Successfully reported this slideshow.
We use your LinkedIn profile and activity data to personalize ads and to show you more relevant ads. You can change your ad preferences anytime.

The Past, Present and Future of Uveal Melanoma - 2019 CURE OM Symposium

18 views

Published on

Dr. Miguel Materin discusses the past, present and future of uveal melanoma research and treatment.

Published in: Health & Medicine
  • Be the first to comment

  • Be the first to like this

The Past, Present and Future of Uveal Melanoma - 2019 CURE OM Symposium

  1. 1. All Rights Reserved, Duke Medicine 2007 Eyes on a Cure: Patients & Caregiver Symposium April 5-7, 2019 Uveal Melanoma: Past, Present and Future Miguel A. Materin, M.D. Professor of Ophthalmology Professor of Radiation Oncology Director, Ophthalmic Oncology
  2. 2. All Rights Reserved, Duke Medicine 2007 YOU ARE NOT ALONE!!!!
  3. 3. All Rights Reserved, Duke Medicine 2007 Disclosure: Castle Biosciences (Advisor/Consultant) Ideaya Biosciences (Advisor/Consultant)
  4. 4. All Rights Reserved, Duke Medicine 2007 • Collaborative Ocular Melanoma Study Group: Accuracy of diagnosis of choroidal melanomas in the Collaborative Ocular Melanoma Study. COMS Report No. 1. Arch Ophthalmol 108:1268-1273, 1990. • Collaborative Ocular Melanoma Study Group: Complications of enucleation surgery. COMS Report No. 2. In: Proceedings of the Symposium on Retina and Vitreous (Rudolph M. Franklin, ed.). New Orleans Academy of Ophthalmology. Kugler Publications, New York, 1993; pp. 181-190. • Collaborative Ocular Melanoma Study Group: Design and methods of a clinical trial for a rare condition: The Collaborative Ocular Melanoma Study. COMS Report No. 3. Controlled Clin Trials 14:362-391, 1993. • Collaborative Ocular Melanoma Study Group: Mortality in patients with small choroidal melanoma. COMS Report No. 4. Arch Ophthalmol 115:886-893, 1997. • Collaborative Ocular Melanoma Study Group: Factors predictive of growth and treatment of small choroidal melanoma. COMS Report No. 5. Arch Ophthalmol 115:1537-1544, 1997. • Collaborative Ocular Melanoma Study Group: Histopathologic characteristics of uveal melanomas in eyes enucleated from the Collaborative Ocular Melanoma Study. COMS Report No. 6. Am J Ophthalmol 125:745-766, 1998. • Collaborative Ocular Melanoma Study Group: Sociodemographic and clinical predictors of participation in two randomized trials: Findings from the Collaborative Ocular Melanoma Study. COMS Report No. 7. Controlled Clin Trials 22:526-537, 2001. • Grossniklaus HE, Albert DM, Green WR, Conway BP, Hovland KR for the Collaborative Ocular Melanoma Study Group: Clear cell differentiation in choroidal melanoma. COMS Report No. 8. Arch Ophthalmol 115:894-898, 1997. • Collaborative Ocular Melanoma Study Group: The Collaborative Ocular Melanoma Study (COMS) randomized trial of pre-enucleation radiation of large choroidal melanoma. I: Characteristics of patients enrolled and not enrolled. COMS Report No. 9. Am J Ophthalmol 125:767-778,1998. • Collaborative Ocular Melanoma Study Group: The Collaborative Ocular Melanoma Study (COMS) randomized trial of pre-enucleation radiation of large choroidal melanoma. II. Initial mortality findings. COMS Report No. 10. Am J Ophthalmol 125:779-796,1998. • Collaborative Ocular Melanoma Study Group: The Collaborative Ocular Melanoma Study (COMS) randomized trial of pre-enucleation radiation of large choroidal melanoma. III. Local complications and