Liquid Biopsy in Colorectal Cancer

A liquid biopsy method that incorporates beads emulsion amplification magnetics, or BEAM, technology proved effective in detecting specific types of colorectal cancer mutations that tissue biopsy might not be able to find. Liquid biopsy also revealed that baseline circulating DNA concentrations were prognostic for clinical outcome in that patients with higher baseline plasma DNA concentrations had shorter median survival than did those with lower plasma DNA concentrations.

Researchers in the CORRECT phase III trial discovered this when they used the BEAMing platform to analyze circulating DNA of more than 500 patients with metastatic colorectal cancer. BEAMing involves “a technique based on emulsion PCR that allows detection of one mutant allele in 10,000 wild-type alleles,” explains an article on the findings in The Lancet Oncology.

This method “offers potential advantages over archival tumour DNA testing, including convenience, non-invasive sample collection, and more accurate representation of a tumour’s current mutational status,” the article stated.

The objective was to look for several tumor gene mutations: KRAS, PIK3CA, and BRAF, and find a correlation between mutation status and progression-free and overall survival.

Patients in the trial, who had previously been given other treatment therapies, received either the multi-kinase inhibitor regorafenib or a placebo.

Researchers determined that regorafenib showed clinical benefits for patients with KRAS and PIK3CA mutations. They also discovered that liquid biopsy proved adept in finding tumor mutations. Among the 503 test subjects, BEAMing of plasma DNA detected KRAS mutations in nearly 70% of the patients, whereas PIK3CA and BRAF mutations were found in 17% and 3% of the patients, respectively.

"This is the first large clinical trial to compare liquid versus conventional tissue biopsy data, and the results show the former (BEAMing technology) obtain more data on tumor mutation throughout the course of the disease, enabling us to better target therapy to the specificities of patient’s tumor,” said the study’s co-director, Josep Tabernero, MD, PhD, head of the Medical Oncology Department of Hospital Universitario Vall d'Hebron and director of the Vall d'Hebron Institute of Oncology (VHIO), in a statement issued by VHIO.

Researchers also conducted a statistical analysis of 15 proteins associated with either colorectal cancer pathogenesis or angiogenesis, drawing from the plasma of 611 patients in the CORRECT trial.

The purpose of this “was to establish whether the treatment effects of regorafenib on overall survival and progression-free survival were affected by the concentrations of any one of the 15 proteins that we measured in baseline plasma samples,” the article explained.

Tabernero and his colleagues acknowledged that the circulating DNA liquid biopsy method had its limitations, including the fact that not all tumors release enough DNA into the blood for it to be detected, and the difficulty in assigning a particular genotype for each tumor in patients with metastatic disease. “Nonetheless, analysis of circulating DNA on a commercial scale could be an invaluable tool in clinical practice,” specifically as a real-time, non-invasive method for detecting tumor genotypes, the article stated.