Table 1_Personalized tumor-informed circulating tumor DNA monitoring for early detection of recurrence in postoperative pancreatic cancer.xlsx

BackgroundUp to 80% of patients with resected pancreatic cancer experience recurrence within 2 years. We evaluated the feasibility and accuracy of a personalized, tumor-informed circulating tumor DNA (ctDNA) test for the early detection of recurrence risk during long-term postoperative surveillance.
MethodsWe recruited 43 patients with pancreatic cancer who underwent curative surgical resections. A personalized panel was developed to detect ctDNA in plasma based on whole-exome mutation information derived from tumor tissues. A total of 139 plasma samples were analyzed to assess recurrence risk and the efficacy of adjuvant therapy.
ResultsA personalized ctDNA monitoring panel was successfully customized in 35 of 43 cases. Sixteen patients relapsed within a median of 15.7 months (range: 5.4–30.0 months) postsurgery. For the 11 patients with positive ctDNA, the median lead time from initial ctDNA positivity to radiological relapse was 4.59 months (range: 0.88–15.61). After completion of adjuvant chemotherapy (ACT), 94.3% (33/35) of patients contributed 52.5% (73/139) of the ctDNA testing samples. These samples exhibited an elevated rate of ctDNA detection (48.5%, 16/33) compared to samples obtained prior to and during the commencement of ACT, with a negative predictive value of 82.4% (14/17) and a positive predictive value of 75.0% (12/16). The presence of ctDNA was significantly correlated with shorter disease-free survival and overall survival.
ConclusionsLong-term dynamic ctDNA monitoring after pancreatic cancer resection, particularly following the completion of ACT, is predictive of recurrence risk. The proactive implementation of ctDNA monitoring after ACT in patients with resectable pancreatic cancer has important implications for clinical practice.

背景 高达80%接受根治性切除的胰腺癌患者会在术后2年内出现复发。本研究评估了一种个性化、肿瘤溯源循环肿瘤DNA（circulating tumor DNA, ctDNA）检测技术在长期术后随访中早期检测复发风险的可行性与准确性。
方法 本研究纳入43例接受根治性手术切除的胰腺癌患者。基于肿瘤组织的全外显子组突变信息，开发了用于检测血浆中ctDNA的个性化检测panel。共分析139份血浆样本，以评估复发风险及辅助治疗的疗效。
结果 43例患者中，35例成功定制了个性化ctDNA监测检测panel。16例患者在术后中位15.7个月（范围：5.4–30.0个月）出现复发。在11例ctDNA检测阳性的患者中，从首次ctDNA阳性至影像学证实复发的中位提前时间为4.59个月（范围：0.88–15.61个月）。辅助化疗（adjuvant chemotherapy, ACT）完成后，35例患者中的94.3%（33/35）贡献了全部ctDNA检测样本的52.5%（73/139）。与辅助化疗前及辅助化疗启动初期采集的样本相比，此类样本的ctDNA检出率更高（48.5%，16/33），其阴性预测值为82.4%（14/17），阳性预测值为75.0%（12/16）。ctDNA阳性与更短的无病生存期及总生存期显著相关。
结论 胰腺癌根治性切除术后的长期动态ctDNA监测，尤其是辅助化疗完成后的监测，可有效预测复发风险。在可切除胰腺癌患者中，辅助化疗完成后主动开展ctDNA监测对临床实践具有重要指导意义。