observations following enucleation. COMS Report No. 11. Am J Ophthalmol 126:362-372, 1998. • Collaborative Ocular Melanoma Study Group: Echography (ultrasound) procedures for the Collaborative Ocular Melanoma Study. COMS Report No. 12. J Ophth Nurs Technol Part I, 18(4):143- 149, Part II, 18(5):219-232, 1999. • Collaborative Ocular Melanoma Study Group: Consistency of observations from echograms made centrally in the Collaborative Ocular Melanoma Study. COMS Report No. 13. Ophthalmic Epidemiol 9:11-27, 2002. • Collaborative Ocular Melanoma Study Group: Cause-specific mortality coding: Methods in the Collaborative Ocular Melanoma Study. COMS Report No. 14. Control Clin Trials 22: 248-262, 2001. Uveal Melanoma: C.O.M.S.
  5. 5. All Rights Reserved, Duke Medicine 2007 • Collaborative Ocular Melanoma Study Group: Assessment of metastatic disease status at death in 435 patients with large choroidal melanoma in the Collaborative Ocular Melanoma Study. COMS Report No. 15. Arch Ophthalmol 119:670-676, 2001. • Collaborative Ocular Melanoma Study Group: Collaborative Ocular Melanoma Study (COMS) randomized trial of I-125 brachytherapy for medium choroidal melanoma. I. Visual acuity after 3 years. COMS Report No. 16. Ophthalmology 108(2):348-366, 2001. • Collaborative Ocular Melanoma Study Group: The COMS randomized trial of iodine 125 brachytherapy for choroidal melanoma. II. Characteristics of patients enrolled and not enrolled. COMS Report No. 17. Arch Ophthalmol 119: 951-965, 2001. • Collaborative Ocular Melanoma Study Group: The COMS randomized trial of iodine 125 brachytherapy for choroidal melanoma. III. Initial mortality findings. COMS Report No. 18. Arch Ophthalmol 119: 969-982, 2001. • Collaborative Ocular Melanoma Study Group: The COMS randomized trial of iodine 125 brachytherapy for choroidal melanoma. Local treatment failure and enucleation in the first 5 years after brachytherapy. COMS Report No. 19. Ophthalmology 198:2197-2206, 2002. • Collaborative Ocular Melanoma Study Group: Trends in size and treatment of recently diagnosed choroidal melanoma, 1987-1997. Findings from patients evaluated at Collaborative Ocular Melanoma Study centers. COMS Report No. 20. Arch Ophthalmol 121:1156-1162, 2003. • Collaborative Ocular Melanoma Study Group: Comparison of clinical, echographic, and histologic measurements from eyes with medium-sized choroidal melanoma in the Collaborative Ocular Melanoma Study. COMS Report No. 21. Arch Opthalmol 121:1163-1171, 2003. • Collaborative Ocular Melanoma Study Group: Ten-year follow-up of fellow eyes of patients enrolled in Collaborative Ocular Melanoma Study (COMS) randomized trials. COMS Report No. 22. Ophthalmology 111:996-976, 2004. • Diener-West M, Reynolds SM, Agugliaro DJ, Caldwell R, Cumming K, Earle JD, Green DL, Hawkins BS, Hayman I, Jaiyesimi I, Kirkwood JM, Koh W-J, Robertson DM, Shaw JM, Thoma J. Screening for metastasis from choroidal melanoma: Experience of the Collaborative Ocular Melanoma Study. Collaborative Ocular Melanoma Study Report No. 23. Am J Clin Oncol 22:2438- 2444, 2004. • Collaborative Ocular Melanoma Study Group: The Collaborative Ocular Melanoma Study (COMS) randomized trial of pre-enucleation radiation of large choroidal melanoma. IV. Ten-year mortality findings and prognostic factors. COMS Report No. 24. Am J Ophthalmol 138:936-951, 2004. • Collaborative Ocular Melanoma Study Group: Second Primary Cancers After Enrollment in the COMS Trials for