11/8/2014 Cutaneous Carcinomas Most common malignancy in world - PowerPoint PPT Presentation

11/8/2014 Cutaneous Carcinomas • Most common malignancy in world Otolaryngology-Head and Neck Surgery Ivan El-Sayed, MD, FACS • Update changes in trends, staging, and Director Center for Minimally Invasive Skull Base Surgery. management of SCC/BCC Head and Neck Nanomedicine Laboratory. Advanced Skin Cancer of the Head and Neck 2 Background Cutaneous Cancer Cutaneous Carcinoma • 82 Types of skin cancer • 3.5 million BCC/SCC new cases/ year in US in about 2 million patients. – Melanoma – Most are BCC – Nonmelanoma skin ca (NMSC) – More new cases than breast, prostate, lung, colon • Merkel cell combined • Epidermal layer (SCC and BCC) – About 3,000 deaths per year – Deeper layers (dermis and adnexal structures) • Range of Prognosis • Incidence increasing for years – Highly aggressive, metastatic (Merkel Cell) – Ozone depletion – Locally destructive (BCCA) – Lifestyle – Detection? 1

11/8/2014 Nonmelanoma Skin Cancer Etiology BCCA and SCCA • UVB (Sunlight) • Chemical exposure hydrocarbons, pesticides • Developing 1 Skin Cancer … • Ionizing radiation – increases risk of developing another cancer • Tobacco – Increases risk second skin cancer • Arsenic (in well water) • 35% at 3 yrs • Chronic Skin conditions • 50% at 5 yrs • Impaired Cell Immunity • Genetic Diseases • HPV 5 6 Two mechanisms of action of UV Impaired Immunity Carcinogenesis? DNA mutations Induced immunosuppression • Disease Related – Lymphoma – Leukemia – Autoimmune – Epidermodysplasia verruciform – Mostly T cell depletion (CD4+ T cells) • Associated with skin cancer Favors generation of suppressor UVB(290-320 nm) is over helper immune pathways 10,000 time more mutagenic than UVA(320- 400 nm) 8 2

11/8/2014 Impaired Immunity Why vary with transplant type? Organ Transplant • Drug Related • Heart transplant requires more immunosuppression – Cyclosporin, azathioprin, tacrolimus – Varies with transplant type • Renal transplant performed in older patients – Less time to develop skin ca • Incidence increases with time after transplant – 10% at 10 years – 40% at 20 years • SCC is predominant cancer • Highly aggressive tumors 9 10 Increased risk of developing NMSC Organ Transplant Population-based Standard Incidence Ratios of Skin Cancer in Transplant Patients • Increased risk of NMSC Skin Cancer Increased Incidence in Transplant Patients • Onset of cancer at a younger age SCC 65 to 250 fold SCC of lip 20 fold • More aggressive tumors BCC 10 fold with increased morbidity and mortality Melanoma 1.6 to 3.4 fold Kaposi’s Sarcoma 84 fold • Some patients develop Scandinavian population-based registries multiple tumors Jensen JAAD 1999;40:17 Hartevelt Transplantation 1990;49:506; Lindelof BJD 2000;143;513 3

11/8/2014 More aggressive tumors with Risk Factors for Skin Cancer with increased morbidity and mortality Organ Transplant Increased • Tumors are more aggressive than in non-transplant General Transplant patients Population Population • Cincinnati Transplant Tumor Registry • 5.2% of individuals with skin cancer died of their Increasing age ++ ++++ tumors • More died from SCC than melanoma Fair skin, light ++ ++++ hair, light eyes Sun exposure ++ ++++ History of 50% risk of 2nd >70% risk of 2nd previous skin cancer skin cancer cancer Precursors lesions? BCCA Types • SCCA • Nodular Ulcerative –most common – Actinic Keratosis • Superficial – Least aggressive – Bowen’s Disease (CIS) • Pigmented • Morhpeaform (sclerosing) – aggressive insidious growth • BCCA • Basosquamous-features of SCCA – No precursors Image Wikipedia Bowen’s Disease 15 16 4

11/8/2014 High Risk Lesions: Aggressive High Risk Features for SCCA Biologic Behavior SCCA • Histology • Thickness in mm • Depth in Clark’s level • Perineural involvement • Size >2cm • Etiology • Immune status • Anatomic site Current Opinion in Otolaryngology & Head & Neck Surgery: April 2011 - Volume 19 - Issue 2 - p 99–105 17 18 Anatomic Site Factors Associated with Metastases • Higher Rate Recurrence and • SCC arising in scar, ulcer, Lymphatic Met burn – Ear The H Zone of – Lip the face along • Large neglected tumors embryonic fusion – Direct invasion parotid (>50% planes metastatic) • Hx of ionizing radiation, PUVA therapy, arsenic • High Rate Recurrence ingestion or immunosuppression – Nasolabial crease – Periorbital – Preauricular 19 20 5

