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Understanding and treating Malignant Melanoma

Understanding and treating Malignant Melanoma

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  • 1. Malignant Melanoma Robert Miller MD www.aboutcancer.com melanocyte melanoma epidermis dermis
  • 2. Malignant Melanoma Accounting for about 3 to 4% of all diagnosed skin cancers, melanoma begins in the melanocytes, cells within the epidermis that give skin its color. The incidence is rising by 3% a year.
  • 3. Most Common Skin Cancers in 2013 Basal Cell : 2,800,000 (78%) Squamous: 700,000 (20%) Melanoma: 76,690 (2%) Between 40 and 50 percent of Americans who live to age 65 will have either BCC or SCC at least once, about 2% will get melanoma
  • 4. Melanoma – Gender Distribution - US Male Female
  • 5. New Cases New Cases 43,890 (5%) 34,590 (4%) Death Death 6,470 3,240 2014 Data
  • 6. Age Distribution 0.25 US (2000-2011) from the NCDB 0.2 0.15 0.1 0.05 0 20 30 40 50 60 Age Distribution 70 80 90
  • 7. Lifetime risk of an American developing invasive melanoma
  • 8. Probability (%) of Getting Melanoma (2008-2010) Age Men Women 0-49 50-59 60-69 70+ 0.4 0.4 0.8 2.1 0.5 0.3 0.4 0.9 Lifetime 2.9% 1.9%
  • 9. 30 Melanoma by Race 25 20 15 10 5 0 white hispanic asian black SEER database from 2000 to 2004, the male incidence rates per 100,000
  • 10. Risk Factors Freckling mild moderate severe
  • 11. Risk Factors Sun (Solar) Skin Damage Severe solar damage
  • 12. Risk Calculator for Melanoma http://www.cancer.gov/melanomarisktool/
  • 13. Appearance and location of melanoma
  • 14. Distribution of superficial spreading melanoma
  • 15. Distribution of Skin Melanomas Men on their back
  • 16. Distribution of Skin Melanomas Women on the back legs
  • 17. 45 yo man with ‘mole’ on his back for years presented with headaches and was found to have widespread (brain, liver, lung, b owel spread) liver biopsy showed metastatic melanoma
  • 18. 45 yo man with ‘mole’ on his back for years presented with headaches and was found to have widespread (brain, liver, lung, b owel spread) liver biopsy showed metastatic melanoma
  • 19. Possible signs and symptoms of melanoma A is for Asymmetry: One half of a mole or birthmark does not match the other. B is for Border: The edges are irregular, ragged, notched, or blurred. C is for Color: The color is not the same all over and may include shades of brown or black, or sometimes with patches of pink, red, white, or blue. D is for Diameter: The spot is larger than 6 millimeters across (about ¼ inch – the size of a pencil eraser), although melanomas can sometimes be smaller than this. E is for Evolving: The mole is changing in size, shape, or color.
  • 20. Superficial Spreading Melanoma
  • 21. Nodular Melanoma
  • 22. Lentigo Maligna Melanoma
  • 23. Variety of Melanoma Skin Lesions
  • 24. Twenty images of skin lesions. Images 1-6, 7-13, and 14-20 show atypical, benign, and malignant lesions, respectively.
  • 25. Recurrent melanoma with subcutaneou s nodules
  • 26. Stage Distribution Melanoma by Race, United States, 2003 to 2009. All White Black
  • 27. Stage Distribution Melanoma by Race, United States, 2003 to 2009. All White Black
  • 28. Stage Distribution for Melanoma – US 2000-2011 from NCDB 45 41% 40 35 30 25 23% 20 12.5% 15 8% 10 3.85% 5 0 Stage 0 Stage I Stage II Stage III Stage IV
  • 29. Stage (Clark’s level or Breslow Depth) Current stage system is based on depth of invasion
  • 30. Clark Classification (Level of Invasion) Level I: Lesions involving only the epidermis (in situ melanoma); not an invasive lesion. Level II: Invasion of the papillary dermis but does not reach the papillary-reticular dermal interface. Level III: Invasion fills and expands the papillary dermis but does not penetrate the reticular dermis. Level IV: Invasion into the reticular dermis but not into the subcutaneous tissue. Level V: Invasion through the reticular dermis into the subcutaneous tissue.
  • 31. Stage System. T or Tumor Category
  • 32. Stage IA and IB Melanoma T1a = 1mm, no ulceration T1b = 1mm, ulceration or T2a = 2mm
  • 33. Stage IIA, B, C Melanoma
  • 34. www.melanomacenter.org/melanomastaging/stagesta rt.cfm
  • 35. Treatment of Melanoma
  • 36. NCCN.com
  • 37. NCCN.org
  • 38. Treatment Guidelines • Early stages: wide local excision • More advanced: wide local excision plus sentinel node biopsy, then based on the pathology consider research trial, observation or interferon • Metastatic: clinical trial, possible radiation and systemic therapy
  • 39. Treatment Guidelines • Early stages: wide local excision • More advanced: wide local excision plus sentinel node biopsy, then based on the pathology consider research trial, observation or interferon • Metastatic: clinical trial, possible radiation and systemic therapy
  • 40. Treatment Guidelines • Early stages: wide local excision • More advanced: wide local excision plus sentinel node biopsy, then based on the pathology consider research trial, observation or interferon • Metastatic: clinical trial, possible radiation and systemic therapy
  • 41. Lymphati c System Which node to biopsy?
