Identification of patients at high risk for relapse by Merlin assay (CP-GEP) in an independent cohort of melanoma patients (pts) that did not undergo sentinel lymph node biopsy: An H&N subgroup analysis.

9567 Background: Sentinel lymph node biopsy (SLNB) is still the gold standard for nodal assessment used in the clinical staging of cutaneous melanoma (CM) pts by AJCC v8. Recently, we showed in a small cohort that CP-GEP also has the potential to risk stratify pts who did not undergo SLNB in low and high-risk for recurrence (Amaral et al, EJC 2023). SLNB may be challenging in pts with head and neck (H&N) melanoma, due to the regional course of cranial nerves and lymphatic drainage. Here we focus on the ability of CP-GEP to stratify pts with H&N melanoma in particular those with lentigo maligna, who did not undergo SLNB, for their risk of recurrence. Methods: We analyzed formalin-fixed paraffin-embedded primary tumor samples of 930 pts of which 206 were localized in the H&N region, with stage I/II CM diagnosed between 2000-2017 who did not receive SLNB. The CP-GEP model used combines the expression of 8 genes (SERPINE2, GDF15, ITGB3, CXCL8, LOXL4, TGFBR1, PLAT and MLANA) by quantitative reverse transcription polymerase chain reaction with age and Breslow thickness to obtain a binary output: CP-GEP Low- or High-Risk. Relapse-free survival (RFS), distant metastasis free survival (DMFS) and Melanoma Specific Survival (MSS) were evaluated using Kaplan-Meier curves. Results: We included 930 pts (stage IA-IIC) of which 206 pts (22.3%) were diagnosed with H&N melanoma. Patient characteristics: 41% were females, median age was 73-year-old, median Breslow thickness was 0.5 mm and 75.6% were lentigo maligna melanomas. Median follow up was 51 months (RFS). All H&N pts showed the following survival: 5-year RFS 82.5%, DMFS 94.0 and MSS 95.5%. CP-GEP risk stratification identified 17 patients as CP-GEP High-Risk and 188 as CP-GEP Low-Risk. The 5-year RFS rate was 86.7% for CP-GEP Low-Risk and 39.7%% for CP-GEP High-Risk pts (HR 7.85; p<0.001), 5-year DMFS was 96.3% for CP-GEP Low-Risk and 68.9% High-Risk pts (HR 10.26; p<0.001) and the 5-year MSS was 98.5% for CP-GEP Low-Risk pts and 64.7% for CP-GEP High-Risk pts (HR 24.45; p<0.01). Conclusions: Pts with H&N CP-GEP Low-Risk tumors have a good long-term survival compared to High-Risk pts even though SLN status was not assessed. This prognostic information may allow the clinicians to skip SLNB in this difficult anatomic localization and in frail and/or older pts.