2024 World Conference on Lung Cancer (WCLC) - Posters-P3.03H.03 Feasibility of Metastatic Lymph Node-informed ctDNA Analysis in Surgically Resected NSCLC Patients

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This study explores the feasibility of using metastatic lymph node (mLN)-informed circulating tumor DNA (ctDNA) analysis to detect molecular residual disease (MRD) in patients with non-small cell lung cancer (NSCLC) who have undergone surgical resection. Traditionally, ctDNA analysis focuses on tracking somatic single nucleotide variants (SNVs) from primary tumor tissues. However, primary tumor tissue is not always accessible, prompting this study to evaluate mLN tissue as an alternative source.<br /><br />Methods involved collecting plasma samples from 46 NSCLC patients (stage IIA-IIIA) at Kindai University Hospital. These samples were collected before surgery, post-surgery, and then biannually for two years. Whole exome sequencing of primary tumors and mLN, alongside normal blood DNA, helped select SNVs. The ctDNA analyses employed a personalized, up to 16-plex assay (SignateraTM by Natera, Inc.) focused on primary tumors and mLN.<br /><br />Findings showed that 95% of the plasma samples from 18 patients with both primary and mLN tissues demonstrated concordant ctDNA status using both assay types. ctDNA positivity post-resection was linked to significantly worse recurrence-free survival (RFS), regardless of whether the primary tumor or mLN-informed assay was used. This highlights the prognostic capabilities of ctDNA analysis in the longitudinal setting. <br /><br />Furthermore, the study found substantial overlap in the variants detected in primary tumors and mLN (averaging 30%, up to 93%); nonetheless, assays designed from either tissue type maintained a high concordance in clinical outcomes.<br /><br />In conclusion, the study supports the idea that mLN can be a viable alternative to primary tumors for designing ctDNA assays, offering a reliable method for tracking MRD and predicting patient outcomes after NSCLC surgery. This approach could be particularly beneficial when primary tumor samples are unavailable.

Asset Subtitle

Shuta Ohara

Meta Tag

Speaker Shuta Ohara

Topic Tumor Biology – Translational Biology

Keywords

metastatic lymph node

circulating tumor DNA

molecular residual disease

non-small cell lung cancer

surgical resection

somatic single nucleotide variants

whole exome sequencing

Signatera

recurrence-free survival

prognostic capabilities