Zhang Yuqi, Esmail Abdullah, Hassanain Hala, Dhillon Vikramjit, Abdelrahim Waseem, Al-Najjar Ebtesam, Khasawneh Bayan, Abdelrahim Maen
Section of GI Oncology, Houston Methodist Neal Cancer Center, Houston Methodist Hospital, Houston, TX 77094, USA.
Michael E. DeBakey HS for Health Professions, Houston, TX 77030, USA.
Biomedicines. 2025 May 6;13(5):1124. doi: 10.3390/biomedicines13051124.
Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer with poor prognosis due to late-stage diagnosis, limited surgical resectability, and frequent recurrence. Traditional biomarkers like CA19-9 and imaging techniques often fail to detect minimal residual disease (MRD) or early recurrence. Circulating tumor DNA (ctDNA) is a promising non-invasive biomarker that may provide early detection of disease recurrence, offering a potential improvement in patient management. This study aimed to assess the utility of ctDNA as a prognostic tool for PDAC patients, specifically in predicting recurrence and overall survival (OS). This retrospective study analyzed data from 39 PDAC patients who underwent surgery and were monitored for ctDNA levels using Signatera™, a tumor-informed multiplex PCR next-generation sequencing assay. Blood samples were collected both preoperatively and postoperatively, and ctDNA levels were measured to detect MRD. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of ctDNA were compared with CA19-9 in detecting disease recurrence. Clinical outcomes, including progression-free survival (PFS) and OS, were evaluated in relation to ctDNA status. Among 39 patients, 153 plasma samples were analyzed, with 17 patients testing positive for ctDNA. Sensitivity of ctDNA in detecting relapse was 91%, compared to 83% for CA19-9, with combined testing reaching 98% sensitivity. ctDNA positivity was associated with significantly shorter OS and PFS, with patients testing negative for ctDNA having a median OS of 37.6 months versus 13.4 months in ctDNA-positive patients ( = 0.003). The median time from ctDNA positivity to imaging-confirmed relapse was 81 days. Positive ctDNA was also linked to higher rates of lymphovascular invasion and positive surgical margins, highlighting the aggressive nature of the disease in these patients. CtDNA is a highly sensitive and specific biomarker for detecting MRD and predicting recurrence in PDAC patients, offering superior performance over CA19-9. Positive ctDNA results were associated with worse prognosis, including shorter OS and PFS, and may help guide treatment decisions. These findings suggest that ctDNA could be a valuable tool for personalized management in PDAC, though further prospective studies are needed to validate its clinical role in treatment stratification.
胰腺导管腺癌（PDAC）是一种侵袭性很强的癌症，由于诊断较晚、手术可切除性有限以及频繁复发，其预后较差。像CA19-9这样的传统生物标志物和成像技术常常无法检测到微小残留疾病（MRD）或早期复发。循环肿瘤DNA（ctDNA）是一种很有前景的非侵入性生物标志物，可能能够早期检测疾病复发，为患者管理带来潜在改善。本研究旨在评估ctDNA作为PDAC患者预后工具的效用，特别是在预测复发和总生存期（OS）方面。这项回顾性研究分析了39例接受手术的PDAC患者的数据，并使用Signatera™（一种肿瘤知情多重PCR下一代测序检测方法）监测ctDNA水平。术前和术后均采集血样，并测量ctDNA水平以检测MRD。在检测疾病复发方面，将ctDNA的敏感性、特异性、阳性预测值（PPV）和阴性预测值（NPV）与CA19-9进行了比较。根据ctDNA状态评估了包括无进展生存期（PFS）和OS在内的临床结局。在39例患者中，分析了153份血浆样本，其中17例患者ctDNA检测呈阳性。ctDNA检测复发的敏感性为91%，而CA19-9为83%，联合检测的敏感性达到98%。ctDNA阳性与明显更短的OS和PFS相关，ctDNA检测阴性的患者中位OS为37.6个月，而ctDNA阳性患者为13.4个月（P = 0.003）。从ctDNA阳性到影像学确认复发的中位时间为81天。ctDNA阳性还与更高的淋巴管侵犯率和手术切缘阳性相关，突出了这些患者疾病的侵袭性。CtDNA是检测PDAC患者MRD和预测复发的一种高度敏感和特异的生物标志物，其性能优于CA19-9。ctDNA阳性结果与更差的预后相关，包括更短的OS和PFS，可能有助于指导治疗决策。这些发现表明，ctDNA可能是PDAC个性化管理的一种有价值的工具，不过还需要进一步的前瞻性研究来验证其在治疗分层中的临床作用。
