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Clinical utilization of a CLIA-certified cell-free DNA (cfDNA) blood test for identification of targetable molecular alterations in patients with non-small cell lung cancer (NSCLC).
Background: The availability to have tumor genomic information from simple blood collection can significantly impact patient care. We report the clinical utility of a CLIA-certified cfDNA next generation sequencing (NGS) blood test in our patients (pts) with NSCLC. Methods: From April 2015 to January 2016, blood samples from 50 NSCLC pts were analyzed using cfDNA NGS with a panel of 70 cancer-related genes at a CLIA-certified lab (Guardant360, Guardant Health, Redwood City, CA) with reported sensitivity of 0.1% mutant allele fraction with high specificity ( > 99.9999%) (PLoS One, 10(10), 2015). Results: Fifty-three Guardant360 tests were completed in 50 pts (28/F:22/M); histology: adenocarcinoma(47), squamous(2) and sarcomatoid(1). Rationale for blood tests: insufficient tissue(32%), addition to tissue analysis(32%), alternative to tissue biopsy(13%), treatment evaluation/resistant(20.7%), no documentation(1.8%). Based on Guardant360 results, 37 pt samples demonstrated either no alterations(n = 8) or alterations that were not targetable(n = 29); concordance with at least 1 genomic alteration from paired tissue analysis in 8 pt samples and new genomic alterations dictating change in therapies in another 8 pts included: EGFR-T790M(n = 4), EML4-ALK fusion(n = 2), EGFR-e19del(n = 1), multikinase targets(n = 1). Serial testing was done in 2 cases, one had no targetable molecular alterations, with confirmation from tissue at second testing. The other pt had 3 serial tests over a 8-month period; while on erlotinib-based therapy, 1st test revealed EGFR-e19del at 0.31%, decreasing to 0.18% 4 months later; then, at progression, showed increased to 0.54% with appearance of EGFR-T790M (0.23%). At which time osimertinib was initiated. Complete clinical outcomes will be updated. Conclusions: Molecular testing of cfDNA is a simple, minimally invasive test when tissue sample is not available or inadequate for molecular analysis. It is particularly useful in the long-term management of patients for monitoring of emergence and confirmation of resistance-associated molecular alterations; such as EGFR-T790M.
Abstracts by Hai T. Tran:
Meeting: 2016 ASCO Annual Meeting
| Abstract No: e23222
Category: Tumor Biology - Tumor-Based Biomarkers
Association of prior treatment with anti-EGFR monoclonal antibodies with downregulation of circulating TRAIL and upregulation of EGFR and VEGF family ligands in metastatic colorectal cancer.Meeting: 2014 Gastrointestinal Cancers Symposium | Abstract No: 452