# Long-Term Clinical Outcomes for Adolescent and Young-Adult Uveal Melanoma Patients Treated with Dedicated Particle-Beam Radiation

## TL;DR

This study shows that proton and helium-ion radiation offer excellent long-term outcomes for young uveal melanoma patients, preserving vision and improving survival.

## Contribution

The study provides the first detailed long-term analysis of particle-beam radiation outcomes in adolescent and young adult uveal melanoma patients.

## Key findings

- 15-year local control rates were 94% for proton-beam and 99% for helium-ion radiation.
- AYA patients had better distant metastasis-free and overall survival rates than older patients.
- Tumor size and dose-volume parameters were key predictors of treatment success.

## Abstract

Uveal melanoma (UM) is a rare eye cancer, especially in adolescent and young-adult patients (AYAs), and it can significantly impact vision, quality of life, and survival. This study examines the long-term clinical outcomes of AYA UM patients (aged 13 to 45) treated with proton-beam (PBRT) and helium-ion radiation. We aim to determine the effectiveness of these treatments by measuring clinical outcomes, including local control, eye preservation, distant metastasis (DM), and overall survival. The results confirm excellent long-term local control and eye preservation (15 years: 94% PBRT and 99% Helium cohort) and demonstrate better DM-free and overall survival rates at 15 years in AYAs than older UM patients.

Background: Limited long-term data exist regarding post-particle-beam radiation (RT) for adolescents and young adults (AYA) with uveal melanoma (UM), and hence an in-depth analysis of clinical outcomes is presented. Methods: We identified AYA patients with UM (aged 13 to 45) treated with proton-beam radiation (PBRT, dose 56 GyE, n = 240) and helium-ion RT (median dose 70 GyE, n = 78). Patients were analyzed for local control (LC), eye preservation, distant metastasis (DM), and overall survival (OS) with univariate and multivariate analysis. Results: For the PBRT cohort, the median age and follow-up were 38.3 years (13.3–45.9) and 85.7 months (3–301), respectively. The 15-year (y) LC rate was 94%. Ciliary body (CB) tumors showed lower LC (p = 0.01). Largest tumor diameter (LTD) was the only independent predictor of LC (hazard ratio (HR) = 1.19, p = 0.017)). The 10-year eye preservation was 83%. Improved eye preservation was noted with a ≤50% dose delivered to the lens (p = 0.004), disc (p = 0.001), and nerve (p = 0.0004), and <20% of CB volume (p = 0.0002). Decreased tumor height (HR = 1.12, 95% CI: 1.01–1.2, p = 0.036), dose < 20% to CB (HR = 1.04, 95% CI: 1.01–1.06, p = 0.0002), and tumor–disc distance > 2 mm (HR = 0.27, p = 0.0003) were independent predictors of eye preservation. The 15-year DM-free rate was 73%, and the 15-year OS rate was 76%. The T category was the most significant predictor of DM (p < 0.0001), followed by LTD (p = 0.04). For the Helium cohort, median age and follow-up were 37.1 years (18.1–45.5) and 256.7 months (24–450), respectively. The Helium cohort 15-year LC was 99%, with 82% 10-year eye preservation. The 15-year DM-free and OS rates for Helium patients were both 83%. Conclusions: Excellent long-term LC and eye preservation can be seen in AYA UM patients treated with proton and helium-ion radiation. AYAs with UM appear to have better DM-free and overall survival rates than older patients with UM. Specific clinical and dose–volume parameters can help improve treatment planning and prognosis for younger patients with UM.