Circulating Tumor DNA in Colorectal Cancer Liver Metastasis: Analysis of Patients Receiving Liver Resection and Transplant

Abstract

PURPOSE Liver metastases occur in about 50% of colorectal cancer cases and drive patient outcomes. Circulating tumor DNA (ctDNA) is emerging as a diagnostic, surveillance, and tumor mutational information tool. METHODS Patients with colorectal cancer liver metastasis (CCLM) seen in a multidisciplinary liver tumor clinic from January to August 2022 received ctDNA testing on each visit. ctDNA was obtained using the Guardant360 platform. Tumor mutational burden (TMB) is defined as the number of identified mutations per megabase of genome analyzed. RESULTS Fifty-two patients had available ctDNA, with 34 (65%) tested preoperatively and 18 (35%) postoperatively; nine patients had sequential pre- and postoperative testing. The median time to test result was 12 days (IQR, 10-13.5). There were a greater number of somatic mutations identified preoperatively (n = 29 v n = 11) and a greater genomic heterogeneity ( P = .0069). The mean TMB score was 12.77 in those without pathologic response to cytotoxic therapy and 6.0 in those with pathologic response ( P = .10). All nine patients with sequential testing were positive preoperatively, compared with just three (33.3%) postoperatively ( P = .0090). Positive postoperative ctDNA was associated with the increased likelihood of disease recurrence after resection (57%) versus negative ctDNA (0%, P = .0419). CONCLUSION Routine ctDNA screening in patients with CCLM is logistically feasible. Liver resection and/or transplant may be associated with clearance of detectable ctDNA and a reduction in TMB or genomic heterogeneity. Persistence of ctDNA alterations postresection appears predictive of disease recurrence. Further studies are necessary to confirm these findings, and longitudinal ctDNA testing is needed to monitor changing tumor biology.