<p>Detection of minimal residual disease (MRD) by circulating tumor DNA (ctDNA) analysis arises as a promising strategy for localized colorectal cancer (CRC) management. Here, we 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&#xa0;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 biomarker. 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.</p>

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Insights into ctDNA assessment to detect minimal residual disease (MRD) in localized colorectal cancer

  • Ibone Labiano,
  • David Guerrero-Setas,
  • Ana Elsa Huerta,
  • Elena Mata,
  • Gorka Alkorta-Aranburu,
  • Gonzalo R Ordoñez,
  • Pedro Berraondo,
  • Arturo Lecumberri,
  • Patricia Ochoa,
  • Irene Caseda,
  • Rosalinda Termini,
  • Borja Agirre-Mikelarena,
  • Irene Amat,
  • Natalia Castro,
  • Hugo Arasanz,
  • Maria Alsina,
  • Ruth Vera

摘要

Detection of minimal residual disease (MRD) by circulating tumor DNA (ctDNA) analysis arises as a promising strategy for localized colorectal cancer (CRC) management. Here, we 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 biomarker. 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.