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Intrinsic Tumor Characteristics Related to Recurrence Risk and Overall Survival In Patients with Uveal Melanoma.
Aikaterini Dedeilia*1, Nicholas Stratigakis2, Aleigha Lawless2, Tatyana Sharova2, Kendra Pallin2, Genevieve M. Boland1
1Department of Surgery, Massachusetts General Hospital, Boston, MA; 2Cancer Center, Massachusetts General Hospital, Boston, MA

Objective: To examine the association between clinical, histopathologic, and genomic factors and disease recurrence or mortality in patients with uveal melanoma.

Design: Single-Center Retrospective Analysis from a 15-year cohort of patients with melanoma (2009-2023).

Setting: A tertiary institution that serves as a referral center for melanoma.

Patients: All patients with uveal melanoma who were diagnosed, treated, or followed up in our institution and had agreed to participate in the cohort were included. There were no restrictions based on age, gender, or other characteristics of the patients.

Interventions: No experimental interventions were performed on the patients directly for this retrospective analysis. Instead, clinical data were collected, along with genomic analyses that have been performed on formalin-fixed, paraffin-embedded tissue samples via an internal NGS platform (SNaPshot) prior to the start of this study.

Main Outcome Measures: All required outcomes and methods to assess those have been planned prior to the start of the data collection. The primary outcomes are the Relapse-Free Survival (RFS) and the Overall Survival (OS), calculated until the date of last follow-up or the date of relapse or death, respectively. Statistical analysis with the use of univariable and multivariable Cox regressions was performed to calculate if any clinical or genetic factor affects RFS or OS with the lever of statistical significance set at 95% (p=0.05). Hazard Ratios for each factor were calculated to illuminate any risk factors that can predict the natural history of uveal melanomas.

Results: A total of 178 patients with a median age of 62 years (IQR: 54-70 years) were included, with a female/male ratio of 1.15/1. Disease recurrence was observed in 52% of patients until the last follow-up, with 80% of them having a first metastasis in the liver, followed by 7% in the lung, and 7% having a widespread metastatic disease at once. The median time to recurrence was 31 months (IQR: 17-51 months) and the median overall survival was 41 months (IQR: 23-68 months), with 70% of patients being alive until the date of last follow-up. An increased height of the primary uveal tumor was associated with a decreased RFS and OS (p<0.001, p=0.001). The same statistical significance was found for an increased age at diagnosis (RFS: p<0.001, OS: p=0.002). Also, recurrence-free survival significantly decreased with an FGFR3 mutation (p=0.031), a SMARCA4 mutation (p=0.03), and a JAK2 mutation (p=0.03).

Conclusions: Traditional histopathologic and clinical factors, as well as genetic mutations can display a significant correlation with disease recurrence and patient overall survival. This study lays the foundation for the rationale to apply genomic testing in uveal melanoma patients for prognostic prediction and risk stratification. Further studies are needed to replicate and validate these findings.

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