Vitello Dominic J, Shah Dhavan, Wells Amy, Masnyk Larissa, Cox Madison, Janczewski Lauren M, Abad John, Dawravoo Kevin, D'Souza Arlene, Suh Grace, Bayer Robert, Cristofanilli Massimo, Bentrem David, Liu Yingzhe, Zhang Hui, Santana-Santos Lucas, Jennings Lawrence J, Zhang Qiang, Chawla Akhil
Northwestern Quality Improvement, Research & Education in Surgery, Department of Surgery, Northwestern University Feinberg School of Medicine, Chicago, IL.
Northwestern Medicine Cancer Centers, Northwestern Medicine Regional Medical Group, Winfield, IL.
Ann Surg. 2024 Oct 14. doi: 10.1097/SLA.0000000000006562.
The primary objective was to determine the prognostic significance of circulating tumor DNA (ctDNA) in patients receiving neoadjuvant chemotherapy (NAC) for localized pancreatic ductal adenocarcinoma (PDAC) using digital droplet polymerase chain reaction (ddPCR).
Increasingly, ctDNA is being used for clinical decision-making in a variety of solid malignancies. However, the detection and prognostic value of KRAS ctDNA as assessed by ddPCR during NAC has yet to be characterized.
Patients with localized PDAC eligible to receive NAC were prospectively enrolled. Peripheral blood samples were obtained at diagnosis, after NAC, and after resection and analyzed for ctDNA using ddPCR. Log-rank tests and Cox proportional hazards model were used to assess for association with OS.
84 patients were included in the analysis. Mutant KRAS ctDNA was detected in 49.3% of patients at diagnosis, 69.6% of patients after NAC, and 69.7% of patients after resection, respectively. There were 15 (17.9%) patients that cleared mutational ctDNA over the course of treatment. Clearance of ctDNA during NAC was associated with improved overall survival (OS) (18.4 mo. vs NR, P <0.05). Detection of mutant KRAS G12V after NAC and resection was associated with shorter OS (18.0 versus NR months, P <0.031). Detection of the KRAS G12V mutation after resection was associated with reduced OS (aHR 36.75, 95% CI 2.93-461.38).
Throughout treatment, KRAS ctDNA is detectable by ddPCR in patients with localized PDAC treated with NAC. Detection of mutant KRAS G12V after resection was associated with reduced OS.
主要目的是使用数字液滴聚合酶链反应（ddPCR）确定循环肿瘤DNA（ctDNA）在接受新辅助化疗（NAC）的局部胰腺导管腺癌（PDAC）患者中的预后意义。
越来越多的ctDNA被用于多种实体恶性肿瘤的临床决策。然而，在NAC期间通过ddPCR评估的KRAS ctDNA的检测和预后价值尚未得到明确。
前瞻性纳入符合接受NAC条件的局部PDAC患者。在诊断时、NAC后和切除后采集外周血样本，并使用ddPCR分析ctDNA。使用对数秩检验和Cox比例风险模型评估与总生存期（OS）的相关性。
84例患者纳入分析。诊断时、NAC后和切除后分别有49.3%、69.6%和69.7%的患者检测到突变型KRAS ctDNA。有15例（17.9%）患者在治疗过程中清除了突变型ctDNA。NAC期间ctDNA的清除与总生存期（OS）改善相关（18.4个月对未达到，P<0.05）。NAC和切除后检测到突变型KRAS G12V与较短的OS相关（18.0个月对未达到，P<0.031）。切除后检测到KRAS G12V突变与OS降低相关（风险比36.75，95%可信区间2.93-461.38）。
在整个治疗过程中，ddPCR可检测到接受NAC治疗的局部PDAC患者的KRAS ctDNA。切除后检测到突变型KRAS G12V与OS降低相关。
