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Patient-Specific MRD Liquid Biopsy in Resected NSCLC: Plasma and Bronchial Washing ctDNA (LUNG-MRDetect)

2 novembre 2026 aggiornato da: Eun Hye Lee

Development of a Patient-Specific MRD Liquid Biopsy Platform in Resected NSCLC: Combined Analysis of Plasma and Bronchial Washing ctDNA

This is a multicenter, prospective, observational pilot cohort study in patients with surgically resected non-small cell lung cancer (NSCLC, pathologic stage IA3-IIIA). Whole exome sequencing (WES) of each patient's resected tumor tissue and matched normal blood (buffy coat) is used to build a patient-specific (tumor-informed) minimal residual disease (MRD) panel, after excluding germline and clonal hematopoiesis variants. MRD is then assessed in paired plasma circulating tumor DNA (ctDNA) and bronchial washing fluid (BWF) ctDNA collected at 6, 12, 18 and 24 months after surgery. The study evaluates whether MRD positivity in plasma and/or BWF is associated with subsequent clinical or radiologic recurrence, compares MRD detection rates and quantitative values between plasma and BWF, and explores the lead time of MRD detection relative to standard surveillance with chest CT and serum CEA. MRD results are not used to confirm recurrence or to change treatment; all clinical decisions follow standard of care. Forty participants will be enrolled at three Severance hospitals in Korea.

Panoramica dello studio

Stato

Reclutamento

Condizioni

Intervento / Trattamento

Descrizione dettagliata

Background. Postoperative recurrence is frequent in resected early-stage and locally advanced NSCLC (stage I-IIIA), most often within 2-3 years after surgery. Standard surveillance relies on chest CT and serum tumor markers such as CEA, which cannot detect molecular recurrence at the MRD stage before it appears on imaging. ctDNA-based MRD assessment is being actively investigated in several solid tumors. In early-stage lung cancer, however, plasma ctDNA levels after surgery are very low, which may limit detection sensitivity. Bronchial washing fluid reflects the local tumor environment of the lung, and prior studies suggest it may detect tumor-derived mutations with higher sensitivity than plasma. This study builds a patient-specific, tumor-informed MRD panel for each participant, instead of relying on a fixed generic gene panel, and evaluates plasma and BWF MRD in parallel.

Hypotheses. (1) A patient-specific MRD panel built from resected tumor tissue and normal control specimens can detect postoperative recurrence earlier than conventional imaging-based diagnosis. (2) BWF ctDNA, which reflects the local tumor environment, may show higher MRD detection sensitivity than plasma ctDNA.

Objectives. The primary objective is to evaluate whether MRD positivity in plasma and BWF is associated with subsequent clinical or radiologic recurrence in resected NSCLC. The secondary objectives are (a) to compare MRD detection rates and quantitative values between plasma and BWF and determine which specimen is more sensitive for detecting recurrence, and (b) to explore the lead time of MRD detection relative to recurrence confirmation and compare it with CT and CEA.

Design and procedures. At baseline (first outpatient visit within 1 month after surgery), unstained (10) and stained (1) slides of the surgical pathology specimen are obtained, together with blood for normal control and cfDNA. WES is performed on tumor tissue and buffy coat, and a patient-specific mutation panel is designed. At 6, 12, 18 and 24 months after surgery, 20 mL of blood and 20 mL of BWF (collected by bronchoscopy from the lobe or segment of the original lesion, using saline) are obtained for MRD analysis. Additional blood/BWF MRD assessments may be performed at unscheduled visits when recurrence is clinically suspected. MRD follow-up ends at 24 months, recurrence or death. After 24 months, participants are followed under standard practice (CT and CEA every 3 months) without additional MRD testing. All specimens are shipped under anonymized serial codes to an external laboratory (IMBDx) for analysis and are handled according to the participant's consent regarding retention and secondary use.

Statistical analysis. The main analysis set includes enrolled participants whose patient-specific panel was successfully built and who have at least one evaluable postoperative MRD result. Recurrence-free survival (RFS) of MRD-positive and MRD-negative groups is estimated by the Kaplan-Meier method and compared with the log-rank test. Hazard ratios with 95% confidence intervals are estimated by Cox regression as exploratory analyses. Paired plasma-BWF detection rates are compared with McNemar's test, and paired quantitative values (variant allele frequency) with the paired t-test or Wilcoxon signed-rank test. Sensitivity, specificity, PPV, NPV, ROC curve and AUC are computed exploratorily. Lead time is summarized descriptively. Missing data are not imputed. Because this is a pilot study of 40 participants, results are interpreted by effect sizes and confidence intervals rather than formal significance testing.

Safety and monitoring. MRD results are not used alone to confirm recurrence or change adjuvant therapy. Adverse events related to blood sampling and bronchoscopy are recorded. An independent safety monitor, who is not a member of the study team, will perform two monitoring visits. Serious adverse events are reported according to each institution's IRB requirements. Data from all sites are de-identified, coded, and managed centrally.

