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

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Peripheral and Portal Venous KRAS ctDNA Detection as Independent Prognostic Markers of Early Tumor Recurrence in Pancreatic Ductal Adenocarcinoma. / Nitschke, Christine; Markmann, Benedikt; Walter, Philipp; Badbaran, Anita; Tölle, Marie; Kropidlowski, Jolanthe; Belloum, Yassine; Goetz, Mara R; Bardenhagen, Jan; Stern, Louisa; Tintelnot, Joseph; Schönlein, Martin; Sinn, Marianne; van der Leest, Paul; Simon, Ronald; Heumann, Asmus; Izbicki, Jakob R; Pantel, Klaus; Wikman, Harriet; Uzunoglu, Faik G.

In: CLIN CHEM, Vol. 69, No. 3, 01.03.2023, p. 295-307.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Nitschke, C, Markmann, B, Walter, P, Badbaran, A, Tölle, M, Kropidlowski, J, Belloum, Y, Goetz, MR, Bardenhagen, J, Stern, L, Tintelnot, J, Schönlein, M, Sinn, M, van der Leest, P, Simon, R, Heumann, A, Izbicki, JR, Pantel, K, Wikman, H & Uzunoglu, FG 2023, 'Peripheral and Portal Venous KRAS ctDNA Detection as Independent Prognostic Markers of Early Tumor Recurrence in Pancreatic Ductal Adenocarcinoma', CLIN CHEM, vol. 69, no. 3, pp. 295-307. https://doi.org/10.1093/clinchem/hvac214

APA

Nitschke, C., Markmann, B., Walter, P., Badbaran, A., Tölle, M., Kropidlowski, J., Belloum, Y., Goetz, M. R., Bardenhagen, J., Stern, L., Tintelnot, J., Schönlein, M., Sinn, M., van der Leest, P., Simon, R., Heumann, A., Izbicki, J. R., Pantel, K., Wikman, H., & Uzunoglu, F. G. (2023). Peripheral and Portal Venous KRAS ctDNA Detection as Independent Prognostic Markers of Early Tumor Recurrence in Pancreatic Ductal Adenocarcinoma. CLIN CHEM, 69(3), 295-307. https://doi.org/10.1093/clinchem/hvac214

Vancouver

Nitschke C, Markmann B, Walter P, Badbaran A, Tölle M, Kropidlowski J et al. Peripheral and Portal Venous KRAS ctDNA Detection as Independent Prognostic Markers of Early Tumor Recurrence in Pancreatic Ductal Adenocarcinoma. CLIN CHEM. 2023 Mar 1;69(3):295-307. https://doi.org/10.1093/clinchem/hvac214

Bibtex

@article{5bec479c5c974bbc82b4c564b9b97205,
title = "Peripheral and Portal Venous KRAS ctDNA Detection as Independent Prognostic Markers of Early Tumor Recurrence in Pancreatic Ductal Adenocarcinoma",
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.",
author = "Christine Nitschke and Benedikt Markmann and Philipp Walter and Anita Badbaran and Marie T{\"o}lle and Jolanthe Kropidlowski and Yassine Belloum and Goetz, {Mara R} and Jan Bardenhagen and Louisa Stern and Joseph Tintelnot and Martin Sch{\"o}nlein and Marianne Sinn and {van der Leest}, Paul and Ronald Simon and Asmus Heumann and Izbicki, {Jakob R} and Klaus Pantel and Harriet Wikman and Uzunoglu, {Faik G}",
note = "{\textcopyright}American Association for Clinical Chemistry 2023.",
year = "2023",
month = mar,
day = "1",
doi = "10.1093/clinchem/hvac214",
language = "English",
volume = "69",
pages = "295--307",
journal = "CLIN CHEM",
issn = "0009-9147",
publisher = "American Association for Clinical Chemistry Inc.",
number = "3",

}

RIS

TY - JOUR

T1 - Peripheral and Portal Venous KRAS ctDNA Detection as Independent Prognostic Markers of Early Tumor Recurrence in Pancreatic Ductal Adenocarcinoma

AU - Nitschke, Christine

AU - Markmann, Benedikt

AU - Walter, Philipp

AU - Badbaran, Anita

AU - Tölle, Marie

AU - Kropidlowski, Jolanthe

AU - Belloum, Yassine

AU - Goetz, Mara R

AU - Bardenhagen, Jan

AU - Stern, Louisa

AU - Tintelnot, Joseph

AU - Schönlein, Martin

AU - Sinn, Marianne

AU - van der Leest, Paul

AU - Simon, Ronald

AU - Heumann, Asmus

AU - Izbicki, Jakob R

AU - Pantel, Klaus

AU - Wikman, Harriet

AU - Uzunoglu, Faik G

N1 - ©American Association for Clinical Chemistry 2023.

PY - 2023/3/1

Y1 - 2023/3/1

N2 - 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.

AB - 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.

U2 - 10.1093/clinchem/hvac214

DO - 10.1093/clinchem/hvac214

M3 - SCORING: Journal article

C2 - 36644936

VL - 69

SP - 295

EP - 307

JO - CLIN CHEM

JF - CLIN CHEM

SN - 0009-9147

IS - 3

ER -