Peripheral and Portal Venous KRAS ctDNA Detection as Independent Prognostic Markers of Early Tumor Recurrence in Pancreatic Ductal Adenocarcinoma

Christine Nitschke, Benedikt Markmann, Philipp Walter, Anita Badbaran, Marie Tölle, Jolanthe Kropidlowski, Yassine Belloum, Mara R. Goetz, Jan Bardenhagen, Louisa Stern, Joseph Tintelnot, Martin Schönlein, Marianne Sinn, Paul van der Leest, Ronald Simon, Asmus Heumann, Jakob R. Izbicki, Klaus Pantel, Harriet Wikman*, Faik G. Uzunoglu*

*Corresponding author for this work

    Research output: Contribution to journalArticleAcademicpeer-review

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    Abstract

    BACKGROUND: KRAS circulating tumor DNA (ctDNA) has shown biomarker potential for pancreatic ductal adenocarcinoma (PDAC) but has not been applied in clinical routine yet. We aim to improve clinical applicability of ctDNA detection in PDAC and to study the impact of blood-draw site and time point on the detectability and prognostic role of KRAS mutations. METHODS: 221 blood samples from 108 PDAC patients (65 curative, 43 palliative) were analyzed. Baseline peripheral and tumor-draining portal venous (PV), postoperative, and follow-up blood were analyzed and correlated with prognosis. RESULTS: Significantly higher KRAS mutant detection rates and copy numbers were observed in palliative compared to curative patients baseline blood (58.1% vs 24.6%; P = 0.002; and P < 0.001). Significantly higher KRAS mutant copies were found in PV blood compared to baseline (P < 0.05) samples. KRAS detection in pre- and postoperative and PV blood were significantly associated with shorter recurrence-free survival (all P < 0.015) and identified as independent prognostic markers. KRAS ctDNA status was also an independent unfavorable prognostic factor for shorter overall survival in both palliative and curative cohorts (hazard ratio [HR] 4.9, P = 0.011; HR 6.9, P = 0.008). CONCLUSIONS: KRAS ctDNA detection is an independent adverse prognostic marker in curative and palliative PDAC patients-at all sites of blood draw and a strong follow-up marker. The most substantial prognostic impact was seen for PV blood, which could be an effective novel tool for identifying prognostic borderline patients-guiding future decision-making on neoadjuvant treatment despite anatomical resectability. In addition, higher PV mutant copy numbers contribute to an improved technical feasibility.

    Original languageEnglish
    Pages (from-to)295-307
    Number of pages13
    JournalClinical chemistry
    Volume69
    Issue number3
    DOIs
    Publication statusPublished - Mar-2023

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