SF3B1 and BAP1 Mutations Predict Survival Outcomes in Metastatic Uveal Melanoma Treated with Hepatic Artery Embolization

To investigate tumor-specific genetic mutations as predictive markers of response to hepatic artery embolization (HAE) in patients with metastatic uveal melanoma in the liver.

Materials and Methods:

This retrospective study included patients with (1) biopsy-proven metastatic uveal melanoma to the liver, (2) treated with hepatic artery embolization, and (3) who underwent MSK-IMPACT (MSK Integrated Mutation Profiling of Actionable Cancer Targets) sequencing between 09/2011 and 08/2024 at a tertiary cancer center. MSK-IMPACT is a next-generation sequencing assay targeting the exons and selected introns of key cancer genes. Somatic mutations (single-nucleotide variants, indels, and splice variations) identified in five or more patients were included in the analysis. Demographic data, tumor characteristics, treatment details, and dates of death or last clinical encounter were collected. Overall survival was calculated from the date of embolization to the last follow-up or death using Kaplan-Meier analysis and Cox proportional hazards model.

Results:

A total of 40 patients (20 men and 20 women) with a median age of 65 years (range: 25–85) at the time of HAE were identified to meet the inclusion criteria through a retrospective review of electronic medical records. All patients received checkpoint inhibitor immunotherapy during the study period. Mutations in 12 genes were identified in at least five patients each (gene/patient count: GNAQ/23, BAP1/20, GNA11/16, MYC/12, RECQL/11, RAD21/11, SF3B1/9, NBN/8, AGO2/7, SOX17/6, TCEB1/6, PRDM14/5). The median overall survival (OS) from the first embolization was 11.8 months (95% CI: 8.3–21.7) for the entire cohort. The presence of SF3B1 mutations significantly correlated with improved OS (p=0.05, OS 27.8 months [95% CI: 21.7–not reached] vs. 10.4 months [95% CI: 8.2–14.8]) for patients without SF3B1 mutations. The presence of BAP1 mutations showed a trend toward worse OS (p=0.1, OS 10.4 months [95% CI: 7.2–not reached] vs. 11.8 months [95% CI: 8.3–18.7]). Two-year survival was significantly higher in patients without BAP1 mutations (48%) compared to those with BAP1 mutations (6.6%, p=0.008). No other mutations were significantly associated with OS.

Conclusion:

The presence of SF3B1 mutations and absence of BAP1 mutations predict prolonged overall survival following hepatic artery embolization in patients with metastatic uveal melanoma. This study demonstrates that molecular diagnostics may be helpful in the risk stratification of patients with uveal melanoma undergoing locoregional treatments, such as HAE.