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Detection and Monitoring of Tumor Associated Circulating DNA in Patient Biofluids
06:53

Detection and Monitoring of Tumor Associated Circulating DNA in Patient Biofluids

Published on: June 8, 2019

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A method for treatment monitoring using circulating tumour DNA in cancer patients without targetable mutations

Christina Demuth1, Anne Winther-Larsen1, Anne Tranberg Madsen1

  • 1Department of Clinical Biochemistry, Aarhus University Hospital, Aarhus, Denmark.

Oncotarget
|August 21, 2018
PubMed
Abstract

Insights

Circulating tumor DNA (ctDNA) monitoring using next-generation sequencing and ddPCR can detect non-response early in non-small cell lung cancer patients lacking targetable mutations, supplementing imaging. This aids treatment decisions for a wider patient group.

Area of Science:

  • Oncology
  • Molecular Diagnostics
  • Genomics

Background:

  • Circulating tumor DNA (ctDNA) shows potential for non-invasive disease monitoring in cancer patients with targetable mutations.
  • However, most cancer patients lack targetable mutations, limiting current ctDNA applications.
  • A combined workflow of targeted next-generation sequencing (NGS) and droplet digital PCR (ddPCR) may enable treatment monitoring for these patients.

Purpose of the Study:

  • To evaluate a ctDNA monitoring workflow using NGS and ddPCR for non-small cell lung cancer (NSCLC) patients without targetable mutations.
  • To assess the utility of this workflow in predicting treatment response or non-response.

Main Methods:

  • Prospective study of 40 NSCLC patients.
  • Plasma samples collected pre-treatment and during therapy.
  • Targeted NGS on pre-treatment ctDNA to identify mutations, followed by ddPCR for monitoring in serial samples.

Main Results:

  • Mutations were detected in 21 patients, with TP53 and KRAS being the most common.
  • An increase in ctDNA concentration was observed in 16 of 18 patients with discontinued treatment due to non-response.
  • A twofold ctDNA increase in a second sample predicted non-response on subsequent imaging in 83% of patients.

Conclusions:

  • ctDNA monitoring is effective for early detection of non-response in NSCLC patients without targetable mutations.
  • This approach can supplement imaging data for treatment monitoring in this patient subset.
  • Enables personalized treatment adjustments based on molecular response.
Keywords:
circulating tumour DNAdigital PCRnext-generation sequencingnon-small cell lung cancerwild-type EGFR

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