2807 - Pencil-Beam Proton Therapy for Large-Size and Unfavorably Located Uveal Melanoma: Safety, Toxicity, and Tumor Response
Presenter(s)
N. Martynova1, V. Nikolay1,2, I. E. Panova3, E. V. Samkovich3, E. M. Svistunova3, G. Andreev1, A. Lyubinskiy1, M. Linnik1, N. Kataev1, E. V. Boyko3, and K. Suprun1,2; 1Dr. Berezin Medical Institute, Saint-Petersburg, Russian Federation, 2Saint-Petersburg State University, Saint-Petersburg, Russian Federation, 3S. Fyodorov Eye Microsurgery Federal State Institution, Saint-Petersburg, Russian Federation
Purpose/Objective(s): Particle beam therapy (PBS) is a cornerstone treatment for large-size and unfavorably located uveal melanoma (UM), offering ocular and visual preservation as an alternative to enucleation. While passive scattering proton therapy historically served as the gold standard, PBS eliminates the need for patient-specific collimators/compensators, enabling rapid workflows critical for aggressive tumors. As PBS replaces passive scattering globally, its safety and efficacy in high-risk UM require rigorous evaluation.
Materials/Methods: Thirty-eight patients with large-size (median volume: 1.6 cc, range: 0.2–3.44 cc) and unfavorably located (proximity to optic nerve/disc) UM received PBS proton therapy (49 Gy RBE in 7 fractions). Eye immobilization utilized a modified thermoplastic head-mask with gaze fixation on a marker located on focal distance (25 cm). Treatment planning incorporated robust multifield optimization (2 mm setup, 3.5% range uncertainty), 2–3 fields (one with a range-shifter), and a 1 mm margin for eye motion. Movement control was achieved by CBCT and kV-control with every field accompanied by voice commands. Follow-up occurred at a dedicated ophthalmo-oncology center.
Results: Linear and angular median offsets during all treatments from 252 measurements was 0.15 mm (lng) and 0.7°(rtn) respectively, which did not exceed a safe margin. At a median follow-up of 12.5 months (3–54), no local recurrences occurred. Tumor response started with reduced blood flow by ultrasound and structural changes by MRI, with shrinkage observed =6 months post-treatment. Early toxicity (dermatitis, keratitis) was =Grade 2 by CTCAE v6.0. Late ocular hypertension (OH) due to neovascular glaucoma (NVG) occurred in 12 patients (6–10 months post-treatment). NVG correlated strongly with pre-treatment Bruch’s membrane rupture (p=0.0056), macular high dose (p=0.0137), and total visual field loss (p=0.00016). Seven patients (18.4%) required enucleation (median 17 months post-treatment; 6 with uncorrected OH due to NVG).
Conclusion: PBS proton therapy demonstrates promising local control and manageable acute toxicity for high-risk UM. However, NVG-driven ocular hypertension remains a critical late risk, underscoring the importance of macula dose optimization and patient selection—particularly in cases with pre-existing Bruch’s membrane rupture or visual field loss. Longer follow-up is needed to validate predictive models for NVG and refine vision-preservation strategies.