The comparison of mutation-based biomarkers for early-stage and advanced-stage non-small cell lung caner.

Abstract

e21176 Background: In recent years, immune checkpoint inhibitors have shown promise in the treatment of advanced-stage non-small cell lung cancer (NSCLC), more and more clinical studies have proved this treatment could also be effective for early-stage NSCLC. It’s confirmed that the count of somatic mutations (SM) and tumor mutation burden (TMB) were related to the effect of immunotherapy for advanced stage tumors but this relationship was not proved in early stage tumors, the inherent difference between early stage and advanced stage cancer is unclear. So we compared the SM count and driver mutation frequency for the ES and AS NSCLC cancer. Methods: We retrospectively analyzed the genetic aberrations in 288 patients of Chinese NSCLC patients. All the patients were detected by hybridization capture-based NGS 1021-gene panel sequencing with tumor tissue and peripheral blood control samples. Results: The genetic alterations in 288 patients with NSCLC were analyzed by defined stage categories, the tumors in clinical stage I-IIIa were classified as early-stage (ES) group and stage IIIb-IV were classified as advanced-stage (AS) group. The results showed that the actionable mutation frequency in driver genes such as EGFR/BRAF/MET/ERBB2/KRAS and structural variations called Fusions in ALK/ROS1/RET/NTRK was different in the two groups but was not statistically significant (Table). The average SM count (9.6 versus 6.25, p=0.0001) and the TMB-high (TMB-H) frequency (3.6% versus 13.2%, p=0.002) was significantly higher in AD group (Table). In other words, the driver mutation frequencies has no significant difference between the ES and AS groups but the AS group showed more somatic mutation count and TMB-H frequency, revealing there were more non-driver mutations in AS tumors. The proved relationship between SM count and TMB and the clinical effect of immunotherapy for advanced-stage patients may inapplicable for early-stage tumors, new biomarkers need to be explored for the immunotherapy of early-stage NSCLC patients. Conclusions: There was no significant variation between the early-stage and advanced-stage patients with driver mutations, but more non-driver mutations in advanced-stage patients. The immunotherapy biomarkers such as somatic mutation count and TMB for advanced-stage tumors could be inapplicable for early-stage tumors. The biomarkers for immunotherapy of early-stage NSCLC patients need further research.[Table: see text]