1055P The gene landscape of lung adenocarcinoma patients with progressive disease of the leptomeninges

Abstract

The epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) provide a better prognosis in EGFR-mutant non-small cell lung cancer (NSCLC). Still, the outcome of leptomeningeal metastasis (LM) remains poor. In addition, due to the limited access to intracranial tumor tissue, gene alterations associated with leptomeningeal metastasis from lung adenocarcinoma (LM-LUAD) are unclear. 45 LM-LUAD from May 2019 to June 2021 in the Guangdong Sanjiu Brain Hospital enrolled in this study. 75% (34/45) of patients with LM harboring EGFR mutation, patients with progressive disease (PD) of LM have 3rd generation EGFR-TKI therapy, defined as Cohort 1; without 3rd generation, EGFR-TKI therapy, defined as Cohort 2. Next-generation targeted panel sequencing (NGS) was performed in each cerebrospinal fluid (CSF) sample of the two cohorts, and 9/45 LM-LUAD patients have matched plasma (PLA). The common gene alterations discovered in CSF of LM-LUAD were EGFR mutation (34/45, 75%), TP53 (25/45, 56%), CDKN2A (9/45, 20%), ALK (7/45, 16%), CTNNB1 (6/45, 13%), MET (5/45, 11%), APC (4/45, 9%), FGF4 (4/45, 9%), FGF3 (4/45, 9%), ERBB2 (4/45, 9%), PIK3CG (4/45, 9%). Co-occurring mutations of TP53 and EGFR were found in 49% (22/45) patients and correlated with poor prognosis. CDKN2A mutation was identified in 20% (9/45) patients and presented slightly shorter OS than those without (OS, 7.1 versus 8.8 months, p=0.2). Cohort 1 has more genes associated with poor prognosis, consisting of CDK4, CDKN2A, PIK3CG, or PIK3CA, and YES1 and MET were more likely to be detected in cohort 2. The alternation of EGFR was comparable between CSF and matched PLA. Incidences of gene alterations such as (CDK4, CDKN2A, MET, APC, KRAS, FGFR3, JAK2, BRAF, PIK3CG) more likely identified in CSF. All the mutant allele frequency (MAF) were much higher in CSF compared to matched PLA. CSF could be a potential candidate for the genetic profiling of LM-LUAD, demonstrating the genetic characteristic of LM in EGFR-mutated lung adenocarcinoma on diversity EGFR-TKI therapy.