Abstract
45 Background: Esophagogastric junction (EGJ) and gastric (GC) cancer, together GEA, have a poor prognosis, high molecular heterogeneity, and few targeted therapeutic options. Guardant360 is a clinical gene panel test for next generation sequencing (NGS) of plasma circulating tumor (ct) DNA. Methods: We evaluated a large cohort of ctDNA-derived genomic results (Guardant Health, Inc.), including a subset of pts from the University of Chicago (UC) with clinical data. GEA pts in these 2 cohorts were assessed for genomic alteration (GA) distribution: mutations (mt), indels, amplifications (amp) and fusions. UC survival analyses were performed using log-rank test and select gene-by-gene alteration frequency by pt with chi-square comparisons. Results: The overall ctDNA cohort comprised 1128 pts with median age 64 yrs (range 19-98) and 73% males. At least 1 detectable GA (median 4, range 0-102) was observed in 870 pts (77%). The UC subset of pts (n=171), median age 63 yrs (range 19-87), included 2/10/27/61% stage I/II/III/IV, 77/13/5/5% Caucasian/African American/Asian/Hispanic, 74% male and 63% EGJ. At least 1 detectable GA (median 4, range 1-102) was observed in 157 pts; median GAs per test by stage I vs II/III vs IV was 1.5/3.5/4.5. GA distributions were similar to the larger cohort (Table 1). Stage IV pts tested within 6 weeks of diagnosis/recurrence (n=34) had a median survival of 8.7 months. In these pts, BRAF/ FGFR2 amps and ARAF mts were each prognostic for worse survival ( p<0.05), and MET and KRAS amps trended towards significance. Mt allele frequency (MAF) ctDNA burden inversely correlated with survival ( p=0.01) . In 138 pts with ≥2 serial tests, non-synonymous GAs in MET, PIK3CA, and FGFR1 were more commonly late events (all p<0.05 ). Conclusions: GAs in plasma ctDNA were detected in 77% of GEA pts including numerous actionable targets. ctDNA analysis merits further evaluation as a prognostic biomarker assessing specific genes, overall ctDNA burden, and molecular heterogeneity at baseline and serially. [Table: see text]
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