Clinical characteristics and gene mutation analysis of patients with transformed small-cell lung cancer

Abstract Background Transformed small-cell lung cancer (T-SCLC) is one of the mechanisms by which lung adenocarcinoma (LADC) becomes resistant to treatment with epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs). However, this phenomenon remains poorly understood. The study aims to analyze the clinical features and gene mutation characteristics of T-SCLC patients in our hospital. Methods Clinical data were collected from 2013–2022 on patients with the initial diagnosis of LADC treated with EGFR-TKIs followed by re-biopsy case type transform into SCLC in our hospital, and their clinical features, tumor pathology, gene mutation characteristics, clinical treatment, and prognosis were analyzed. Results A total of 6 (6/362, 1.7%) patients with T-SCLC who were all initially diagnosed with LADC and all had EGFR 19 or 21 mutation, the same mutation status as after transformation, as well as combined RB1, TP53, PIK3CA, PTEN, FGFR, YES1 mutation. The mean progression-free survival after EGFR-TKIs treatment was 33.3 months (IQR, 28.8–37.5 months), compared to 3.6 months (IQR, 2.6-5.0 months) after T-SCLC. 4 cases transformed to SCLC and 2 cases to compound SCLC after TKIs treatment; the mean increase in Neuron-specific enolase (NSE) after conversion was 11.6-fold. The follow-up first-line treatment regimen was etoposide-platinum in all cases. There are currently 3 cases of survival and 3 deaths, with a mean overall survival of 51.7 months (IQR, 42.8–60.5 months). Conclusions LADC may transform into SCLC after the failure of EGFR-TKIs. Dynamic NSE changes should be monitored and aggressive re-biopsy should be performed to clarify the mechanism of drug resistance. Multidisciplinary treatment should be provided for T-SCLC, and an integrated treatment strategy based on chemotherapy, Anlotinib and radiotherapy should be considered to improve the prognosis.