Circulating tumour DNA linked to worse outcomes in melanoma

Melanoma patients with detectable levels of circulating tumour (ct)DNA carrying mutations in the BRAF, NRAS, and TERT genes tend to have unfavourable disease outcomes, a recent study has found.

After determining the limits of detection (LOD) and blank in tumour cell lines and healthy plasma samples, respectively, the researchers enrolled 19 stage III and IV melanoma patients (aged 34–79 years; 63.2 percent female). Somatic mutations in tumour tissue were identified through next-generation and Sanger sequencing methods.

All but two of the enrolled patients had at least one somatic mutation in the tumour-associated genes. Twelve patients showed BRAF mutations, while mutations in NRAS and TERT were reported in two and 14 patients, respectively. Eleven had alterations in more than one gene. By the end of the study, five patients died and 14 were still under follow-up.

Of the 17 patients carrying at least one somatic mutation, seven (41 percent) had detectable levels of ctDNA. Assessing by mutation, the researchers saw that BRAF mutations were detectable in five of 12 patients, and TERT mutations were detectable in five of 14 patients. One patient had detectable levels of NRAS mutation in their plasma sample.

In turn, prognostic factors and disease outcomes were worse among patients who had plasma ctDNA levels within the LOD. For example, among patients who had more than one metastasis site, detectable ctDNA levels were more common.

In addition, progression-free survival (p=0.01) was worse in patients who had detectable plasma ctDNA levels, and their median time to progression was much shorter (50 vs 146 days). Cox proportional hazards regression analysis confirmed that ctDNA was a significant risk factor for progression (hazard ratio, 6.38, 95 percent confidence interval, 1.26–32.1; p=0.025).