9 months (95% CI, 6.5 to 9.2) than 5.7 months (95% CI, 2.1 to 9.2) for patients without mutations (P = 0.889, Figure 1C). Moreover, PFS of patients with EGFR mutant tumors was
consistent to that of patients CX-5461 supplier with EGFR mutant cfDNA in plasma (P = 0.094) and serum (P = 0.176), whereas PFS of patients with wild-type tumor was significantly shorter than that of patients with wild-type cfDNA in plasma (P = 0.023) and serum (P = 0.023). Further, all 68 patients received EGFR-TKIs were stratified into 4 subgroups based on their mutational genotypes: (1) positive for EGFR activating mutations in both tumor tissue and blood (n = 20), (2) positive for EGFR activating mutations in tumor tissue but negative in blood (n = 18), (3) positive for EGFR activating mutations in blood but negative in tumor tissue (n = 4), and (4) negative for EGFR activating mutations in both tumor tissue and blood (n
= 26). PFS Selleckchem MDV3100 for each group was graphed in Figure 1D. Patients in subgroup two had a favorable PFS of 19.7 months (95% CI, 11.5 to 28.0), compared with 11.0 months (95% CI, 3.1 to 19.0) of those in subgroup one (P = 0.102) and 1.7 (95% CI, 0.9 to 2.5) months of those in subgroup three (P < 0.001). Patients in subgroup four had a comparable PFS of 2.3 months (95% CI, 0.3 to 4.3) with those in subgroup three (P = 0.508). EGFR mutation analysis is recommended in clinical practice to direct personalized management for NSCLC patients. This study demonstrates the possibility of using blood to detect EGFR mutations, PtdIns(3,4)P2 though tumor tissue remains the best sample. The concordance of EGFR mutation
status between blood and tumor tissue has been reported to be varying from 58.3% to 93.1%, with minimal false positive rate and variable false negative rate , , ,  and . This study showed that compared with matched tumor tissue the concordance rate in plasma and serum was 73.6% and 66.3%, respectively. ARMS for EGFR mutation detection in cfDNA showed low sensitivity but high specificity. High specificity led to low false positive rate, suggesting that EGFR mutations identified in blood may be highly predictive of identical mutations in corresponding tumor. Low sensitivity caused high false negative rate, which was responsible for the significantly lower EGFR mutation rate in blood compared with tumor tissue. Thus, EGFR mutation-negative results in blood should be interpreted with caution as more than half of patients with EGFR mutant tumors were not detected in cfDNA by ARMS. It is notable that 41 patients with mutant tumors had no detectable EGFR mutations in matched blood samples. This phenomenon has been observed in previous studies ,  and . The trace amount and low percentage of mutant cfDNA could be below the detection limit of ARMS, giving rise to false negative results in blood.