Predicting Metastases in Patients With Colorectal Cancer Using ctDNA
Posted: Wednesday, February 5, 2020
Findings from a study presented in Clinical Cancer Research suggest that circulating tumor DNA (ctDNA) may predict disease progression in patients with colorectal cancer. The study tracked tumor DNA from patients’ plasma using droplet digital polymerase chain reaction (PCR) and metastases via MRI.
“Responses to neoadjuvant chemoradiotherapy are variable in patients with rectal cancer,” stated David Cunningham, MD, of The Royal Marsden Hospital NHS Foundation Trust, in an American Association for Cancer Research press release. “If we can accurately differentiate the good responders from the poor responders, we may be able to adapt treatment and move away from a one-size-fits-all approach.” Initial study author Shelize Khakoo, MD, also of The Royal Marsden, added: “Our results indicate that ctDNA can be used to identify patients who have a greater risk of developing metastases or experiencing relapse.”
A total of 47 patients with localized colorectal cancer undergoing chemoradiotherapy were identified for participation in the study. Blood samples were collected pretreatment, 3 to 4 weeks from the start of treatment, and 4 to 12 weeks after treatment; they then were analyzed for somatic variants using droplet PCR. An MRI was conducted for all patients 3 to 6 weeks after treatment to assess tumor progression and metastases.
The authors found ctDNA to be detectable in 74% of patients prior to treatment, 21% during treatment, and 21% after treatment. The levels of detectable tumor DNA at mid-treatment and post-treatment time points were higher in patients who developed metastases (P = .01 and P = .03, respectively). The analysis predicted metastases with 100% sensitivity for patients with tumor DNA levels detectable at mid-treatment or post-treatment. It had a specificity of 83.3% for patients with detectable DNA mid-treatment and 66.7% for detectable DNA after treatment. The research group also observed a shorter metastases-free survival in patients with tumor DNA levels detectable in blood samples at any time point during the study (hazard ratio = 7.1; P < .001). All three patients who underwent a pathologic complete response had detectable tumor DNA levels before treatment but undetectable levels mid- and post-treatment.
Disclosure: For full disclosures of study authors, visit clincancerres.aacrjournals.org.