'Plasma first' approach for detecting epidermal growth factor receptor mutation in advanced non-small cell lung carcinoma.

The treatment approach for recently diagnosed advanced non-small cell lung cancer (NSCLC) with EGFR mutations primarily relies on confirming the tissue diagnosis as non-squamous NSCLC. This routine clinical practice of tissue diagnosis imposes several barriers and delays in turnaround time (TAT) for biomarker testing, significantly delaying the time to treatment. The objective of this study is to investigate the 'plasma first' approach for detection of EGFR mutation in advanced stage treatment naïve NSCLC patients. We prospectively collected blood samples of treatment naïve patients with clinical and radiological suspicion of advanced stage NSCLC prior to obtaining tissue biopsy. Plasma cfDNA was tested for EGFR mutation using two different methods. We compared the sensitivity and TAT of liquid biopsy with tissue biopsy. In total, we analyzed plasma cell-free DNA (cfDNA) of 236 patients suspected of having advanced NSCLC for EGFR mutations. We observed a notably shorter turnaround time (TAT) of 3 days, which was significantly quicker compared to the 12-day TAT for tissue biopsy (p < 0.05). The ddPCR method had a sensitivity of 82.8%, which was higher than 66.34% sensitivity of ARMS-PCR. The current study also highlights that there is no significant difference in the clinical outcome of the patients whether treated based on liquid biopsy only or tissue biopsy (median progression-free survival of 11.56 vs. 11.9 months; p = 0.94). Utilizing a 'plasma first' strategy, given its shorter turnaround time, strong positive concordance and comparable outcomes to tissue biopsy, emerges as a highly specific and reliable method for detecting EGFR mutations in advanced-stage NSCLC.

Rathor A ，Malik PS ，Tanwar P ，Khurana S ，Baskarane H ，Pushpam D ，Nambirajan A ，Jain D ... -  《-》

Lessons learned from routine, targeted assessment of liquid biopsies for EGFR T790M resistance mutation in patients with EGFR mutant lung cancers.

Mondaca S ，Offin M ，Borsu L ，Myers M ，Josyula S ，Makhnin A ，Shen R ，Riely GJ ，Rudin CM ，Ladanyi M ，Yu HA ，Li BT ，Arcila ME ... -  《-》

Correlation of epidermal growth factor receptor mutation status in plasma and tissue samples of patients with non-small cell lung cancer.

Roh MS ，Yoon NB ，Lee S ，Kang BH ，Um SJ ，Lee DH ，Son C ... -  《-》

Molecular profiling and utility of cell-free DNA in nonsmall carcinoma of the lung: Study in a tertiary care hospital.

Ghosh M ，Mukhopadhyay M ，Das C ，Chatterjee S ，Naskar BG ... -  《-》

A Comparison of ddPCR and ARMS for detecting EGFR T790M status in ctDNA from advanced NSCLC patients with acquired EGFR-TKI resistance.

A sensitive and convenient method for detecting epidermal growth factor receptor (EGFR) T790M mutations from circulating tumor DNA (ctDNA) in advanced non-small cell lung cancer (NSCLC) patients with acquired EGFR-TKI resistance would be desirable to direct patient sequential treatment strategy. A comparison of two platforms for detecting EGFR mutations in plasma ctDNA was undertaken. Plasma samples and tumor samples were collected from patients with acquired EGFR-TKI resistance in Zhejiang Cancer Hospital from December 2014 to December 2015. Extracted ctDNA was analyzed using two platforms (Droplet Digital PCR and ARMS [dPCR]). A total of 108 patients were enrolled in this study. One hundred and eight patient plasma samples were detected by ddPCR and 75 were detected by ARMS. And 16 patients obtained tissue re-biopsy, using ARMS assay for detecting EGFR T790M mutation. In all, 43.7% (47/108) had acquired T790M mutation by ddPCR. In 75 patient plasma samples, comparing ddPCR with ARMS, the rates of T790M mutation were 46.7% (35/75) and 25.3% (19/75) by ddPCR and ARMS, respectively. Of all, 16 patients both had tumor and plasma samples, the T790M mutation rates were 56.3% (9/16) by ARMS in tissue and 50.5% (8/16) by ddPCR in plasma ctDNA. The progression mode tended to gradual progression in T790M mutation patients (40.4%), but the T790M negative was inclined to the mode of dramatic progression (39.3%). The patients with T790M-positive tumors had a longer time to disease progression after treatment with EGFR-TKIs (median, 13.1 months vs. 10.8 months; P = 0.010) and overall survival (median, 35.3 months vs. 30.3 months; P = 0.214) compared with those with T790M-negative patients. Our study demonstrates ddPCR assay may provide a highly sensitive method to detect EGFR T790M gene in plasma. And T790M-positive patients have better clinical outcomes to EGFR-TKIs than T790M-negative patients.

Wang W ，Song Z ，Zhang Y 《Cancer Medicine》