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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.

Objective: With the rapid development of cancer genomics and immunomics, some new treatments of small cell lung cancer (SCLC) are emerging. However, there are limitations to the clinical use of tumor tissue. Our study aimed to evaluate the potential use of bronchial washing fluid (BWF) in the liquid biopsy of SCLC.Methods: Twenty-one extensive SCLC (ES-SCLC) patients were enrolled in this study. For all patients, four sample types, BWF supernatant (BWFs), BWF precipitate (BWFp), plasma and tumor tissue, were collected before receiving chemotherapy, and one type, plasma, was collected after chemotherapy. All samples were conducted to NGS using the 1021-gene panel. The concordance rates of genomic profiling using NGS in the four types of samples were evaluated. Multiple clinical information was analyzed for correlation.Results: We successfully tested 20 BWFs samples, 21 BWFp samples, 21 tumor tissue samples, 20 pre-treatment plasma, and 13 post-treatment plasma of these 21 patients. The detectability of somatic mutations was 100% for BWFs, BWFp, tumor tissues, and post-treatment plasma, and only one pre-treatment plasma was absent with any mutation. Matched tumor tissue, BWFs, BWFp, and pre-treatment plasma samples were subsistent for 19 patients. For these patients, 204 genomic alterations were identified in tissue samples, while 189 (92.6%), 175 (85.5%), and 163 (79.9%) alterations were detected in the matched BWFs, BWFp, and pre-treatment plasma, respectively. Moreover, we found that the three tumor markers associated with SCLC have a lower sensitivity than genomic alterations. The endocrine resistance pathway was found enriched in hyponatremia patients which may be related to the hyponatremia. The TMBs of BWF, BWFp, and pre-treatment plasma samples all had a strong correlation with that of tissue samples. Both the VAF and the MVAF of mutations in post-treatment plasma were less than those in pre-treatment plasma, which was in accordance with the evaluation of curative effect.Conclusions: For ES-SCLC patients, the liquid biopsy of BWF showed a highly potential advantage to identify DNA alterations, which suggested that genomic analysis of BWF liquid biopsy may have clinical value as a supplement for tissue and blood detection. Through the restricted validation, it can be widely used in routine clinical practice.

BACKGROUND Insertions in exon 19 in the epidermal growth factor receptor gene (EGFR) is a rarely seen mutation in non-small cell lung cancer. These patients have been effectively treated with sequential EGFR tyrosine kinase inhibitors (TKIs). CASE SUMMARY Here, we presented a case of non-small cell lung cancer, stage IIIB, with EGFR exon 19 insertion mutation as detected in the right lower lobe by next-generation sequencing. The patient was sequentially treated with first, second, and third-generation EGFR TKIs after the surgical operation. The overall survival of the patient was 21.3 mo. There was no dynamic analysis of drug resistance mechanisms in targeted therapy. CONCLUSION This case emphasized the importance of following the guidelines. In patients with EGFR mutations, repeated and dynamic next-generation sequencing monitoring is necessary to prescribe a personalized treatment plan.