31 Uveal Melanoma

Uveal Melanoma

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THE GEC ESTROHANDBOOKOF BRACHYTHERAPY | Part II Clinical Practice Version 1 - 15/04/2020

Beside its nodular growth, melanoma of the ciliary body can also extend into the posterior part of the globe along the uvea and the sclera and into the anterior part towards the iris. Ciliary body melanoma is often diagnosed late as the lesion remains hidden behind the iris, and the patient seldom has any clinical symptoms until the lesion is large. The iridocorneal angle can be infiltrated rather early, whichmay lead to a secondary glaucoma. On the other hand, the lens may become displaced because of tumour growth.

Various clinical, histopathological, cytogenetic and gene expression features help in estimating the prognosis of uveal melanoma. The clinical features associated with poor prognosis in patients with uveal melanoma include older age at presentation, male gender, larger tumour basal diameter and thickness, ciliary body location, diffuse tumour configuration, association with ocular/oculodermal melanocytosis, extraocular tumour extension, and advanced tumour staging by the American Joint Committee on Cancer (AJCC) classification. The histopathological features suggestive of poor prognosis include epithelioid cell type, high mitotic activity, higher microvascular density, extravascular matrix patterns, tumour-infiltrating macrophages. Monosomy 3, 1p loss, 6q loss, and 8q gain and those classified as Class II by gene expression are predictive of poor prognosis of uveal melanoma. (Table 1, 2, 3, 4, 5)

5. WORK UP

There is general consensus that clinical diagnosis of uveal melanoma is sufficient and adequate for treatment. The diagnosis of uveal melanoma is based on the ocular oncologist’s comprehensive clinical judgement taking into account results from the different diagnostic methods applied. Histopathologic verification is not required. For experienced ophthalmologists the rate of false positive findings is nowadays reported to be below 1 - 2%. In doubtful cases, biopsy could be considered, although with an increasing risk of complications. Iris melanoma typically is visible through the cornea, and the diagnosis is carried out by slit-lamp biomicroscopy. Gonioscopy is useful to assess the involvement of the anterior chamber angle. For small tumours, anterior segment optical coherence tomography (AS-OCT) is useful with high-resolution imaging of anterior and lateral surfaces. Ultrasound biomicroscopy (UBM) assists in visualization of the posterior tumour extent. Choroidal and ciliary bodymelanomas commonly are diagnosed, measured, and assessed based on clinical examination, including slit-lamp biomicroscopy, ophthalmoscopy for detailed fundus evaluation, and ultrasonography (US). US is an important diagnostic tool used to define tumour extent and shape, and to measure tumour dimensions. Typical features of a posterior uveal melanoma on US include acoustic hollowing, choroidal excavation, and orbital shadowing. Additional methods, such as UBM imaging, OCT, autofluorescence, standard and wide-field photography, fluorescein and indocyanine green angiography, CT, PET/CT, and MR imaging may enhance the accuracy of assessment, especially in atypical cases. The large prospective randomized COMS trial demonstrated 99.6% accuracy in the diagnosis of medium-sized and large choroidal melanoma using standardized echography, fundus photography and fluorescein angiography. Smaller melanomas typically exhibit fewer diagnostic characteristics, making them more difficult to diagnose. A small uveal melanoma cannot be distinguished from a naevus. Clinical findings that may help to identify melanoma include the following: orange pigment on the tumour surface, subretinal fluid, tumour thickness of more than 2 mm, low internal reflectivity on ultrasound examination, and documented growth. Staging for uveal melanoma follows the AJCC Tumour-Node-Metastasis (TNM) staging system for eye cancer. In this classification iris melanoma is graded according to tumour extent, associated secondary glaucoma, and extraocular extension. Posterior uveal (ciliary body and choroid) melanoma is graded according to tumour basal diameter and thickness, ciliary body involvement, and extraocular extension. The T categories are defined by the tumour dimensions. (Table 1, 2, 3, 4, 5)

6. INDICATIONS, CONTRA-INDICATIONS

Enucleation has been the treatment of choice for decades, until European experience especially using Rutenium106 plaque, and later the Collaborative Ocular Melanoma Study (COMS) demonstrated that mortality rates following brachytherapy did not differ from mortality rates following enucleation for up to 12 years after treatment of patients with uveal melanoma. Although enucleation remains the accepted treatment for a large choroidal melanoma, multiple treatment options are now available for small and limited size UMwhichmay include observation, transpupillary thermotherapy (TTT), trans-scleral resection, and in particular radiotherapy using episcleral brachytherapy, charged particle radiotherapy or stereotactic radiotherapy. Brachytherapy is the most commonly used conservative treatment for the UM. Recent advances have expanded the use of plaque brachytherapy as well as improved the surgical technique, allowing more tumours to be treated effectively. Small melanomas can be treated based on the eye cancer specialist’s opinion, considering personal experience, clinical examination and evidence of growth although a discussion in the multidisciplinary Tumor Board is recommended, as early treatment provides best results. AJCC T1, T2, T3, and T4a-d uveal melanoma patients can be treated, after counseling about likely vision loss, eye retention, and local control outcomes. Patients with posterior melanomas, even those peripapillary and subfoveal, and those with exudative retinal detachments can be successfully treated, but typically have poorer resultant vision. They should be accordingly counseled. General exclusion criteria for brachytherapy include only tumours with T4e extraocular extension, basal diameters that exceed the limits of brachytherapy, blind painful eyes, and those with no light perception. Patients with these characteristics should always be evaluated in themultidisciplinary Tumour Board and brachytherapy could be indicated in selected cases. There is some controversy about treatment of certain uveal melanomas. For example, brachytherapy for tumours near, touching, or surrounding the optic disc. Optic nerve anatomy presents a unique obstacle for radioactive plaque placement. The optic disc face has a mean diameter of 1.8 mm and is surrounded by choroid. Thus, choroidal melanomas can touch or encircle the disc. Also, as the optic nerve exits the eye, it is enveloped by the