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<p>The clinical utility of liquid biopsy (LB) for pancreatic ductal adenocarcinoma (PDAC) remain understudied. Our single-institution cohort of 311 PDAC patients with non-tumor tissues informed LB found 81.2% positivity (<i>N</i> = 186) in metastatic cases and in 52.4% (<i>N</i> = 43) of localized disease. <i>KRAS</i> mutations were detected in 64.6% (<i>N</i> = 148) of metastatic cases and 16% (<i>N</i> = 13) for localized disease. Positive LB, especially <i>KRAS</i> mutation detection, is associated with worse overall survival (OS) in metastatic PDAC (median 14.5 vs. 31.3 months, HR = 2.7, 95%CI = 1.7–4.3, <i>P</i> &lt; 0.0001). The positive concordance rates of <i>KRAS</i> and <i>TP53</i> mutations were 63% and 68% in metastatic disease but only 7% (<i>KRAS</i>) and 33% (<i>TP53</i>) in localized disease, respectively. Among the 41 patients who underwent serial liquid biopsy testing, 25% tested positive after an initial negative result. LB detects therapeutically targetable mutations in 58.5% of PDAC patients and is associated with OS.</p>

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KRAS mutation detection by liquid biopsy for pancreatic ductal adenocarcinoma

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年4月17日

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  • Mahmoud Yousef,
  • Abdelrahman Yousef,
  • Mark W. Hurd,
  • Ashwathy Pillai,
  • Saikat Chowdhury,
  • Rebecca Snyder,
  • Mark Knafl,
  • Ryan L. Lewis,
  • Paul M. Roy,
  • Mohammad Fanaeian,
  • Sali Albarouki,
  • Luca F. Castelnovo,
  • Jennifer Peterson,
  • Brandon G. Smaglo,
  • Robert A. Wolff,
  • Shubham Pant,
  • Jason Willis,
  • Ryan Huey,
  • Michael Overman,
  • Ching-Wei Tzeng,
  • Michael P. Kim,
  • Naruhiko Ikoma,
  • Jess E. Maxwell,
  • Matthew H. G. Katz,
  • Huamin Wang,
  • Anirban Maitra,
  • Eugene Koay,
  • Ethan B. Ludmir,
  • Anthony Chen,
  • Camila Lopez,
  • Haoqiang Ying,
  • John Paul Shen,
  • Dan Zhao

摘要

The clinical utility of liquid biopsy (LB) for pancreatic ductal adenocarcinoma (PDAC) remain understudied. Our single-institution cohort of 311 PDAC patients with non-tumor tissues informed LB found 81.2% positivity (N = 186) in metastatic cases and in 52.4% (N = 43) of localized disease. KRAS mutations were detected in 64.6% (N = 148) of metastatic cases and 16% (N = 13) for localized disease. Positive LB, especially KRAS mutation detection, is associated with worse overall survival (OS) in metastatic PDAC (median 14.5 vs. 31.3 months, HR = 2.7, 95%CI = 1.7–4.3, P < 0.0001). The positive concordance rates of KRAS and TP53 mutations were 63% and 68% in metastatic disease but only 7% (KRAS) and 33% (TP53) in localized disease, respectively. Among the 41 patients who underwent serial liquid biopsy testing, 25% tested positive after an initial negative result. LB detects therapeutically targetable mutations in 58.5% of PDAC patients and is associated with OS.