Timing might affect the results of an EGFR mutation–frequency circulating tumor DNA (ctDNA) test among patients with advanced non–small cell lung cancer (NSCLC), according to a study published in Thoracic Cancer.1

EGFR mutations predict response to tyrosine kinase inhibitors (TKIs) such as gefitinib, erlotinib, and afatinib. Unlike a direct tumor biopsy, “liquid biopsies” that analyze ctDNA are a non-invasive method of detecting EGFR mutations in a patient with advanced NSCLC.

False negatives are, however, common in ctDNA tests. For this study, researchers evaluated whether sampling time within 1 day affects test results.

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Twenty-two patients with stage IV NSCLC were enrolled. All patients were previously determined to harbor EGFR mutations in TKI-naive tumors and plasma.

The median mutation frequency was 7.13%. The frequency of detected mutations differed — though not significantly — between several time-points in 1 day.

One patient’s mutation status changed from L858R to wild type within the 1-day period.

Gefitinib was the first-line therapy for all included patients. Patients with a mutation frequency greater than 6.76% had a better response to gefitinib than those below this threshold.

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The authors noted some study limitations, which included a lack of nighttime testing and a small sample size. Nonetheless they concluded that ctDNA release may be “a temporal heterogenous process and different sampling time-points do not seem to influence [EGFR mutation] status in ctDNA.”


  1. Wang J, Bai H, Hong C, Wang J, Mei TH. Analyzing epidermal growth factor receptor mutation status changes in advanced non-small-cell lung cancer at different sampling time-points of blood within one day. Thorac Cancer. 2017 Apr 24. doi: 10.1111/1759-7714.12443 [Epub ahead of print]