Retina Center of Oklahoma Sam S. Dahr, M.D. Adult Intraocular Tumors
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1 Adult Intraocular Tumors Sam S. Dahr, M.D. Retina Center of Oklahoma
2 Table of Contents Posterior uveal malignant melanoma Uveal metastasis
3
4 Uveal melanoma incidence 6 cases/one million people/year State of Oklahoma 3,579,212-> 21 cases a year Lifetime risk 1 in 2000 among Caucasians
5 Uveal melanoma incidence Age adjusted rate per million person years Age 15-44: 2.3 Age 45-64: 15 Age 65 and older: 25
6
7 Useful facts Mean age of diagnosis is 60 2/3 are within 3 mm of fovea or optic nerve Up to 30% may be amelanotic
8 Potential risk factors Caucasian race Light colored irides Sunlight exposure Ocular melanocytosis: hyperpigmentation of the uvea and episclera Oculodermal melanocytosis: hyperpigmentation of the uvea, episclera, and periorbital skin
9 Oculodermal melanocytosis Ocular melanosis 1 in 400 risk of uveal melanoma
10 Differential Ch. Hemangioma Ch. Osteoma Wet AMD Choroidal hemorrhage CHRPE Melanocytoms Hemorrhagic retinoschisis
11 Choroidal hemangioma Choroidal hemangioma
12 Melanocytoma
13 Choroidal osteoma
14 Sclerochoroidal calcification
15 CHRPE
16 CHRPE
17 Atypical CHRPE associated with Gardner Syndrome
18 Atypical CHRPE associated with Gardner Syndrome
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22 Ciliary body mass Uveal melanoma Leiomyoma Adenoma of the ciliary epithelium Medulloepithelioma Schwannoma Cyst of pars plana/pigment epithelium Granuloma Metastasis
23 Medulloepithelioma
24 Choroidal freckle or melanocytic pigment cluster of choroid Increased density of normal melanocytes Flat
25 Choroidal nevus--coms 5 mm or smaller in greatest linear dimension 1 mm or less in thickness Prevalence may be up to 30% If in macula may cause photoreceptor atrophy
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27
28 Indeterminate nevus vs. melanoma mm thick <10 mm in greatest dimension
29 Estimate of basal dimensions 20 d lens= 12 mm across 28 d lens= 13 mm across
30 To Find Small Ocular Melanoma TFSOM
31 TFSOM (Archives of Ophthalmology 2000; 118: 360-4) Two mm or more thickness Fluid (subretinal fluid) Symptoms Orange pigment Margin touching optic disc None=4%, One factor=36%, Two factors=45%, Three factors=50%, Four factors=51%, all Five factors=56% risk of growth into choroidal melanoma at 5 years
32 Pre operative screening CT scan abdomen and pelvis Chest X Ray Liver enzymes
33 Treatment
34 Transpupillary thermo-therapy Primary TTT is associated with a 22% local recurrence at 3 years (Shields et al, Ophthalmology 2002; 109: ). Small tumors=recurrent tumor may theoretically be most life threatening
35 Gold plaque 0.44 mm thick Silastic for mounting I125 seeds
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50 Local control with radiation In a follow-up of 650 patients treated with iodine- 125 in the COMS medium tumor study, the risk of treatment failure by 5 years as measured by local recurrence rate was reported at 10.3%.(COMS report 19) With nearly 2000 patients treated with proton beam irradiation, Gragoudas reported a local recurrence rate of 3.2% and 4.3% at 5 and 10 years respectively.(trans Am Ophthalmol Soc 2002; 100:43-8 )
51 Curr Opin Ophthalmol. 2002; 13: Patients with small choroidal melanoma (< 4 mm thickness) develop metastasis in 16% of cases at 5 years follow up, whereas those with medium choroidal melanoma (4-8 mm thickness) and large choroidal melanoma (> 8 mm thickness) develop metastasis in 32 and 53%, respectively.