Tipo di studio

Osservativo

Iscrizione (Stimato)

40

Contatti e Sedi

Questa sezione fornisce i recapiti di coloro che conducono lo studio e informazioni su dove viene condotto lo studio.

Contatto studio

  • Nome: LEE Eunhye, Ph.D.Course of Medical Science
  • Numero di telefono: +82-10-4099-3780
  • Email: hieunhye@yuhs.ac

Backup dei contatti dello studio

  • Nome: SHIN Seonhye, Bachelor Degree, Nursing
  • Numero di telefono: +82-10-7767-3489
  • Email: fresh@yuhs.ac

Luoghi di studio

  • Corea del Sud
      • Seoul, Corea del Sud, 03722
        • Non ancora reclutamento
        • Severance Hospital
        • Contatto:
          • SHIN Seonhye, Bachelor Degree, Nursing
          • Numero di telefono: +82-10-7767-3489
          • Email: fresh@yuhs.ac
        • Contatto:
          • YONG Seunghyun, Ph.D.Course of Medical Science
          • Numero di telefono: +82-10-6366-0213
          • Email: roneirire@yuhs.ac
      • Seoul, Corea del Sud, 06229
        • Non ancora reclutamento
        • Gangnam Severance Hospital
        • Contatto:
          • SHIN Seonhye, Bachelor Degree, Nursing
          • Numero di telefono: +82-10-7767-3489
          • Email: fresh@yuhs.ac
        • Contatto:
          • KIM Chiyoung, Ph.D.Course of Medical Science
          • Numero di telefono: +82-10-4182-1095
          • Email: cykim@yuhs.ac
    • Gyeonggi-do
      • Yongin-si, Gyeonggi-do, Corea del Sud, 16995
        • Reclutamento
        • Yongin Severance Hospital
        • Contatto:
          • LEE Eunhye, Ph.D.Course of Medical Science
          • Numero di telefono: +82-10-4099-3780
          • Email: hieunhye@yuhs.ac
        • Contatto:
          • SHIN Seonhye, Bachelor Degree, Nursing
          • Numero di telefono: +82-10-7767-3489
          • Email: fresh@yuhs.ac

Criteri di partecipazione

I ricercatori cercano persone che corrispondano a una certa descrizione, chiamata criteri di ammissibilità. Alcuni esempi di questi criteri sono le condizioni generali di salute di una persona o trattamenti precedenti.

Criteri di ammissibilità

Età idonea allo studio

19 anni e precedenti (Adulto, Adulto più anziano)

Accetta volontari sani

No

Sessi ammissibili allo studio

Tutto

Metodo di campionamento

Campione non probabilistico

Popolazione di studio

Adult patients (aged 19 years or older) who underwent curative-intent (R0) surgical resection for pathologically confirmed non-small cell lung cancer (NSCLC) with a final pathologic stage of IA3 to IIIA, and who are followed at three tertiary referral hospitals in Korea (Severance Hospital, Gangnam Severance Hospital, and Yongin Severance Hospital). Eligible patients are identified through outpatient and inpatient medical record review and enrolled within 1 month after surgery. A total of 40 participants will be enrolled competitively across the three sites over 2 years.

Descrizione

Inclusion Criteria:

  • Adults aged 19 years or older
  • Pathologically confirmed non-small cell lung cancer who underwent curative-intent complete (R0) surgical resection
  • Final pathologic stage IA3 (tumor size >2 cm) to IIIA after surgery
  • Able to attend the first outpatient visit within 1 month after surgery, and agrees to research blood sampling, provision of surgical tissue slides, and long-term follow-up
  • Provided voluntary written informed consent after adequate explanation of the study purpose and methods

Exclusion Criteria:

  • Pathologic stage IA1 or IA2 (tumor size ≤2 cm), stage IV, or confirmed distant metastasis
  • Incomplete resection (non-R0) or clear residual tumor after surgery
  • History of other malignancy, including synchronous malignancy in another organ, that may confound interpretation of MRD results (cancers judged cured for more than 5 years may be included)
  • Poor performance status or other conditions making repeated blood sampling or bronchoscopy difficult
  • Unstable cardiopulmonary function, or high risk with sedation or additional procedures, in the judgment of the treating physician
  • Unable to provide informed consent, or judged unable to comply with regular follow-up during the study period

Piano di studio

Questa sezione fornisce i dettagli del piano di studio, compreso il modo in cui lo studio è progettato e ciò che lo studio sta misurando.

Come è strutturato lo studio?

Dettagli di progettazione

  • Modelli osservazionali: COHORT
  • Prospettive temporali: PROSPECTIVE

Coorti e interventi

Gruppo / Coorte
Intervento / Trattamento
Resected NSCLC (stage IA3-IIIA)

Adults who underwent curative-intent (R0) resection for pathologic stage IA3-IIIA NSCLC. Participants undergo patient-specific MRD panel construction and serial plasma and BWF MRD testing at 6, 12, 18 and 24 months after surgery.
Test diagnostico: Patient-specific tumor-informed MRD assay (plasma and bronchial washing ctDNA)

WES of surgical tumor tissue and matched normal blood to design a patient-specific mutation panel, followed by MRD detection in plasma ctDNA and BWF ctDNA at 6, 12, 18 and 24 months after surgery and at unscheduled visits if recurrence is suspected. Results are not used for treatment decisions.

