ctDNA can detect minimal residual disease in curative treated non-small cell lung cancer patients using a tumor agnostic approach

Lærke Rosenlund; Kasper Guldbrandsen; Lise Barlebo Ahlborn; Martin Bloch; Kristin Skougaard; Elisabeth Albrecht-Beste; Hanne Marie Nellemann; Martin Krakauer; Peter Michael Gørtz; Joan Fledelius; Anne Lerberg Nielsen; Paw Christian Holdgaard; Søren Steen Nielsen; Julie Marie Grüner; Anette Højsgaard; Rene Horsleben Petersen; Lars Borgbjerg Møller; Morten Dahl; Malene Støchkel Frank; Jeanette Haar Ehlers; Zaigham Saghir; Mette Pøhl; Svetlana Borissova; Lotte Holm Land; Charlotte Kristiansen; Tine McCulloch; Lise Saksø Mortensen; Malene Søby Christophersen; Ole Hilberg; Thor Lind Rasmussen; Signe Høyer Simonsen Schwaner; Christian B Laursen; Uffe Bodtger; Markus Nowak Lonsdale; Christian Niels Meyer; Oke Gerke; Jann Mortensen; Torben Riis Rasmussen; Karin Hjorthaug; Klaus Richter Larsen; Peter Meldgaard; Barbara Malene Fischer; Boe Sandahl Sorensen

doi:10.1016/j.lungcan.2025.108528

ctDNA can detect minimal residual disease in curative treated non-small cell lung cancer patients using a tumor agnostic approach

Lærke Rosenlund
, Kasper Guldbrandsen
, Lise Barlebo Ahlborn
, Martin Bloch
, Kristin Skougaard
, Elisabeth Albrecht-Beste
, Hanne Marie Nellemann
, Martin Krakauer
, Peter Michael Gørtz
, Joan Fledelius
, Anne Lerberg Nielsen
, Paw Christian Holdgaard
, Søren Steen Nielsen
, Julie Marie Grüner
, Anette Højsgaard
, Rene Horsleben Petersen
, Lars Borgbjerg Møller
, Morten Dahl
, Malene Støchkel Frank
, Jeanette Haar Ehlers

Zaigham Saghir, Mette Pøhl, Svetlana Borissova, Lotte Holm Land, Charlotte Kristiansen, Tine McCulloch, Lise Saksø Mortensen, Malene Søby Christophersen, Ole Hilberg, Thor Lind Rasmussen, Signe Høyer Simonsen Schwaner, Christian B Laursen, Uffe Bodtger, Markus Nowak Lonsdale, Christian Niels Meyer, Oke Gerke, Jann Mortensen, Torben Riis Rasmussen, Karin Hjorthaug, Klaus Richter Larsen, Peter Meldgaard, Barbara Malene Fischer, Boe Sandahl Sorensen^*

^*Corresponding author af dette arbejde

Publikation: Bidrag til tidsskrift › Artikel › Forskning › peer review

Abstract

BACKGROUND: Circulating tumor DNA (ctDNA) has the potential to become a reliable biomarker for identifying minimal residual disease (MRD) and predicting recurrence in patients with non-small cell lung cancer (NSCLC) following curative treatment. However, there is a lack of studies that investigate the clinical validity of ctDNA using a tumor-agnostic approach, which can provide significant clinical benefits.

METHODS: We analyzed samples from 45 NSCLC patients recruited in a prospective national multicenter study, all of whom had undergone curative treatment. A total of 38 pre-treatment plasma samples and 76 post-treatment plasma samples were examined using a commercially available cancer personalized profiling by deep sequencing (CAPP-seq) strategy, and a tumor-agnostic approach. Post-treatment samples were collected at two distinct landmark time points: Follow-up 1 (0.5-4.5 months post-treatment) and Follow-up 2 (4.5-7.5 months post-treatment).

RESULTS: Detectable ctDNA post-treatment was significantly associated with increased risk of tumor recurrence and shorter recurrence-free survival (RFS). Using only a single blood sample taken from Follow-up 2, we correctly identified MRD in 50% of the patients who later experienced recurrence. However, subgroup analysis further revealed that in patients treated with radiotherapy or chemoradiotherapy (CRT), ctDNA detection was significantly linked to shorter RFS in the MRD analysis from Follow-up 2, but not in the MRD analysis from Follow-up 1.

