Colon cancer DNA in blood can guide chemo decisions

A simple blood test could change how doctors decide which patients with colon cancer need chemotherapy, according to the results of an international study.

The DYNAMIC-III clinical trial found that testing for tiny fragments of cancer DNA in the bloodstream, known as circulating tumour DNA (ctDNA), can reveal if cancer is present after surgery and help tailor treatment accordingly. The findings were presented at the recent European Society for Medical Oncology (ESMO) Congress and simultaneously published in the journal Nature Medicine.

More than 1000 people with stage III colon cancer across Australia, New Zealand and Canada took part in the study and all had blood taken about six weeks after surgery to remove their primary colon cancer. If no ctDNA was detected, patients were considered ‘low risk’; if ctDNA was present, they were ‘high risk’. Participants were randomly assigned to receive either standard chemotherapy or treatment guided by their ctDNA results.

Study leader Professor Jeanne Tie, from the Peter MacCallum Cancer Centre (Peter Mac) and the Walter and Eliza Hall Institute (WEHI), said the findings show how ctDNA could bring true precision medicine to colon cancer.

“ctDNA is a powerful tool that can help guide treatment choices and identify which patients might safely receive less intensive treatment and those who might need to seek alternative options,” she said.

“Right now, we give most stage III patients the same chemotherapy, but ctDNA testing can help tailor treatment based on individual risk.

“For some patients, this means a less intensive approach may be just as effective, while reducing unnecessary toxicity from chemotherapy such as oxaliplatin and improving their quality of life.

“The DYNAMIC-III study shows that a blood test can help to give patients more personalised, risk-adapted chemotherapy by identifying who may benefit from full-intensity chemotherapy and who can safely receive a reduced regimen.”

Outcomes were deemed excellent among the patients identified as low risk based on their ctDNA levels, with 87% remaining cancer-free three years after surgery.

“These patients were able to safely receive less chemotherapy, leading to fewer hospitalisations and a reduction in side effects such as nerve damage, with only slightly lower cancer-free survival,” Tie said.

By contrast, patients whose ctDNA remained detectable after surgery had a much higher risk of recurrence — only about half remained cancer-free at three years, and the risk worsened as ctDNA levels rose. For this group, receiving more intensive chemotherapy did not improve results, suggesting new treatment approaches are needed.

The study was conducted in collaboration with the Canadian Cancer Trials Group (CCTG), the Australasian Gastro-Intestinal Trials Group (AGITG) and WEHI. Dr Jonathan Loree, DYNAMIC-III Canadian Study Chair and CCTG Senior Investigator, said he was thrilled to work with Australian collaborators on such an important trial.

“This study provides the best available prospective evidence of the prognostic value of ctDNA in selecting adjuvant chemotherapy for patients with resected stage III colon cancer,” Loree said.

“Its results are crucial as we build the evidence needed to move ctDNA into the clinic.”

Image credit: iStock.com/Mohammed Haneefa Nizamudeen