Circulating Tumor DNA: A Promising Biomarker for Predicting Recurrence in Patients with BRAF-Negative Melanoma

Area of Science:

• Oncology
• Genomics
• Molecular Diagnostics

Background:

• Advanced melanoma (Stage III-IV) lacking BRAF mutations requires prognostic and predictive biomarkers.
• Circulating tumor DNA (ctDNA) shows promise as a non-invasive blood-based biomarker in various cancers, including melanoma.

Purpose of the Study:

• To identify tumor-derived mutations in blood for BRAF wild-type melanoma patients.
• To explore ctDNA as a tool for treatment alternatives and improved outcomes in this patient group.

Main Methods:

• Deep sequencing (CAPP-seq) of a pan-cancer gene panel was used to analyze ctDNA from 150 plasma samples (106 patients).
• Serial blood collections were performed on a subset of patients (n=16).

Main Results:

• ctDNA variants were detected in 85% of patients, targeting actionable pathways (VEGFR, EGFR, PI3K/AKT, mTOR, ALK/MET, CDK4/6).
• Stage IV patients with low ctDNA (<10 ng/mL) exhibited significantly better disease-specific and progression-free survival.
• High ctDNA concentration and detectable variants correlated with the worst prognosis.
• Longitudinal ctDNA changes mirrored treatment response and radiological disease progression.

Conclusions:

• ctDNA serves as a viable non-invasive liquid biopsy for detecting recurrent disease and actionable mutations in late-stage melanoma.
• ctDNA analysis can aid in prognostication and monitoring treatment response in BRAF wild-type melanoma.