CONCLUSION: These findings suggest that post-treatment ctDNA, detected using a tumor-agnostic approach, is a reliable biomarker for predicting recurrence in NSCLC patients following curative treatment. However, the optimal timing for blood sampling to detect MRD appears to depend on the type of curative treatment received.

Originalsprog	Engelsk
Artikelnummer	108528
Antal sider	12
Tidsskrift	Lung Cancer
Vol/bind	203
Tidlig onlinedato	4 apr. 2025
DOI	https://doi.org/10.1016/j.lungcan.2025.108528
Status	Udgivet - maj 2025

Finansiering

Bevillingsgivere
Roche
Novo Nordisk Foundation
Danish Cancer Society
Axel Muusfeldts Fond
Helsefonden
Toyota Foundation
NEYE-Fonden
Danish Comprehensive Cancer Center
Krista og Viggo Petersens Fond

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10.1016/j.lungcan.2025.108528Licens: CC BY

Citationsformater

Rosenlund, L., Guldbrandsen, K., Ahlborn, L. B., Bloch, M., Skougaard, K., Albrecht-Beste, E., Nellemann, H. M., Krakauer, M., Gørtz, P. M., Fledelius, J., Nielsen, A. L., Holdgaard, P. C., Nielsen, S. S., Grüner, J. M., Højsgaard, A., Petersen, R. H., Møller, L. B., Dahl, M., Frank, M. S., ... Sorensen, B. S. (2025). ctDNA can detect minimal residual disease in curative treated non-small cell lung cancer patients using a tumor agnostic approach. Lung Cancer, 203, Artikel 108528. https://doi.org/10.1016/j.lungcan.2025.108528

@article{3bf35a013cba4b30a145f9565c7f57cd,

title = "ctDNA can detect minimal residual disease in curative treated non-small cell lung cancer patients using a tumor agnostic approach",

abstract = "BACKGROUND: Circulating tumor DNA (ctDNA) has the potential to become a reliable biomarker for identifying minimal residual disease (MRD) and predicting recurrence in patients with non-small cell lung cancer (NSCLC) following curative treatment. However, there is a lack of studies that investigate the clinical validity of ctDNA using a tumor-agnostic approach, which can provide significant clinical benefits.METHODS: We analyzed samples from 45 NSCLC patients recruited in a prospective national multicenter study, all of whom had undergone curative treatment. A total of 38 pre-treatment plasma samples and 76 post-treatment plasma samples were examined using a commercially available cancer personalized profiling by deep sequencing (CAPP-seq) strategy, and a tumor-agnostic approach. Post-treatment samples were collected at two distinct landmark time points: Follow-up 1 (0.5-4.5 months post-treatment) and Follow-up 2 (4.5-7.5 months post-treatment).RESULTS: Detectable ctDNA post-treatment was significantly associated with increased risk of tumor recurrence and shorter recurrence-free survival (RFS). Using only a single blood sample taken from Follow-up 2, we correctly identified MRD in 50\% of the patients who later experienced recurrence. However, subgroup analysis further revealed that in patients treated with radiotherapy or chemoradiotherapy (CRT), ctDNA detection was significantly linked to shorter RFS in the MRD analysis from Follow-up 2, but not in the MRD analysis from Follow-up 1.CONCLUSION: These findings suggest that post-treatment ctDNA, detected using a tumor-agnostic approach, is a reliable biomarker for predicting recurrence in NSCLC patients following curative treatment. However, the optimal timing for blood sampling to detect MRD appears to depend on the type of curative treatment received.",

keywords = "Liquid Biopsy, Time Factors, Nsclc, Tumor-agnostic, Mrd, ctDNA, Curative Therapy",

