Natural history and evaluation of abnormal or nonreportable NIPT results and its association with maternal neoplasia

这项研究的首字母缩写是识别研究：通过非侵入性细胞游离DNA分析偶然检测母体肿瘤。在NIH IRB最终批准本方案后，第一名IDENTIFY研究参与者于2019年12月入组。招聘工作虽然最初受到COVID疫情影响，但仍属可接受。参与者在临床中心接受初步评估，以诊断可能的肿瘤。所有收集的临床、实验室和影像学信息在每月的多学科小组会议上进行讨论。如果发现肿瘤，结果将与参与者和转诊医生共享，并可采取行动。参与者将在产后几年内接受随访，以收集所有可用的医疗信息。 到目前为止，我们已经观察到参与者异常或不可报告的NIPT结果的各种生物学解释，包括局限性胎盘镶嵌，克隆性造血，良性子宫平滑肌瘤和恶性肿瘤。患有癌症的参与者被诊断患有一系列肿瘤类型和阶段。 除了完成临床评估以诊断可能的肿瘤外，参与者还进行定性访谈，以帮助我们了解接受NIPT结果提示母体恶性肿瘤的个人影响，并提供临床评估以检测妊娠期间可能的癌症。在访问NIH之前和了解临床评估结果之后，对个人进行访谈。我们在蒙特利尔举行的国际产前诊断学会会议（2022年6月）上以海报和闪电交流（5分钟谈话）的形式介绍了我们的初步研究结果。我们的海报接收产前筛查结果暗示产妇癌症：在美国国立卫生研究院确定研究并列最佳海报奖参与者的定性探索。 征聘方面持续存在的挑战包括潜在参与者不愿意旅行，虚假地保证医疗建议，以及虚假地保证当地提供者、肿瘤学家、产科医生和护士助产士提供的不完整的检查，从而阻止进一步的后续行动。我们继续通过地方，国家和国际演讲与关键利益相关者接触，以建立参与者招募来源，并强调当NIPT结果提示母体恶性肿瘤时及时和全面临床评估的重要性。这也是我们在《临床肿瘤学杂志》上发表的一篇社论的主题，该社论强调了在美国对接受恶性肿瘤可疑NIPT结果的孕妇实施协调诊断和治疗计划的障碍。

The acronym for this study is the IDENTIFY Study: Incidental DEtection of maternal Neoplasia Through non-Invasive cell Free DNA analYsis. Following final NIH IRB approval of this protocol, the first IDENTIFY study participant enrolled in December 2019. Recruitment, although initially impacted by the COVID pandemic, has been acceptable. Participants undergo an initial evaluation at the Clinical Center to diagnose possible neoplasia. All collected clinical, laboratory and imaging information is discussed in monthly multidisciplinary team meetings. If neoplasia is discovered, results are shared with participants and referring physicians and are actionable. Participants will be followed for several years post-partum to collect all available medical information. To date, we have observed a variety of biological explanations for participants abnormal or non-reportable NIPT results, including confined placental mosaicism, clonal hematopoiesis, benign uterine leiomyomas, and malignant neoplasms. Participants with cancer have been diagnosed with a range of tumor types and stages. In addition to completing a clinical evaluation to diagnose possible neoplasia, participants engage in qualitative interviews to help us understand the personal impact of receiving NIPT results suggestive of maternal malignancy and being offered a clinical evaluation to detect possible cancer during pregnancy. Individuals are interviewed before their visit to the NIH and after they have learned the results of their clinical evaluations. We presented our preliminary findings as a poster and Lightning Communication (5-minute talk) at the International Society for Prenatal Diagnosis Conference in Montreal (June 2022). Our poster Receiving Prenatal Screening Results Suggestive of Maternal Cancer: A Qualitative Exploration of Participants in the NIH Identify Study tied for the Best Poster Award. Ongoing challenges to recruitment include prospective participants reluctance to travel, falsely reassuring medical advice and falsely reassuring incomplete workups provided by local providers, oncologists, obstetricians and nurse-midwives that prevented further follow-up. We continue to reach out to key stakeholders through local, national and international presentations to establish sources of participant recruitment and to emphasize the importance of a timely and thorough clinical evaluation when NIPT results are suggestive of maternal malignancy. This was also the topic of an editorial we published in the Journal of Clinical Oncology that highlights the barriers to implementing a coordinated diagnostic and treatment plan for pregnant women who receive malignancy suspicious NIPT results in the United States.