Treatment of Choroidal Melanoma. COMS Report No. 25. Arch Ophthalmol 123:601-604, 2005. • Collaborative Ocular Melanoma Study Group. Development of metastatic disease after enrollment in the COMS trials for treatment of choroidal melanoma. Collaborative Ocular Melanoma Study Group Report No. 26.Arch Ophthalmol 123:1639-1643, 2005. • Collaborative Ocular Melanoma Study Group. Incidence of cataract and outcomes after cataract surgery in the first 5 years after 125I brachytherapy in the COMS. COMS Report No. 27. Ophthalmology 2007. • Collaborative Ocular Melanoma Study Group. The COMS randomized trial of iodine 125 brachytherapy for choroidal melanoma. V. Twelve-year mortality rates and prognostic factors. COMS Report No. 28. Arch Ophthalmol 124:1684-1693, 2006. Uveal Melanoma: C.O.M.S. High diagnostic accuracy: medium and large size tumors Medium size tumors: enucleation is not better than brachytherapy Large size tumors: previous radiation has no benefit before enucleation
  6. 6. All Rights Reserved, Duke Medicine 2007 Cutaneous Melanoma
  7. 7. All Rights Reserved, Duke Medicine 2007 NCCN Guidelines for Patients®, translations of the NCCN clinical guidelines, are meant to help patients with cancer talk with their physicians about the best treatment options for their disease. The National Comprehensive Cancer Network® (NCCN®) is a not-for-profit alliance of 28 leading cancer centers devoted to patient care, research, and education. NCCN is dedicated to improving and facilitating quality, effective, efficient, and accessible cancer care so patients can live better lives. NCCN Resources NCCN offers a variety of resources to patients and their caregivers, including NCCN Guidelines for Patients®, patient and payment assistance information, and clinical trial enrollment information.
  8. 8. All Rights Reserved, Duke Medicine 2007 • Workup and staging, tumor size, primary treatment • Risk of distant metastases, systemic imaging based on risk • Treatment of tumor recurrence/metastases • Risk factors for development of uveal melanoma • Clinical trials • Others
  9. 9. All Rights Reserved, Duke Medicine 2007 • Ophthalmology. 2012 Aug;119(8):1596-603. doi: 10.1016/j.ophtha.2012.02.017. Epub 2012 Apr 21. Collaborative Ocular Oncology Group report number 1: prospective validation of a multi-gene prognostic assay in uveal melanoma. • Collaborative Ocular Oncology Group 2: In progress (enrolling phase) 28 centers Uveal Melanoma: MULTICENTER COLLABORATION
  10. 10. All Rights Reserved, Duke Medicine 2007 • Most common primary intraocular malignancy in adults (3%-5% of all melanomas) • 5-7 new cases per million per year • Median age at diagnosis: 55-60 years • Caucasian • Metastases to liver and lungs Uveal Melanoma • Incidence of noncutaneous melanomas in the U.S. 2005 American Cancer Society. • Trends in incidence, survival, and management of uveal melanoma: a population-based study of 7,516 patients from the Surveillance, Epidemiology, and End Results database (1973-2012). Clin Ophthalmol. 2016 Oct 25;10:2113-2119
  11. 11. All Rights Reserved, Duke Medicine 2007 • Males • Non-Hispanic whites • Low incidence in Asians and African Americans • In Europe incidence increases with latitude o 2 per million (Spain and Italy) o 8 per million (Denmark and Norway) Uveal Melanoma: Epidemiology Virgili G, Gatta G, Ciccolallo L, et al. Incidence of uveal melanoma in Europe. Ophthalmology. 2007;114(12):2309–2315
