Biopsy-free circulating tumor DNA assay identifies actionable mutations in lung cancer.
BACKGROUND
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.
Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
Victoria
V
Villaflor
University of Chicago School of Medicine, MC 2115, Chicago, IL 60637, USA.
Brian
B
Won
Guardant Health, Redwood City, CA 94063, USA.
Rebecca
R
Nagy
Guardant Health, Redwood City, CA 94063, USA.
Kimberly
K
Banks
Guardant Health, Redwood City, CA 94063, USA.
Richard B
RB
Lanman
Guardant Health, Redwood City, CA 94063, USA.
AmirAli
A
Talasaz
City of Hope, Duarte, CA 91010, USA.
Ravi
R
Salgia
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood / Q000175:diagnosis / Q000235:genetics*; D000074141:Circulating Tumor DNA / Q000032:analysis*; D004273:DNA, Neoplasm / Q000032:analysis*; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000235:genetics; D005260:Female; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods; D006801:Humans; D000073890:Liquid Biopsy / Q000379:methods; D008168:Lung / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008175:Lung Neoplasms / Q000097:blood / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009360:Neoplastic Cells, Circulating / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D055815:Young Adult
D014408:Biomarkers, Tumor; D000074141:Circulating Tumor DNA; D004273:DNA, Neoplasm; D066246:ErbB Receptors
cell-free DNA; circulating tumor DNA; next-generation sequencing; non-small cell lung cancer