11/8/2014 Mortality From SCCA Who dies from NMSC? • BCCA • Elderly – Rare – Pts refused treatment • Suppressed immune system – HIV • SCCA – Organ Transplant – Is 2 nd most common cause after melanoma • Refused Treatment – Most common if lymphatic spread (>50%) – Upset about a positive margin – Not hx of refused treatment in medial canthus 20 years prior. America Cancer Society Fact Sheet 21 22 Treatment: Early Stage Surgical Excision • Moh’s – H zone lesion (high risk) • Cryotherapy (Actinic Keratosis) – Recurrent, indistinct boarders, cosmetically important areas, aggressive histologies, priorly radiated, • Electrocautery and Curretage (<.5cm) immunosuppressed, basal nevus • Diffuse Treatments : 5FU, chemical/laser peel • Wide Local Excision – When Moh’s no longer adequate • Surgical Excision (Moh’s, WLE) – Recurrent lesions • Radiation 23 24 6

11/8/2014 Radiation therapy Drawbacks to Radiotherapy • Lack of histological margins • IS effective for BCC/SCC but not often used as – Subepithelial spread can be several cm primary treatment – RT Avoided in poorly defined lesion – 95% cure rate small lesions – 80% cure rate for large lesions (w high risk features) • Side effects/Scarring with radiation can be significant • Radiation is generally reserved for – High risk SCC/BCC • Significant commitment and access to an skilled – Poor surgical candidates radiotherapist can be an issue – Recurrence after surgery – Manage nodal disease prophylactically • Recurrence of NMSC after RT may be more aggressive 25 26 Hedgehog signaling is normally active in Chemotherapy embryonic development (GDC-0499) • SCC • BCC – Topical 5 FU – Topical • 5 FU – Chemoprevention retinoids • Imiquimod In BCC Activation of Smoothened (SMO) protein or functional loss of PTCH in >90 % of BCC Erivedge inhibits SMO – Intravascular vismodegib • Vismodegib (erivedge) C l – FDA 2012 N O H N C l O S O Teh et al., Cancer Res 2005: 27 28 7

11/8/2014 Vismodegib in locally advanced Hedgehog Inhibitor Phase I trial BCC • 15 patients with advanced disease Baseline Week 8 Week 20 • 13 had clinical response – Overall “response rate”= 60% • 2 had complete response • 4 had stable disease 9 months • FDA approved 2012 Week 16: no BCC on biopsy • (Trial carried out in part at UCSF) Slide Courtesy Sarah Arron, UCSF Department of Dermatology Von Hoff 2009 NEJM Phase 1 trial 30 29 Vismodegib Updates Sekuklic et al NEJM 2012 • Indications • When and where to use • Changes in Staging System not firmly established – “inappropriate for surgery” – Generally well • Signifcant responses • Surgical Management of T4 recalcitrant lesions tolerated • 50% discontinued – Duration of • Adverse events response? (“9.5mo progression free – 25% serious survival”) – 100% mild – Cost $7500/mo x 10mo 31 32 8

11/8/2014 Changes in AJCC Staging Advanced Cutaneous Skin Cancer • T1 <2cm with less than 2 high risk features • Changes in AJCC • T2 >2cm or any size with 2 HR features • T3 Invades maxilla, mandible, orbit, t bone • Unresectable � “Advanced” • T4 invades skeleton or perineural invasion skull base • N1 single node 3cm or less • N2a-c same as head and neck • N3 >6cm 33 T Staging Extradermal Invasion • 6 th Edition • 7 th Edition • 6 th ed • 7 th ed • T:1:</=2cm • T1: Same • Used to • Eliminated determine T4 – Lack of data • T2:2-5cm • T2: >2cm • Lack of evidence • T3:>5cm to support 5cm threshold 9

11/8/2014 Histopathologic Grade Anatomic Site • 6 th Edition • 7 th Edition • 6 th ed • 7 th ed • Not included • Now included • Not used for T or • Added as high final stage risk feature – Degree of differentiation reported as risk factor 38 Cranial or facial bone involvement Invasion skull base or axial skeleton • 6 th ed • 7 th ed • 7 th ed • 6th ed • Included as T4, • T3: invasion • Included as T4 • T4 redefined as invasion of maxilla, mandible, tumor involving extradermal orbit, T bone skull base or structure axial skeleton • Correlates w HN Ca staging • Or perinueral skull base invasion 10

11/8/2014 N staging Distant Metastases • 6 th ed • 7 th ed • No Change • N0 Absence node • N0-N3 based on size and number of • N1 Presence node mets • Congruent with HN Staging • Data shows decreased survival with size and # nodes High Risk Lesions: Patient Recall T4 Lesions Approach • Resectable? • Invades skeleton or perineural invasion skull base • Radiotherapy? • Direct Extension • Medical Therapy? through skull • Patient compliance? • Perineural skull base – V1,2,3 – Facial nerve – Auriculotemporal nerve 43 44 11