Evidence map›Paper›PMID 42353230›Full record

SynthesisInternational journal of molecular sciences2026

The Predictive Role of ctDNA and CTCs in Patients with Advanced Non-Small Cell Lung Cancer Receiving Immunotherapy: A Systematic Review and Meta-Analysis.

Andrea C Kakouri, Maria Spiliotaki, Constantinos Deltas, Gregory Papagregoriou, Haris Charalambous

Abstract readSystematic ReviewMeta-Analysis
In one paragraph

Synthesis in International journal of molecular sciences, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors.

Andrea C Kakouribiobank.cy Center of Excellence in Biobanking and Biomedical Research, University of Cyprus, Nicosia 2029, Cyprus.ORCID 0000-0003-2982-679X
Maria Spiliotakibiobank.cy Center of Excellence in Biobanking and Biomedical Research, University of Cyprus, Nicosia 2029, Cyprus.ORCID 0000-0003-3781-2048
Constantinos Deltasbiobank.cy Center of Excellence in Biobanking and Biomedical Research, University of Cyprus, Nicosia 2029, Cyprus.ORCID 0000-0001-5549-9169
Gregory Papagregorioubiobank.cy Center of Excellence in Biobanking and Biomedical Research, University of Cyprus, Nicosia 2029, Cyprus.ORCID 0000-0002-2440-9789
Haris CharalambousMedical Oncology Department, Bank of Cyprus Oncology Centre, Acropoleos Ave 32, Nicosia 2006, Cyprus.ORCID 0000-0002-6518-1936

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Circulating tumour DNA (ctDNA) and circulating tumour cells (CTCs) have emerged as promising non-invasive biomarkers for the immunotherapy response in advanced non-small cell lung cancer (NSCLC). However, their clinical utility remains uncertain due to variability in findings across studies. We conducted a systematic review and meta-analysis of studies from 2014 to 2024, assessing the predictive value of ctDNA and CTCs in advanced NSCLC patients receiving immunotherapy. Primary outcomes were progression-free survival (PFS) and overall survival (OS). Forty-four studies were included (28 ctDNA, 16 CTC cohorts). High baseline ctDNA was associated with worse OS (pooled HR = 1.38, 95% CIs: 1.17-1.63), while baseline CTC detection predicted worse PFS (pooled HR of 3.65 (95% CIs: 1.58-8.41) and OS (pooled HR = 2.30, 95% CIs: 1.54-3.44). An on-treatment ctDNA decrease or clearance was associated with improved PFS (pooled HR = 0.34, 95% CIs: 0.25-0.47) and OS (pooled HR = 0.33, 95% CIs: 0.24-0.44). Evidence for other ctDNA- and CTC-derived biomarkers (blood tumour mutational burden, genomic alterations, dynamic CTC changes, and CTC PD-L1 expression) was limited or inconsistent. The interpretation of these findings is limited by heterogeneity in assay platforms, biomarker definitions, the analytical threshold, and sampling timepoints across studies. While ctDNA and CTCs show significant potential as predictive biomarkers in advanced NSCLC, further validation is needed in larger prospective studies using standardized assays. At present, ctDNA and CTC monitoring can complement but cannot replace radiological assessments in guiding immunotherapy decisions for NSCLC patients.

Indexed as

Biomarkers, TumorCarcinoma, Non-Small-Cell LungCirculating Tumor DNAImmunotherapyLung NeoplasmsNeoplastic Cells, CirculatingHumansPrognosisBiomarkers, TumorCirculating Tumor DNAbiomarkersCTCsctDNAimmunotherapyliquid biopsyNSCLCresponse

Identifiers

PMID42353230
PMCPMC13300314

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.