## 4 Proton-Beam Irradiation  
Proton-beam radiotherapy (PBRT) is a good alternative to enucleation or exenteration in complex cases of conjunctival melanoma. These include cases with extensive eyelid, conjunctival or caruncular involvement, as an alternative to aggressive surgery [25; 26]. PBRT has the advantage of precise dose release, better than other irradiation modalities. This ballistic advantage permit to release very high-dose gradients close to organs at risk (OAR), avoiding them and respecting their dose constraints [25]. So, it is feasible to treat accurate volumes with a homogenous dose on the target (unlike brachytherapy, which delivers highly inhomogeneous doses on target volumes) and to preserve structures in the direct neighbourhood of the target volume. To protect the tissues localized, only 1-2 mm behind the target volume, the dose can be reduced to zero, thanks to the distal dose fall-off of the Bragg Peak phenomenon. It is responsible for an increasing dose deposition of these particles as they travel through the tissue, with an approximately constant low entry dose, a region of high dose at a depth determined by the initial proton energy, and no dose beyond the end of the range [25]. The majority of Protontherapy centers use a 60-70 MeV proton beam to treat ocular tumors, as it happens at the Center Antoine-Lacassagne in Nice or at Catana Centre in Catania. There are few reports on the use of PBRT for CM, unlike the great experience in the treatment of uveal melanoma. [PERSON] et al. reported in a retrospective study the treatment of 20 patients with conjunctival melanoma. The dose was 31 GyRBE in 6 fractions with a boost of 14 GyRBE in two fractions on the main target (total dose 45 GyRBE). The median follow-up was 34 months. Local recurrence happened in six patients (30%). Three of them detect in the target volume which had received 31 Gy, two recurrences place outside the target volume and one was localized in the primary target volume (45 Gy). Patients with relapse underwent enucleation (2 pts), external radiation (1 pt), and 106-Ruthenium-plaque brachytherapy (2 pts). One patient refused further treatment. Six patients (30%) had distant metastases after 24.8 \(\pm\) 13 months after PBI. A total of 19 patients developed a sicca-syndrome. A focal cataract developed in seven patients (35%). There was madarosis in the area of irradiated eyelids. In four cases, a limbal stem cell deficiency occurred with the consequence of corneal vascularization. None of the patients complained retinopathy, secondary glaucoma, iris neovascularization or optic disc neuropathy [26]. [PERSON] et al. reported in a retrospective study the treatment of 89 patients with conjunctiva melanoma from 1993 to 2015. The total delivered dose was 45 Gy with a 65 Mev proton-beam. The treatment was carried out in two phases: 31 Gy in six fractions on the main volume including the suspected areas of microscopic disease and a boost of 14 Gy in two fractions on the primary disease localization. The mean follow-up was 4.2 years. Twenty-nine patients (33%) experienced local recurrence: 16 inside and 13 outside the irradiation field. A total of 18 patients underwent exenteration: 16 with disease recurrence and two without. A total of 14 patients developed distant lymphatic or hematogenous metastases. Fifteen patients underwent salvage therapy with chemo-immunotherapy (Mitomycin C/INF alpha), brachytherapy or external beam radiotherapy. Main collateral effects after proton radiotherapy were secondary glaucoma (11%) limbal stem cell deficiency (8%) and sicca-syndrome (30%) [27]. [PERSON] et al. reported in a retrospective study the treatment of 96 patients with conjunctiv melanoma from 1992 to 2018. The delivered dose was 45 Gy in eght fractions. In case of wide tumors with macroscopic and microscopic components, a two-step treatment was used with a large field including the full quadrants from limbus to conjunctival folds to 31.2 Gy and a reduced boost to the macroscopic lesion for 13.8 additional Gy.