Additional Evidence Found To Connect ctDNA’s Potential Role in Colon Cancer

Additional information has been found to show that colon cancer patients with detectable levels of circulating tumor DNA (ctDNA) may be candidates for additional therapy.

More Evidence for ctDNA’s Potential Role in Colon Cancer


Circulating tumor DNA (ctDNA) in post-chemotherapy blood samples identified patients with stage III colorectal cancer at high risk of disease recurrence, a prospective study from Australia found.

In 96 consecutive patients, 30% of those with detectable ctDNA following adjuvant chemotherapy were disease-free 3 years later versus 77% of those with undetectable ctDNA (HR 6.8, P<0.001), reported Jeanne Tie, MD, of Walter and Eliza Hall Institute of Medical Research in Parkville, Australia, and colleagues in JAMA Oncology.

“The novel data presented herein suggest that post-chemotherapy ctDNA analysis could lead to a more informed selection of patients who could benefit from additional therapeutic approaches, supporting the pursuit of clinical trials of novel agents in this high-risk population,” they wrote.

“Numerous clinical studies have suggested that the treatment of patients with low burdens of metastatic disease is far more efficacious than the treatment of patients with radiologically detectable disease,” Tie’s group continued. “Thus, the treatment of patients with detectable ctDNA levels but without radiological evidence of disease after adjuvant chemotherapy could, in theory, eradicate residual disease and increase the chance of cure.”

Examining ctDNA following surgery showed that 47% of patients with detectable were disease-free at 3 years compared with 76% of those with undetectable ctDNA (HR 3.8, 95% CI 2.4-21.0, P<0.001). The investigators found that presence of ctDNA following surgery had the strongest independent association with disease recurrence.

The findings mirror similar results in stage II disease from Tie and colleagues and expands on the potential role of liquid biopsies to guide which patients are candidates for more treatment. Numerous trials are currently recruiting that aim to examine this approach in patients who test positive on ctDNA and have no radiologic evidence of disease.

“After administering a therapy with curative intent, patients and physicians have one key question in mind: is the cancer cured?” wrote Harry Burke, MD, PhD, of the Uniformed Services University of the Health Sciences in Bethesda, Maryland, and Scott Kopetz, MD, PhD, of MD Anderson Cancer Center in Houston, in an accompanying editorial. “Unfortunately, because of the limitations of our current standard of surveillance, we can never be sure that all the tumor cells have been eradicated and therefore never be sure of a cure.”

Burke and Kopetz pointed out, however, that the investigators’ hypothesis that ctDNA could accurately predict patients at high risk for disease recurrence “was not well supported” in the post-surgical setting where the receiver operating characteristic (ROC) was 0.64 (95% CI 0.60-0.66), though this improved with the addition of pathologic tumor and nodal staging.

ROC following chemotherapy was 0.70 (95% CI 0.66-0.72) and improved to 0.78 (95% CI, 0.73-0.81) with the addition of pathologic tumor and nodal staging.

“An early concern of ctDNA-based prognosis was that the presence of detectable ctDNA after surgery might define a population for which there was no benefit from adjuvant chemotherapy,” wrote Burke and Kopetz. Yet they pointed out that the current study identified a subset of patients who had detectable post-surgery ctDNA but achieved a long disease-free period following chemotherapy and have been potentially cured.

“This is a valuable piece of information that increases the potential utility of this technology,” they added.

From 2014 to 2017, Tie and colleagues prospectively enrolled 100 consecutive colorectal cancer patients (median age 64) undergoing surgery for their newly diagnosed stage III disease, followed by 6 months of adjuvant chemotherapy with either oxaliplatin-based therapy or fluoropyrimidine alone.

Fifteen genes that are frequently mutated in colorectal cancer were sequenced, and at least one somatic mutation was identified in all 96 patients included in the final analysis (three were excluded for having stage IV disease and in the fourth patient, a post-surgery blood sample could not be attained). Post-surgery, ctDNA was found in 20 of the 96 patients; following both surgery and chemotherapy, ctDNA was found in 15 of 89 patients.

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