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Ocular Melanoma Basics and Post Treatment Eye Care - Dan Gombos, MD, FACS
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Transcript of Ocular Melanoma Basics and Post Treatment Eye Care - Dan Gombos, MD, FACS
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Dan S Gombos MD FACSProfessor & ChiefSection of OphthalmologyMD Anderson Cancer CenterHouston, Texas
Sapna Patel MD, Scott Woodman MD PhDLiz Grimm PhD, Chandrani Chattopadhyay PhDDae Won Kim PhD, Bita Esmaeli MD
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Disclosure
• Paid Consultant to Castle Biosciences• Paid Consultant to Aura Biosciences- MDACC
site for upcoming trial• Investigator Children’s Oncology Group
– travel paid by NIH/COG• Collaborator on numerous drug and clinical
trials– metastatic uveal melanoma– Bristol-Myers Squibb
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Texas
is
Where?
Right Here!
(And here is Houston)
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Basics of Ocular Melanoma
• Definitions• Symptoms• Diagnosis• Staging• Treatment• Prognostic Testing• Surveillance• New Therapies
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‘Ocular’ Melanoma
• Uvea– Choroid– Ciliary Body– Iris
• Conjunctiva• Eye lid skin melanoma• Orbital melanoma
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Diagnosis Of Uveal Melanoma
• Non-invasive assessment• No tissue• Clinical exam and diagnostic testing• Collaborative Ocular Melanoma Study
– 1527 enucleated eyes only 5 did not contain a uveal melanoma
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Multi-step Process
• History/symptoms/risk factors• Important clinical features
– absence/presence• Non-invasive diagnostic testing
– ultrasound• Putting it all together• Tissue diagnosis (rarely)
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Symptoms
• History-Symptoms– Asymptomatic
• Routine eye exam– Flashing lights & floaters– Distorted or blurry vision
• Retina
• No Pain
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Examination
MassSize/Shape/Location
FluidOrange PigmentDrusenPigment ChangesHalo
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Ancillary Ocular Testing
• Fundus Photography• Fluorescein Angiography• Indocyanine Green Angiography• Ocular Coherence Tomography OCT• Echography A & B Scan• Ultrasound Biomicroscopy UBM
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Ultrasound
• Standardized A and B scan echography– Size
• Features on ultrasound that assist you in the diagnosis
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Anterior Segment Tumor
• Ultrasound Biomicroscopy– Anterior
segment/ciliary body
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Putting it all together• Review the history• Clinical features• Ultrasonography• Factors
– Thickness – Location– Symptoms– Orange pigment– Subretinal fluid
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Testing the rest of your body
• Systemic evaluation– COMS
• Liver enzymes, CXR
– Liver Imaging• CT scan• Liver ultrasound
• CT– Chest/abdomen
• PET
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Staging
• Cornerstone of cancer management• So why did my ophthalmologist not tell me
my stage ?• Melanoma- small/medium/large• Most new patients will only have ocular
disease at first visit– Initial therapy is likely to be focused on the
eye
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Staging
• Staging system under constant revision– AJCC- American Joint Committee on Cancer
• Cumbersome– Location and size
• Little utility to your ocular oncologist• Small/Medium/Large
– Direct ocular therapy options
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Ocular Management Options• Observation• Laser treatment • Excision (Cut it out)• Radiotherapy
– (brachytherapy-plaques/charged particle)• Enucleation (removal of the eye)• Combination
– Plaque & Laser– Excision & Plaque
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Excision
Small tumors of the iris and ciliary body
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Enucleation
• Good alternative for larger tumors• Provides pathologic confirmation of diagnosis• Avoids radiation toxicity• “Most aggressive approach”• Tissue for research
– TIL harvesting• Excellent cosmesis
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Plaque Radiation Therapy
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Plaque Radiation Therapy
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Bebig 106Ru Plaques
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After Plaque Radiotherapy• No ocular effect for months or years• Success either regression or lack of continued
growth• Close serial follow up eye exams, photos and
ultrasounds• Long follow up (years)-late recurrences have
been well documented• Adjuvant Diode Laser Hyperthermia TTT
Sandwich Therapy
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Regression Following 125I Plaque
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Complications from ocular radiation therapy
• Acutely– Retinal detachments– Bleeding– Double vision– Optic nerve damage
• Chronic– Radiation induced damage– Cataract– Dry Eye (proton beam)
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Prognostic Features
• Anatomic (location)• Tumor dimension (size)• Histopathologic (cell type)• Cytogenetic (chromosomes)• Gene Expression
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Anatomic• Ciliary body • Choroid• Iris
Onken et al. Gene Expression Profiling in Uveal Melanoma Reveals Two Molecular Classes and Predicts Metastatic Death. Clin Cancer Res 2007.
