From rinse to result: Feasibility of genotyping core biopsy supernatant in lung cancer.

e20051 Background: Non-small cell lung cancer (NSCLC) patients require molecular testing, even in early stage, to inform the optimal approach to their disease. Diagnosis can be made using core needle biopsy (CNB); however, tissue samples can be insufficient for molecular testing, and plasma-based detection can be falsely negative. CNB cell-free DNA (cfDNA) isolated from supernatant may offer an alternate rapid diagnostic sample. Methods: In this prospective single-arm study, stage I-III non-squamous NSCLC patients undergoing diagnostic evaluation at the University Health Network (Toronto, Canada) were enrolled, with a planned accrual of 100 patients. Next-generation sequencing (NGS) was performed on CNB supernatant (TruSight Oncology 500), or CNB pellet genomic DNA if insufficient cfDNA (TSO500), CNB tissue (Oncomine Comprehensive Assay v3), and plasma cfDNA NGS (TSO500). Turnaround time (TAT) was calculated from biopsy date NGS test request to the molecular result date. Sensitivity was calculated in patients with tier 1 variants in tissue NGS. Results: As of Nov. 2025, 29 patients were enrolled with median age 74 years, 62% female, and 81% had stage I-II disease. 19 patients had tier 1 variants in tumour tissue, and available CNB results. Sensitivity and alterations are shown in Table 1. TAT was similar between supernatant and tissue biopsy. Conclusions: Overall, CNB supernatant had high sensitivity compared to tissue biopsy. Plasma NGS testing had low sensitivity in patients with early-stage disease. Similar TAT is likely influenced by sample batching. Further study is required to examine workflow to accelerate molecular results using CNB supernatant. Tier 1 variant sensitivity with tissue biopsy. Sample Sensitivity Alterations Tissue N/A see below CNB totalCNB pelletCNB supernatant 19/19 (100%)13/13 (100%)6/6 (100%) EGFR exon 21 L858R (n=4) EGFR exon 19 del (n=5) EGFR exon 20 ins (n=1) EGFR G719C (n=1) ALK (n=2) ROS1 (n=1) MET exon 14 skipping (n=3) KRAS (n=2) Plasma 0/9 (0%) N/A N/A = not applicable.