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Clinical significance of circulating tumor DNA in localized non-small cell lung cancer: a systematic review and meta-analysis

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Abstract

Circulating tumor DNA (ctDNA) detection holds promise for genetic analyses and quantitative assessment of tumor burden. A systematic review and meta-analysis were conducted to investigate the clinical relevance of ctDNA among patients with localized non-small cell lung cancer (NSCLC). PubMed, EMBASE, and the Cochrane Library were searched for eligible studies published from January 2001 to April 2022. After quality assessments and data extraction, diagnostic accuracy variables and prognostic data were calculated and analyzed by Meta-Disc 1.4, Review Manager 5.4.1, and STATA 17.0. Eight prospective studies and one retrospective study including 784 patients with localized NSCLC were used in our meta-analysis. The pooled sensitivity and specificity of ctDNA for minimal residual disease (MRD) detection were 0.58 and 0.93, respectively. The pooled positive and negative likelihood ratios were 7.57 (95% confidence interval (CI) 2.84–20.20) and 0.45 (95% CI 0.37–0.55), respectively. The area under the summary receiver operating characteristic curve was 0.8967, and the diagnostic odds ratio was 32.26 (95% CI 14.63–71.12). In addition, both precurative-treatment and postcurative-treatment ctDNA positivity was associated with worse recurrence-free survival (hazard ratio (HR), 3.82 and 8.32, respectively) and worse overall survival (HR, 3.82 and 4.73, respectively). The findings suggested that ctDNA detection has beneficial utility regarding MRD detection specificity; moreover, positive ctDNA was associated with poor prognosis in patients with localized NSCLC.

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Abbreviations

CI:

Confidence interval

ctDNA:

Circulating tumor DNA

DOR:

Diagnostic odds ratio

HR:

Hazard ratio

MOOSE:

Meta-analysis of Observational Studies in Epidemiology

MRD:

Minimal residual disease

NLR:

Negative likelihood ratio

NSCLC:

Non-small cell lung cancer

OS:

Overall survival

PLR:

Positive likelihood ratio

PRISMA:

Preferred Reporting Items for Systematic Reviews and Meta-analysis

QUADAS- 2:

Revised Quality Assessment of Diagnostic Accuracy Studies

RFS:

Recurrence-free survival

SROC:

Summary receiver operating characteristic

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Authors and Affiliations

  1. Minimally Invasive Tumor Therapies Center, Beijing Hospital, National Center of Gerontology; Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, People’s Republic of China

    Run-Qi Guo, Jin-Zhao Peng, Jie Sun & Yuan-Ming Li

  2. Graduate School of Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, 100730, People’s Republic of China

    Jin-Zhao Peng

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  1. Run-Qi Guo
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Contributions

RQG and JZP designed and conducted the systematic search to identify all relevant studies, assessed the eligibility of each study, and participated in statistical analysis and data interpretation. JS coordinated the study and performed data acquisition. RQG participated in manuscript drafting. YML participated in critical revision and supervision. All the authors approved the final manuscript.

Corresponding authors

Correspondence to Run-Qi Guo or Yuan-Ming Li.

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This study was a systematic review and meta-analysis. Ethics committee approval was not necessary because all data were carefully extracted from the literature, and this article did not involve handling individual patient data. In addition, neither patients nor the public were involved in the design and planning of the study.

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Guo, RQ., Peng, JZ., Sun, J. et al. Clinical significance of circulating tumor DNA in localized non-small cell lung cancer: a systematic review and meta-analysis. Clin Exp Med 23, 1621–1631 (2023). https://doi.org/10.1007/s10238-022-00924-y

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  • DOI: https://doi.org/10.1007/s10238-022-00924-y

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