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ctDNA Accurately Detects BRAF Mutations in Advanced Melanoma, Study Finds


A new report shows better than 80% concordance between liquid biopsy and tissue biopsy.

Liquid biopsy and analysis of circulating tumor DNA (ctDNA) is a viable option for determining the presence of BRAF mutations in patients with advanced melanoma, according to a new report based on real-world data.

These findings show that ctDNA analysis is feasible in routine clinical practice, and not just in a clinical trial setting. They were published in Cancers.

The study authors, of the Medical University of Warsaw, in Poland, explained that patients with advanced melanoma tend to have unsatisfactory results with chemotherapy. However, the development of BRAF inhibitors and MEK inhibitors has substantially changed the treatment landscape for these patients. These developments have also made it essential to test patients for mutations, they added.

“Testing for the presence of somatic BRAF mutations in melanoma is a crucial step in diagnosis and the qualification for treatment,” the authors wrote.

In a clinic setting, the most common method of assessing BRAF mutations is through formalin-fixed paraffin-embedded tissue specimens, but the authors said these samples can sometimes be difficult to obtain. Liquid biopsies, evaluating circulating tumor cells or ctDNA in blood and urine, can be simpler options, they said, although the technique has yet to gain popularity in routine practice.

“Despite the progress in the field of liquid biopsies, [the method] is most commonly used in clinical trials and research settings,” the investigators wrote. “Its availability in everyday clinical practice is becoming more common but remains very limited.”

Previous work has validated liquid biopsy as a method of BRAF mutation detection. Still, the authors wanted to see how the method worked in real-world practice. They retrospectively identified 46 patients treated at Skłodowska-Curie National Research Institute of Oncology in Warsaw who had advanced melanoma and underwent ctDNA testing for BRAF mutations. Twenty-one patients were female, and 25 patients were male. Twenty-nine of the patients also underwent tissue-sample testing for mutations.

Among the 46 patients undergoing liquid biopsies, 21 (45.7%) had BRAF mutations. In the 29 tissue-sample tests, 13 patients had BRAF mutations (44.8%). Further, among patients who underwent both tests, the concordance between the tests was 82.8%, the authors said. The concordance rate was in line with previous research, although the investigators noted that most of the previous research was based on clinical trial settings rather than on routine clinical practice.

Eighteen patients began therapy with BRAF/MEK inhibitors based on the results of liquid biopsy. In those patients, the objective response rate was 77.8%, and the median progression-free survival was 6.0 months. One patient had a complete response, and 13 reported partial responses.

The authors cautioned that their analysis was based on a small, retrospective cohort, and ctDNA testing in these patients was only used in cases where tissue testing was deemed impossible or where particularly prompt commencement of therapy was necessary. Still, they said the data clearly show that liquid biopsy is feasible and accurate in a clinic setting.

“Their minimal invasiveness, low cost, reproducibility, and short time required to obtain the results are the main advantages of liquid biopsies,” the investigators concluded. “Moreover, they allow overcoming limitations such as the availability and quality of tissue material and tumor heterogeneity.”


Sobczuk P, Kozak K, Kopeć S, et al. The use of ctDNA for BRAF mutation testing in routine clinical practice in patients with advanced melanoma. Cancers (Basel). Published online February 2, 2022. doi:10.3390/cancers14030777

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