Bespoke ctDNA for longitudinal detection of molecular residual disease in high-risk melanoma patients

Abstract

Background: Locally advanced melanoma has a variable prognosis. Currently, there are no reliable criteria to stratify the risk of disease relapse and identify those patients who will benefit the most from adjuvant therapies. Circulating tumor DNA (ctDNA) is an emerging biomarker measuring the presence of tumor-derived DNA in blood.

Patients and methods: We used a bespoke, tumor-informed assay (RaDaR®, NeoGenomics, Inc.) to detect ctDNA in 276 prospectively collected plasma samples from 66 melanoma patients receiving definitive treatment. Collection time points included landmark (after completion of local treatment) and every 3-6 months for up to 2 years.

Results: ctDNA was detected in at least one plasma sample in 19 patients (29%), including 6/65 (9%) at landmark (post-surgical sample). Positive ctDNA at landmark was associated with shorter overall survival (OS; median OS 22.7 months versus not reached, log-rank P value = 0.01) and a trend towards a shorter relapse-free survival (RFS; median RFS 15.7 months versus not reached, log-rank P value = 0.07). In 10 patients, ctDNA detection preceded disease relapse by a median of 128 days (range 8-406 days).

Conclusions: Our data indicate that ctDNA detection after surgery can identify patients with worse prognosis, and serial ctDNA measurements may enable earlier identification of disease recurrence.

Keywords: biomarker; circulating tumor DNA; liquid biopsy; melanoma; molecular residual disease.