  12. 12. All Rights Reserved, Duke Medicine 2007 • Light eyes • Fair skin • Ocular melanocytosis • BAP1 mutations • Role of sun exposure: controversial • Welding? Uveal Melanoma: Risk Factors
  13. 13. All Rights Reserved, Duke Medicine 2007 • Posterior choroidal melanomas: might be associated with adenine-to- cytosine mutations • Ciliochoroidal melanomas: might be associated with adenine-to-thymine mutations and light eye color Uveal Melanoma: Risk Factors de Lange MJ, Razzaq L, Versluis M, et al. Distribution of GNAQ and GNA11 mutation signatures in uveal melanoma points to a light dependent mutation mechanism. PLoS One. 2015;10(9):e0138002.
  14. 14. All Rights Reserved, Duke Medicine 2007 Uveal Melanoma • Choroid: 85%-90% • Ciliary Body: 5%-10% • Iris: 3%-5%
  15. 15. All Rights Reserved, Duke Medicine 2007 Uveal Melanoma • Blurred vision • Flashes/floaters • No symptoms • Pain • Red eye • Others
  16. 16. All Rights Reserved, Duke Medicine 2007 15 year-old girl
  17. 17. All Rights Reserved, Duke Medicine 2007 Radiation Retinopathy
  18. 18. All Rights Reserved, Duke Medicine 2007 Small Choroidal Melanoma vs Large Choroidal Nevus
  19. 19. All Rights Reserved, Duke Medicine 2007 Choroidal Melanocytic Lesions
  20. 20. All Rights Reserved, Duke Medicine 2007 #1. Cytogenetic analysis #2. Cytology #3. Cell line Fine Needle Aspiration Biopsy
  21. 21. All Rights Reserved, Duke Medicine 2007 Metastasis by Category % at 1 Yr % at 3 Yrs % at 5 Yrs % at 10 Yrs % at 15 Yrs % at 20 Yrs T1 1% 4% 8% 15% 20% 25% T2 1% 7% 14% 25% 32% 40% T3 3% 19% 31% 49% 60% 62% T4 11% 32% 51% 63% 68% 68% American Joint Cancer Committee, 7th Edition Classification in 7731 Patients Is Predictive of Melanoma Metastasis
  22. 22. All Rights Reserved, Duke Medicine 2007 Choroidal Melanoma: Prognosis Class 1B SF3B1 6p+ 8q+ Class 1A EIF1AX 6p+ Class 2 BAP1 M3 8q+ Higher risk Intermediate risk Lower risk
  23. 23. All Rights Reserved, Duke Medicine 2007 • More than 80% of uveal melanomas carry somatic mutations in either GNAQ or GNA11 • Mutation of either gene is necessary but not sufficient for malignant transformation • Downstream effectors of are potential targets for therapy Gαq and Gα11 The New England Journal of Medicine (Editorial) Dec. 2010
  24. 24. All Rights Reserved, Duke Medicine 2007 Signaling Pathway in Uveal Melanoma • Wild type for BRAF and NRAS (cutaneous melanoma) • Point mutation in G protein alpha subunit o GNAQ and GNA11 genes Carvajal et al. Uveal melanoma: epidemiology, etiology, and treatment of primary disease. Clinical Ophthalmology 2017:11 279–289
  25. 25. All Rights Reserved, Duke Medicine 2007 Immunotherapy T-cell therapy Proliferation inhibitors MEKi PI3Ki PKCi Epigenetic modulators HDACi DNMTi EZH2i Uveal Melanoma Clin Cancer Res. 2016 Mar 1; 22(5): 1234–1242. NIHMSID: NIHMS735478 PRAME as an independent biomarker for metastasis in uveal melanoma Matthew G. Field,1 Christina L. Decatur,1 Stefan Kurtenbach,1 Gülçin Gezgin,2 Pieter A. van der Velden,2 Martine J. Jager,2 Kaleigh N. Kozak,1 and J. William Harbour1
  26. 26. All Rights Reserved, Duke Medicine 2007 • 20 year-old male • Blurry vision OS • OD: 20/20 • OS: 20/400 • MGGF ocular tumor with liver metastases Melan A (+)
  27. 27. All Rights Reserved, Duke Medicine 2007 27 Choroidal Melanoma: Epitheliod Cell Type Gene Expression Profile: Class 2
  28. 28. All Rights Reserved, Duke Medicine 2007 Melanoma cell line: DNA sequencing RPE Melanoma BAP 1 (+) Lung nodules BAP 1 (+) Mother MGGF died liver mets from ocular tumor Wild type: B-RAF N-RAS
