tomosynthesis. A sample size increase is much more efficient than designing a new confirmatory trial for the assessment of interval cancer rates.

随机对照 TOSYMA 研究检验了这样的假设：与标准数字 2D 乳房 X 光检查相比，数字乳房断层合成 (DBT) 和合成 2D 乳房 X 光检查的结合可导致浸润性乳腺癌筛查检出率临床相关性增加。然而，DBT 导致的癌症检出率预期增加也可能是由于过度诊断所致。因此，评估 DBT 的使用是否不仅可以提高癌症检出率，还可以减少间期癌症的发生率，这一点非常重要。为了平衡 DBT 在提高癌症检出率方面的潜在益处与过度诊断的可能性，研究方案中定义了两个主要终点：浸润性乳腺癌的检出率和浸润性间期癌症的 24 个月累积发病率。将应用分层测试程序来考虑多重性，评估分层排序假设序列中第一个的检出率和第二个位置的间隔癌症率。预先定义的假设顺序对应于医学背景中的自然层次结构：只有在癌症检测增加的情况下才会提出间隔癌症发生率降低的问题。根据计划阶段预先定义的假设顺序和研究的主要目标，初始样本量的计算仅基于第一个主要终点（检出率）。然而，随着对间期癌症进行调查以评估断层合成引起的潜在过度诊断的影响，已获得越来越多的国家和国际关注，为评估两个主要终点获得合理的统计功效似乎是最重要的。这需要将最初计算的样本量增加到 80,000 至 120,000 名女性。修订后的样本量计算同时考虑了检出率和间隔癌症率。该研究是在不了解当前招募的 TOSYMA 研究数据的情况下进行的，即所有计划假设均基于不属于正在进行的研究的外部数据。关于第一个主要终点的假设（初始计算所依据的）已根据同时获得的数据进行了更新和修订。 5% 的多重显着性水平仍保持不变。预期样本量的增加为评估这两个主要假设提供了独特的潜力，并可能有助于提供目前普遍缺乏的关于断层合成乳腺癌检测有效性的见解。增加样本量比设计新的验证性试验来评估间期癌症发生率要有效得多。