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

BACKGROUND: We investigated whether different sampling time‐points within one day would influence epidermal growth factor receptor mutation (EGFRm) status in plasma and evaluated the clinical outcomes according to the quantity analysis of EGFRm in circulating tumor DNA (ctDNA) in non‐small‐cell lung cancer (NSCLC). METHODS: EGFR‐tyrosine kinase inhibitor naïve advanced NSCLC patients who carried EGFRm in both tissues and ctDNA were enrolled in this study. Plasma samples were collected at three time‐points within one day (at 8 am, 11 am and 2 pm) for EGFRm analysis by droplet digital PCR. RESULTS: Twenty‐two advanced NSCLC patients were enrolled in the study. In a total of 66 blood specimens, the median EGFRm frequency was 7.13% (range 0–35.09%), and among them six specimens had less than 1.0% EGFRm frequency. Moreover, one time‐point blood specimen did not display any EGFRm, even by droplet digital PCR. The frequency of EGFRm changed dynamically across different time‐points within one day, but the differences were not significant (P = 0.557). We observed that patients with a relatively high frequency of EGFRm (>6.76%) had a better response to gefitinib (P = 0.024). CONCLUSION: The release of ctDNA maybe a temporal heterogenous process. The different sampling time‐points within one day did not seem to influence EGFRm status in ctDNA. The relative EGFRm frequency in ctDNA could predict a benefit of EGFR‐tyrosine kinase inhibitor treatment for advanced NSCLC patients.