52 Proton beam therapy
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57 Prognosis: tumor size
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59 COMS small melanoma (<2.5 mm) observational study 204 patients Risks for growth: orange pigment, thickness >2 mm, LBD 12 mm or more, absence of drusen, absence of RPE changes Melanoma specific mortality at 5 years=1%
60 COMS medium size arm 660 enucleation 657 I125 plaque radioatherapy
61 COMS medium size arm Half lose six or more lines at 5 years Local failure 10% at 5 years 5 year melanoma specific mortality 11% in enucleation arm and 9% in plaque arm
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64 Large (> 10 mm thick or >16 mm LBD)
65 Based on the Collaborative Ocular Melanoma Study (COMS), large melanomas are tumors with > 16 mm longest tumor basal diameter, > 10 mm apical height or tumors with > 8 mm apical height and < 2 mm distance to optic disc
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67 Metastatic death based on largest basal dimension
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69 Plaque>8 mm (Ophthalmology 2002; 109: ) Using Kaplan-Meier estimates, local tumor recurrence was found in 9% at 5 years and 13% at 10 years follow-up. Tumorrelated metastases were found in 30% at 5 years and 55% at 10 years follow-up. At 10 years follow-up, enucleation was necessary in 34% of patients, and metastasis developed in 55% of patients.
70 Prognosis: Histopathology spindle cell, mixed cell (composed of epithelioid cells with a variable proportion of spindle cells), and necrotic
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72 Spindle cell melanoma
73 Epithelioid melanoma
74 Prognosis: Extrascleral extension
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77 Prognosis: genetics
78 Monosomy 3 with polysomy 8q Gene profile
79 CANCER RESEARCH 64, , October 15, 2004] Class 1 low grade; Class 2 high grade cell communication (13 genes), development (11 genes), cell growth (7 genes), cell motility (4 genes), and cell death (3 genes)
80
81 What to expect post radiation Shrink over 2 years May look darker May develop surround radiation atrophy
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83 Ultrasound post plaque Increeased sonoreflectivity within tumor hypoechoic space behind the sclera where the radioactive plaque had been positioned
84 In the COMS, 10% of eyes were enucleated because of suspected or documented tumor recurrence.
85 Post operative followup screening Once a year
86 Radiation retinopathy 30-52% at 5 years
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90 Radiation optic neuropathy 46% at 5 years
91
92 Neovascular glaucoma 12-69% at 5 years
93 Between 5% and 10% of patients treated with radiotherapy ultimately require enucleation because of tumor recurrence or radiation complications.
94 Liver Lungs Bone Skin Site of metastasis
95 Metastasis Median survival 6 months Treatment: chemotherapy; intra-arteria chemotherapy, chemoembolization, immune therapy, surgery
96 Vignettes
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102 Amelanotic, break through bruchs
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107 Orange pigment
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109 Orange pigment
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111 Diffuse melanoma
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113 Post plaque edema
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115 Uveal metastasis
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120 Extrascleral extension
121 Metastasis More sonoreflective Grow rapidly Associated serous RD Less prominent intrinsic vessels on FA
122 Sites of origin Breast Lung GI, Renal, cutaneous melanoma, prostate
123 If a cutaneous melanoma metastasizes to the eye it will inevitably have metastasized elsewhere in the body
124 If systemic metastases-> consider systemic therapy (chemo, hormonal, immune modulation, etc.) If confined to uvea but multifocal-> external beam If confined to uvea and unifocal-> can consider an I125 plaque.
125 External beam 40 Gy in 20 fractions
126
127 Primary intraocular lymphoma Intermediate uveitis May have infiltrates at level of RPE May simulate retinal necrosis Relationship with PCNSL
128 New onset intermediate or posterior uveitis in a patient over 50 Sarcoidosis Syphillis P. acnes if pseudophakic PIOL as a masquerade
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131 Thank you! Sam S. Dahr, M.D. Retina Center of Oklahoma
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134 In a study of 255 peripapillary melanomas, the COMS Group observed optic nerve head invasion in 6.9% of cases, and in 1.1% the extension extended posterior to the lamina cribrosa. (COMS Report #6).
135 Philosophical debate in eye tumor world Are we affecting survival? The COMS could not have a natural history control arm but
136 Philosophy re: metastasis onset and the relationship of large tumor size with increased metastasis Early onset: tumors metastasize early in their course and large size at presentation simply reflects a more aggressive tumor Late onset: as tumors grow they differentiate into a more aggressive tumor
137 If you believe early onset hypothesis, we re only making a difference in terms of survival when we catch and successfully treat a small tumor e.g. <3 mm in size. We are probably not making a difference for medium or large size tumors.
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