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Updated: Mar 15, 2026
Detection and Monitoring of Tumor Associated Circulating DNA in Patient Biofluids
Published on: June 8, 2019
Biopsy-free circulating tumor DNA assay identifies actionable mutations in lung cancer
Victoria Villaflor1, Brian Won2, Rebecca Nagy3
1Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
Introduction:
The potential of oncogene-driven targeted therapy is perhaps most fully realized in non-small cell lung cancer (NSCLC), given the number of genomic targets and approved matched therapies. However, invasive tissue biopsy at the time of each disease progression may not be possible and is associated with high morbidity and cost. Use of newly available "liquid biopsies" can circumvent these issues.
Results:
83% of subjects had at least one genomic alteration identified in plasma. Most commonly mutated genes were TP53, KRAS and EGFR. Subjects with no detectable ctDNA were more likely to have small volume disease, lepidic growth pattern, mucinous tumors or isolated leptomeningeal disease.
Methods:
Subjects were individuals with NSCLC undergoing analysis of cell-free circulating tumor DNA using a validated, commercially-available next-generation sequencing assay at a single institution. Demographic, clinicopathologic information and results from tissue and plasma-based genomic testing were reviewed for each subject.
Conclusions:
This is the first clinic-based series of NSCLC patients assessing outcomes of targeted therapies using a commercially available ctDNA assay. Over 80% of patients had detectable ctDNA, concordance between paired tissue and blood for truncal oncogenic drivers was high and patients with biomarkers identified in plasma had PFS in the expected range. These data suggest that biopsy-free ctDNA analysis is a viable first choice when the diagnostic tissue biopsy is insufficient for genotyping or at the time of progression when a repeated invasive tissue biopsy is not possible/preferred.
Insights
Liquid biopsies detect genomic alterations in 83% of non-small cell lung cancer (NSCLC) patients, offering a viable alternative to invasive tissue biopsies for guiding targeted therapy.
Area of Science:
- Oncology
- Genomics
- Molecular Diagnostics
Background:
- Non-small cell lung cancer (NSCLC) treatment benefits from oncogene-driven targeted therapies.
- Invasive tissue biopsies for genomic profiling can be challenging due to morbidity and cost.
- Liquid biopsies offer a less invasive alternative for genomic analysis.
Purpose of the Study:
- To assess the utility of a commercially available cell-free circulating tumor DNA (ctDNA) assay in NSCLC patients.
- To evaluate the concordance between tissue and plasma-based genomic testing.
- To determine the feasibility of biopsy-free ctDNA analysis for guiding targeted therapy.
Main Methods:
- Analysis of cell-free circulating tumor DNA (ctDNA) using a validated, commercially available next-generation sequencing assay.
- Review of demographic, clinicopathologic, and genomic testing results from paired tissue and plasma samples.
- Retrospective review of a single-institution NSCLC patient cohort.
Main Results:
- 83% of NSCLC subjects had detectable genomic alterations in plasma ctDNA.
- TP53, KRAS, and EGFR were the most commonly mutated genes.
- High concordance was observed between tissue and plasma for truncal oncogenic drivers.
Conclusions:
- Commercially available ctDNA assays can detect genomic alterations in over 80% of NSCLC patients.
- Biopsy-free ctDNA analysis is a viable option when tissue biopsy is insufficient or repeated invasive procedures are not feasible.
- Plasma-based genomic profiling supports targeted therapy decisions in NSCLC.
