V52: Circulating Tumor DNA in Stage II and III Melanoma

Serial testing of circulating tumor DNA (ctDNA) in melanoma has the potential to detect minimal residual disease or identify early relapse after surgery. The Signatera^TM test generates a tumor-informed ctDNA assay based on primary or metastatic tumor and shows promising predictive power in other malignancies, but its role in patients with high-risk resectable melanoma is unknown.


Methods:

Clinical stage IIB/C or resectable stage III melanoma patients were prospectively recruited in a pilot study at two tertiary care centers. Primary tumor or regional metastases were used to develop personalized, tumor-informed ctDNA assays using an mPCR-NGS technology (Signatera^TM). Patients underwent wide excision with sentinel lymph node biopsy or therapeutic node dissection depending on clinical stage. Pre- and post-op plasma samples were collected and evaluated for ctDNA. The primary aim was to assess feasibility of generating tumor-informed ctDNA assays in these high-risk patients. Secondary aims included evaluating ctDNA levels pre/post-op and in relation to sentinel lymph node (SLN) status.


Results:

Of 32 patients consented, 12 were excluded, most due to insufficient tissue for assay development. Of 20 eligible patients (mean 64.8 years, 55% male), all ctDNA assays were generated and resulted within 6 weeks of tissue receipt. All pathologic stage IIB (n=3) pre-op samples were negative for ctDNA. Pre-op ctDNA was positive in 1/3 IIC (33%), 2/3 IIIB (67%), 5/9 IIIC (56%), and 2/2 IIID (100%) samples (Figure 1). Levels of ctDNA ranged from 0.09 to 75.19 (mean tumor molecules/mL). The majority of SLN-positive stage III patients had negative pre-op ctDNA (4/5, 80%). In contrast, almost all clinically evident stage III patients were positive for pre-op ctDNA (8/9, 89%). All post-op samples were negative for ctDNA regardless of stage or disease burden.


Conclusions:

Generation of a tumor-informed ctDNA assay for melanoma is feasible, and surgical patients with higher stage, clinically evident nodal disease frequently had detectable ctDNA pre-op. However, assay generation may be limited in patients with thinner primary tumors. Given clearance of ctDNA post-op, serial monitoring of ctDNA should be investigated for use in clinical surveillance.