Longitudinal monitoring of ctDNA EGFR mutation burden from urine correlates with patient response to EGFR TKIs: A case series

Lung Cancer. 2017 Jun:108:22-28. doi: 10.1016/j.lungcan.2017.02.010. Epub 2017 Feb 20.

Abstract

Targetable, somatic EGFR mutations are highly prevalent in patients with non-small cell lung cancer (NSCLC), making them eligible for tyrosine kinase inhibitor (TKI) therapy. Circulating tumor DNA (ctDNA), isolated from blood or urine, has been demonstrated to reliably identify somatic tumor associated EGFR mutations, specifically in patients with inconclusive biopsy. When conventional imaging modalities are inconclusive, quantitative assessment of systemic ctDNA burden has the potential to assess therapeutic response. We report on the clinical use of non-invasive, urinary ctDNA liquid biopsies for the ultrasensitive detection and longitudinal monitoring of ctDNA EGFR systemic mutation burden in five patients with NSCLC treated with EGFR TKIs. Urinary ctDNA-based quantitative assessment of systemic EGFR mutant allele burden is a non-invasive molecular diagnostic testing modality that has the potential to be utilized as an ancillary tool to assess disease burden and response to therapy.

Keywords: Circulating tumor DNA; EGFR; Longitudinal monitoring; Non-small cell lung cancer; Systemic mutation burden; Tyrosine kinase inhibitors.

Publication types

  • Case Reports

MeSH terms

  • Alleles
  • Amino Acid Substitution
  • Antineoplastic Agents / therapeutic use
  • Biopsy
  • Carcinoma, Non-Small-Cell Lung / diagnosis
  • Carcinoma, Non-Small-Cell Lung / drug therapy
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / mortality
  • Circulating Tumor DNA*
  • DNA, Neoplasm / urine*
  • ErbB Receptors / genetics*
  • Female
  • Humans
  • Longitudinal Studies
  • Lung Neoplasms / diagnosis
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / mortality
  • Magnetic Resonance Imaging / methods
  • Middle Aged
  • Mutation*
  • Protein Kinase Inhibitors / therapeutic use
  • Tomography, X-Ray Computed
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • Circulating Tumor DNA
  • DNA, Neoplasm
  • Protein Kinase Inhibitors
  • ErbB Receptors