ctDNA-guided treatment for colon cancer

An Australian trial has shown that stage II colon cancer patients can safely reduce chemotherapy – and the associated side effects of the treatment – without compromising a positive survival outcome when using circulating tumor DNA (ctDNA) to guide treatment decisions.

Conducted by one of Australia’s leading biomedical research institutes over five years, the DYNAMIC trial studied 441 stage II colon cancer patients with a median age of 64, randomly assigned to either the ctDNA-guided treatment group (294 patients) or the standard management group (147 patients) following surgery.

While a previous primary analysis showed 15 percent of patients who had liquid biopsy received follow-up chemotherapy following identification of ctDNA, compared to 28 percent of patients who had chemotherapy under standard management, the five-year results were almost identical.

Published in the journal Nature Medicine, the results put overall survival rates at 93.8 percent and 93.3 percent for those in the ctDNA-guided group and standard management group respectively.

The recurrence-free survival rate was also similar, with 88 percent of patients in the ctDNA-guided group and 87 percent in the standard management group remaining free from a cancer recurrence.

“Five years on, and despite the reduced use of chemotherapy in patients who had liquid biopsies, survival outcomes in both groups are virtually the same,” reported lead investigator Professor Jeanne Tie, an oncologist with the Walter and Eliza Hall Institute of Medical Research and Peter MacCallum Cancer Centre in Melbourne.

“These findings confirm that ctDNA liquid biopsies are an effective way to guide treatment for stage II colon cancer patients, allowing many to avoid chemotherapy and its associated toxicities, without compromising survival outcomes.”

For patients with more advanced T4 disease, ctDNA-guided management showed a 90.5 percent survival rate compared to 80 percent in the standard management group. Recurrence-free survival rates for people in this cohort were 81.2 percent (ctDNA group) versus 70 percent (standard group).

The promising findings of the DYNAMIC trial suggest ctDNA testing could transform the way clinicians approach treatment for stage II colon cancer, given this method both minimises chemotherapy while also providing a more tailored treatment plan based on individual patient risk.

“The DYNAMIC data also suggest continued improvement in survival outcomes over time, with lower recurrence rates in this more contemporary stage II cohort when compared to historical practice-defining trials of adjuvant therapy,” noted researchers.

While some international oncologists have previously urged a cautious approach in interpreting the practical implications of the trial’s findings, and further research is required, the DYNAMIC trial’s five-year results offer compelling evidence that ctDNA-guided treatment can reduce the need for chemotherapy in many colon cancer patients while maintaining survival rates.