e14753 Background: The liquid biopsy is a noninvasive route to evaluate circulating tumor cells (CTCs) during the course of treatment to gain understanding of tumor biology, with potential prognostic utility. CTCs could serve as a predictive biomarker while aiding in the identification of resistance mechanisms to treatment through single cell genomic and proteomic analysis providing a longitudinal snapshots of tumor heterogeneity. Methods: Through the use of the high definition single cell assay (HD-SCA) workflow, we characterized the rare circulating cells to determine prognostic value of the liquid biopsy in monitoring the efficacy of andecaliximab in a combinational treatment as 1st or 2nd line therapy in patients with metastatic colorectal cancer (mCRC). 174 samples from 95 patients were analyzed to determine the significance of CTCs during treatment. Results: HD-CTCs were detected in 31% of samples, with 41 (43%) patients being CTC positive in at least 1 timepoint during the study. Patients receiving 1st line therapy presented with a median of 0 (range 0-346.04) and a mean of 9.49 (±14.06) HD-CTC/mL at baseline (BL). At initiation of 2nd line therapy, patients presented with a median of 0 HD-CTC/mL (range 0-277.37) and a mean of 10.94 (±15.32). There was no association between BL HD-CTC/mL and response, but for the 20 patients with > 1 HD-CTC at BL, there was a trend toward response for higher HD-CTC/mL (non-response: mean 2.8, n = 12; response: mean 89.7, n = 8; p = .04). The 3 patients with > 10 HD-CTC/mL at BL had undetectable HD-CTC on-treatment, which accompanied radiologic partial response; however, the 2 patients with complete radiological response had no HD-CTC detected at BL. In case studies, treatment pressure led to an observable change in HD-CTC morphology and genomic instability (single cell CNV analysis), suggesting these parameters may inform prognosis. Conclusions: Characterization of CTCs from patients with mCRC is feasible and may provide prognostic information to guide clinical decision making. Further evaluation of CTCs for pharmacodynamics and clinical monitoring in patients with mCRC is warranted.
Molecular Characterization of Circulating Tumor Cells in Human Metastatic Colorectal Cancer
