Neuroendocrine Transformation in RB1/TP53 Inactivated NSCLC

Histology transformation from non-small cell lung cancer (NSCLC) to neuroendocrine carcinomas (NEC), especially from epidermal growth factor receptor (EGFR) mutant lung adenocarcinoma (LADC) to small cell lung cancer (SCLC), is widely recognized as a rare mechanism for NSCLC to confer tyrosine kinase inhibitors (TKIs) resistance. The probability of its occurrence is about 3-14% in NSCLC patients who are resistant to TKI treatment. In addition to EGFR mutations, NSCLC patients carrying ALK/ROS1 mutations and receiving corresponding TKI treatment may also experience NEC transformation(NET). In a previous study \[Pubmed ID: 35609408\], the investigators demonstrated that NET also develops in NSCLCs without TKI targets or treatments. This phenomenon could be under-recognized, because re-biopsy was less frequently performed in these patients. The investigators had also shown that p53/Rb inactivation might correlated with NET and should be considered for NET risk prediction. In another retrospective studies, it was found that NSCLC patients with RB1/TP53 dual inactivation mutations had a significantly higher probability of NEC pathological transformation than those without RB1/TP53 inactivation mutations (43 times higher than those without mutations). Therefore, the subgroup of NSCLC patients with tumor suppressor gene RB1/TP53 dual inactivation might have elevated risk for NET. In this study, the investigators proposed to prospectively follow up NSCLC patients with dual RB1/TP53 inactivation (approximately 5% of the total NSCLC). Through prospective and systematic collection of baseline pathological information, clinical treatment process, and imaging data, and as much as possible, repeat pathological biopsies will be performed during disease progression.