BIOM-23. EVALUATING THE MOLECULAR CONCORDANCE BETWEEN LIQUID BIOPSY AND BRAIN METASTASIS TISSUE IN PATIENTS WITH BRAIN METASTASES

Abstract BACKGROUND Management of patients with brain metastases requires knowledge of the molecular profile of the disease. Although molecular discordance between systemic disease and brain metastases is recognized, the extent to which peripheral liquid biopsy (ctDNA) recapitulates the molecular profile of intracranial lesions remains unclear. METHODS De-identified data from patients who underwent liquid biopsy testing and tissue-based sequencing of brain metastases using Guardant360® CDx, Guardant360®, and TissueNext platforms were analyzed. A panel of up to 83 genes was examined to identify actionable alterations (i.e., those with associated therapeutic indications). Statistical comparisons between groups were conducted using chi-squared analysis. RESULTS Of the 272 patients evaluated, 226 (183 lung, 19 melanoma, 19 breast, and 5 colorectal) harbored ≥1 actionable alteration (genes or variants) identified by either peripheral blood (liquid) or CNS tissue samples with a median time between samples of 20 days (range, 0-90 days). Among the 226, 77 patients (34.1%) had at least one shared alteration detected in tissue and liquid assays. Additionally, 115 patients (50.9%) had alterations detected exclusively in tissue, 34 (15.0%) had alterations identified only in liquid samples, and 21 had non-overlapping alterations identified either in tissue only or in liquid specimens only, that is, alterations different between the two sample sources. Concordance rates of actionable alterations were not impacted by the time interval between sample acquisition (36.2% for 0-30 days vs. 40.6% for 31-90 days, p>0.05). Of the 91 patients with any actionable variant detected, 36 (39.6%) had ≥1 variant detected in both tissue and liquid assays. CONCLUSIONS Tissue-based profiling of brain metastases identified more actionable alterations than liquid biopsy alone, though each method captured additional unique variants. Given the modest concordance (34.1%) and complementary findings, integrating both tissue and liquid assays may improve molecular characterization and guide treatment strategies in patients with brain metastases.