  29. 29. All Rights Reserved, Duke Medicine 2007 11/15/2017 37 year-old female 20/40 OD 20/20 OS (wnl) PGF: colon cancer PGM: uterine cancer MGF: lung cancer
  30. 30. All Rights Reserved, Duke Medicine 2007
  31. 31. All Rights Reserved, Duke Medicine 2007 More info: • On 11/15/2017 (day of presentation): 32 weeks pregnant • Twins • Scheduled C-section around Christmas (38 weeks) • Patient is from Huntersville, NC
  32. 32. All Rights Reserved, Duke Medicine 2007 Results: • FNAB: abnormal pigmented spindle cells and epithelioid cells, compatible with clinical impression of melanoma • Pathology: uveal melanoma (choroid, CB and TM), mixed cell type • GEP: Class 2; PRAME + • Had uneventful C-section as originally planned
  33. 33. All Rights Reserved, Duke Medicine 2007 HUMAN INTEREST (PEOPLE.COM) Mom of 4 Diagnosed with Rare Cancer Loses Eye Weeks Before Giving Birth to Twins North Carolina mother with rare eye cancer gives birth to healthy twins (ABC7 NEWS)
  34. 34. All Rights Reserved, Duke Medicine 2007
  35. 35. All Rights Reserved, Duke Medicine 2007 Case Report • 2013, 53 year-old white male • Asymptomatic • VA: 20/25 OD; 20/20 OS • Pigmented choroidal mass superior to optic disc • 6.5 x 6.5 x 3 mm • (+) Sub-retinal fluid, (+) orange pigmentation
  36. 36. All Rights Reserved, Duke Medicine 2007 Small Choroidal Melanoma in a patient with Oculo-Dermal Melanocytosis - FNAB for GEP: Class 1A - I 125 plaque
  37. 37. All Rights Reserved, Duke Medicine 2007 Pre-treatment 2 years post-treatment
  38. 38. All Rights Reserved, Duke Medicine 2007 2 years post-treatment
  39. 39. All Rights Reserved, Duke Medicine 2007 2 years post-treatment 2017
  40. 40. All Rights Reserved, Duke Medicine 2007 Choroidal Melanoma #2: 10x10x3.5
  41. 41. All Rights Reserved, Duke Medicine 2007 Choroidal Melanoma #2: 10x10x3.5 • FNAB for GEP • I 125 plaque (#2) CLASS 2
  42. 42. All Rights Reserved, Duke Medicine 2007 Choroidal Melanoma x 2 • #1: Class 1A, good prognosis (2013) • #2: Class 2, poor prognosis (2017) First tumor located superior to the optic nerve, before treatment (A) and after treatment (B). Wide-view showing the first (treated) tumor superior to the optic nerve (black arrow) and the second tumor along the distal inferotemporal arcade at diagnosis (white arrow) (C). External photo demonstrating episcleral pigmentation typical of ocular melanocytosis (D).
  43. 43. All Rights Reserved, Duke Medicine 2007 • Enucleation • Radiation o Radioactive plaque o Proton Beam o Others • Transpupillary Thermotherapy • Tumor resection Choroidal Melanoma: Treatment Goals 1. Life 2. Eye 3. Vision
  44. 44. All Rights Reserved, Duke Medicine 2007 Choroidal Melanoma Treatment: Enucleation
  45. 45. All Rights Reserved, Duke Medicine 2007 Choroidal Melanoma: Radioactive Plaque S L I D E 11 Eye Physics Bebig COMS
  46. 46. All Rights Reserved, Duke Medicine 2007 Transpupillary Thermotherapy (TTT) as Primary Treatment Choroidal Melanoma Adjuvant Treatment to Brachytherapy
  47. 47. All Rights Reserved, Duke Medicine 2007 Choroidal Melanoma: Stereotactic Body Radiation Therapy
  48. 48. All Rights Reserved, Duke Medicine 2007 Choroidal Melanoma: Stereotactic Body Radiation Therapy 03/2018
  49. 49. All Rights Reserved, Duke Medicine 2007 Choroidal Melanoma: Stereotactic Body Radiation Therapy 01/2019
  50. 50. All Rights Reserved, Duke Medicine 2007 Thank you…

×