TY - JOUR
T1 - Cell-free DNA from cerebrospinal fluid can be used to detect the EGFR mutation status of lung adenocarcinoma patients with central nervous system metastasis
AU - Liu, Yang
AU - Yang, Sen
AU - Zhao, Jiuzhou
AU - He, Zhen
AU - Ma, Jie
AU - Guo, Yongjun
AU - Wang, Wei
AU - Yoshizawa, Akihiko
AU - Prelaj, Arsela
AU - Tiseo, Marcello
AU - Normanno, Nicola
AU - Van Schil, Paul E.
AU - Wang, Qiming
AU - Yang, Xiaopeng
N1 - Funding Information:
Marcello Tiseo is currently supported by the Associazione Italiana per la Ricerca sul Cancro (AIRC) under Investigator Grant (IG) No. IG2017-20074. Funding: This study was supported by the Henan Province Health and Youth Subject Leader Training Project {[2020]60}; the Leading Talent Cultivation Project of Henan Health Science and Technology Innovation Talents (YXKC2020009); the Zhongyuan Qianren Jihua (ZYQR201912118); the Henan International Joint Laboratory of drug resisitance and reversal of targeted therapy for lung cancer {[2021]10}; the Henan Medical Key Laboratory of Refractory lung cancer {[2020]27}; the Henan Refractory Lung Cancer Drug Treatment Engineering Technology Research Center {[2020]4}; the 51282 Project Leading Talent of Henan Provincial Health Science and Technology Innovation Talents {[2016]32}; the Huilan Charity Fund (HL-HS2020-129); Major public welfare projects in Henan Province (201300310400).
Publisher Copyright:
© 2021 AME Publishing Company. All rights reserved.
PY - 2021/2
Y1 - 2021/2
N2 - 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.
AB - 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.
KW - Cerebrospinal fluid (CSF)
KW - EGFR mutation
KW - Leptomeningeal metastasis (LM)
KW - Liquid biopsy
KW - Non-small cell lung cancer (NSCLC)
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U2 - 10.21037/tlcr-21-62
DO - 10.21037/tlcr-21-62
M3 - Article
AN - SCOPUS:85103106340
VL - 10
SP - 914
EP - 925
JO - Translational Lung Cancer Research
JF - Translational Lung Cancer Research
SN - 2226-4477
IS - 2
ER -