Circulating tumor DNA analysis guiding adjuvant therapy in stage II colon cancer: 5-year outcomes of the randomized DYNAMIC trial

Tie, J; HORVATH, L; Wang, Y; Lo, SN; Lahouel, K; Cohen, JD; Wong, R; Shapiro, JD; Harris, SJ; Khattak, A; Burge, ME; Lee, M; Harris, M; McLachlan, SA; Karapetis, C; Shannon, J; Singh, M; Yip, D; Ananda, S; Underhill, C; Ptak, J; Silliman, N; Dobbyn, L; Popoli, M; Papadopoulos, N; Tomasetti, C; Kinzler, KW; Vogelstein, B; Gibbs, P

Author(s): Tie, J; HORVATH, L; Wang, Y; Lo, SN; Lahouel, K; Cohen, JD; Wong, R; Shapiro, JD; Harris, SJ; Khattak, A; Burge, ME; Lee, M; Harris, M; McLachlan, SA; Karapetis, C; Shannon, J; Singh, M; Yip, D; Ananda, S; Underhill, C; Ptak, J; Silliman, N; Dobbyn, L; Popoli, M; Papadopoulos, N; Tomasetti, C; Kinzler, KW; Vogelstein, B; Gibbs, P;
Details: Publication Year 2025-05,Volume 31,Issue #5,Page 1509-1518
Journal Title: Nature Medicine
Abstract: 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 .
Publisher: Springer Nature
Keywords: Humans; *Circulating Tumor DNA/blood/genetics; *Colonic Neoplasms/drug therapy/genetics/blood/pathology/mortality; Female; Male; Chemotherapy, Adjuvant; Middle Aged; Aged; Neoplasm Staging; Treatment Outcome; Biomarkers, Tumor/blood/genetics; Neoplasm Recurrence, Local/genetics; Adult; Disease-Free Survival
Research Division(s): Personalised Oncology
PubMed ID: 40055522
Publisher's Version: https://doi.org/10.1038/s41591-025-03579-w
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Creation Date: 2025-04-10 09:58:45

Last Modified: 2025-05-29 02:41:25