Circulating tumor DNA for surveillance in high-risk melanoma patients: a study protocol

BACKGROUND AND PURPOSE: Melanoma is one of the deadliest skin cancers and challenges clinicians worldwide due to rising incidence, potential aggressiveness, and propensity for metastasis, necessitating comprehensive follow-up programs after primary treatment. Circulating tumor DNA (ctDNA) is a promising biomarker that may indicate disease progression earlier than traditional surveillance methods, including 18F-FDG PET-CT, ultrasound, and clinical examination. This study examines ctDNA detection in blood as a minimally invasive method for early identification of progression following primary treatment of melanoma. The aim is to overcome the limitations of current methods, potentially improving prognosis and survival. PATIENTS/MATERIAL AND METHODS: Patients with high risk of recurrence following primary treatment of melanoma are offered inclusion. Blood sampling is performed at each follow-up visit. In case of recurrence, patient-specific mutations are identified through next-generation sequencing (NGS) of formalin and paraffin embedded tissue from diagnostic routine. Detection of mutation-specific ctDNA is performed on blood using digital droplet polymerase chain reaction (ddPCR) or NGS. This allows determination of the value and sensitivity of ctDNA for early detection of recurrence. RESULTS AND INTERPRETATION: For validation purposes, we conducted a small pilot study using blood samples from 10 patients who had experienced recurrence and had a clinically confirmed BRAF V600E mutation. Detection of BRAF V600E ctDNA using ddPCR varied from 0/5 (0%) in DNA harvested from 4 mL plasma, to 3/5 (60%) in DNA from 8 mL of plasma. These results show promise and highlight the importance of high sensitivity and sampling volumes to ensure accurate detection of low levels of ctDNA.