International Journal of Clinical Case Reports, 2026, Vol.16, No.1, 1-10 http://medscipublisher.com/index.php/ijccr 8 sampling time, and failing to meet the required detection sensitivity can all lead to the actual residual being "missed". Therefore, a more accurate understanding of ctDNA negativity should be "no signal detected at present", rather than complete clearance. On the other hand, CHIP, technical noise, and threshold differences between different platforms may also lead to false positives. If there is a lack of strict preprocessing procedures and variant filtering strategies, the interpretation of results can easily be disturbed, and even unnecessary examinations or treatment intensification may be triggered. ctDNA-MRD does not work well as a standalone decision tool. In practice, its results need to be interpreted alongside imaging findings, pathological features, and the broader clinical context. ctDNA may signal molecular relapse earlier than structural changes appear, but it cannot indicate where the lesion is or how extensive it is— questions that imaging still answers more directly. Looking at both together usually provides a clearer and more dependable picture of residual disease. With further integration of multi-omics data, functional imaging, and artificial intelligence models, ctDNA-MRD may gradually move beyond simple risk estimation toward a more practical role in clinical decision-making. However, until stronger prospective evidence is available, a cautious approach remains advisable—combining multiple modalities, discussing cases within multidisciplinary teams, and, whenever possible, enrolling patients in clinical trials to ensure that potential benefits do not come at the expense of safety. Acknowledgments The author extends sincere thanks to Dr. Shou for his feedback on the manuscript. Conflict of Interest Disclosure The author affirms that this research was conducted without any commercial or financial relationships that could be construed as a potential conflict of interest. References Abidoye O., Ahn D., Borad M., Wu C., Bekaii-Saab T., Chakrabarti S., and Sonbol M., 2025, Circulating Tumor DNA testing for minimal residual disease and its application in colorectal cancer, Cells, 14(3): 161. https://doi.org/10.3390/cells14030161 Azzi G., Slavin T., Izaguirre-Carbonell J., Sloane H.S., Edelstein D., and Ma C.X., 2025, Advanced minimal residual disease detection using a novel circulating tumor DNA assay: a report of two cases, Case Reports in Oncology, 18: 1105-1110. https://doi.org/10.1159/000547249 Bent A., Raghavan S., Dasari A., and Kopetz S., 2022, The future of ctDNA-defined minimal residual disease: personalizing adjuvant therapy in colorectal cancer, Clinical Colorectal Cancer, 21(2): 89-95. https://doi.org/10.1016/j.clcc.2022.03.004 Boukouris A., Michaelidou K., Joosse S., Charpidou A., Mavroudis D., Syrigos K., and Agelaki S., 2025, A comprehensive overview of minimal residual disease in the management of early-stage and locally advanced non-small cell lung cancer, NPJ Precision Oncology, 9(1): 178. https://doi.org/10.1038/s41698-025-00984-9 Chen H., and Zhou Q., 2023, Detecting liquid remnants of solid tumors treated with curative intent: circulating tumor DNA as a biomarker of minimal residual disease (Review), Oncology Reports, 49(5): 106. https://doi.org/10.3892/or.2023.8543 Chen J., Geng Y., and Lucci A., 2025, Applications of ctDNA testing to monitor and detect residual disease in breast cancer, Expert Review of Molecular Diagnostics, 25: 263-274. https://doi.org/10.1080/14737159.2025.2498545 Chidharla A., Rapoport E., Agarwal K., Madala S., Linares B., Sun W., Chakrabarti S., and Kasi A., 2023, Circulating tumor DNA as a minimal residual disease assessment and recurrence risk in patients undergoing curative-intent resection with or without adjuvant chemotherapy in colorectal cancer: a systematic review and meta-analysis, International Journal of Molecular Sciences, 24(12): 10230. https://doi.org/10.3390/ijms241210230 Comino-Méndez I., Velasco-Suelto J., Pascual J., López-López E., Quirós-Ortega M., Gaona-Romero C., Martín-Muñoz A., Losana P., Heredia Y., Alba E., and Guerrero-Zotano A., 2025, Identification of minimal residual disease using the clonesight test for ultrasensitive ctDNA detection to anticipate late relapse in early breast cancer, Breast Cancer Research, 27(1): 65. https://doi.org/10.1186/s13058-025-02016-7 Dasari A., Bent A., Alfaro-Munoz K., Huey R., Johnson B., Lee M., Morelli M., Morris V., Overman M., Parseghian C., Raghav K., Shen J., Willis J., Newhook T., Uppal A., You Y., Konishi T., Chang G., Kopetz S., and Wolff R., 2023, Association of positive ctDNA-based minimal residual disease assays during surveillance and undiagnosed concomitant radiographic recurrences in colorectal cancer (CRC): results from the MD Anderson INTERCEPT program, Journal of Clinical Oncology, 41(16_suppl): 3522. https://doi.org/10.1200/JCO.2023.41.16_suppl.3522
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