P2.03b-010 EGFR Mutation Status Analysis in Cerebrospinal Fluid and Plasma of Advanced Lung Adenocarcinoma with Brain Metastases: Topic: Brain Meta

Abstract

We aimed to investigate the feasibility of droplet digital PCR (ddPCR) for the detection of epidermal growth factor receptor (EGFR) mutations in circulating free DNA (cfDNA) from cerebrospinal fluid (CSF) and plasma of advanced Lung Adenocarcinoma (ADC) with brain metastases (BM). Fourteen advanced ADC patients with BM carrying activating EGFR mutations in tumor tissues were enrolled in this study, and their matched CSF and plasma samples were collected. EGFR mutations were detected by the Amplification Refractory Mutation System (ARMS) in tumor tissues. EGFR mutations, including 19del, L858R, and T790M were examined in cfDNA isolated from 2 milliliter CSF or plasma by ddPCR assay. The clinical response was assessed according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 guidelines. Overall survival (OS) and progression free survival (PFS) after the diagnosis of BM were also evaluated. Out of 14 patients, eleven were females and three males aged from 34 to 74 years old (median age of 55 years old). In all of cases, CSF cytology were negative. In ddPCR assays, EGFR mutations were detected in CSF of three patients (21.4%; one of 19del and two of L858R), and in plasma of six patients (42.9%; one of 19del, one of L858R, one of T790M, two of L858R&T790M, and one of 19del&T790M). All EGFR T790M mutations were found during or after EGFR-TKIs treatments. The three patients with activating EGFR mutations in CSF achieved partial response (PR) of BM after treated with combination of WBRT and EGFR-TKIs. The median OS and PFS after the diagnosis of BM were 18.0 months and 9.0 months, respectively.Tabled 1PatientTissue EGFRCSF EGFRPlasma EGFRSystematic TreatmentBM Treatment119delWTT790MErotinib+ChemotherapyWBRT+Gamma knife219delWT19delErotinib+ChemotherapyWBRT3L858RL858RL858RGefitinib+ChemotherapyWBRT4L858RWTWTGefitinib+ChemotherapyWBRT519delWTWTGefitinib+ChemotherapyWBRT6L858RWTL858R/T790MErotinib+ChemotherapyWBRT7L858RWTWTGefitinibWBRT819del19Del19Del/T790MGefitinibWBRT9L858RWTWTErotinib+ChemotherapyNONE1019delWTWTErotinib+ChemotherapyWBRT1119delWTWTIcotinib+ChemotherapyWBRT12L858RWTL858R/T790MChemotherapyWBRT13L858RL858RWTIcotinibWBRT1419delWTWTGefitinib+ChemotherapyWBRT Open table in a new tab It was feasible to test EGFR mutation in CSF. CSF may serve as liquid biopsy of advanced ADC with BM by enabling measurement of cfDNA within CSF to characterize EGFR mutations.