Nature medicine. 2025 Mar 7. doi: 10.1038/s41591-025-03579-w Q158.72024
Circulating tumor DNA analysis guiding adjuvant therapy in stage II colon cancer: 5-year outcomes of the randomized DYNAMIC trial
Jeanne Tie 1 2 3, Yuxuan Wang 4, Serigne N Lo 5 6, Kamel Lahouel 7 8, Joshua D Cohen 4, Rachel Wong 9 10, Jeremy D Shapiro 11, Samuel J Harris 12, Adnan Khattak 13 14, Matthew E Burge 15, Margaret Lee 9 16, Marion Harris 17, Sue-Anne McLachlan 18, Lisa Horvath 19, Christos Karapetis 20, Jenny Shannon 21, Madhu Singh 22, Desmond Yip 23, Sumitra Ananda 24, Craig Underhill 25 26, Janine Ptak 4, Natalie Silliman 4, Lisa Dobbyn 4, Maria Popoli 4, Nickolas Papadopoulos 4, Cristian Tomasetti 7 8, Kenneth W Kinzler 4, Bert Vogelstein 4, Peter Gibbs 27 28 16
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作者单位
1 Division of Personalised Oncology, Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia. jeanne.tie@petermac.org.2 Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia. jeanne.tie@petermac.org.3 Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne, Victoria, Australia. jeanne.tie@petermac.org.4 Ludwig Center for Cancer Genetics and Therapeutics, Johns Hopkins University School of Medicine, Baltimore, MD, USA.5 Research and Biostatistics, Melanoma Institute Australia, The University of Sydney, Sydney, New South Wales, Australia.6 Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia.7 Center for Cancer Prevention, Early Detection and Monitoring, City of Hope, Duarte, CA, USA.8 Division of Integrated Cancer Genomics, Translational Genomics Research Institute, Phoenix, AZ, USA.9 Department of Medical Oncology, Eastern Health, Melbourne, Victoria, Australia.10 Eastern Health Clinical School, Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, Victoria, Australia.11 Department of Medical Oncology, Cabrini Health, Melbourne, Victoria, Australia.12 Department of Medical Oncology, Bendigo Health, Bendigo, Victoria, Australia.13 Department of Medical Oncology, Fiona Stanley Hospital, Perth, Western Australia, Australia.14 Edith Cowan University, Perth, Western Australia, Australia.15 Department of Medical Oncology, Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia.16 Department of Medical Oncology, Western Health, Melbourne, Victoria, Australia.17 Department of Medical Oncology, Monash Health, Melbourne, Victoria, Australia.18 Department of Medical Oncology, St Vincent's Hospital, Melbourne, Victoria, Australia.19 Department of Medical Oncology, Chris O'Brien Lifehouse, Sydney, New South Wales, Australia.20 Department of Medical Oncology, Flinders Medical Centre, Adelaide, South Australia, Australia.21 Department of Medical Oncology, Nepean Cancer Care Centre, Kingswood, New South Wales, Australia.22 Department of Medical Oncology, Barwon Health, Geelong, Victoria, Australia.23 Department of Medical Oncology, Canberra Hospital, Canberra, Australian Capital Territory, Australia.24 Epworth Freemasons, Richmond, Melbourne, Victoria, Australia.25 Border Medical Oncology, Albury, New South Wales, Australia.26 Rural Medical School, Albury Campus, University of NSW, Albury, New South Wales, Australia.27 Division of Personalised Oncology, Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia.28 Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne, Victoria, Australia.
DOI: 10.1038/s41591-025-03579-w PMID: 40055522
摘要 翻译
Early data from the DYNAMIC study of circulating tumor DNA (ctDNA)-guided adjuvant chemotherapy (ACT) versus standard approach met its primary outcome demonstrating reduced ACT use without compromising 2-year recurrence-free survival (RFS) for stage II colon cancer. We report here other prespecified analyses of overall survival, ctDNA clearance and ctDNA level. At a median follow-up of 59.7 months, 5-year RFS was 88% and 87% with ctDNA-guided and standard management, respectively (difference 1.1%, 95% confidence interval -5.8% to 8.0%), and 5-year overall survival is similar (93.8% versus 93.3%, hazard ratio (HR) 1.05; P = 0.887). For treated ctDNA-positive patients, ctDNA clearance was observed at the end of ACT (EOT) in 35 out of 40 patients (87.5%). A higher than median postoperative tumor-derived mutant molecules per milliliter plasma was associated with worse 5-year RFS (HR 10.62; P = 0.005). For treated ctDNA-positive patients, post hoc analysis of ctDNA clearance at EOT assessed by a new assay that evaluated an average of 29 tumor-derived mutations per patient predicted for a favorable 5-year recurrence-free probability of 97% versus 0% for ctDNA persistence (P < 0.001). Mature DYNAMIC outcome data support a ctDNA-guided approach to ACT for stage II colon cancer, with potential to further risk stratify ctDNA-positive patients based on ctDNA burden and EOT results. Australian New Zealand Clinical Trials Registry Identifier: ACTRN12615000381583 .
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