This multicenter pilot observational study aims to assess the feasibility of introducing liquid biopsy at an early stage of the diagnostic pathway for patients with suspected advanced non-small cell lung cancer (NSCLC).
Liquid biopsy is a minimally invasive blood test that can detect tumor-related genetic alterations in circulating nucleic acids. The study will evaluate whether this approach can provide molecular information more rapidly than standard tissue-based testing and how closely the results obtained from blood samples match those obtained from tumor tissue.
Approximately 70 adult patients with radiological evidence of locally advanced or metastatic lung cancer will be enrolled. Participants will undergo a blood draw for liquid biopsy and will continue to follow the standard diagnostic pathway, including tissue biopsy or cytological sampling when indicated.
The results generated within the study are intended for research purposes and will not replace standard diagnostic procedures or independently determine treatment decisions. The findings will be used to identify practical and methodological issues and to support the design of future clinical studies on the plasma-first approach.
Age ≥ 18 years.
Radiological suspicion of locally advanced lung cancer not amenable to locoregional treatment or metastatic lung cancer (stage III-IV).
Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1.
Tissue biopsy and/or cytological sampling planned but not yet performed, or already performed without an available histopathological diagnosis of non-small cell lung cancer (NSCLC).
Previous or current history of non-small cell lung cancer (NSCLC).
Histopathological diagnosis of NSCLC already available following tissue biopsy.
Eligibility for surgical removal of tumor tissue.
Ongoing or previous systemic oncological treatment for lung cancer.
The study population includes adult patients with radiological suspicion of locally advanced lung cancer not suitable for locoregional treatment or metastatic lung cancer. Participants are enrolled before completion of the standard diagnostic pathway, when tissue biopsy or cytological sampling is planned but not yet performed, or has already been performed without an available histopathological diagnosis of NSCLC. Eligible patients are recruited at participating centers during thoracic surgery assessment or the first oncology visit and undergo plasma-based liquid biopsy while continuing the standard diagnostic pathway.
Cohort
Prospective
Plasma-based liquid biopsy
Diagnostic testParticipants will undergo a peripheral blood draw for plasma-based liquid biopsy within one week of the first clinical assessment. Circulating cell-free nucleic acids extracted from plasma will be analyzed using next-generation sequencing (NGS) to identify molecular alterations and evaluate turnaround time, concordance with tissue-based molecular profiling, and tumor fraction. The liquid biopsy is performed for research purposes within this pilot observational study. Participants will continue the standard diagnostic pathway of the enrolling center, including tissue biopsy or cytological sampling, histopathological diagnosis, PD-L1 assessment, and standard tissue-based molecular testing. The study procedure will not independently determine treatment decisions.
Feasibility of establishing a structured plasma-first molecular profiling dataset
Proportion of enrolled participants with a complete structured dataset including liquid biopsy results, tissue-based diagnostic and molecular profiling results, and relevant clinical data required for the feasibility assessment of the plasma-first approach.
Turnaround time for plasma-based molecular profiling
Time in days from peripheral blood collection to availability of the liquid biopsy molecular profiling report.
Proportion of participants with informative liquid biopsy results
Proportion of enrolled participants in whom plasma-based molecular profiling identifies at least one clinically actionable genomic alteration with established evidence supporting targeted therapy.
Concordance between plasma-based and tissue-based molecular profiling
Proportion of participants with concordant molecular profiling results between plasma-derived circulating nucleic acids and matched tissue or cytological samples.
Tumor fraction in plasma samples
Distribution of estimated tumor fraction values in plasma samples and proportion of samples with sufficient circulating tumor DNA concentration for molecular analysis.
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