Analysis of EGFR mutation status in blood and CSF in lung adenocarcinoma patients with EGFR mutation and CNS metastasis by ddPCR

Abstract

Background: Patients with non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations benefit a great deal from EGFR tyrosine kinase inhibitors (TKIs). However, most patients get recrudesced within one or two years, and many of them progressed in central nerve system (CNS). Owing to the bloode brain barrier, detecting tumor-derived cell-free DNA (cfDNA) in the blood of brain metastasis tumor patients is challenging. Detecting tumor-specific mutations in cerebral spinal fluid (CSF) became an alternative method. Method: 41 initial or progressed lung adenocarcinoma patients with EGFR mutation and CNS metastasis from Henan Cancer Hospital were included in this study. 41 patients were all detected EGFR mutation status in CSF with dropplet digital PCR (ddPCR) and 37 in 41 patients were detected EGFR mutation status in blood with the same method. Their clinical informations were also collected at the same time. Result: The rate of EGFR mutations in CSF (15/41, 36.6%) were obviously lower than that in blood (24/37, 64.9%) (P=0.013), especially in those with EGFR exon 19del mutation patients (7/18 vs 13/16, P = 0.017), without TKIs treated patients (3/13 vs 8/11, P = 0.038) and less than 60 years patients (10/25 vs 17/22, P = 0.010). In patients with CNS symptoms positive, the rate of EGFR mutations in CSF was higher than those negative (13/27 vs 2/14 , P=0.033). In patients with MRI indicating leptomeningeal metastasis, the rate of EGFR mutations in CSF was higher than those not indicating(8/11 vs 7/30 , P=0.003). Conclusion: The EGFR mutations status in CSF is different from that in blood in patients with EGFR mutation and CNS metastasis. This warrants confirmation in larger cohorts and further more studies are needed to find out the internal mechanism. Detecting EGFR mutations status in both blood and CSF will be helpful to make individualized treatment. (Table Presented).