Mutant KRAS in Circulating Tumor DNA as a Biomarker in Localized Pancreatic Cancer in Patients Treated with Neoadjuvant Chemotherapy.

IF 7.5 1区 医学 Q1 SURGERY Annals of surgery Pub Date : 2024-10-14 DOI:10.1097/SLA.0000000000006562
Dominic J Vitello, Dhavan Shah, Amy Wells, Larissa Masnyk, Madison Cox, Lauren M Janczewski, John Abad, Kevin Dawravoo, Arlene D'Souza, Grace Suh, Robert Bayer, Massimo Cristofanilli, David Bentrem, Yingzhe Liu, Hui Zhang, Lucas Santana-Santos, Lawrence J Jennings, Qiang Zhang, Akhil Chawla
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Abstract

Objective: 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).

Summary and background data: 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.

Methods: 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.

Results: 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).

Conclusions: 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.

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循环肿瘤 DNA 中的突变 KRAS 作为新辅助化疗患者局部胰腺癌的生物标记物
研究目的主要目的是利用数字液滴聚合酶链反应(ddPCR)确定接受新辅助化疗(NAC)的局部胰腺导管腺癌(PDAC)患者体内循环肿瘤DNA(ctDNA)的预后意义:ctDNA越来越多地被用于各种实体恶性肿瘤的临床决策。然而,NAC期间通过ddPCR评估的KRAS ctDNA的检测和预后价值尚未定性:方法:前瞻性地招募了符合接受 NAC 的局部 PDAC 患者。在诊断时、NAC 后和切除术后采集外周血样本,并使用 ddPCR 分析 ctDNA。采用对数秩检验和Cox比例危险模型评估与OS的关系:84例患者纳入分析。诊断时检测到突变 KRAS ctDNA 的患者占 49.3%,NAC 后检测到突变 KRAS ctDNA 的患者占 69.6%,切除术后检测到突变 KRAS ctDNA 的患者占 69.7%。有 15 例(17.9%)患者在治疗过程中清除了突变 ctDNA。NAC期间ctDNA的清除与总生存期(OS)的改善有关(18.4个月 vs NR,PConclusions.):在整个治疗过程中,接受 NAC 治疗的局部 PDAC 患者可通过 ddPCR 检测到 KRAS ctDNA。切除术后检测到突变 KRAS G12V 与 OS 下降有关。
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来源期刊
Annals of surgery
Annals of surgery 医学-外科
CiteScore
14.40
自引率
4.40%
发文量
687
审稿时长
4 months
期刊介绍: The Annals of Surgery is a renowned surgery journal, recognized globally for its extensive scholarly references. It serves as a valuable resource for the international medical community by disseminating knowledge regarding important developments in surgical science and practice. Surgeons regularly turn to the Annals of Surgery to stay updated on innovative practices and techniques. The journal also offers special editorial features such as "Advances in Surgical Technique," offering timely coverage of ongoing clinical issues. Additionally, the journal publishes monthly review articles that address the latest concerns in surgical practice.
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