Ocular Melanoma Basics and Post Treatment Eye Care - Dan Gombos, MD, FACS
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This document discusses ocular melanoma, including uveal melanoma and conjunctival melanoma. It covers diagnosis and staging, treatment options like radiation and enucleation, prognostic features, and the role of biopsy and surveillance. It also mentions new clinical trials for therapies like adoptive cell transfer and a light-activated nanoparticle drug being tested by Aura Biosciences.
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Ocular Melanoma Basics and Post Treatment Eye Care - Dan Gombos, MD, FACS
- 1. Dan S Gombos MD FACS Professor & Chief Section of Ophthalmology MD Anderson Cancer Center Houston, Texas Sapna Patel MD, Scott Woodman MD PhD Liz Grimm PhD, Chandrani Chattopadhyay PhD Dae Won Kim PhD, Bita Esmaeli MD
- 2. 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
- 3. Texas is Where? Right Here! (And here is Houston)
- 4. Basics of Ocular Melanoma • Definitions • Symptoms • Diagnosis • Staging • Treatment • Prognostic Testing • Surveillance • New Therapies
- 5. ‘Ocular’ Melanoma • Uvea – Choroid – Ciliary Body – Iris • Conjunctiva • Eye lid skin melanoma • Orbital melanoma
- 6. 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
- 7. Multi-step Process • History/symptoms/risk factors • Important clinical features – absence/presence • Non-invasive diagnostic testing – ultrasound • Putting it all together • Tissue diagnosis (rarely)
- 8. Symptoms • History-Symptoms – Asymptomatic • Routine eye exam – Flashing lights & floaters – Distorted or blurry vision • Retina • No Pain
- 10. Ancillary Ocular Testing • Fundus Photography • Fluorescein Angiography • Indocyanine Green Angiography • Ocular Coherence Tomography OCT • Echography A & B Scan • Ultrasound Biomicroscopy UBM
- 11. Ultrasound • Standardized A and B scan echography – Size • Features on ultrasound that assist you in the diagnosis
- 12. Anterior Segment Tumor • Ultrasound Biomicroscopy – Anterior segment/ciliary body
- 13. Putting it all together • Review the history • Clinical features • Ultrasonography • Factors – Thickness – Location – Symptoms – Orange pigment – Subretinal fluid
- 14. Testing the rest of your body • Systemic evaluation – COMS • Liver enzymes, CXR – Liver Imaging • CT scan • Liver ultrasound • CT – Chest/abdomen • PET
- 15. 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
- 16. 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
- 17. 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
- 18. Excision Small tumors of the iris and ciliary body
- 19. Enucleation • Good alternative for larger tumors • Provides pathologic confirmation of diagnosis • Avoids radiation toxicity • “Most aggressive approach” • Tissue for research – TIL harvesting • Excellent cosmesis
- 23. 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
- 25. Complications from ocular radiation therapy • Acutely – Retinal detachments – Bleeding – Double vision – Optic nerve damage • Chronic – Radiation induced damage – Cataract – Dry Eye (proton beam)
- 26. Prognostic Features • Anatomic (location) • Tumor dimension (size) • Histopathologic (cell type) • Cytogenetic (chromosomes) • Gene Expression
- 27. 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.
- 28. 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.
- 29. Pathology • Epitheliod • Spindle • Vascular Networks • Extraocular extension • Mitosis
- 30. 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
- 31. 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
- 32. 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 ?
- 33. No good standard therapy for metastasis • Poor survival with metastatic uveal melanoma MEDIAN SURVIVAL (MONTHS) COMS, 2005 (n = 739) 3.6 Harvard, 1991 (n = 145) 3.7 M.D. Anderson Hospital, 1981 (n = 73) 7.0 Roswell Park Memorial Institute, 1983 (n = 35) 8.3 Helsinki University, 2003 (n = 91) 8.4 Universität Essen, 1993 (n = 24) 9.0 John Wayne Cancer Center, 2004 (n = 112) 11.0 Memorial 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.
- 34. 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)
- 35. Benefits • Knowledge about your tumor – Knowledge is empowerment (for some) • Medical Oncologist • Clinical Trials – Adjuvant therapy – Low tumor burden
- 36. 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 Melanoma Aura Biosciences
- 37. 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
- 38. 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 Cells Proliferate Cancer Cells Die T Cells IL-2 38
- 39. Pre-therapy Post-therapy Patient #2150 Pre-therapy Post-therapy Patient #2150 Pre-therapy Post-therapy Patient #2199 Pre-therapy Post-therapy Patient #2199 Responses to TIL Therapy 39
- 40. Fresh Tissue Harvesting • Harvest cells from enucleated eyes • Grow them for TIL • Available if patient develops metastasis
- 41. Conclusions • Ocular Melanoma – Uveal melanoma & Conjunctival melanoma • Diagnosis & Staging • Treatment option – Radiation Removal of the eye • Prognostic Features • Biopsy & Surveillance • New Trials