Conventional real-time PCR-based detection of T790M using tumor tissue or blood in patients with EGFR TKI-resistant NSCLC

Blood biopsy has many advantages over tissue biopsy for diagnosing acquired T790M mutation in patients with non-small-cell lung cancer, such as being less risky and painful. New techniques with high sensitivity (eg, droplet digital PCR) show promising results during blood biopsy, but the positive rates of identification are still quite unclear. Whether there are other factors, except technology, affecting the results of blood biopsy is unclear. In this study, we used conventional amplification refractory mutation system to detect tumor tissue or blood for T790M mutation in patients clinically resistant to tyrosine kinase inhibitors. A total of 45 patients treated at West China Hospital between 2014 and 2016 were analyzed. The positive rate of T790M mutation was 70.8% based on tissue biopsy and 37.5% based on blood biopsy. Of the 24 patients whose epidermal growth factor receptor gene was genotyped through tissue and blood biopsy, 10 (41.7%) were concordant for T790M mutation status (κ=0.006). Of the 17 patients positive for T790M by tissue biopsy, 7 (41.2%) were positive for T790M by blood biopsy, and 3 of these 7 were only weakly positive. Of the 7 patients negative for T790M by tissue biopsy, 2 (28.6%) were positive by blood biopsy. Our T790M detection rate is higher than that reported by other studies using digital droplet PCR. These results suggest that other factors (eg, clinical features), intrinsically connected with circulating tumor DNA level, also affect the results of blood biopsy, and thus cannot be controlled through technological optimization.