About 15 years ago, researchers at Ludwig Johns Hopkins and their colleagues at the former Ludwig Melbourne Branch began a collaboration to determine whether circulating tumor (ct) DNA could consistently predict disease recurrence after surgery for stage II colon cancer—and do so well enough to safely spare patients unnecessary adjuvant chemotherapy (ACT). The researchers reported in 2022 in the New England Journal of Medicine that early data from the DYNAMIC trial, which enrolled 455 patients, suggested the answer is yes. ctDNA analysis accurately predicted risk of recurrence; and directing ACT only to ctDNA-positive patients reduced chemotherapy use overall without compromising recurrence-free survival. In March, the team—led by Ludwig Johns Hopkins’ Yuxuan Wang and Bert Vogelstein with Ludwig Melbourne alumni Jeanne Tie and Peter Gibbs—reported in Nature Medicine their analyses of mature outcome data from DYNAMIC, including overall survival, ctDNA levels and ctDNA clearance in enrollees. Their analysis confirmed previous findings: after five years, both recurrence-free and overall survival were about the same for ctDNA-guided and standard management. The researchers found there’s potential to further risk-stratify ctDNA-positive patients based on ctDNA burden and results after ACT ends. This research was partly supported by a five-year, $10 million program launched by the Conrad N. Hilton Foundation and the Ludwig Institute for Cancer Research for the prevention and early detection of colon cancer.
Circulating tumor DNA analysis guiding adjuvant therapy in stage II colon cancer: 5-year outcomes of the randomized DYNAMIC trial
Nature Medicine, 2025 March 7