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 recrudesce within one or two years, and many of them progress in the central nerve system (CNS). Owing to the blood–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) may become an alternative 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 information were also collected at the same time.
The rate of EGFR mutations in blood (15/41, 36.6%) was obviously higher than that in CSF (24/37, 64.9%) (P = 0.013), especially in those with EGFR exon 19del mutation patients (13/16 vs 7/18, P = 0.017), without EGFR TKIs treated patients (8/11 vs 3/13, P = 0.038) and less than 60 years patients (17/22 vs 10/25, 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).
The EGFR mutation status in blood are different from that in CSF in patients with EGFR mutations and CNS metastasis. CNS symptoms and MRI indicating leptomeningeal metastasis are closely related with EGFR mutations status in CSF. Detecting EGFR mutation status in both extracranial and intracranial tumors will be helpful to make precise treatment, and detecting in blood and CSF with ddPCR may be an alternative.
Clinical trial identification
Legal entity responsible for the study
The Affiliated Cancer Hospital of Zhengzhou University
All authors have declared no conflicts of interest.
|≥ 60||16 (39)|
|< 60||25 (61)|
|Brain metastases (MRI)|
|Only metastatic tumors||30 (73.2)|
|With meningeal lesions||11 (26.8)|
|Brain metastatic tumor number|
|Prior TKIs treat|
|CSF EGFR mutation|
|Blood EGFR mutation|