Single-center Experience with Comprehensive Genomic Profiling Using Circulating Tumor DNA for Metastatic Colorectal Cancer
TL;DR
Re-evaluation of molecular profiles using ctDNA enabled the exploratory identification of NeoRAS wild-type patients, who could potentially benefit from anti-EGFR therapy, in a real-world setting.
Abstract
Comprehensive genomic profiling (CGP) using circulating tumor DNA (ctDNA) has recently become available in Japan, but its clinical utility in daily practice remains unclear. We retrospectively evaluated 19 patients with metastatic colorectal cancer (mCRC) who underwent plasma-based CGP (Guardant360 CDx) between November 2023 and May 2025. ctDNA was detected in 18 of 19 patients (95%) with previously treated mCRC. The median turnaround time from blood collection to result was 11 days (range: 7–15). The median number of gene alterations was 5 (range: 1–29), and pathogenic/likely pathogenic alterations were identified in 15 patients (79%). ctDNA was preferentially selected over tissue CGP in patients with small tumor burden, lack of contemporary tumor sample, or double cancer (considering spatial and temporal heterogeneity). Three patients initially identified with RAS mutant tumors by tissue were subsequently identified as RAS wild-type by plasma CGP. Those were treated with anti-epidermal growth factor receptor (EGFR) therapy, resulting in partial response or stable disease. These observations suggest that plasma-based CGP may provide additional molecular information that could be clinically informative in mCRC in a real-world setting. Although the findings should be interpreted as exploratory, re-evaluation of molecular profiles using ctDNA enabled the exploratory identification of NeoRAS wild-type patients, who could potentially benefit from anti-EGFR therapy.