Utility and Future Perspectives of Circulating Tumor DNA Analysis in Non-Small Cell Lung Cancer Patients in the Era of Perioperative Chemo-Immunotherapy
Abstract
1. Introduction
2. Literature Search
3. Current Clinical Challenges of Perioperative/Neoadjuvant Chemo-Immunotherapy
3.1. Need for Neoadjuvant Chemo-Immunotherapy
3.2. Adequate Treatment Courses of Neoadjuvant Chemo-Immunotherapy
3.3. Monitoring Tumor Response to Neoadjuvant Treatment
3.4. Recurrence Risk Stratification After Pulmonary Resection
4. Utility of ctDNA Analysis as a Tool to Solve the Above Clinical Questions
4.1. Utility of ctDNA Analysis Before and During Neoadjuvant Treatment
4.2. Utility of ctDNA Analysis Before Surgical Resection
4.3. Landmark ctDNA Status as a Tool for MRD Detection
4.4. Longitudinal ctDNA Analysis for Early Detection of Disease Recurrence
5. Ongoing Clinical Trials Involving ctDNA During Perioperative Chemo-Immunotherapy
6. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
References
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Ref. | Year | N | Neoadjuvant Regimen | Adjuvant Regimen | ctDNA Assay |
---|---|---|---|---|---|
[35] | 2022 | 22 | ICI + CTx vs. ICI combo vs. CTx | - | Tumor-agnostic |
[36] | 2022 | 46 | Nivo + CTx | Nivo vs. placebo | Tumor-agnostic |
[37] | 2023 | 358 | Nivo + CTx vs. CTx | - | Tumor-informed |
[38] | 2023 | 52 | Nivo + CTx vs. Nivo | - | Tumor-informed |
[39] | 2023 | 78 | Camrelizumab + apatinib | - | Tumor-agnostic |
[40] | 2025 | 45 | Sintilimab + CTx | - | Tumor-agnostic |
[30] | 2025 | 358 | Nivo + CTx vs. CTx | - | Tumor-informed |
[31] | 2025 | 461 | Nivo + CTx vs. CTx | Nivo vs. placebo | - |
[32] | 2025 | 802 | Durval + CTx vs. CTx | Durval vs. placebo | Tumor-informed |
[33] | 2025 | 86 | Nivo + CTx vs. CTx | Nivo vs. placebo | Tumor-agnostic |
NCT | Primary Endpoints | Secondary Endpoints | Exploratory Analysis |
---|---|---|---|
NCT04638582 | ctDNA clearance (pre/post-surgery) | MPR, pCR, radiologic response | Correlation of ctDNA dynamics with DFS/OS |
NCT05382052 | Association of ctDNA clearance with PFS | DFS, OS | Longitudinal ctDNA monitoring feasibility |
NCT05778253 | ctDNA clearance, AI-based prediction of pCR | MPR, ORR, DFS, OS, QoL, surgical outcomes | Correlation of AI pathology with clinical outcomes |
NCT06111807 | Sensitivity/specificity of ctDNA assays | Association of ctDNA with recurrence/DFS | ctDNA-guided risk stratification |
NCT06123754 | MPR (pre-op), EFS (post-op) | pCR, DFS, OS, safety | Biomarker analysis, ctDNA dynamics |
NCT06221462 | pCR/MPR, safety, surgical feasibility | DFS, OS, AEs | ctDNA clearance, radiologic-pathologic correlation |
NCT06284317 | DFS in non-pCR patients | DFS/OS in pCR group, safety, ctDNA analysis | Correlation of ctDNA with recurrence and survival |
NCT06743555 | Feasibility and safety of surgery omission | EFS, OS, recurrence rate | ctDNA monitoring for recurrence detection |
NCT06902272 | Correlation between ctDNA and pCR/MPR | DFS, OS, ctDNA kinetics | ctDNA MRD detection, longitudinal profiling |
NCT06977074 | pCR, MPR, surgical eligibility | DFS, OS, AEs | ctDNA-guided treatment optimization |
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Ohara, S.; Suda, K.; Tsutani, Y. Utility and Future Perspectives of Circulating Tumor DNA Analysis in Non-Small Cell Lung Cancer Patients in the Era of Perioperative Chemo-Immunotherapy. Cells 2025, 14, 1312. https://doi.org/10.3390/cells14171312
Ohara S, Suda K, Tsutani Y. Utility and Future Perspectives of Circulating Tumor DNA Analysis in Non-Small Cell Lung Cancer Patients in the Era of Perioperative Chemo-Immunotherapy. Cells. 2025; 14(17):1312. https://doi.org/10.3390/cells14171312
Chicago/Turabian StyleOhara, Shuta, Kenichi Suda, and Yasuhiro Tsutani. 2025. "Utility and Future Perspectives of Circulating Tumor DNA Analysis in Non-Small Cell Lung Cancer Patients in the Era of Perioperative Chemo-Immunotherapy" Cells 14, no. 17: 1312. https://doi.org/10.3390/cells14171312
APA StyleOhara, S., Suda, K., & Tsutani, Y. (2025). Utility and Future Perspectives of Circulating Tumor DNA Analysis in Non-Small Cell Lung Cancer Patients in the Era of Perioperative Chemo-Immunotherapy. Cells, 14(17), 1312. https://doi.org/10.3390/cells14171312