author = "L{\ae}rke Rosenlund and Kasper Guldbrandsen and Ahlborn, \{Lise Barlebo\} and Martin Bloch and Kristin Skougaard and Elisabeth Albrecht-Beste and Nellemann, \{Hanne Marie\} and Martin Krakauer and G{\o}rtz, \{Peter Michael\} and Joan Fledelius and Nielsen, \{Anne Lerberg\} and Holdgaard, \{Paw Christian\} and Nielsen, \{S{\o}ren Steen\} and Gr{\"u}ner, \{Julie Marie\} and Anette H{\o}jsgaard and Petersen, \{Rene Horsleben\} and M{\o}ller, \{Lars Borgbjerg\} and Morten Dahl and Frank, \{Malene St{\o}chkel\} and Ehlers, \{Jeanette Haar\} and Zaigham Saghir and Mette P{\o}hl and Svetlana Borissova and Land, \{Lotte Holm\} and Charlotte Kristiansen and Tine McCulloch and Mortensen, \{Lise Saks{\o}\} and Christophersen, \{Malene S{\o}by\} and Ole Hilberg and Rasmussen, \{Thor Lind\} and \{Simonsen Schwaner\}, \{Signe H{\o}yer\} and Laursen, \{Christian B\} and Uffe Bodtger and Lonsdale, \{Markus Nowak\} and Meyer, \{Christian Niels\} and Oke Gerke and Jann Mortensen and Rasmussen, \{Torben Riis\} and Karin Hjorthaug and Larsen, \{Klaus Richter\} and Peter Meldgaard and Fischer, \{Barbara Malene\} and Sorensen, \{Boe Sandahl\}",

note = "Copyright {\textcopyright} 2025. Published by Elsevier B.V.",

year = "2025",

month = may,

doi = "10.1016/j.lungcan.2025.108528",

language = "English",

volume = "203",

journal = "Lung Cancer",

issn = "0169-5002",

publisher = "Elsevier Ireland Ltd",

}

Rosenlund, L, Guldbrandsen, K, Ahlborn, LB, Bloch, M, Skougaard, K, Albrecht-Beste, E, Nellemann, HM, Krakauer, M, Gørtz, PM, Fledelius, J, Nielsen, AL, Holdgaard, PC, Nielsen, SS, Grüner, JM, Højsgaard, A, Petersen, RH, Møller, LB, Dahl, M , Frank, MS , Ehlers, JH, Saghir, Z, Pøhl, M, Borissova, S, Land, LH, Kristiansen, C, McCulloch, T, Mortensen, LS, Christophersen, MS, Hilberg, O, Rasmussen, TL, Simonsen Schwaner, SH, Laursen, CB, Bodtger, U, Lonsdale, MN, Meyer, CN, Gerke, O, Mortensen, J, Rasmussen, TR, Hjorthaug, K, Larsen, KR, Meldgaard, P, Fischer, BM & Sorensen, BS 2025, 'ctDNA can detect minimal residual disease in curative treated non-small cell lung cancer patients using a tumor agnostic approach', Lung Cancer, bind 203, 108528. https://doi.org/10.1016/j.lungcan.2025.108528

TY - JOUR

T1 - ctDNA can detect minimal residual disease in curative treated non-small cell lung cancer patients using a tumor agnostic approach

