Researchers use a ctDNA guided approach to help stage II colon cancer patients

Circulating tumor DNAs may be the key to detecting micrometastases.
Mert Erdemir
Saline solution stock photo.Amornrat Phuchom/iStock

Chemotherapy, or chemo, in short, is a drug-related treatment that uses powerful chemicals to eradicate cancer cells in your body. Though a very potent method in cancer treatment, it also has very severe side effects that can be life-altering for a patient. It cannot be said that chemotherapy is a requirement to cure cancer, but determining its necessity is another challenging issue.

And now, a new study led by scientists at the Johns Hopkins Kimmel Cancer Center and WEHI provides a circulating tumor DNA (ctDNA) guided approach to identify treatment responses in stage II colon cancer patients.

In treating colon cancer, chemotherapy aims to eliminate micrometastases, cancer cells that are not visible on radiologic pictures but move through the bloodstream and cause the disease to return or spread to other body regions. Using ctDNA to detect these invisible cells, researchers can now determine which individuals are more likely to suffer micrometastases and hence benefit from treatment.

As its name suggests, circulating tumor DNAs are fragmented parts of a tumor's DNA that circulate in the bloodstream. Importantly, they are not parts of a tumor cell but just the DNA from the tumor.

Helping individuals with stage II colon cancer

This is not the first study to work on ctDNA, and it is known by scientists that the presence of ctDNA in the bloodstream after surgery indicates the likelihood of cancer recurrence. However, the new study is the first clinical research to demonstrate that a ctDNA-guided approach after surgery can considerably help individuals with stage II colon cancer.

"Stage II colon cancer presents a unique challenge," stated Anne Marie Lennon, Ph.D. and director of the division of gastroenterology and hepatology at Johns Hopkins University School of Medicine. "In stage I colon cancer, patients do not receive chemotherapy because their prognosis for survival is over 90 percent. The risk of discomfort and toxicities from the therapy outweigh the benefits it can provide. On the other hand, every stage III colon cancer patient currently receives chemotherapy because the risk of relapse is high."

"A ctDNA-guided approach to stage II colon cancer reduced adjuvant chemotherapy use without compromising recurrence-free survival," wrote gastrointestinal oncologist Jeanne Tie in the new paper.

Researchers believe that this research may spur more research into ctDNA in patients with advanced colon cancer and other cancer types. People with early-stage pancreatic cancer and stage III colon cancer will be studied to determine if ctDNA may identify patients who would benefit from more aggressive treatment than is presently available.

The results of this study were published in the New England Journal of Medicine.


The role of adjuvant chemotherapy in stage II colon cancer continues to be debated. The presence of circulating tumor DNA (ctDNA) after surgery predicts very poor recurrence-free survival, whereas its absence predicts a low risk of recurrence. The benefit of adjuvant chemotherapy for ctDNA-positive patients is not well understood.

We conducted a trial to assess whether a ctDNA-guided approach could reduce the use of adjuvant chemotherapy without compromising recurrence risk. Patients with stage II colon cancer were randomly assigned in a 2:1 ratio to have treatment decisions guided by either ctDNA results or standard clinicopathological features. For ctDNA-guided management, a ctDNA-positive result at 4 or 7 weeks after surgery prompted oxaliplatin-based or fluoropyrimidine chemotherapy. Patients who were ctDNA-negative were not treated. The primary efficacy end point was recurrence-free survival at 2 years. A key secondary end point was adjuvant chemotherapy use.

Of the 455 patients who underwent randomization, 302 were assigned to ctDNA-guided management and 153 to standard management. The median follow-up was 37 months. A lower percentage of patients in the ctDNA-guided group than in the standard-management group received adjuvant chemotherapy (15% vs. 28%; relative risk, 1.82; 95% confidence interval [CI], 1.25 to 2.65). In the evaluation of 2-year recurrence-free survival, ctDNA-guided management was noninferior to standard management (93.5% and 92.4%, respectively; absolute difference, 1.1 percentage points; 95% CI, −4.1 to 6.2 [noninferiority margin, −8.5 percentage points]). Three-year recurrence-free survival was 86.4% among ctDNA-positive patients who received adjuvant chemotherapy and 92.5% among ctDNA-negative patients who did not.

A ctDNA-guided approach to the treatment of stage II colon cancer reduced adjuvant chemotherapy use without compromising recurrence-free survival.

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