Circulating Tumor DNA Minimal Residual Disease Detection of Non-Small-Cell Lung Cancer Treated With Curative Intent

J Clin Oncol. 2022 Feb 20;40(6):567-575. doi: 10.1200/JCO.21.01929. Epub 2022 Jan 5.

Abstract

Circulating tumor DNA (ctDNA) minimal residual disease (MRD) is a powerful biomarker with the potential to improve survival outcomes for non-small-cell lung cancer (NSCLC). Multiple groups have shown the ability to detect MRD following curative-intent NSCLC treatment using next-generation sequencing-based assays of plasma cell-free DNA. These studies have been modest in size, largely retrospective, and without thorough prospective clinical validation. Still, when restricting measurement to the first post-treatment timepoint to assess the clinical performance of ctDNA MRD detection, they have demonstrated sensitivity for predicting disease relapse ranging between 36% and 100%, and specificity ranging between 71% and 100%. When considering all post-treatment follow-up timepoints (surveillance), including those beyond the initial post-treatment measurement, these assays' performances improve with sensitivity and specificity for identifying relapse ranging from 82% to 100% and 70% to 100%, respectively. In this manuscript, we review the evidence available to date regarding ctDNA MRD detection in patients with NSCLC undergoing curative-intent treatment and the ongoing prospective studies involving ctDNA MRD detection in this patient population.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Biomarkers / blood
  • Carcinoma, Non-Small-Cell Lung / blood
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / secondary
  • Carcinoma, Non-Small-Cell Lung / therapy*
  • Circulating Tumor DNA / blood
  • Circulating Tumor DNA / genetics*
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Lung Neoplasms / blood
  • Lung Neoplasms / genetics
  • Lung Neoplasms / pathology
  • Lung Neoplasms / therapy*
  • Neoplasm Recurrence, Local
  • Neoplasm, Residual
  • Predictive Value of Tests
  • Reproducibility of Results
  • Risk Assessment
  • Risk Factors
  • Time Factors
  • Treatment Outcome

Substances

  • Biomarkers
  • Circulating Tumor DNA