EGFR mutation status of paired cerebrospinal fluid and plasma samples in EGFR mutant non-small cell lung cancer with leptomeningeal metastases.
PURPOSE
Central nervous system (CNS) is the prevalent site for metastases in epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI)-relapsed NSCLC patients. To understand the EGFR mutation status in paired cerebrospinal fluid (CSF) and plasma samples after EGFR-TKI treatment failure might be useful to guide the treatment of intra- and extracranial tumors in those patients.


METHODS
Paired CSF and plasma samples were collected from seven NSCLC patients with CNS metastases after EGFR-TKI failure. EGFR mutations were tested by amplification refractory mutation system (ARMS) and droplet digital PCR (ddPCR) methods. Gefitinib concentrations were evaluated by high-performance liquid chromatography-mass spectrometry (HPLC-MS/MS).


RESULTS
EGFR mutations were detected in all seven CSF samples, including three of E19-Del, three of L858R and one of E19-Del&T790M by both methods. On the other hand, majority of the matched plasma samples (5/7) were negative for EGFR mutations by both methods. The other two plasma samples were positive for E19-Del&T790M by ddPCR, and one of them had undetectable T790M by ARMS. Gefitinib concentration in CSF was much lower than that in plasma (mean CSF/plasma ratio: 1.8 %).


CONCLUSIONS
After EGFR-TKI failure, majority of the NSCLC patients with CNS metastases remained positive detection of EGFR sensitive mutations in CSF, but much less detection in the matched plasma. Significantly low exposure of gefitinib in CSF might explain the intracranial protection of the EGFR sensitive mutation positive tumor cells.
['Zhao|Jing|J|', 'Ye|Xin|X|', 'Xu|Yan|Y|', 'Chen|Minjiang|M|', 'Zhong|Wei|W|', 'Sun|Yun|Y|', 'Yang|Zhenfan|Z|', 'Zhu|Guanshan|G|', 'Gu|Yi|Y|', 'Wang|Mengzhao|M|']
D000328:Adult D002289:Carcinoma, Non-Small-Cell Lung D066246:ErbB Receptors D005260:Female D000077156:Gefitinib D006801:Humans D008175:Lung Neoplasms D008297:Male D008577:Meningeal Neoplasms D008875:Middle Aged D009154:Mutation D011799:Quinazolines
Cerebrospinal fluid Non-small cell lung cancer Brain metastasis EGFR mutation testing Leptomeningeal metastasis