Abstract
406 Background: Treatment for EG cancer is increasingly complex and the role of predictive and prognostic biomarkers is critical in selecting the optimal therapy. Longitudinal, non-invasive methods that characterize dynamic molecular profiles and detect molecular residual disease are needed. Methods: Patients with EG cancer receiving care at Memorial Sloan Kettering (MSK) had cfDNA analysis with an ultrasensitive capture based liquid biopsy for detection of somatic alterations in 129 cancer associated genes (MSK ACCESS). Results: 98 patients with EG adenocarcinoma underwent cfDNA analysis; 18% had esophageal tumors, 44% had GEJ, and 38% had gastric. 78 (80%) patients had cfDNA obtained prior to treatment (48 [50%] metastatic; 29 [30%] locally advanced) and 21 (21%) at time of progression. 85% had matched tumor NGS performed with MSK IMPACT: median TMB was 5.3 mut/Mb (IQR 3.3-7.4) and median alterations per tumor sample was 11 (IQR 7-17). cfDNA identified a similar molecular profile compared to tumor NGS (TP53 [62 v 72%], ARID1A [12 v 20%], CDKN2A [10 v 16%], APC [10 v 13%], ATM [10 v 12%], PIK3CA [7 v 12%]), although cfDNA was detected more frequently in patients with metastatic disease compared to localized disease (p=0.02). cfDNA did not detect copy number alterations as frequently as patient-matched tumor NGS (41 v 16%, p<0.01), including ERBB2amp (22 v 10%, p=0.05), though patients with HER2 IHC 3+ tumors were more likely to have detectable ERBB2amp on cfDNA compared to HER2 IHC 2+ tumors (50 v 9% p=0.03). Additionally, those with detectable ERBB2amp on cfDNA had a higher copy number on tumor NGS compared to those with undetectable cfDNA (median 39 [IQR 23-46] v 10 [IQR 6-15] p<0.01). Baseline detection of ctDNA may indicate a poor prognosis; among patients with locally advanced disease (median follow up 20.1 months), 0 of 10 with undetectable ctDNA died compared to 5 (26%) of 19 with detectable ctDNA (p=0.08). Among patients with untreated, metastatic disease (median follow up 24.3 months), patients with undetectable ctDNA had a non-significant, improvement in PFS (HR 0.28 95% CI 0.08-1.17; p=0.08) and OS (HR 0.45 95% CI 0.10-1.96; p=0.20) compared to patients with detectable ctDNA, independent of disease burden. Conclusions: Our findings highlight the utility of cfDNA with MSK ACCESS as a complimentary tool for molecular characterization and potential prognostication in patients with EG cancer. [Table: see text]
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