Prognostic utility of circulating tumor DNA assessment in immune checkpoint inhibitor-treated advanced non-small cell lung cancer: a systematic review and meta-analysis.

Authors

Yulin Wang, Shuang Wu, Yanfang Wei, Shize Fan, Zihui Xu, Dongyang Li, Zan Teng, Jin Wang

Published in

Frontiers in immunology. Volume 17. Pages 1812209. Epub Jun 09, 2026.

Abstract

This meta-analysis aimed to assess the prognostic value of circulating tumor DNA (ctDNA) in predicting progression-free survival (PFS) and overall survival (OS) of advanced non-small cell lung cancer (NSCLC) patients treated with immune checkpoint inhibitors (ICIs), thereby providing evidence-based support for clinical decision-making.
Six major English and Chinese databases (PubMed, Embase, Cochrane Library, etc.) were scanned from inception to August 2025. Studies evaluating the association between ctDNA and survival outcomes in advanced NSCLC patients receiving ICIs were included. Thirty-one eligible studies (2,107 patients) were selected following predefined criteria. Study quality was evaluated using Cochrane RoB-2 and the Newcastle-Ottawa Scale (NOS). Hazard ratios (HRs) and 95% confidence intervals (95% CIs) were pooled using random/fixed-effects models. Heterogeneity was assessed via Cochran's Q test and I² statistics. Subgroup analyses, sensitivity tests, and funnel plots were conducted to evaluate robustness and publication bias.
Patients with undetectable ctDNA at baseline showed significantly prolonged PFS (HR = 0.49, 95% CI: 0.34-0.70, P < 0.01) and OS (HR = 0.45, 95% CI: 0.32-0.65, P < 0.01). Patients achieving ctDNA reduction or response during treatment exhibited substantial PFS (HR = 0.27, 95% CI: 0.21-0.35, P < 0.01) and OS (HR = 0.23, 95% CI: 0.17-0.31, P < 0.01) benefits, with complete molecular response (100% reduction in variant allele frequency, VAF) demonstrating the strongest predictive power, characterized by the lowest heterogeneity and favorable HRs for PFS (HR = 0.27, 95% CI: 0.18-0.41, P < 0.01) and OS (HR = 0.19, 95% CI: 0.12-0.29, P < 0.01). Subgroup analyses revealed three key patterns: superior predictive value in combination therapy versus monotherapy; higher sensitivity of next-generation sequencing (NGS) over digital polymerase chain reaction (PCR); and enhanced predictive power in later-line therapy compared to first-line therapy. Sensitivity analyses confirmed the stability of the results.
Baseline ctDNA status and early dynamic changes are reliable prognostic indicators in advanced NSCLC patients receiving ICI therapy, particularly in combination regimens and cases achieving complete molecular clearance. These findings support ctDNA as a biomarker for personalized treatment strategies.
https://www.crd.york.ac.uk/PROSPERO, CRD420251025308.

PMID:
42344896
Bibliographic data and abstract were imported from PubMed on 25 Jun 2026.

Read full publication at:
Please sign in to see all details.

Stats

1-terrible, 9-excellent. How would you rate this publication? Sign in in to submit your rating.

Post a comment

You need to be signed in to post comments. You can sign in here.

Comments

There are no comments yet.