Key points
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Plaque brachytherapy is suitable for small- and medium-sized uveal melanomas.
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Proton beam radiotherapy is feasible for large-sized tumors with challenging location.
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Enucleation is indicated for advanced melanomas and painful eyes because of complications.
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Radiation-induced necrosis is hypointense on T2-weighted sequences, because of melanin pigment dispersion.
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Panuveitis and endophthalmitis represent frequent inflammatory complications of proton beam radiotherapy.
Introduction
Therapeutic management
Technique | Method | Effects | Indication | Main complications | Limitations |
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Laser therapy (LT) | |||||
Laser photocoagulation | Xenon or argon laser | Rise temperature inducting denaturization of proteins and cellular apoptosis | Small-sized tumours (< 3 mm) | Retinal vein occlusion, vitreous hemorrhage, optic atrophy, thrombotic glaucoma, macular involvement, cystoid macular oedema | No more used (superseded by TTT) because poor tissue penetration and multiple treatment sessions |
Transpupillary thermotherapy (TTT) | Infrared diode laser (810 nm) | Rise temperature (45°–60°) inducting cytotoxic effects, vascular occlusion and tumour necrosis | Tumours thickness < 4 mm Distance from the fovea > 3 mm Not touching the optic disc Adjuvant treatment combined with other eye-sparing therapy | Retinal oedema Fine intraretinal hemorrhage | Amelanotic or poor melanotic choroidal melanoma Long-term possibility of recurrence and/or high metastatic risks Limited tissue penetration of 4 mm |
Radiotherapy (RT) | |||||
Brachytherapy (BRT) | Saucer-shaped plaque, sutured to the sclera, containing radioactive sources (62–70 Gy to the tumour apex): X-ray isotopes; γ-ray isotopes: Cobalt-60, Palladium-103, Iridium-192, Iodine-125; β-ray isotope: Ruthenium-106 | Radiation-induced irreversible DNA damage that leads to cell death, cell cycle redistribution and microenvironment changes | AJCC-UICC T1, T2, T3 and T4a-d Basal diameter tumor < 16 mm Tumor thickness < 11 mm Supero-temporal quadrant | Radiation-induced retinopathy, cataract and maculopathy, secondary glaucoma, vitreous hemorrhage and retinal detachment, scleral necrosis, diplopia, strabismus, involvement of extra-ocular muscles | Large tumors (diameters > 15 mm; height > 10 mm) Distance from optic disc < 2 mm Limited tissue penetration of 4–5 mm Not eligible in case of: Blind painful eyes Extraocular extension (T4e) Limited light perception Damage to surrounding normal choroid |
Charged-particles beam radiotherapy | Tumor irradiation with charged particles, protons and helium ions (53–70 Gy), over 4 consecutive days | Bragg Peak: particles release ionizing radiation when they stop traveling High dose of radiation leading to DNA damage and subsequent cell death | Basal diameter tumor < 28 mm Tumor thickness < 14 mm Neoadjuvant therapy before surgical resection | Retinopathy, rubeosis iridis, cataract, uveitis, optic neuropathy, maculopathy, dry eye, loss of eyelashes, retinal detachment, keratopathy | Low rates of visual prognosis and eye conservation for large melanomas Involvement of lacrimal glands (supero-temporal quadrant lesion) |
Stereotactic radiotherapy (SRT) | |||||
Gamma-Knife and Cyber-Knife | Stereotactic and robot-assisted radiosurgery with fractionated ionizing radiation (total dose of 30–50 Gy) delivered to a relatively small target, decreasing progressively at the margins (25–35 Gy) | Extremely focused dose of radiation leading to DNA damage and subsequent cell death | Tumor confined to the eye, sparing extra-ocular tissue (T4e) Juxtapapillary uveal melanoma Patients not eligible for BRT or surgery | Cataract, dry eye disease, vitreous hemorrhage, radiation retinopathy, radiation maculopathy, optic neuropathy, neovascular glaucoma | Lower availability Ocular fixation High rates of radiation-induced retinopathy and neovascular glaucoma |
Linear accelerator (LINAC) | Stereotactic fractionated and hypofractionated photon radiotherapy (50–70 Gy in 5–7 Gy single-dose fractions) | Extremely focused dose of photon leading to DNA damage and subsequent cell death | Tumor confined to the eye, sparing extra-ocular tissue (T4e) Juxtapapillary uveal melanoma Patients not eligible for BRT or surgery | Conjunctivitis, skin reaction, maculopathy, cataract, ischemic retinopathy, glaucoma, retinal detachment, corneal ulcer, vitreous hemorrhage, optic nerve damage | Lower availability High rates of radiation-induced retinopathy and neovascular glaucoma |
Laser techniques
Laser photocoagulation therapy
Transpupillary thermal therapy (TTT)
Radiation therapy
Episcleral plaque radiotherapy
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gamma-ray emitting isotopes: iodine-125 (125I), palladium-103 (103Pd), iridium-192 (192Ir) and cobalt-60 (60C0);
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beta-particle-emitting isotopes: ruthenium-106 (106Ru).
Charged-particle beam radiotherapy
Differences between proton beam radiotherapy and plaque brachytherapy
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highly collimated beams with very low scattering (relative sparing of healthy tissues adjacent to the beam path),
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boosted radiation dose at the end of the pathway,
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optimal and uniform radiation dose delivery at the level of the tumor,
Stereotactic radiosurgery
Surgery
Local resection
Enucleation
Orbital exenteration
Effects of radiotherapy on uveal melanomas
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increased membrane permeability (radiation dose ≤ 30 Gy);
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breaking of cellular membrane with inflow of extracellular fluid into the cell (radiation dose > 30 Gy);
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disruption of cytoplasmic lysosomes with spillage of enzymes that digest cellular structures (radiation dose 5–100 Gy);
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disruption of mitochondria and interruption of adenosine triphosphate (ATP) production (radiation dose 5–100 Gy) [4].
Effects of radiotherapy on neoplastic tissue: pathologic features of irradiated uveal melanomas
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the type of radiation therapy,
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the tumor cell-doubling time (shorter in high-grade tumors) [4].
Direct radiation-related cytotoxic effect: necrosis—immune response—fibrosis
Vascular changes
Electron microscopic findings
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degeneration and reduction in number of mitochondria;
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hardly recognizable Golgi’s apparatus;
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patchy melanin granules;
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augmented cytoplasmic filaments;
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storage of lipid vacuoles in cytoplasm;
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presence of phagolysosomes and autophagic vacuoles within cytoplasm;
Evolution of the tumor following radiotherapy
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recurrence at the margins of the lesion, the most frequent, presumably related to insufficient dose of radiation at the boundary of radiation field;
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recurrence at the inferior periphery, far from the initial location of the lesion, because of migration of neoplastic cells inside retinal detachment;