Identifying genomic alterations in small cell lung cancer using the liquid biopsy of bronchial washing fluid.

Abstract

e21098 Background: With the rapid development of cancer genomics, the precision medicine of small cell lung cancer (SCLC) is emerging. However, there are limitations to the clinical use of tumor tissue and peripheral blood biopsies. The main purpose of this study was to evaluate the potential use of bronchial washing fluid (BWF) in the liquid biopsy of SCLC. Methods: Twenty-one SCLC patients diagnosed in 2019 were enrolled in this study. BWF (separated as supernatant and precipitate), treatment-naive plasma and tumor tissue samples were collected from all of patients and subjected to next-generation sequencing (NGS) using a 1021-gene panel. The concordance rates of genomic profiling using NGS in these four types of samples were evaluated. Results: Of these 21 patients, 20 BWF supernatant (BWFs) samples, 21 BWF precipitate (BWFp) samples, 21 tumor tissue samples and 20 plasma samples were successfully tested. The detectability of somatic mutations was 100% for BWFs, BWFp and tumor tissues, and only one plasma was absent with any mutation. Matched tumor tissue, BWFs, BWFp and plasma samples were subsistent for 19 patients. For these patients, 204 genomic alterations were identified in tissue samples, of which 189 (92.6%), 175 (85.5%) and 163 (79.9%) alterations were detected in the matched BWFs, BWFp and plasma samples, respectively. Moreover, tumor mutation burden (TMB) was also calculated. Compared with the proportion of TMB-H samples in tissue samples counting 61.9% (13/21), 60% (12/20) of BWFs samples and 52.38 % (11/21) of BWFp samples were TMB-H (defined as more than or equal to 9 mutations per megabase), which was a molecular biomarker that can be used in immunotherapy efficacy prediction. The TMBs of BWFs, BWFp and treatment-naive plasma samples all had strong correlation with that of tissue samples. The TMB of BWFs had the strongest correlation (Pearson r = 0.9512, p < 0.0001), and the TMB of treatment-naive plasma had relatively lower correlation (Pearson r = 0.8782, p < 0.0001) compared with those of BWFs (Pearson r = 0.936, p < 0.0001) and BWFp (Pearson r = 0.8782, p < 0.0001). Conclusions: For SCLC patients, the liquid biopsy of BWF showed high potential to identify DNA alterations and calculate TMB grades, which suggested that genomic analysis of BWF liquid biopsy may have clinical value in predicting the effectiveness of targeted therapy and immunotherapy. It can be widely used in routine clinical practice.