Clinical Application of In-House Comprehensive Genomic Profiling for Thoracic Cancer: Insights From a Japanese Hospital

Abstract

Comprehensive genomic profiling (CGP) is useful for optimizing targeted therapy and immunotherapy strategies for thoracic malignancies. This study aimed to evaluate the clinical utility and diagnostic complementarity of the in-house sequencing platform Rapid-Neo. We retrospectively analyzed 110 patients with thoracic malignancies who underwent Rapid-Neo testing. The baseline characteristics, sequencing results, concordance with companion diagnostics (CDx), and clinical outcomes were assessed. Of 110 patients, 100 (90.9%) had primary lung cancer. Rapid-Neo identified at least one genomic alteration in 99.1% of cases and well-established driver alterations in 66.0% of lung cancer cases. TMB-high and MSI-high statuses were observed in 9.0% and 2.0% of cases, respectively. Among the 90 cases with prior CDx, Rapid-Neo identified driver alterations in 10.0% of the cases, including EGFR, KRAS, MET, RET, and ERBB2, suggesting its potential to overcome the limitations of conventional CDx tests. High concordance (96.8%) was observed between the Rapid-Neo and CDx results, finally. In EGFR-mutant lung adenocarcinoma, high tumor mutation burden (TMB) was associated with a significantly shorter progression-free survival (PFS) after EGFR-TKI therapy (HR = 2.58, p = 0.018) and remained an independent prognostic factor in multivariate analysis. Furthermore, among patients receiving immune checkpoint inhibitors (ICIs), favorable genomic markers such as TMB-high or MSI-high were associated with prolonged PFS. Rapid-Neo demonstrated high sensitivity and concordance with CDx, while also identifying actionable driver alterations missed by the initial CDx. Moreover, the genomic markers identified by Rapid-Neo may provide predictive values for both targeted therapy and immunotherapy responses, supporting their integration into routine clinical decision-making.