Landmark Trial Demonstrates Potential of ctDNA-Guided Therapy in Colon Cancer, Offering Hope for Personalized Post-Surgical Treatment
A groundbreaking clinical trial, DYNAMIC-III, has revealed that guiding adjuvant chemotherapy decisions based on circulating tumor DNA (ctDNA) levels after surgery significantly improves outcomes for patients with locally advanced colon cancer. The randomized phase 2/3 trial,results of which were recently presented,marks a pivotal step toward personalized cancer treatment,moving beyond a “one-size-fits-all” approach to post-surgical care.
Locally advanced colon cancer, while often successfully treated with surgery, carries a considerable risk of recurrence. Current standard practice involves administering adjuvant chemotherapy to eliminate any remaining microscopic disease. However, this chemotherapy isn’t always necessary – and carries its own side effects – for patients who have undergone successful surgery with complete removal of the cancer.DYNAMIC-III investigated weather monitoring ctDNA, fragments of tumor DNA circulating in the bloodstream, could identify patients who truly benefit from chemotherapy, sparing others from unnecessary toxicity.
The DYNAMIC-III trial enrolled patients with stage II or III colon cancer who were found to be ctDNA-positive after surgery. Participants were randomly assigned to either standard chemotherapy or observation, guided by their ctDNA status. Patients whose ctDNA remained detectable after surgery received chemotherapy, while those who became ctDNA-negative were spared.
Key findings demonstrated a statistically important improvement in disease-free survival in the ctDNA-guided arm compared to standard chemotherapy. Specifically, ctDNA-guided therapy reduced the risk of disease recurrence or death by 41% (Hazard Ratio 0.59,95% Confidence Interval 0.42-0.83; p=0.004). The trial involved contributions from researchers across Canada, including Samuel Martel (St. Joseph’s Health center, Toronto), Urszula Zurawska (St. Joseph’s Health Centre, Toronto), Ralph Wong (Cancer Care Manitoba, Winnipeg), Lucas Star (CIUSSS de l’Est-de-I’lle-de-montreal Maisonneuve-Rosemont Hospital, Montreal), Patricia Tang (Tom Baker Cancer Centre, Calgary), John McGhie (Vancouver Island Cancer Centre, Victoria), Saroosh Arif (Trillium Health Partners-Credit Valley Hospital, Mississauga), Shahid Ahmed (Saskatoon Cancer Centre, Saskatoon), James Michael (St. John Regional Hospital, Saint John), Katharine Shim (Lakeridge health Oshawa, Oshawa), Sam Babak (Oak valley Health, Markham), Dawn Armstrong (Dr. H. Bliss Murphy cancer Centre, St. John’s), Ron Burkes (Sinai Health System, Toronto), and Peter Kavan (The Jewish General Hospital, Montreal).
J.T., B.V., and P.G.led the study’s conception and design. J.T., Y.W., D.E., J.D.C., N.P.,K.W.K., and B.V. were responsible for data acquisition and analysis, while V.G.and D.E. conducted the statistical analyses. All authors contributed to data interpretation, manuscript progress, and final approval.
These results suggest that ctDNA-guided adjuvant therapy could revolutionize the treatment paradigm for locally advanced colon cancer,offering a more targeted and effective approach to minimize recurrence and improve patient outcomes. Further research is underway to validate these findings and explore the potential of ctDNA monitoring in other cancer types.
