WCLC 2025 - Posters & ePosters-P2.06.76 Molecular Profiling of Lung Cancer Brain Metastases: Analysis Between Liquid Biopsy and Brain Metastasis Tissue Results

P2.06.76 Molecular Profiling of Lung Cancer Brain Metastases: Analysis Between Liquid Biopsy and Brain Metastasis Tissue Results

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This study investigates the concordance between molecular profiles obtained from brain metastasis tissue and peripheral liquid biopsies (circulating tumor DNA, ctDNA) in patients with metastatic non-small cell lung cancer (NSCLC). Molecular profiling is crucial for targeted therapy selection, yet data comparing brain metastasis tissue and liquid biopsy results are limited, and discordance between primary and metastatic sites is common.<br /><br />In this proof-of-concept analysis of 115 NSCLC patients, samples from brain metastases and blood ctDNA were examined for up to 83 actionable gene variants relevant for targeted treatments. Nearly all patients (92/115) harbored at least one actionable mutation in either tissue or liquid biopsy samples. Among these, 47 patients showed actionable genes detectable by both assays. At the variant level (n=1071), the overall distribution of variants in actionable genes was similar between tissue and ctDNA (22% vs 21%, p=0.005). However, out of 40 patients with 45 actionable variants identified, only 37.5% (15/40) had concordant actionable variants detected by both methods. More actionable variants were uniquely found in tissue (22) compared to ctDNA alone (5).<br /><br />The findings suggest tissue biopsy from brain metastases has higher sensitivity for detecting actionable mutations than liquid biopsy. This likely reflects biological challenges such as limited ctDNA shedding due to the blood-brain barrier in central nervous system (CNS) disease. Importantly, each assay identified unique variants, indicating complementary diagnostic value.<br /><br />Future research should explore integrating both tissue and liquid biopsy analyses to improve diagnostic yield and optimize personalized management of NSCLC patients with brain metastases. Combining approaches may better capture the full mutational landscape to guide systemic and intracranial therapies in this challenging clinical setting.

Asset Subtitle

Rupesh Kotecha

Meta Tag

Speaker Rupesh Kotecha

Topic Pathology and Biomarkers

Keywords

brain metastasis

non-small cell lung cancer

NSCLC

molecular profiling

liquid biopsy

circulating tumor DNA

ctDNA

actionable gene variants

blood-brain barrier

diagnostic concordance