Insights into ctDNA assessment to detect minimal residual disease (MRD) in localized colorectal cancer
Detection of minimal residual disease (MRD) by circulating tumor DNA (ctDNA) analysis arises as a promising strategy for localized colorectal cancer (CRC) management. Here, ee present a pilot, prospective, single-center experience on ctDNA-based MRD detection with long-term follow-up and detailed clinical data.  Patients (n=47) with high-risk stage II and III colorectal adenocarcinoma were included. Tissue was sequenced with Oncomine Comprehensive Plus assay. Plasma (4 weeks post-surgery) was sequenced with Avenio ctDNA Targeted Panel V2 assays. ctDNA positivity was defined according to different criteria for their evaluation as predictive biomarkers. Follow-up plasma samples were sequenced for selected patients.   Predictive values varied depending on ctDNA positivity criteria. Only blood findings rendered a sensitivity and specificity of 37.5% and 84.6%, respectively. The “tissue-based” criteria increased sensitivity and specificity to 50% and 97.4%, respectively. Low concordance between tissue and plasma was observed, up to 40% of patients presenting variants only in plasma. Lung and peritoneal relapses were undetected by ctDNA.  Our data support evidence on the potential of ctDNA analyses to detect MRD in high-risk stage II and III CRC. Important limitations, mainly sensitivity values need to be addressed. Further analyses are needed in order to position this technique in the routine clinical practice.
Detection of minimal residual disease (MRD) by circulating tumor DNA (ctDNA) analysis arises as a promising strategy for localized colorectal cancer (CRC) management. Here, ee present a pilot, prospective, single-center experience on ctDNA-based MRD detection with long-term follow-up and detailed clinical data.  Patients (n=47) with high-risk stage II and III colorectal adenocarcinoma were included. Tissue was sequenced with Oncomine Comprehensive Plus assay. Plasma (4 weeks post-surgery) was sequenced with Avenio ctDNA Targeted Panel V2 assays. ctDNA positivity was defined according to different criteria for their evaluation as predictive biomarkers. Follow-up plasma samples were sequenced for selected patients.   Predictive values varied depending on ctDNA positivity criteria. Only blood findings rendered a sensitivity and specificity of 37.5% and 84.6%, respectively. The “tissue-based” criteria increased sensitivity and specificity to 50% and 97.4%, respectively. Low concordance between tissue and plasma was observed, up to 40% of patients presenting variants only in plasma. Lung and peritoneal relapses were undetected by ctDNA.  Our data support evidence on the potential of ctDNA analyses to detect MRD in high-risk stage II and III CRC. Important limitations, mainly sensitivity values need to be addressed. Further analyses are needed in order to position this technique in the routine clinical practice.
Navarrabiomed