Tracking Down 'Hidden DNA' in The Blood Could Help Some Cancer Patients Avoid Chemo

Chemotherapy is a fantastic weapon for destroying cancer cells, but it also targets our healthy cells, resulting in life-altering adverse effects.

Chemotherapy, or chemo for short, isn't always necessary for successful treatment, but determining whether or not someone needs it is both an art and a science. A new research now gives physicians access to a strategy that has already helped some stage II colon cancer patients skip chemo while maintaining their clinical results.

A form of DNA termed circulating tumor DNA is used in this new study's approach (ctDNA). This is self-explanatory — it's microscopic fragments of tumor DNA circulating in the bloodstream. They are not, however, part of a tumor cell; rather, they are the DNA from the tumor on their own.

Circulating tumor DNA (ctDNA) and how it's found in blood.

This isn't the first study to look at ctDNA, and scientists already know that the presence of ctDNA in the bloodstream after surgery predicts the likelihood of cancer recurrence.

However, the latest study has taken this information a step further. It's the first clinical research to indicate that a ctDNA-guided method following surgery can considerably help individuals with stage II colon cancer.

"Stage II colon cancer presents a unique challenge," says Anne Marie Lennon, a gastroenterologist at Johns Hopkins.

"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." 

The cancer has progressed through the muscular layers of the colon wall in stage II colon cancer, but has not yet migrated to other organs. In this situation, the patient will have surgery to remove the tumor, but the physician will have to decide whether or not to follow up with chemotherapy.

We know that roughly 75 percent of persons with stage II colon cancer do not require chemotherapy following surgery, but about 25% do. It's critical to figure out which individuals will gain the most from chemotherapy, yet getting it wrong can be fatal.

Currently, there are a lot of characteristics of a tumor that may trigger a doctor to order chemotherapy, such as if the tumor seems aberrant under a microscope or if the disease has spread to other tissues.

However, a recent study suggests that this strategy isn't flawless, and that many cancer patients may be receiving chemotherapy when they don't require it.

A total of 455 individuals with type II colon cancer were enrolled in the research between 2015 and 2019. 302 of them were given the ctDNA-guided treatment, while the others were given normal care. The patients were followed up with after about 37 months, which meant the research had data on them for more than three years.

Both conventional therapy and guided treatment showed equal rates of survival and no cancer recurrence over the research period (92.4 vs 93.5 percent). However, the amount of chemotherapy given was a significant variation. Only 15.3% of patients in the ctDNA guided therapy group needed chemo, compared to 27.9% in the usual treatment group.

This is nearly double the number of individuals who had chemotherapy, with no improvement in survival or tumor recurrence.

"A ctDNA-guided approach to stage II colon cancer reduced adjuvant chemotherapy use without compromising recurrence-free survival," said the researchers – led by Walter and Eliza Hall Institute gastrointestinal oncologist Jeanne Tie – in their latest publication.

"The low recurrence rate in ctDNA-positive patients who received chemotherapy suggests a survival benefit from adjuvant therapy." 

The researchers anticipate that ctDNA will be a useful signal for how to treat various forms of cancer and different stages of colon cancer, and they are currently looking into whether ctDNA may help with early stage pancreatic and stage III colon cancer.

"We have an opportunity to change clinical practice," says Joshua Cohen, a biomedical engineer at Johns Hopkins University School of Medicine.

"Using ctDNA to guide treatment, a stage II colon cancer patient who is negative for ctDNA has a lower chance of cancer recurrence than the average stage I colon cancer patient."