Department of Epidemiology & Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York.
Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.
Cancer Prev Res (Phila). 2019 Sep;12(9):599-608. doi: 10.1158/1940-6207.CAPR-18-0272. Epub 2019 Jul 23.
Germline mutations in are risk factors for pancreatic ductal adenocarcinoma (PDAC). The aim of this study was to evaluate whether results of surveillance for PDAC in high risk individuals (HRI) differ between those with and without a pathogenic mutation. This prospective study was conducted within the Pancreatic Tumor Registry at a major cancer center. There were 83 HRIs with ≥1 first-degree relative with PDAC who underwent surveillance and testing for pathogenic germline mutations in A secondary analysis includes 18 HRIs with known mutations in but with weaker family history. HRIs were evaluated over time using magnetic resonance cholangiopancreatography (MRCP) and endoscopic ultrasound when indicated by MRCP findings. We reviewed imaging results, blinded to mutation status. Demographic information was obtained from interviewer-administered questionnaires. The outcome was the proportion with any pancreatic abnormality identified at initial or follow-up surveillance. Among the 83 HRIs in the main analysis, 48 had a mutation in and 35 did not. Overall, 16 of 48 (33%) -positive and 13 of 35 (37%) -negative participants had pancreatic abnormalities on imaging; in each group, all but one finding was an intraductal papillary mucinous neoplasm. Among those with pathogenic mutations but weaker family history, results were similar: 7 of 18 (39%) with pancreatic abnormalities. Results of surveillance for pancreatic abnormalities on imaging are similar regardless of mutation status. While the results from this small study need confirmation in other studies, at present there does not appear to be increased yield from targeting individuals with mutations for surveillance.
胚系突变是胰腺导管腺癌（PDAC）的危险因素。本研究旨在评估高危个体（HRI）中 PDAC 监测结果是否因有无致病性突变而不同。这项前瞻性研究在一家主要癌症中心的胰腺肿瘤登记处进行。有 83 名 HRI，其≥1 名一级亲属患有 PDAC，他们接受了监测和种系突变的检测，以确定是否存在致病性突变。次要分析包括 18 名具有已知突变的 HRI，但家族史较弱。根据 MRCP 结果，当需要时，通过磁共振胆胰管成像（MRCP）和内镜超声对 HRI 进行评估。我们回顾了成像结果，对突变状态进行了盲法评估。从访谈者管理的问卷中获得了人口统计学信息。结果是在初始或随访监测中确定任何胰腺异常的比例。在主要分析的 83 名 HRI 中，48 名有突变，35 名没有。总的来说，48 名突变阳性的 HRI 中有 16 名（33%）和 35 名突变阴性的 HRI 中有 13 名（37%）在影像学上有胰腺异常；在每组中，除了一个发现外，所有的都是导管内乳头状黏液性肿瘤。在具有致病性突变但家族史较弱的患者中，结果相似：18 名中有 7 名（39%）有胰腺异常。无论是否存在突变，影像学监测胰腺异常的结果相似。虽然这项小型研究的结果需要在其他研究中得到证实，但目前似乎没有增加针对具有突变的个体进行监测的收益。
