P59.13 The Prediction Performance of TP53 / RB1 Co-Mutation on Small-Cell Lung Cancer Transformation in Patients With Non-Small Cell Lung Cancer

Abstract

It has been proven that patients with EGFR mutant non-small cell lung cancer (NSCLC) who harbored loss-of-function mutation in both TP53 and RB1 are more prone to small-cell lung cancer transformation (SCLC-T). This study aims to investigate the prediction performance of TP53 / RB1 mutations on SCLC-T in patients with NSCLC. Patients with pathologically confirmed SCLC-T who performed hybridization capture based next-generation sequencing of 1021 cancer-related genes using tumor tissue and / or malignant effusion samples were retrospectively enrolled in this study. Their clinicopathological characteristics, genetic profiles and treatment were reviewed. From 2016 to 2021, a total of nine patients were enrolled. The median age at diagnosis was 53 years (range 44-65 years); 55.6% (5/9) patients were male and 33.3% (3/9) patients were ever-smokers. All patients except for one with NSCLC (P5, details not known) were initially diagnosed with adenocarcinoma. One patient had pleural effusion sample sequenced at initial diagnosis and tumor tissue samples at the time of transformation (P1), and the remaining cases had only tissue and / or effusion samples at the time of transformation or after that time. Mutation in EGFR, TP53 and RB1 was detected in 100%, 88.9% and 55.6% of patients, respectively (Figure). All patients with RB1 mutations had TP53 mutations detected. All patients were previously treated with EGFR tyrosine kinase inhibitors before transformation. For P1, RB1 mutation was detected at initial diagnosis. After SCLC-T, 2 mutations disappeared and 14 mutations emerged, which may be caused by tumor heterogeneity or evolutional pressure, or related to phenotypic transformation. Copy number variants were more frequently identified in patients with RB1 mutation (100%, 5/5) than in patients without RB1 mutation (50%, 2/4). RB1 mutation was not detected in the tumor sample for P8 at the time of transformation, but was subsequently found in the cerebrospinal fluid collected after 6 months. TP53 / RB1 co-mutation was identified in about half of patients with SCLC-T and may be presented after transformation. Inferring phenotypic transformation only through the presence of TP53 / RB1 co-mutation may result in missed diagnosis of SCLC-T, which should be combined with other techniques such as serum tumor marker neuron specific enolase or pathological exanimations of re-biopsy samples.