In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 37, No. 15_suppl ( 2019-05-20), p. e13125-e13125
Abstract:
e13125 Background: LCNEC is an aggressive, biologically heterogenous carcinoma which can be molecularly characterized as SCLC-like and NSCLC-like. Accurate distinction of molecular subset is of major clinical relevance since it may guide treatment choices in LCNEC. Here we determined the genomic characteristics of the two LCNEC subsets in a Chinese cohort to clarify their correlations with traditional lung cancer histologies. Methods: FFPE samples from 31 LCNECs were sequenced using a 520-cancer-related gene panel, with an average sequencing depth of 1353X. Comparative mutational analysis was conducted between NSCLC-like LCNECs from our cohort and adenocarcinomas from TCGA dataset. Results: Despite similar clinical features in terms of stage and age at diagnosis, NSCLC-like (42%, 13/31) and SCLC-like (32%, 10/31) subsets from LCNEC displayed distinct molecular characteristics. NSCLC-like subset harbored significant higher mutation frequencies of STK11, KEAP1 and FAT3 (53.8%, 38.5% and 38.5%, p = .007, .046 and .046), while SCLC-like subset was characterized by highly mutated RB1 (100%, p 〈 .001) and PTEN (50%, p = .007). Compared with TCGA adenocarcinomas, NSCLC-like LCNEC displayed more frequent mutations in TP53, STK11, APC, KMT2D and SMARCA4 (76.9%, 53.8%, 30.8%, 30.8% and 23.1%; p = .043, .004, .045, .005 and .049). In addition, potential targetable alterations were present in 46.2% (6/13) pts of NSCLC-like subset. For those advanced stage pts, 2/5 NSCLC-like and 5/5 SCLC-like pts received relevant chemotherapy according to their molecular characteristics. The clinical outcomes of these pts are still under follow-up. Conclusions: This study demonstrates the distinct molecular features between NSCLC-like and SCLC-like subsets, and highlights the predominant genomic similarity and separate entities between NSCLC-like LCNEC with adenocarcinoma. Given the evidence that genomic profiling may aid in informing treatment decisions for pts with LCNEC, our study indicates that, based on accurate molecular typing, 46.2% NSCLC-like pts may benefit from potential targeted therapy and the rest of them may be more suitable to receive NSCLC-chemotherapy.
Type of Medium:
Online Resource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/JCO.2019.37.15_suppl.e13125
Language:
English
Publisher:
American Society of Clinical Oncology (ASCO)
Publication Date:
2019
detail.hit.zdb_id:
2005181-5
