ArticleClinical cancer research : an official journal of the American Association for Cancer Research2025
ctDNA Clearance as an Early Indicator of Improved Clinical Outcomes in Advanced NSCLC Treated with TKI: Findings from an Aggregate Analysis of Eight Clinical Trials.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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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.
Who cites it
17 citing papers in PubMed.
- Associations between early changes in circulating tumor DNA (ctDNA) and outcomes across randomized trials: Insights from the ctMoniTR project.The journal of liquid biopsy · 2026Article
- Longitudinal methylated ctDNA increases predict immunotherapy progression across solid tumors.The journal of liquid biopsy · 2026Article
- Molecular Response Assessment From Circulating Tumor DNA in Patients With Ovarian Cancer Treated With the WEE1 Inhibitor Azenosertib.JCO precision oncology · 2026Article
- Common analysis pitfalls in longitudinal ctDNA studies: lead time, sensitivity and immortal time bias.EBioMedicine · 2026Review
- Should we optimise or revise the management of initially unresectable stage III non-small cell lung cancer: rethinking consolidation therapy.Journal of the National Cancer Center · 2026Article
- Advances in Multi-Modal Biomarkers for Immunotherapy Response in Non-Small Cell Lung Cancer: ctDNA, Microbiome, and Radiomics.Cancers · 2026Review
- Individualized management strategies for advanced non-small cell lung cancer withOncology letters · 2026Article
- Circulating tumor DNA dynamics predict pathological response and guide therapy personalization in the neoadjuvant setting.Discover oncology · 2026Review
- Targeted protein degradation dismantles undruggable targets to reverse immune evasion and therapy resistance in cancer.Frontiers in immunology · 2026Review
- From detection to action: ctDNA-MRD surveillance and translational strategies in early breast cancer.Frontiers in oncology · 2026Review
- Editorial: Liquid biopsy in non-small cell lung cancer for diagnosis, treatment selection and monitoring.Frontiers in oncology · 2026Article
- The Clinical Utility of Cell-Free DNA in Brain Tumor Management: A Comprehensive Review.Journal of molecular neuroscience : MN · 2025Review
- Chemotherapy response monitoring with DNA methylation-based ctDNA tumor fraction: Evidence from a real-world cohort of patients with advanced common solid malignancies.The journal of liquid biopsy · 2025Article
- Article
- Monitoring and Assessment of Circulating Tumor DNA in Cancers Using Ultrarapid Sensitivity as an Innovative Practice.Health science reports · 2025Article
- Molecular response cutoffs and ctDNA collection timepoints influence on interpretation of associations between early changes in ctDNA and overall survival in patients treated with anti-PD(L)1 and/or chemotherapy.Journal for immunotherapy of cancer · 2025Article
- Reprogramming the tumor microenvironment: synergistic mechanisms of antibody-drug conjugates and immune checkpoint inhibitors.Antibody therapeutics · 2025Review
Corrections and comments
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Authors and funding
26 authors.
Funding
Abstract
purposeCirculating tumor DNA (ctDNA) holds promise as an early endpoint to predict overall survival (OS). The creation and structured interrogation of aggregated datasets inform the hypothesis that ctDNA is reasonably likely to predict treatment benefit. Friends of Cancer Research convened a diverse working group to establish and implement an analysis plan assessing patient-level associations between changes in ctDNA levels with OS and progression-free survival (PFS). EXPERIMENTAL
designThe aggregate dataset included eight clinical trials representing 940 patients with biomarker-positive advanced non-small cell lung cancer treated with tyrosine kinase inhibitors. Detection of baseline and on-treatment ctDNA was assessed for associations with OS and PFS. Additionally, combinations of ctDNA detection and RECIST measurements up to 10 weeks on treatment were considered.
resultsPatients with detected ctDNA at baseline that became nondetected on treatment ("clearance") experienced improved OS compared with patients with persistently detected ctDNA (adjusted HR = 2.12, P < 0.001). This pattern was also seen in the subset of patients with stable disease as measured by RECIST within 10 weeks of treatment initiation (adjusted HR = 4.15, P < 0.001). Results were similar for PFS.
conclusionsIn patients with oncogene-driven advanced non-small cell lung cancer treated with tyrosine kinase inhibitors, ctDNA clearance within 10 weeks of treatment initiation was associated with improved OS and PFS. These patient-level results support the growing evidence that demonstrates a change in ctDNA levels during treatment is associated with clinical benefit. Future prospective trials should include predefined thresholds of molecular response to advance the utility of ctDNA as an early endpoint.
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Registered trials
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.