Distinct margin mutation dissemination patterns in <i>EGFR</i> L858R-mutated lung cancers.

Abstract

e20046 Background: It has been revealed that non-small-cell lung cancer (NSCLC) classified as R0 resection margins under microscopic assessment still contain mutations that can be identified by next-generation sequencing (NGS). However, the relationship between the dissemination of margin mutations and tumor tissue remains to be clarified. Methods: This study included patients who underwent lobectomy for stages I-IV lung cancer, with collection of tumor and three sets of tumor margin tissues from each participant, with margin samples taken at distances of 0.5, 1, and 1.5 times the maximum tumor diameter from the tumor edge. All the tumor and margin tissues were subjected to multi-gene NGS analysis respectively. Results: A total of 45 patients with lung adenocarcinoma and 3 with squamous cell lung carcinoma patients were enrolled, yielding 48 primary tumor tissues and 144 margin samples. The positive rate of margin mutations decreased with increasing distance from the tumor, being 73%, 60%, and 44% respectively. Analysis of clinical features revealed that the negative margin rate was higher in patients’ tumor spread through air spaces (STAS) (64% vs. 22%), regardless of the distance from the tumor. Samples were classified as "normal" if the number of mutations decreased or remained stable with increasing margin distance, and as "abnormal" if the mutation count fluctuated or increased. Notably, the normal group exhibited a significant enrichment of EGFR L858R mutations (p=0.009). Further analysis of EGFR L858R-positive samples revealed an infiltrative margin dissemination pattern, contrasting with the more disordered patterns associated with lung cancers harboring other driver mutations. Conclusions: Our findings highlight a unique margin dissemination pattern in NSCLC, especially in EGFR L858R-mutated lung adenocarcinoma, which is characterized by an infiltrative nature, differentiating them from tumors driven by other mutations.