Lenaerts Liesbeth, Brison Nathalie, Maggen Charlotte, Vancoillie Leen, Che Huiwen, Vandenberghe Peter, Dierickx Daan, Michaux Lucienne, Dewaele Barbara, Neven Patrick, Floris Giuseppe, Tousseyn Thomas, Lannoo Lore, Jatsenko Tatjana, Bempt Isabelle Vanden, Van Calsteren Kristel, Vandecaveye Vincent, Dehaspe Luc, Devriendt Koenraad, Legius Eric, Bogaert Kris Van Den, Vermeesch Joris Robert, Amant Frédéric
Department of Oncology, KU Leuven, Herestraat 49, Leuven, Belgium.
Center for Human Genetics, University Hospitals Leuven, Herestraat 49, Leuven, Belgium.
EClinicalMedicine. 2021 May 13;35:100856. doi: 10.1016/j.eclinm.2021.100856. eCollection 2021 May.
Implausible false positive results in non-invasive prenatal testing (NIPT) have been occasionally associated with the detection of occult maternal malignancies. Hence, there is a need for approaches allowing accurate prediction of whether the NIPT result is pointing to an underlying malignancy, as well as for organized programs ensuring efficient downstream clinical management of these cases.
Using a data set of 88,294 NIPT performed at University Hospital Leuven (Belgium) between November 2013 and March 2020, we retrospectively evaluated the positive predictive value (PPV) of our NIPT approach for cancer detection. In this approach, whole-genome cell-free DNA (cfDNA) data from NIPT were scrutinized for the presence of (sub)chromosomal copy number alterations (CNAs) predictive for a malignancy, using an unbiased NIPT analysis pipeline coined GIPSeq. For suspected cases, the presence of a maternal cancer was evaluated via subsequent multidisciplinary clinical follow-up examinations. The cancer-specificity of the identified CNAs in cfDNA was assessed through genetic analyses of a tumor biopsy.
Fifteen women without a cancer history were identified with a GIPSeq result suggestive of a malignant process. Their cfDNA profiles showed either genome-wide aberrations or a single trisomy 8. Upon clinical examinations, a solid or hematological cancer was identified in 4 and 7 cases, respectively. Three women were identified as having a clonal mosaicism. For one case no underlying condition was found. These numbers add to a PPV of 73%. Based on this experience, we presented a multidisciplinary care path for efficient clinical management of these cases.
The presented approach for analysing NIPT results has a high PPV, yet unknown sensitivity, for detecting asymptomatic malignancies upon routine NIPT. Given the complexity of diagnosing a pregnant woman with cancer, clinical follow-up should occur in a well-designed multidisciplinary setting, such as via the care model that we presented here.
This work was supported by Research Foundation Flanders and KU Leuven funding.
无创产前检测（NIPT）中出现的难以置信的假阳性结果偶尔与隐匿性母体恶性肿瘤的检测有关。因此，需要能够准确预测NIPT结果是否指向潜在恶性肿瘤的方法，以及需要有组织的项目来确保对这些病例进行有效的下游临床管理。
我们使用2013年11月至2020年3月在比利时鲁汶大学医院进行的88294例NIPT数据集，回顾性评估了我们的NIPT方法对癌症检测的阳性预测值（PPV）。在这种方法中，使用一种名为GIPSeq的无偏NIPT分析流程，对NIPT的全基因组游离DNA（cfDNA）数据进行仔细检查，以寻找预测恶性肿瘤的（亚）染色体拷贝数改变（CNA）。对于疑似病例，通过后续的多学科临床随访检查来评估母体癌症的存在。通过对肿瘤活检的基因分析来评估cfDNA中鉴定出的CNA的癌症特异性。
15名无癌症病史的女性被鉴定为GIPSeq结果提示存在恶性过程。她们的cfDNA谱显示全基因组畸变或单一的8号染色体三体。经临床检查，分别在4例和7例中发现实体癌或血液系统癌症。3名女性被鉴定为具有克隆性镶嵌现象。1例未发现潜在疾病。这些数字使PPV达到73%。基于这一经验，我们提出了一种多学科护理路径，用于对这些病例进行有效的临床管理。
所提出的分析NIPT结果的方法在常规NIPT中检测无症状恶性肿瘤时具有较高的PPV，但灵敏度未知。鉴于诊断孕妇癌症的复杂性，临床随访应在精心设计的多学科环境中进行，例如通过我们在此提出的护理模式。
这项工作得到了弗拉芒研究基金会和鲁汶大学的资助。
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