Dynamic Monitoring of Circulating Tumor DNA in Patients With Metastatic Colorectal Cancer.

Abstract

Plasma circulating tumor DNA (ctDNA) is a valuable resource for tumor characterization and for monitoring of residual disease during treatment; however, it is not yet introduced in metastatic colorectal cancer (mCRC) routine clinical practice. In this retrospective exploratory study, we evaluated the role of ctDNA in patients with mCRC treated with chemotherapy plus bevacizumab. Fifty-three patients were characterized for <i>RAS</i> and <i>BRAF</i> status on tumor tissue before the start of treatment. Plasma was collected at baseline, at first clinical evaluation, and at disease progression. ctDNA analysis was performed using Oncomine Colon cfDNA Assay on the Ion S5 XL instrument. At baseline, from a plasma sample, <i>RAS</i>, <i>BRAF</i>, or <i>PIK3CA</i> mutations were detected in 44 patients. A high correspondence was observed between ctDNA and tumor tissue mutations (<i>KRAS</i> 100%, <i>NRAS</i> 97.9%, <i>BRAF</i> 97.9%, <i>PIK3CA</i> 90%). Low baseline variant allele frequency (VAF) was found to be associated with longer median progression-free survival (PFS) compared with those with high VAF (15.9 <i>v</i> 12.2 months, <i>P</i> = .02). A higher PFS {12.29 months (95% CI, 9.03 to 17.9) <i>v</i> 8.15 months (95% CI, 2.76 to not available [NA]), <i>P</i> = .04} and overall survival (34.1 months [95% CI, 21.68 to NA] <i>v</i> 11.1 months [95% CI, 3.71 to NA], <i>P</i> = .003) were observed in patients with large decline in VAF at first evaluation. ctDNA analysis is useful for molecular characterization and tumor response monitoring in patients with mCRC. Quantitative variations of released ctDNA are associated with clinical outcomes.