Title Potential clinical utility of liquid biopsy in early-stage non-small cell lung cancer
Authors Shen, Haifeng
Jin, Yichen
Zhao, Heng
Wu, Manqi
Zhang, Kai
Wei, Zihan
Wang, Xin
Wang, Ziyang
Li, Yun
Yang, Fan
Wang, Jun
Chen, Kezhong
Affiliation Peking Univ, Peoples Hosp, Thorac Oncol Inst, Dept Thorac Surg, Xi Zhi Men South Ave 11, Beijing 100044, Peoples R China
Keywords CIRCULATING TUMOR DNA
MOLECULAR RESIDUAL DISEASE
RECURRENCE DYNAMICS
PLASMA DNA
METHYLATION
SURVIVAL
IMMUNOTHERAPY
PREDICTORS
BIOMARKERS
DIAGNOSIS
Issue Date 14-Dec-2022
Publisher BMC MEDICINE
Abstract Background Liquid biopsy has been widely researched for early diagnosis, prognostication and disease monitoring in lung cancer, but there is a need to investigate its clinical utility for early-stage non-small cell lung cancer (NSCLC). Methods We performed a meta-analysis and systematic review to evaluate diagnostic and prognostic values of liquid biopsy for early-stage NSCLC, regarding the common biomarkers, circulating tumor cells, circulating tumor DNA (ctDNA), methylation signatures, and microRNAs. Cochrane Library, PubMed, EMBASE databases, ClinicalTrials.gov, and reference lists were searched for eligible studies since inception to 17 May 2022. Sensitivity, specificity and area under the curve (AUC) were assessed for diagnostic values. Hazard ratio (HR) with a 95% confidence interval (CI) was extracted from the recurrence-free survival (RFS) and overall survival (OS) plots for prognostic analysis. Also, potential predictive values and treatment response evaluation were further investigated. Results In this meta-analysis, there were 34 studies eligible for diagnostic assessment and 21 for prognostic analysis. The estimated diagnostic values of biomarkers for early-stage NSCLC with AUCs ranged from 0.84 to 0.87. The factors TNM stage I, T1 stage, N0 stage, adenocarcinoma, young age, and nonsmoking contributed to a lower tumor burden, with a median cell-free DNA concentration of 8.64 ng/ml. For prognostic analysis, the presence of molecular residual disease (MRD) detection was a strong predictor of disease relapse (RFS, HR, 4.95; 95% CI, 3.06-8.02; p < 0.001) and inferior OS (HR, 3.93; 95% CI, 1.97-7.83; p < 0.001), with average lead time of 179 & PLUSMN; 74 days between molecular recurrence and radiographic progression. Predictive values analysis showed adjuvant therapy significantly benefited the RFS of MRD + patients (HR, 0.27; p < 0.001), while an opposite tendency was detected for MRD - patients (HR, 1.51; p = 0.19). For treatment response evaluation, a strong correlation between pathological response and ctDNA clearance was detected, and both were associated with longer survival after neoadjuvant therapy. Conclusions In conclusion, our study indicated liquid biopsy could reliably facilitate more precision and effective management of early-stage NSCLC. Improvement of liquid biopsy techniques and detection approaches and platforms is still needed, and higher-quality trials are required to provide more rigorous evidence prior to their routine clinical application.
URI http://hdl.handle.net/20.500.11897/662023
ISSN 1741-7015
DOI 10.1186/s12916-022-02681-x
Indexed SCI(E)
Appears in Collections: 人民医院

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