Ocular Melanoma BasicsMelanoma Research Foundation

5th Annual Eyes on a Cure:Patient and Caregiver Symposium

Chris Bergstrom, MDMarch 4-6, 2016

Financial Disclosures I have no financial disclosures

Outline Ocular Melanoma Basics Diagnosis of Ocular Melanoma Treatment of Ocular Melanoma Management of Ocular Melanoma Post Treatment Prognosis in Ocular Melanoma Metastatic Surveillance for Ocular Melanoma

Ocular Melanoma Basics Ocular Melanoma

› Uveal Melanoma-arise from melanocytes in the uveal tract Anterior Uveal Melanoma (5%)

Iris melanoma Posterior Uveal Melanoma

(95%) Ciliary body melanoma (5%) Choroidal melanoma (90%)

Epidemiology of Uveal Melanoma Most common primary intraocular malignancy in adults Uveal melanoma accounts for 5-10% of all melanoma Incidence of 6-8 cases per 1 million population per year The incidence rate is one eighth that of cutaneous

melanoma Most patients have no known family history Hematogenous metastasis; liver 93%, lung 24%, bone

16% Survival of approximately 50% at 10-15 years

Epidemiology of Uveal Melanoma Host Factors

Age and sex› Incidence increases with age and peaks around

sixty years› No sex preponderance

Race and ancestral origin› Rare in nonwhite races

Genetics› Most cases sporadic with no known family history

Risk Factors› Fair skin, blue or grey iris color› Congenital ocular melanocytosis and

neurofibromatosis

Ocular Melanocytosis

Epidemiology of Uveal Melanoma Environmental Factors

Sunlight exposure› The association of uveal melanoma and sun exposure is unclear

Diet and smoking› No data implicating diet or smoking on the incidence of uveal

melanoma Geography

› No latitudinal gradient association as seen in cutaneous melanoma

Occupational and chemical exposures› No specific occupation or causative agent identified in uveal

melanoma

Clinical Features of Uveal Melanoma Blurred or distorted vision Visual field loss or flashing

lights Astigmatism or cataract Pain, inflammation or

glaucoma Visible nodule

Clinical Features 30-40% are asymptomatic and discovered at time of

routine examination.

Differential Diagnosis of Uveal Melanoma

› Choroidal nevus› Metastasis› Hemangioma› Choroidal hemorrhage› Pseudotumor

Choroidal Nevus Common benign pigmented

lesions of the uveal tract Present in approximately

10% of the population

Asymptomatic Less than 2 mm thickness No orange pigment No subretinal fluid Drusen and pigment changes on

surface Medium or high internal

reflectivity Choroidal neovascular membrane Dormant lesion Halo of atrophy around the lesion

Choroidal Nevus

Diagnosis of Uveal Melanoma Clinical diagnosis (>95% accuracy)

› Funduscopic examination Thickness, Fluid, Symptoms, Orange Pigment, Margin of Disc To Find Small Ocular Melanoma

› Ultrasonography Shape, Acoustic Hollowness, Vascularity

› Fluorescein angiography Vascularity

Thickness>2 mm

Subretinal Fluid

Symptoms

Orange Pigment

Margin of Disc

Ultrasound Features of Uveal Melanoma

Ultrasound Features of Uveal Melanoma

Indeterminate Melanocytic Lesions

Indeterminate Melanocytic Lesions

Management of Posterior Uveal Melanoma

Observation Enucleation Brachytherapy Charged particle irradiation (Proton Beam) Surgical resection Thermal Laser treatment

Management of Posterior Uveal Melanoma Enucleation

Indicated for advanced melanomas

Melanomas that have produced severe secondary glaucoma

Melanomas invading the optic nerve

Management of Posterior Uveal Melanoma Brachytherapy

Most common method of treating choroidal melanoma

Iodine 125, Palladium 103, Ruthenium 106

Local tumor control rates >90%

Dose dependent radiation complications inhibit vision in 50% of patients

Goals of Treatment Save the life Save the eye Save the vision

Management of Uveal Melanoma Post Treatment

Fundus photography and Ultrasound Metastatic surveillance Management of post radiation complications

› Exudative or hemorrhagic retinal detachment› Cataract› Diplopia› Radiation retinopathy/neuropathy› Vitreous hemorrhage› Neovascular glaucoma

Risk Factors for Metastasis Tumor size Tumor location Cell type (spindle vs epithelioid) Vascular patterns within the tumor Patient age Tumor genetics

Prognostic Testing Genetic analysis of tumor

biopsies can identify patients at high risk for developing metastatic disease (Monosomy 3/Class2)

Patients with Uveal Melanoma Desire Prognostic Information

Study Number of Patients % Desiring Prognostic Info

Benefits of Info

Cook, S.A. Eye, 2009 298 97% 1.Info provided sense of control2.Results provided hope that surveillance would increase survival

Beran, T.M. J. Genet. Counsel., 2009

99 97% 1.Test provided hope/relief2.Test allowed for preparation for possible shortened future

Systemic Evaluation and Management of Patients with Choroidal Melanoma

All patients require metastatic evaluation prior to definitive treatment of ocular melanoma

CT scan or MRI of chest, abdomen, and liver Rule out other medical conditions Rule out metastatic melanoma

Systemic Evaluation and Management of Patients with Choroidal Melanoma

Metastatic disease present less than 2% at time of initial diagnosis

Hypothesized that micro-metastatic disease is present in many patients

Liver is the predominant organ involved

Yes No Sometimes0.00%

10.00%20.00%30.00%40.00%50.00%60.00%70.00%80.00%90.00%

100.00%

Survey of Ocular OncologistsDo you recommend metastatic screening after treatment?

Indications for Metastatic Screening Reassurance to patients without detectable

metastases Early detection may allow treatment of metastatic

disease when targeted systemic therapies or surgery may be more effective

Identify patients for enrollment in clinical trials to assess the efficacy of adjuvant therapies

Patients desire information for life planning

LFT's/C

XR

Abdo

minal U

ltrasou

nd

CT/PET

Scan MRI

Other

0.00%5.00%

10.00%15.00%20.00%25.00%30.00%

Survey of Ocular OncologistsWhat tests do you recommend for screening?

Annual Biannual More than twice a yr

Depends on the tumor

0.00%5.00%

10.00%15.00%20.00%25.00%30.00%35.00%40.00%45.00%50.00%

Survey of Ocular OncologistsAt what frequency do you recommend screening?

5 years 10 years For Life Depends on size or genetics of

tumor

0%5%

10%15%20%25%30%35%40%45%50%

Survey of Ocular OncologistsHow long do you recommend screening after treatment of the primary tumor?

0%15%30%45%

Survey of Ocular OncologistsDo you adjust your screening based on biopsy results?

Tumor biopsy and genetic testing allows us to identify high risk patients with high sensitivity and specificity

Screening protocols can and should be individualized for each patient› Tumor genetics› Patient age› Overall health of the patient› Patient desires/motivation