P2.03b-023 Circulating Tumor DNA (ctDNA)-Based Genomic Profiling of Known Cancer Genes in Lung Squamous Cell Carcinoma (LUSC): Topic: Biomarkers

Abstract

Next-generation sequencing (NGS) of ctDNA is increasingly used for non-invasive genomic profiling of human cancers. However, studies to date have not detailed the ctDNA genomic landscape in LUSC. From June 2014 to June 2016, ctDNA from 467 patients with stage 3 or 4 (AJCC 7th edition) LUSC (60% male, 40% female; median age of 69 [range 27-96]) were tested with Guardant 360TM, a ctDNA NGS assay that detects single nucleotide variants (SNVs) of 54-70 cancer genes and certain copy number amplifications (CNAs), indels, and fusions. The median time between diagnosis and ctDNA testing was 238 days. Somatic alterations were compared with those in the 2016 LUSC TCGA dataset. 426 patients (92.2%) had at least one somatic alteration detected. The most commonly observed SNVs (> 5% frequency) were TP53 (64.8%), PIK3CA (7.8%), CDKN2A (6.1%), and KRAS (5.9%). Frequencies of SNVs known to be significant in LUSC correlated well between our cohort and the TCGA (Spearman r = 0.93) but were generally lower in our cohort (Table 1). Several of our most frequently observed CNAs are strongly associated with LUSC (EGFR, CDK6, MYC, ERBB2, PDGFRA, KIT, CCND1). In addition, MET exon 14 skipping (1.3%), EGFR exon 19 deletion (1.9%), EGFR exon 20 insertion (0.5%), ERBB2 exon 20 insertion (0.3%) and EML4-ALK fusion (0.7%) were detected. These alterations have rarely been reported in LUSC. Patterns of SNVs and CNAs in LUSC obtained by ctDNA profiling are largely consistent with those from TCGA tissue profiling, although the frequency of key SNVs is lower. The presence of actionable alterations atypical for LUSC in 4.7% of this clinical cohort may represent underappreciated treatment options. Further investigation is warranted to evaluate whether these findings reflect a distinct mutational landscape in heavily treated advanced disease (which is under-represented in the TCGA) and/or challenges in histopathological classification.