ctDNA Blood Test to Help Personalize Postsurgical Colon Cancer Treatment

For patients with Stage 3 colon cancer, current chemotherapy approaches are highly toxic and lack personalization. Standard treatment involves months of dual-agent chemotherapy, which often causes serious side effects, including long-term nerve damage. Now, a new study suggests that circulating tumor DNA (ctDNA)—tiny fragments of genetic material shed by tumors into the bloodstream—can help doctors tailor chemotherapy based on recurrence risk, marking a major step toward personalized cancer care.

The study, known as the DYNAMIC-III trial, was a multi-institutional phase II/III clinical investigation co-led by the Johns Hopkins Kimmel Cancer Center (Baltimore, MD, USA) and included approximately 20 clinical sites across Australia and Canada. The study evaluated whether ctDNA-guided treatment could optimize chemotherapy use for patients with Stage 3 colon cancer, which has spread to nearby lymph nodes but not distant organs.

Researchers tested blood samples for ctDNA five to six weeks after surgery. Patients who tested positive for ctDNA were considered at higher risk for recurrence and received more intensive chemotherapy, while those who tested negative received less aggressive treatment. A total of 1,002 patients were enrolled: 500 received standard management, while 502 were assigned to ctDNA-guided care. In the ctDNA-guided group, positive patients received escalated therapy—half with triple-drug FOLFOXIRI and 43% with six months of oxaliplatin-based doublet therapy—while ctDNA-negative patients had treatment de-escalated to shorter or less frequent regimens.

Researchers then tracked recurrence-free survival over two and three years, respectively, for ctDNA-positive and ctDNA-negative patients. After an average follow-up of 47 months, ctDNA-negative patients experienced significantly fewer recurrences (49%) compared to ctDNA-positive patients (87%). For ctDNA-negative patients, receiving less chemotherapy reduced oxaliplatin exposure (34.8% vs. 88.6%), hospitalizations (8.5% vs. 13.2%), and high-grade adverse events (6.2% vs. 10.6%) without a major difference in recurrence-free survival (85.3% vs. 88.1%).

However, intensifying treatment for ctDNA-positive patients did not improve recurrence-free survival (51% vs. 61%), highlighting a need for new therapies for those with persistent ctDNA. The findings, published in Nature Medicine, showed that persistent ctDNA after treatment was strongly linked to poor outcomes, with a three-year recurrence-free survival of just 14%, compared to 79% in patients who cleared ctDNA after chemotherapy. Among ctDNA-negative participants, 13.5% experienced recurrence, primarily in the lungs and peritoneum—areas known to shed less tumor DNA into the bloodstream. Researchers believe ctDNA testing could soon guide real-time treatment decisions for colon cancer and other tumor types.

“This study demonstrates that likely, in the near future, ctDNA can be used to help make clinical decisions for patients with colon cancers,” said Yuxuan Wang, M.D., Ph.D., assistant professor of oncology at Johns Hopkins. “Conceivably, we can use ctDNA in other tumor types to inform patient management the same way.”

Related Links:
Johns Hopkins Kimmel Cancer Center