Cell-free DNA from cerebrospinal fluid can be used to detect the EGFR mutation status of lung adenocarcinoma patients with central nervous system metastasis.

Background EGFR tyrosine kinase inhibitors (TKIs) have revolutionized the therapeutic approach for EGFR mutated patients. However, acquired resistance to EGFR-TKI therapy is unavoidable. Repeat biopsy cannot be used, and peripheral blood detection shows a low positive rate in cases of brain-only disease progression. Methods Droplet digital polymerase chain reaction (PCR) (ddPCR) was performed on the plasma and cerebrospinal fluid (CSF) samples of 79 lung adenocarcinoma (LUAD) patients with EGFR mutations and central nervous system (CNS) metastasis. The differences in the EGFR mutation status between the paired plasma and CSF samples were assessed, and the role of CSF testing as a predictor of overall survival was evaluated. Results The CSF of patients with neurological symptoms, EGFR-TKI treatment, or leptomeningeal metastasis (LM) had a significantly higher positive rate of EGFR mutation compared to the plasma samples (P=0.001, P=0.035, P=0.019, respectively). Moreover, EGFR mutation status in CSF was consistent with neurological symptoms and LM (kappa =0.455, P<0.001; kappa =0.508, P<0.001; respectively). For the patients with brain metastasis, EGFR mutation-positive rate in CSF samples was lower than that in plasma samples (28.3% vs. 64.2%, P<0.001), while the patients with LM had the opposite result (84.6% vs. 38.5%, P=0.004). Moreover, patients with EGFR mutation in their CSF experienced worse survival [hazard ratio (HR) =2.93, 95% confidence interval (CI): 1.45-5.92; P=0.003, P adjust <0.0001]. Conclusions The EGFR mutation status of CSF was different from that of plasma and is correlated with patient prognosis. CSF could be helpful in detecting the EGFR mutation status of patients, particularly in cases of LM.