Abstract：
BACKGROUND: Personalized and tumor-informed circulating tumor DNA (ctDNA) testing is feasible and allows for molecular residual disease (MRD) identification in patients with pancreatic ductal adenocarcinoma (PDAC).
METHODS: In this retrospective analysis of commercial cases from multiple US institutions, personalized, tumor-informed, whole-exome sequenced, and germline-controlled ctDNA levels were quantified and analyzed in patients with PDAC. Plasma samples (n = 1329) from 299 clinically validated patients were collected at diagnosis, perioperatively (MRD-window; within 2-12 weeks after surgery, before therapy), and during surveillance (>12 weeks post-surgery if no ACT or starting 4 weeks post-ACT) from November 2019 to March 2023.
RESULTS: Of the initially diagnosed patients with stages I-III PDAC who went for resection, the median follow-up time from surgery was 13 months (range 0.1-214). Positive ctDNA detection rates were 29% (29/100) and 29.6% (45/152) during the MRD and surveillance windows, respectively. Positive ctDNA detection was significantly associated with shorter DFS within the MRD window (median DFS of 6.37 months for ctDNA-positive vs 33.31 months for ctDNA-negative patients; HR: 5.45, P < .0001) as well as during the surveillance period (median DFS: 11.40 months for ctDNA-positive vs NR for ctDNA-negative; HR: 12.38, P < .0001). Additionally, DFS was significantly better with KRAS wildtype status followed by KRASG12R (HR: 0.99, P = .97), KRASG12D (HR: 1.42, P = .194), and worse with KRASG12V (HR: 2.19, P = .002) status. In multivariate analysis, ctDNA detection at surveillance was found to be the most significant prognostic factor for recurrence (HR: 24.28, P < .001).
CONCLUSIONS: Perioperative tumor-informed ctDNA detection in PDAC is feasible across all stages and is associated with patient survival outcomes.
METHODS: In this retrospective analysis of commercial cases from multiple US institutions, personalized, tumor-informed, whole-exome sequenced, and germline-controlled ctDNA levels were quantified and analyzed in patients with PDAC. Plasma samples (n = 1329) from 299 clinically validated patients were collected at diagnosis, perioperatively (MRD-window; within 2-12 weeks after surgery, before therapy), and during surveillance (>12 weeks post-surgery if no ACT or starting 4 weeks post-ACT) from November 2019 to March 2023.
RESULTS: Of the initially diagnosed patients with stages I-III PDAC who went for resection, the median follow-up time from surgery was 13 months (range 0.1-214). Positive ctDNA detection rates were 29% (29/100) and 29.6% (45/152) during the MRD and surveillance windows, respectively. Positive ctDNA detection was significantly associated with shorter DFS within the MRD window (median DFS of 6.37 months for ctDNA-positive vs 33.31 months for ctDNA-negative patients; HR: 5.45, P < .0001) as well as during the surveillance period (median DFS: 11.40 months for ctDNA-positive vs NR for ctDNA-negative; HR: 12.38, P < .0001). Additionally, DFS was significantly better with KRAS wildtype status followed by KRASG12R (HR: 0.99, P = .97), KRASG12D (HR: 1.42, P = .194), and worse with KRASG12V (HR: 2.19, P = .002) status. In multivariate analysis, ctDNA detection at surveillance was found to be the most significant prognostic factor for recurrence (HR: 24.28, P < .001).
CONCLUSIONS: Perioperative tumor-informed ctDNA detection in PDAC is feasible across all stages and is associated with patient survival outcomes.
摘要：
背景：个性化和肿瘤知情的循环肿瘤DNA（ctDNA）检测是可行的，并且可以在胰腺导管腺癌（PDAC）患者中识别分子残留病（MRD）。
方法：在对来自多个美国机构的商业案例的回顾性分析中，个性化，肿瘤知情，全外显子组测序，在PDAC患者中定量和分析种系控制的ctDNA水平。在诊断时收集来自299名临床验证患者的血浆样本（n=1329），围手术期（MRD窗口；手术后2-12周内，治疗前)，以及在2019年11月至2023年3月的监测期间（如果没有ACT，则手术后>12周或在ACT后4周开始）。
结果：在最初诊断为I-III期PDAC的患者中，手术后的中位随访时间为13个月(范围0.1-214).在MRD和监测窗口期间，ctDNA阳性检出率分别为29%(29/100)和29.6%(45/152)，分别。在MRD窗口内，ctDNA检测阳性与较短的DFS显着相关（ctDNA阳性患者的中位DFS为6.37个月，ctDNA阴性患者的中位DFS为33.31个月；HR：5.45，P<.0001）以及在监测期间（ctDNA阳性与ctDNA阴性患者的中位DFS：11.40个月；HR：12.38，P<.0001）。此外,KRAS野生型状态下的DFS明显更好，其次是KRASG12R（HR：0.99，P=0.97），KRASG12D（HR：1.42，P=.194），KRASG12V（HR：2.19，P=0.002）状态更差。在多变量分析中，监测时ctDNA检测被认为是复发的最重要预后因素(HR:24.28,P<.001)。
结论：PDAC围手术期肿瘤信息ctDNA检测在所有阶段都是可行的，并且与患者的生存结果相关。
方法：在对来自多个美国机构的商业案例的回顾性分析中，个性化，肿瘤知情，全外显子组测序，在PDAC患者中定量和分析种系控制的ctDNA水平。在诊断时收集来自299名临床验证患者的血浆样本（n=1329），围手术期（MRD窗口；手术后2-12周内，治疗前)，以及在2019年11月至2023年3月的监测期间（如果没有ACT，则手术后>12周或在ACT后4周开始）。
结果：在最初诊断为I-III期PDAC的患者中，手术后的中位随访时间为13个月(范围0.1-214).在MRD和监测窗口期间，ctDNA阳性检出率分别为29%(29/100)和29.6%(45/152)，分别。在MRD窗口内，ctDNA检测阳性与较短的DFS显着相关（ctDNA阳性患者的中位DFS为6.37个月，ctDNA阴性患者的中位DFS为33.31个月；HR：5.45，P<.0001）以及在监测期间（ctDNA阳性与ctDNA阴性患者的中位DFS：11.40个月；HR：12.38，P<.0001）。此外,KRAS野生型状态下的DFS明显更好，其次是KRASG12R（HR：0.99，P=0.97），KRASG12D（HR：1.42，P=.194），KRASG12V（HR：2.19，P=0.002）状态更差。在多变量分析中，监测时ctDNA检测被认为是复发的最重要预后因素(HR:24.28,P<.001)。
结论：PDAC围手术期肿瘤信息ctDNA检测在所有阶段都是可行的，并且与患者的生存结果相关。
