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

Lærke Rosenlund NielsenDepartment of Clinical Biochemistry, Aarhus University Hospital, Aarhus, Denmark; Department of Clinical Medicine, Aarhus University, Aarhus, DenmarkKasper GuldbrandsenDepartment of Clinical Physiology and Nuclear Medicine, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark; Department of Clinical Physiology and Nuclear Medicine, Copenhagen University Hospital - Bispebjerg and Frederiksberg, Copenhagen, DenmarkLise Barlebo AhlbornRigshospitaletM BlochRigshospitaletKristin SkougaardDepartment of Oncology, Copenhagen University Hospital - Herlev and Gentofte, Herlev, Denmark; Department of Oncology, University Hospital of Southern Denmark - Roskilde, DenmarkElisabeth Albrecht‐BesteDepartment of Clinical Physiology and Nuclear Medicine, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, DenmarkHanne Marie NellemannDepartment of Radiology, Aarhus University Hospital, Aarhus, DenmarkMartin KrakauerDepartment of Clinical Physiology and Nuclear Medicine, Copenhagen University Hospital - Bispebjerg and Frederiksberg, Copenhagen, DenmarkPeter Michael GørtzDepartment of Nuclear Medicine, Copenhagen University Hospital - Herlev and Gentofte, Hellerup, DenmarkJoan FledeliusDepartment of Nuclear Medicine & PET-Centre, Aarhus University Hospital, Aarhus, DenmarkAnne Lerberg NielsenDepartment of Nuclear Medicine, Odense University Hospital, Odense, DenmarkPaw Christian HoldgaardDepartment of Nuclear Medicine, University Hospital of Southern Denmark, Lillebaelt Hospital - Vejle, DenmarkSøren Steen NielsenDepartment of Nuclear Medicine, Aalborg University Hospital, Aalborg, DenmarkJulie Marie GrünerDepartment of Clinical Physiology and Nuclear Medicine, Zealand University Hospital - Køge, DenmarkAnette HøjsgaardDepartment of Cardiothoracic and Vascular Surgery, Aarhus University Hospital, Aarhus, DenmarkRené Horsleben PetersenDepartment of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Department of Cardiothoracic Surgery, Copenhagen University Hospital, Rigshospitalet, Copenhagen, DenmarkLars Borgbjerg MøllerDepartment of Cardiothoracic Surgery, Aalborg University Hospital, Aalborg, DenmarkMorten DahlZealand University HospitalMalene Støchkel FrankDepartment of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Department of Clinical Oncology and Palliative Care, Zealand University Hospital, DenmarkJeanette Haar EhlersDepartment of Oncology, University Hospital of Southern Denmark - Roskilde, Denmark; Medicin 2, Holbæk Hospital, Holbæk, DenmarkZaigham SaghirDepartment of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Department of Medicine, Section of Pulmonary Medicine, Copenhagen University Hospital - Herlev and Gentofte, Hellerup, DenmarkMette PoehlRigshospitaletSvetlana BorissovaDepartment of Oncology, Copenhagen University Hospital - Herlev and Gentofte, Herlev, DenmarkLotte Holm LandOdense University HospitalCharlotte KristiansenDepartment of Oncology, University Hospital of Southern Denmark, Lillebaelt Hospital - Vejle, DenmarkTine McCullochAalborg UniversityLise Saksø MortensenDepartment of Oncology, Aarhus University Hospital, Aarhus, DenmarkMalene Søby ChristophersenLillebaelt HospitalOle HilbergLillebaelt HospitalThor Lind RasmussenDepartment of Respiratory Diseases, Aalborg University Hospital, Aalborg, DenmarkSigne Høyer Simonsen SchwanerDepartment of Respiratory Medicine, Copenhagen University Hospital - Bispebjerg and Frederiksberg, Copenhagen, DenmarkChristian B. LaursenDepartment of Respiratory Medicine, Odense University Hospital, Odense, Denmark; Odense Respiratory Research Unit (ODIN), Department of Clinical Medicine, University of Southern Denmark, Odense, DenmarkUffe BødtgerDepartment of Regional Health Research, University of Southern Denmark, Odense, Denmark; Respiratory Research Unit PLUZ, Department of Respiratory Medicine, Zealand University Hospital - Næstved, DenmarkMarkus Nowak LonsdaleDepartment of Clinical Physiology and Nuclear Medicine, Copenhagen University Hospital - Bispebjerg and Frederiksberg, Copenhagen, DenmarkChristian Niels MeyerDepartment of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Department of Medicine, Zealand University Hospital - Roskilde, DenmarkOke GerkeOdense University HospitalJann MortensenDepartment of Clinical Physiology and Nuclear Medicine, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, DenmarkTorben Riis RasmussenDepartment of Respiratory Diseases, Aalborg University Hospital, Aalborg, DenmarkKarin HjorthaugDepartment of Nuclear Medicine & PET-Centre, Aarhus University Hospital, Aarhus, DenmarkKlaus Richter LarsenDepartment of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Department of Respiratory Medicine, Copenhagen University Hospital - Bispebjerg and Frederiksberg, Copenhagen, DenmarkPeter MeldgaardDepartment of Clinical Medicine, Aarhus University, Aarhus, Denmark; Department of Oncology, Aarhus University Hospital, Aarhus, DenmarkBarbara Malene FischerDepartment of Clinical Physiology and Nuclear Medicine, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, DenmarkBoe Sandahl SørensenDepartment of Clinical Biochemistry, Aarhus University Hospital, Aarhus, Denmark; Department of Clinical Medicine, Aarhus University, Aarhus, Denmark. Electronic address: [email protected]

2025en

ABI

Annotatsiya

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.

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DOI: 10.1016/j.lungcan.2025.108528

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