Prospective Evaluation of Circulating Tumor DNA Using Next-generation Sequencing as a Biomarker During Neoadjuvant Chemotherapy in Localized Pancreatic Cancer.

IF 7.5 1区医学 Q1 SURGERY

Annals of surgery Pub Date : 2025-06-01 Epub Date: 2024-01-23 DOI:10.1097/SLA.0000000000006209

Dhavan Shah, Amy Wells, Madison Cox, Kevin Dawravoo, John Abad, Arlene D'Souza, Grace Suh, Robert Bayer, Sohail Chaudhry, Qiang Zhang, Massimo Cristofanilli, David Bentrem, Akhil Chawla

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引用次数: 0

Abstract

Objective: In this prospective study, we aim to characterize the prognostic value of circulating tumor DNA (ctDNA) by next-generation sequencing (NGS) in patients undergoing neoadjuvant chemotherapy (NAC) for pancreatic ductal adenocarcinoma (PDAC).

Background: ctDNA is a promising blood-based biomarker that is prognostic in several malignancies. Detection of ctDNA by NGS may provide insights regarding the mutational profiles in PDAC to help guide clinical decisions for patients in a potentially curative setting. However, the utility of ctDNA as a biomarker in localized PDAC remains unclear.

Methods: Patients with localized PDAC were enrolled in a prospective study at Northwestern Medicine between October 2020 and October 2022. Blood samples were collected to perform targeted tumor-agnostic NGS utilizing the Tempus x|F 105 gene panel at 3 timepoints: pretherapy (at diagnosis), post-NAC, and after local therapy, including surgery. The relationship between ctDNA detection and CA19-9 and the prognostic significance of ctDNA detection were analyzed.

Results: Fifty-six patients were included in the analysis. ctDNA was detectable in 48% at diagnosis, 33% post-NAC, and 41% after local therapy. After completion of NAC, patients with detectable ctDNA had higher CA19-9 levels versus those without (78.4 vs 30.0; P =0.02). The presence of baseline ctDNA was associated with a CA19-9 response; those without ctDNA had a significant CA19-9 response following NAC (109.0 vs 31.5 U/mL; P =0.01), while those with ctDNA present at diagnosis did not (198.1 vs 113.8 U/mL; P =0.77). In patients treated with NAC, the presence of KRAS ctDNA at diagnosis was associated with and independently predicted worse progression-free survival.

Conclusions: This report demonstrates the prognostic value of ctDNA analysis with NGS in localized PDAC. NGS ctDNA is a biomarker of treatment response to NAC. KRAS ctDNA at diagnosis independently predicts worse survival in patients treated with NAC.

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利用新一代测序技术对局部胰腺癌新辅助化疗期间作为生物标记物的循环肿瘤DNA进行前瞻性评估

研究目的在这项前瞻性研究中，我们旨在通过新一代测序技术（NGS）鉴定循环肿瘤DNA（ctDNA）在接受新辅助化疗（NAC）的胰腺导管腺癌（PDAC）患者中的预后价值：循环肿瘤 DNA 是一种很有前景的血液生物标记物，对多种恶性肿瘤具有预后作用。通过 NGS 检测 ctDNA 可以深入了解 PDAC 的突变情况，从而在可能治愈的情况下为患者的临床决策提供指导。然而，ctDNA 在局部 PDAC 中作为生物标记物的效用仍不明确：2020年10月至2022年10月期间，西北医学中心的一项前瞻性研究招募了局部PDAC患者。在三个时间点采集血样，利用 Tempus x|F 105 基因面板进行靶向肿瘤不可知 NGS：治疗前（诊断时）、NAC 后和局部治疗（包括手术）后。分析了ctDNA检测与CA19-9之间的关系以及ctDNA检测的预后意义：诊断时检测到ctDNA的患者占48%，NAC后检测到ctDNA的患者占33%，局部治疗后检测到ctDNA的患者占41%。完成 NAC 后，检测到 ctDNA 的患者的 CA19-9 水平高于未检测到 ctDNA 的患者（78.4 vs. 30.0，P=0.02）。基线ctDNA的存在与CA19-9反应相关；没有ctDNA的患者在NAC治疗后CA19-9反应显著（109.0 U/mL对31.5 U/mL；P=0.01），而诊断时存在ctDNA的患者则没有（198.1 U/mL对113.8 U/mL；P=0.77）。在接受NAC治疗的患者中，诊断时存在KRAS ctDNA与无进展生存期的恶化有关，并且是独立预测因素：本报告证明了在局部 PDAC 中使用 NGS 进行ctDNA 分析的预后价值。NGS ctDNA是NAC治疗反应的生物标志物。诊断时的 KRAS ctDNA 可独立预测接受 NAC 治疗的患者的生存期。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

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.