Favorable Conditions for the Detection of EGFR T790M Mutation Using Plasma Sample in Patients with Non-Small-Cell Lung Cancer

SIMPLE SUMMARY: Up to 60% of patients with non-small-cell lung cancer with epidermal growth factor receptor (EGFR) acquire a T790M mutation after first-line EGFR-tyrosine kinase inhibitors (TKIs). Although a liquid biopsy using plasma samples for the detection of the T790M mutation is recommended initially, some patients receive tissue re-biopsy due to the possible false negative results of liquid biopsy. In this study, 40% of patients with one or two metastatic organs at the time of re-biopsy had false negative plasma sample results, and 69% of patients with three or more metastatic organs at the time of re-biopsy had positive plasma results. In multivariate analysis, three or more metastatic organs at the initial diagnosis were independently associated with detection of the T790M mutation using a plasma sample, which means the detection rate of the T790M mutation using a plasma sample was significantly increased in patients with more tumor burden. ABSTRACT: Background: Detection of the epidermal growth factor receptor (EGFR) T790M mutation using plasma samples has been considered simple and non-invasive, but the relatively high false negative results lead to additional tissue sampling in some patients. Until now, the characteristics of patients who prefer liquid biopsy have not yet been established. Methods: To evaluate the favorable conditions for the detection of T790M mutations using plasma samples, a multicenter retrospective study was performed between May 2018 and December 2021. Patients whose T790M mutation was detected in a plasma sample were classified as the plasma positive group. Study subjects with a T790M mutation not detected in a plasma sample but only in a tissue sample were grouped as the plasma false negative group. Results: Plasma positive and plasma false negative groups were found in 74 and 32 patients, respectively. As a result, 40% of patients with one or two metastatic organs at the time of re-biopsy had false negative plasma sample results, and 69% of patients with three or more metastatic organs at the time of re-biopsy had positive plasma results. In multivariate analysis, three or more metastatic organs at initial diagnosis were independently associated with the detection of a T790M mutation using plasma samples. Conclusion: Our results demonstrated that the detection rate of a T790M mutation using plasma samples was related to the tumor burden, particularly to the number of metastatic organs.