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.
U2 - 10.1016/j.lungcan.2025.108528
DO - 10.1016/j.lungcan.2025.108528
M3 - Journal article
C2 - 40220718
SN - 0169-5002
VL - 203
JO - Lung cancer (Amsterdam, Netherlands)
JF - Lung cancer (Amsterdam, Netherlands)
M1 - 108528
ER -