Validation of CP‐GEP (Merlin Assay) for predicting sentinel lymph node metastasis in primary cutaneous melanoma patients: A U.S. cohort study

Abstract

Background Approximately 85% of melanoma patients who undergo a sentinel lymph node biopsy (SLNB) are node-negative. Melanoma incidence is highest in patients ≥65 years, but their SLNB positivity rate is lower than in younger patients. CP-GEP, a model combining clinicopathologic and gene expression variables, identifies primary cutaneous melanoma (CM) patients who may safely forgo SLNB due to their low risk for nodal metastasis. Here, we validate CP-GEP in a U.S. melanoma patient cohort.Methods A cohort of 208 adult patients with primary CM from the Mayo Clinic and West Virginia University was used. Patients were stratified according to their risk for nodal metastasis: CP-GEP High Risk and CP-GEP Low Risk. The main performance measures were SLNB reduction rate (RR) and negative predictive value (NPV).Results SLNB positivity rate for the entire cohort was 21%. Most patients had a T1b (34%) or T2a (31%) melanoma. In the T1-T2 group (153 patients), CP-GEP achieved an SLNB RR of 41.8% (95% CI: 33.9-50.1) at an NPV of 93.8% (95% CI: 84.8-98.3). Subgroup analysis showed similar performance in T1-T2 patients ≥65 years of age (51 patients; SLNB positivity rate, 9.8%): SLNB RR of 43.1% (95% CI: 29.3-57.8) at an NPV of 95.5% (95% CI: 77.2-99.9). ConclusionWe confirmed the potential of CP-GEP to reduce negative SLNB in all relevant age groups. Our findings are especially relevant to patients ≥65 years, where surgery is often elective. CP-GEP may guide SLNB decision-making in clinical practice.The CP-GEP model was previously developed on a large prospectively collected cohort of 754 archived U.S. patients who underwent an SLNB within 90 days of primary melanoma

Using the Merlin assay for reducing sentinel lymph node biopsy complications in melanoma: a retrospective cohort study

“…Many complications are self-limited, while others require additional interventions. The Merlin assay, which has been validated retrospectively in multiple independent cohorts [7][8][9] and is currently undergoing prospective validation in a multicenter study (NCT04759781), reduced the need for SLNB by over 50% in this cohort and complications by 59% (Fig. 2).…”

“…The cohort consisted of 558 melanoma patients, a subset of a previous cohort used for Merlin test development. 6,7,[10][11][12] All patients had SLNB performed within 90 days of their diagnosis.…”

“…6 This assay uses the CP-GEP model, combining clinicopathological variables with tumor gene expression profiling to identify patients who can forgo SLNB due to their low risk of nodal metastasis. The Merlin assay has been clinically validated in the United States 7 and Europe 8,9 and is commercially available for patient care. Here, we used the Merlin development cohort to determine SLNB complication rates, that is, rates of hematoma, seroma, infection/cellulitis, lymphedema, and wound dehiscence specific to the SLNB procedure.…”

Contrast mechanisms in pump-probe microscopy of melanin

“…If histopathology identifies a tumor as high risk, sentinel lymph node biopsy is standard evaluation but 85% of melanoma patients who undergo sentinal lymph node biopsy have a negative result. There remains a clinical need to more clearly identify which patients with primary melanomas will develop metastases so that appropriate therapy can be given to reduce recurrence [7,8]. The development of biomarkers for metastatic melanoma is currently an active field of research, but still in its early stage [8][9][10][11][12].…”

“…There remains a clinical need to more clearly identify which patients with primary melanomas will develop metastases so that appropriate therapy can be given to reduce recurrence [7,8]. The development of biomarkers for metastatic melanoma is currently an active field of research, but still in its early stage [8][9][10][11][12]. We have already demonstrated that pump-probe microscopy images of primary tumors correlate with metastatic disease [4,5,13,14].…”