Clinicopathological and molecular features of non-small cell lung cancer without TKI therapy that transforms into small-cell lung cancer

Abstract Background Some patients with NSCLC have been found to transformed to SCLC after treatment, but there is little research about it. This study aimed to determine the clinicopathological features and the molecular pathogenesis of NSCLC patients without TKI therapy that transforms into SCLC. Methods We investigated six patients with advanced NSCLC without TKI therapy that were transformed into SCLCs. Whole genome sequencing was applied for six tumor specimens (included NSCLC and SCLC specimens of each patient)acquired from three patients to detect genetic predictors for small-cell transformation. The clinicopathological features of six patients was collected and analyzed. Also, The literature was reviewed in detail to identify similar cases of NSCLC-to-SCLC transformation. Results The basic condition of patients was similar to those without transformation. Five patients (with squamous cell carcinoma) were male, and one (with adenocarcinoma) was male; their average age was 64.7 years. Thoracic imaging revealed solid tumours with unclear borders and lobulated texture with uneven densities in six patients. All five tumours were univocal, and they had an average size of 43 mm. (The image information of one patient was not obtained).The average trasformation time was 9.8 months. After SCLC transformation of three patients with WES, the mutation spectrum changed, C > T decreased and C > A increased. Compared with the initial NSCLC, the CNV burden of transformed SCLC decreased significantly. Clonal evolution analysis showed that there are links and also difference between the clones of initial NSCLC and transformed SCLC. Conclusion Secondary biopsy is very important for evaluating genetic and histological changes and selecting appropriate treatment after treatment resistance. This importance is not only for patients treated with tyrosine kinase inhibitors, but also for patients treated with chemotherapy and immunotherapy. The mutation rate of p53 in transformed SCLC was similar to de novo SCLC, however, the mutation rate of RB1 in transformed SCLC was lower to de novo SCLC.