AU - Rosenlund, Lærke

AU - Guldbrandsen, Kasper

AU - Ahlborn, Lise Barlebo

AU - Bloch, Martin

AU - Skougaard, Kristin

AU - Albrecht-Beste, Elisabeth

AU - Nellemann, Hanne Marie

AU - Krakauer, Martin

AU - Gørtz, Peter Michael

AU - Fledelius, Joan

AU - Nielsen, Anne Lerberg

AU - Holdgaard, Paw Christian

AU - Nielsen, Søren Steen

AU - Grüner, Julie Marie

AU - Højsgaard, Anette

AU - Petersen, Rene Horsleben

AU - Møller, Lars Borgbjerg

AU - Dahl, Morten

AU - Frank, Malene Støchkel

AU - Ehlers, Jeanette Haar

AU - Saghir, Zaigham

AU - Pøhl, Mette

AU - Borissova, Svetlana

AU - Land, Lotte Holm

AU - Kristiansen, Charlotte

AU - McCulloch, Tine

AU - Mortensen, Lise Saksø

AU - Christophersen, Malene Søby

AU - Hilberg, Ole

AU - Rasmussen, Thor Lind

AU - Simonsen Schwaner, Signe Høyer

AU - Laursen, Christian B

AU - Bodtger, Uffe

AU - Lonsdale, Markus Nowak

AU - Meyer, Christian Niels

AU - Gerke, Oke

AU - Mortensen, Jann

AU - Rasmussen, Torben Riis

AU - Hjorthaug, Karin

AU - Larsen, Klaus Richter

AU - Meldgaard, Peter

AU - Fischer, Barbara Malene

AU - Sorensen, Boe Sandahl

PY - 2025/5

Y1 - 2025/5

N2 - BACKGROUND: Circulating tumor DNA (ctDNA) has the potential to become a reliable biomarker for identifying minimal residual disease (MRD) and predicting recurrence in patients with non-small cell lung cancer (NSCLC) following curative treatment. However, there is a lack of studies that investigate the clinical validity of ctDNA using a tumor-agnostic approach, which can provide significant clinical benefits.METHODS: We analyzed samples from 45 NSCLC patients recruited in a prospective national multicenter study, all of whom had undergone curative treatment. A total of 38 pre-treatment plasma samples and 76 post-treatment plasma samples were examined using a commercially available cancer personalized profiling by deep sequencing (CAPP-seq) strategy, and a tumor-agnostic approach. Post-treatment samples were collected at two distinct landmark time points: Follow-up 1 (0.5-4.5 months post-treatment) and Follow-up 2 (4.5-7.5 months post-treatment).RESULTS: Detectable ctDNA post-treatment was significantly associated with increased risk of tumor recurrence and shorter recurrence-free survival (RFS). Using only a single blood sample taken from Follow-up 2, we correctly identified MRD in 50% of the patients who later experienced recurrence. However, subgroup analysis further revealed that in patients treated with radiotherapy or chemoradiotherapy (CRT), ctDNA detection was significantly linked to shorter RFS in the MRD analysis from Follow-up 2, but not in the MRD analysis from Follow-up 1.CONCLUSION: These findings suggest that post-treatment ctDNA, detected using a tumor-agnostic approach, is a reliable biomarker for predicting recurrence in NSCLC patients following curative treatment. However, the optimal timing for blood sampling to detect MRD appears to depend on the type of curative treatment received.

AB - BACKGROUND: Circulating tumor DNA (ctDNA) has the potential to become a reliable biomarker for identifying minimal residual disease (MRD) and predicting recurrence in patients with non-small cell lung cancer (NSCLC) following curative treatment. However, there is a lack of studies that investigate the clinical validity of ctDNA using a tumor-agnostic approach, which can provide significant clinical benefits.METHODS: We analyzed samples from 45 NSCLC patients recruited in a prospective national multicenter study, all of whom had undergone curative treatment. A total of 38 pre-treatment plasma samples and 76 post-treatment plasma samples were examined using a commercially available cancer personalized profiling by deep sequencing (CAPP-seq) strategy, and a tumor-agnostic approach. Post-treatment samples were collected at two distinct landmark time points: Follow-up 1 (0.5-4.5 months post-treatment) and Follow-up 2 (4.5-7.5 months post-treatment).RESULTS: Detectable ctDNA post-treatment was significantly associated with increased risk of tumor recurrence and shorter recurrence-free survival (RFS). Using only a single blood sample taken from Follow-up 2, we correctly identified MRD in 50% of the patients who later experienced recurrence. However, subgroup analysis further revealed that in patients treated with radiotherapy or chemoradiotherapy (CRT), ctDNA detection was significantly linked to shorter RFS in the MRD analysis from Follow-up 2, but not in the MRD analysis from Follow-up 1.CONCLUSION: These findings suggest that post-treatment ctDNA, detected using a tumor-agnostic approach, is a reliable biomarker for predicting recurrence in NSCLC patients following curative treatment. However, the optimal timing for blood sampling to detect MRD appears to depend on the type of curative treatment received.

KW - Liquid Biopsy

KW - Time Factors

KW - Nsclc

KW - Tumor-agnostic

KW - Mrd

KW - ctDNA

KW - Curative Therapy

U2 - 10.1016/j.lungcan.2025.108528

DO - 10.1016/j.lungcan.2025.108528

M3 - Article

C2 - 40220718

SN - 0169-5002

VL - 203

JO - Lung Cancer

JF - Lung Cancer

M1 - 108528

ER -

ctDNA can detect minimal residual disease in curative treated non-small cell lung cancer patients using a tumor agnostic approach

Abstract

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