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Tumor Size- 5 year mortality rates
• 16% for small tumors– < 3 mm in height < 10 mm in base diameter
• 32% for medium tumors – 3-8 mm in height and < 15 mm in base diameter
• 53% for large tumors – > 8 mm in height and > 15 mm in base diameter
Diener-West M et al. A review of mortality from choroidal melanoma. II. A meta-analysis of 5-year mortality rates
following enucleation, 1966 through 1988. Arch Ophthalmol 1992.
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Pathology
• Epitheliod• Spindle• Vascular Networks• Extraocular extension• Mitosis
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Prognostic Biopsy
• Small piece of tissue– Inserting a needle into the eye
• Two types of tests (Castle & Impact)– Chromosome testing (3/8/6)
• Monosomy 3 (loss of one copy of chromosome 3)– Gene Expression Profile
• ‘Pattern recognition’ of certain genes (on or off)• Class Ia/Ib/II• Class II
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Surveillance
• Monitor you for spread • Most common organ liver• Chest X-Ray & blood work• Liver ultrasound (Europe)• CT scans• MRI• PET• Frequency - 3 months to annually
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Controversy Biopsy & Surveillance
• Not all doctors offer it• Different doctors believe in different testing• Small risk to eye and vision• Insurance coverage• What clinical value does it offer the patient ?• How will biopsy alter treatment and or
prognosis ?• Could a biopsy cause harm ?
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No good standard therapy for metastasis
• Poor survival with metastatic uveal melanoma
MEDIAN SURVIVAL (MONTHS)COMS, 2005 (n = 739) 3.6Harvard, 1991 (n = 145) 3.7M.D. Anderson Hospital, 1981 (n = 73) 7.0Roswell Park Memorial Institute, 1983 (n = 35) 8.3Helsinki University, 2003 (n = 91) 8.4Universität Essen, 1993 (n = 24) 9.0John Wayne Cancer Center, 2004 (n = 112) 11.0Memorial Sloan-Kettering, 2005 (n = 119) 12.5
Augberger et al. QUALITY OF EVIDENCE ABOUT EFFECTIVENESS OF TREATMENTS FOR METASTATIC UVEAL MELANOMA. Trans Am Ophthalmol Soc 2008.
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Utility of Biopsy and Surveillance• Absence of effective standard therapy• Prognostic testing does not change standard
treatment of melanoma– After eye is treated we monitor you
• Biopsy has not improved the survival and not changed your treatment
• Surveillance not proven to improve survival• Harm of surveillance – cost travel anxiety (Do no
harm)
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Benefits
• Knowledge about your tumor– Knowledge is empowerment (for some)
• Medical Oncologist• Clinical Trials
– Adjuvant therapy– Low tumor burden
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CONFIDENTIAL
Tumor cell
Irradiation with NIR light
Necrotic tumor cell
HSPG
Viral nanoparticle conjugates (VNC) are delivered by intra-vitreal injection and target tumor cells in the choroid.
VNCs bind specifically to HSPGs on the tumor cell surface (multivalent binding).
Ophthalmic laser 689nm activates the drug. The light-activated drug disrupts the tumor cell membrane, leading to necrosis.
36
Trial for a new therapy of Uveal MelanomaAura Biosciences
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Phase I Trial
• Safety• One patient treated so far
– First in human study– Six patients total
• Limited availability• Multi-center trial based on Phase I study
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Adoptive Cell Therapy (ACT aka TIL) Adoptive Cell Therapy (ACT aka TIL) with Antigen Specific T-cellswith Antigen Specific T-cells
Surgical Removal of
Cancer Nodule
Tumor Cells Incubated with IL-2
T CellsProliferate
Cancer CellsDie
T CellsIL-2
38
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Pre-therapy Post-therapyPatient #2150
Pre-therapy Post-therapyPatient #2150
Pre-therapy Post-therapyPatient #2199
Pre-therapy Post-therapyPatient #2199
Responses to TIL Therapy
39
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Fresh Tissue Harvesting
• Harvest cells from enucleated eyes
• Grow them for TIL• Available if patient
develops metastasis
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Conclusions
• Ocular Melanoma– Uveal melanoma & Conjunctival melanoma
• Diagnosis & Staging• Treatment option
– Radiation Removal of the eye• Prognostic Features• Biopsy & Surveillance• New Trials