Long Term Clinical Outcomes With Dedicated Proton Ocular Beam and Helium Ion Radiation for Uveal Melanoma Patients Aged 45 and Younger

Abstract

<h3>Purpose/Objective(s)</h3> Uveal melanoma (UM) is particularly rare and potentially devastating for patients ≤ 45 years old (yo). Limited long term data exist post-particle beam radiation (RT) for this age group and hence an in-depth analysis of clinical outcomes is presented. <h3>Materials/Methods</h3> Patients were identified in a single institution's prospectively maintained database (n = 2558) of eye treatment with proton beam radiation (PBRT, 1994-2020) and helium ion RT (1979-1992). All included patients were treated for UM. Post-local eyewall resection or salvage RT patients were excluded. Patients were aged ≤ 45 yo at radiation (PBRT, n = 247 and helium, n = 80). PBRT patients undergoing 56 GyE in 4 fractions (n = 240) were further analyzed for local control (LC), eye preservation, distant metastasis (DM), and overall survival (OS). Univariate analysis using the Kaplan-Meier method (log rank test) and multivariate regression analysis using Cox's proportional hazard model (likelihood ratio test) were performed. <h3>Results</h3> Median follow-up for PBRT pts was 85.7 months (3.0-317.5). Median age at RT was 38.3 years (13.3-45.9); tumor location was 87% choroidal, 11% ciliary body (CB), and 2% iris only; tumor height 4.4 mm (0.8-15.8), largest tumor diameter (LTD) 10.5 mm (2.1-25.1), distance to disc/fovea 3.1/1.9 mm. 5-year (y) LC was 95% and 10y 94%. Ciliary body (CB) tumors showed lower LC (<i>P</i> = 0.02). LTD was the one independent multivariate predictor of LC (<i>P</i> = 0.04). Three patients had very late local failures (LF), all showed spindle-cell features [time-to-LF 13.2, 16.1, 17.5 years]. 10y overall eye preservation was 83%. Enucleation risk decreased with greater tumor-disc distance (<i>P</i> = 0.0001). Improved eye preservation was noted with ≤ 50% dose to lens (<i>P</i> = 0.01), ≤ 20% CB (<i>P</i> = 0.02), disc (<i>P</i> = 0.004), macula (<i>P</i> = 0.03), and nerve (<i>P</i> = 0.009). Multivariate analysis identified nerve length receiving 50% dose (<i>P</i> = 0.0003) and tumor height (<i>P</i> = 0.0008) as significant independent predictors of enucleation. 10y DM-free rate was 81% and 10y OS was 83%. LTD was the most significant predictor of DM (<i>P</i> = 0.0001) followed by age > 30 vs ≤ 30 (<i>P</i> = 0.03). The age ≤ 30 subgroup (n = 44) had a 5y DM-free of 100%, and had only 2% CB tumors. Two of seven early (1994-1995) proton patients receiving 48 GyE in 4 fx, had LF. The helium cohort median follow-up was 160.9 months (23.9-292.8). Median age at RT was 37.2 (18.1-45.9), tumor height 6.2 mm (2.9-14), LTD 10.5 mm (5-25), distance to disc/fovea 3.8/3.0 mm, and 24% had tumors with ciliary body involvement. Median (range) for helium RT dose was 70 GyE (48-80). Helium cohort 10y LC was 99%, 10y eye preservation was 82%. <h3>Conclusion</h3> Excellent long-term local control (10y 94% PBRT and 99% Helium cohorts) and eye preservation is seen in UM patients aged ≤ 45 treated with proton and helium ion radiation. Specific clinical and dose-volume parameters may be utilized to assess patient prognosis.