Procedura: Bronchoscopy with bronchial washing for reserach

Bronchoscopy performed by the treating pulmonologist, with 20 mL saline bronchial washing from the lobe or segment of the original tumor, at 6, 12, 18 and 24 months after surgery.

Cosa sta misurando lo studio?

Misure di risultato primarie

Misura del risultato
Misura Descrizione
Lasso di tempo
Recurrence-free survival (RFS) according to MRD status in plasma and/or BWF ctDNA
Lasso di tempo: Up to 24 months after surgery

RFS of MRD-positive versus MRD-negative participants, defined as the time from surgery to first clinical or radiologic recurrence (or death, if applicable). Estimated by the Kaplan-Meier method and compared with the log-rank test. Hazard ratio with 95% confidence interval estimated exploratorily by Cox regression.
Up to 24 months after surgery

Misure di risultato secondarie

Misura del risultato
Misura Descrizione
Lasso di tempo
MRD detection rate in plasma ctDNA versus BWF ctDNA
Lasso di tempo: 6, 12, 18 and 24 months after surgery

Proportion of MRD-positive results in paired plasma and BWF samples collected at the same time point, compared with McNemar's test.
6, 12, 18 and 24 months after surgery
Quantitative MRD value (variant allele frequency) in plasma versus BWF
Lasso di tempo: 6, 12, 18 and 24 months after surgery

ariant allele frequency of patient-specific variants in paired plasma and BWF samples, compared with the paired t-test or Wilcoxon signed-rank test.
6, 12, 18 and 24 months after surgery
Diagnostic performance of MRD for recurrence
Lasso di tempo: Up to 24 months after surgery

Sensitivity, specificity, positive predictive value, negative predictive value, and area under the ROC curve (AUC) of plasma and BWF MRD for detecting recurrence, evaluated exploratorily and compared descriptively with CT and CEA.
Up to 24 months after surgery
Lead time of MRD positivity before recurrence confirmation
Lasso di tempo: Up to 24 months after surgery

Interval (months) from first MRD positivity to recurrence confirmed by CT or clinical diagnosis, summarized as mean ± SD or median (IQR), range, and 95% confidence interval, and compared with CT and CEA.
Up to 24 months after surgery

Collaboratori e investigatori

Qui è dove troverai le persone e le organizzazioni coinvolte in questo studio.

Sponsor

Eun Hye Lee

Collaboratori

Gangnam Severance Hospital
Severance Hospital

Investigatori

  • Investigatore principale: LEE Eunhye, Ph.D.Course of Medical Science, Division of Pulmonology, Allergy and Critical Care Medicine, Department of Internal Medicine, Yongin Severance Hospital, Yonsei University College of Medicine

Pubblicazioni e link utili

La persona responsabile dell'inserimento delle informazioni sullo studio fornisce volontariamente queste pubblicazioni. Questi possono riguardare qualsiasi cosa relativa allo studio.

Pubblicazioni generali

Studiare le date dei record

Queste date tengono traccia dell'avanzamento della registrazione dello studio e dell'invio dei risultati di sintesi a ClinicalTrials.gov. I record degli studi e i risultati riportati vengono esaminati dalla National Library of Medicine (NLM) per assicurarsi che soddisfino specifici standard di controllo della qualità prima di essere pubblicati sul sito Web pubblico.

Studia le date principali

Inizio studio (Effettivo)

28 settembre 2026

Completamento primario (Stimato)

31 dicembre 2030

Completamento dello studio (Stimato)

31 dicembre 2031

Date di iscrizione allo studio

Primo inviato

2 novembre 2026

Primo inviato che soddisfa i criteri di controllo qualità

2 novembre 2026

Primo Inserito (Effettivo)

6 novembre 2026

Aggiornamenti dei record di studio

Ultimo aggiornamento pubblicato (Effettivo)

6 novembre 2026

Ultimo aggiornamento inviato che soddisfa i criteri QC

2 novembre 2026

Ultimo verificato

1 novembre 2026

Maggiori informazioni

Termini relativi a questo studio

Parole chiave

Termini MeSH pertinenti aggiuntivi

Altri numeri di identificazione dello studio

  • 9-2026-0153

Piano per i dati dei singoli partecipanti (IPD)

Hai intenzione di condividere i dati dei singoli partecipanti (IPD)?

NO

Descrizione del piano IPD

Data will be de-identified and managed centrally; individual participant data are not planned to be shared at this time.

Informazioni su farmaci e dispositivi, documenti di studio

Studia un prodotto farmaceutico regolamentato dalla FDA degli Stati Uniti

No

Studia un dispositivo regolamentato dalla FDA degli Stati Uniti

No

Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .

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