  • 42. Sentinel Node Biopsy Lymph node Sentinel node Sentinel nodes removed Dye Cancer Lesion on the arm, which axillary node needs to be
  • 43. Injection site Surgically exposed node
  • 44. nomograms.mskcc.org/Melanoma/PositiveSentinelNode.aspx
  • 45. nomograms.mskcc.org/Melanoma/PositiveSentinelNode.asp x
  • 46. www.lifemath.net/cancer
  • 47. Treatment Guidelines • Early stages: wide local excision • More advanced: wide local excision plus sentinel node biopsy, then based on the pathology consider research trial, observation or interferon • Metastatic: clinical trial, possible radiation and systemic therapy
  • 48. http://www.mayoclinic.org/medicalprofessionals/adjuvant-systemic-therapytools/melanoma
  • 49. Treatment Guidelines • Early stages: wide local excision • More advanced: wide local excision plus sentinel node biopsy, then based on the pathology consider research trial, observation or interferon • Metastatic: clinical trial, possible radiation and systemic therapy
  • 50. Systemic Therapy for Melanoma • Until recently the only approved drugs were chemotherapy (dacarbazine DTIC 9% response) or toxic immunotherapy with interleukin-2 (IL-2 response rate 16%)
  • 51. Activating definition of molecular subtypes of melanoma and provided potential drug targets. BRAF are the most frequent mutation in cutaneous melanoma. Approximately 40% to 60% Oncogenic NRAS mutation in 15% to 20% of melanomas c-KIT mutation, or increased copy number, is associated with mucosal and acral melanomas (which comprise 6% to 7% of melanomas in Caucasians but are the most common subtype in the Asian population). CDK4 mutations have been described in approximately 4% of melanomas and are also more common in acral and mucosal melanomas.
  • 52. New Therapies for Melanoma
  • 53. Systemic Therapy for Melanoma Targeted therapies that block oncogenic pathways. BRAF inhibitors (vemurafenib or debrafenib) MEK inhibitors (trametinib) or KIT inhibitors (imatinib)
  • 54. Systemic Therapy for Melanoma Drugs that disrupt immunologic checkpoints CTLA-4 (cytotoxic T-lymphocyte antigen 4) : ipilimumab and tremelimumab or PD-1 (programmed death-1) receptor: nivolumab, lambrolizumab also PD-L1 (the ligand for PD-1)
  • 55. Median overall survival in the YERVOY (ipilimumab) group was 10 months YERVOY is the only metastatic melanoma therapy proven in a phase 3 study to deliver a durable longterm survival benefit at 2 years for 24% of patients, with some patients still alive up to 4.5 years*2
  • 56. Systemic Therapy for Melanoma
  • 57. Trends in 5 Year Survival for Melanoma by Year and Race Race 1975-77 1987-89 2003-09 White 82% 88% 93% Black 57% 79% 77%
  • 58. Five-Year Relative Survival Rates for Selected Cancers by Race and Stage at Diagnosis, United States, 2003 to 2009. All White Black
  • 59. Long Term Survival with Melanoma by Depth Breslow Depth <0.25mm 0.25 - .49mm 0.50 – 0.74mm 0.75mm – 1.0mm 20 Year Survival 98.3% 98.1% 96.2% 89.0%
  • 60. 5 Year Melanoma Survival Ulceration Depth <1.0mm 1.01 – 2.0mm 2.01 – 4.0mm > 4mm No Ulceration 91% 77% 63% 45% 95% 89% 79% 67% Nodes Involved 1 52% 2–3 50% 4 or + 37% 69% 63% 27%
  • 61. www.melanomaprognosis.or g
  • 62. www.lifemath.net/cancer
  • 63. Cellular Classification of Melanoma Following is a list of clinicopathologic cellular subtypes of malignant melanoma. These should be considered descriptive terms of historic interest only as they do not have independent prognostic or therapeutic significance. Superficial spreading. Nodular. Lentigo maligna. Acral lentiginous (palmar/plantar and subungual). Miscellaneous unusual types: Mucosal lentiginous (oral and genital). Desmoplastic. Verrucous.
  • 64. Melanoma Calculators Melanoma staging tool here Memorial Sloan Kettering clinic has lymph node calculators for melanoma here Mayo clinic calculator for the benefit of adjuvant interferon here NCI, the risk of getting it melanoma here MGH has calculators for melanoma (survival and risk of lymph node spread) here Prognosis for melanoma here Risk of getting melanoma from Harvard here aboutcancer.com/melanoma_calculators
  • 65. Malignant Melanoma Robert Miller MD www.aboutcancer.com