Biopsy-free circulating tumor DNA assay identifies actionable mutations in lung cancer
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Victoria Villaflor1, Brian Won2, Rebecca Nagy3, Kimberly Banks3, Richard B. Lanman3, AmirAli Talasaz3, Ravi Salgia4
1Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA
2University of Chicago School of Medicine, MC 2115, Chicago, IL 60637, USA
3Guardant Health, Redwood City, CA 94063, USA
4City of Hope, Duarte, CA 91010, USA
Victoria Villaflor, email: email@example.com
Ravi Salgia, email: firstname.lastname@example.org
Keywords: circulating tumor DNA, cell-free DNA, non-small cell lung cancer, next-generation sequencing
Received: April 17, 2016 Accepted: August 13, 2016 Published: September 01, 2016
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.
Richard B. Lanman
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