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Malignant Melanoma Robert Miller MD www.aboutcancer.com melanocyt e melanoma epidermis dermis

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Understanding and treating Malignant Melanoma

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  • Malignant Melanoma Robert Miller MD www.aboutcancer.com melanocyte melanoma epidermis dermis
  • 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.
  • 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
  • Melanoma Gender Distribution - US Male Female
  • New Cases New Cases 43,890 (5%) 34,590 (4%) Death Death 6,470 3,240 2014 Data
  • 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
  • Lifetime risk of an American developing invasive melanoma
  • 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%
  • 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
  • Risk Factors Freckling mild moderate severe
  • Risk Factors Sun (Solar) Skin Damage Severe solar damage
  • Risk Calculator for Melanoma http://www.cancer.gov/melanomarisktool/
  • Appearance and location of melanoma
  • Distribution of superficial spreading melanoma
  • Distribution of Skin Melanomas Men on their back
  • Distribution of Skin Melanomas Women on the back legs
  • 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
  • 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
  • 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 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.
  • Superficial Spreading Melanoma
  • Nodular Melanoma
  • Lentigo Maligna Melanoma
  • Variety of Melanoma Skin Lesions
  • Twenty images of skin lesions. Images 1-6, 7-13, and 14-20 show atypical, benign, and malignant lesions, respectively.
  • Recurrent melanoma with subcutaneou s nodules
  • Stage Distribution Melanoma by Race, United States, 2003 to 2009. All White Black
  • Stage Distribution Melanoma by Race, United States, 2003 to 2009. All White Black
  • 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
  • Stage (Clarks level or Breslow Depth) Current stage system is based on depth of invasion
  • 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.
  • Stage System. T or Tumor Category
  • Stage IA and IB Melanoma T1a = 1mm, no ulceration T1b = 1mm, ulceration or T2a = 2mm
  • Stage IIA, B, C Melanoma
  • www.melanomacenter.org/melanomastaging/stagesta rt.cfm
  • Treatment of Melanoma
  • NCCN.com
  • NCCN.org
  • 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
  • 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
  • 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
  • Lymphati c System Which node to biopsy?
  • Sentinel Node Biopsy Lymph node Sentinel node Sentinel nodes removed Dye Cancer Lesion on the arm, which axillary node needs to be
  • Injection site Surgically exposed node
  • nomograms.mskcc.org/Melanoma/PositiveSentinelNode.aspx
  • nomograms.mskcc.org/Melanoma/PositiveSentinelNode.asp x
  • www.lifemath.net/cancer
  • 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
  • http://www.mayoclinic.org/medicalprofessionals/adjuvant-systemic-therapytools/melanoma
  • 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
  • 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%)
  • 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.
  • New Therapies for Melanoma
  • Systemic Therapy for Melanoma Targeted therapies that block oncogenic pathways. BRAF inhibitors (vemurafenib or debrafenib) MEK inhibitors (trametinib) or KIT inhibitors (imatinib)
  • 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)
  • 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
  • Systemic Therapy for Melanoma
  • 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%
  • Five-Year Relative Survival Rates for Selected Cancers by Race and Stage at Diagnosis, United States, 2003 to 2009. All White Black
  • Long Term Survival with Melanoma by Depth Breslow Depth