Division of Hematology and Oncology, Department of Medicine, University of California San Diego Moores Cancer Center, La Jolla, CA 92037, United States.
Section of GI Oncology, Department of Medical Oncology, Houston Methodist Cancer Center, Houston, TX 77030, United States.
Oncologist. 2024 Oct 3;29(10):859-869. doi: 10.1093/oncolo/oyae155.
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).
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 298 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.
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).
Perioperative tumor-informed ctDNA detection in PDAC is feasible across all stages and is associated with patient survival outcomes.
个性化且基于肿瘤信息的循环肿瘤 DNA（ctDNA）检测是可行的，并可在胰腺导管腺癌（PDAC）患者中识别分子残留疾病（MRD）。
在这项对来自多个美国机构的商业案例的回顾性分析中，对 PDAC 患者进行了个性化、基于肿瘤信息的全外显子组测序和种系控制的 ctDNA 水平定量分析。从 2019 年 11 月至 2023 年 3 月，共采集了 298 例经临床验证的患者的血浆样本（n=1329），这些患者在诊断时、围手术期（MRD 窗口期；手术 2-12 周内，在治疗前）以及术后监测期（如果没有 ACT 或在 ACT 后 4 周开始）进行采集。
在最初被诊断为 I-III 期 PDAC 并接受手术的患者中，自手术以来的中位随访时间为 13 个月（范围 0.1-214）。在 MRD 和监测窗口期，ctDNA 阳性检出率分别为 29%（29/100）和 29.6%（45/152）。ctDNA 阳性检测与 MRD 窗口期内较短的无病生存期（ctDNA 阳性患者的中位无病生存期为 6.37 个月，ctDNA 阴性患者为 33.31 个月；HR：5.45，P<0.0001）以及监测期内较短的无病生存期（ctDNA 阳性患者的中位无病生存期为 11.40 个月，ctDNA 阴性患者无进展；HR：12.38，P<0.0001）显著相关。此外，KRAS 野生型状态后无病生存期明显更好，KRASG12R（HR：0.99，P=0.97）、KRASG12D（HR：1.42，P=0.194）状态下的无病生存期更差，而 KRASG12V（HR：2.19，P=0.002）状态下的无病生存期更差。在多变量分析中，监测时的 ctDNA 检测被发现是复发的最显著预后因素（HR：24.28，P<0.001）。
在 PDAC 中进行基于肿瘤信息的围手术期 ctDNA 检测是可行的，并且与患者的生存结局相关。
