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

11/8/2014 1

Advanced Skin Cancer of the Head and Neck

Ivan El-Sayed, MD, FACS Director Center for Minimally Invasive Skull Base Surgery. Head and Neck Nanomedicine Laboratory. Otolaryngology-Head and Neck Surgery

Cutaneous Carcinomas

• Most common malignancy in world
• Update changes in trends, staging, and

management of SCC/BCC

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Background Cutaneous Cancer

• 82 Types of skin cancer

– Melanoma – Nonmelanoma skin ca (NMSC)

• Merkel cell
• Epidermal layer (SCC and BCC)

– Deeper layers (dermis and adnexal structures)

• Range of Prognosis

– Highly aggressive, metastatic (Merkel Cell) – Locally destructive (BCCA)

Cutaneous Carcinoma

• 3.5 million BCC/SCC new cases/ year in US in

about 2 million patients.

– Most are BCC – More new cases than breast, prostate, lung, colon combined – About 3,000 deaths per year

• Incidence increasing for years

– Ozone depletion – Lifestyle – Detection?

11/8/2014 2 Nonmelanoma Skin Cancer

• Developing 1 Skin Cancer …

– increases risk of developing another cancer – Increases risk second skin cancer

• 35% at 3 yrs
• 50% at 5 yrs

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Etiology BCCA and SCCA

• UVB (Sunlight)
• Chemical exposure hydrocarbons, pesticides
• Ionizing radiation
• Tobacco
• Arsenic (in well water)
• Chronic Skin conditions
• Impaired Cell Immunity
• Genetic Diseases
• HPV

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Two mechanisms of action of UV Carcinogenesis?

DNA mutations Induced immunosuppression

Favors generation of suppressor

• ver helper immune pathways

UVB(290-320 nm) is 10,000 time more mutagenic than UVA(320- 400 nm)

Impaired Immunity

• Disease Related

– Lymphoma – Leukemia – Autoimmune – Epidermodysplasia verruciform – Mostly T cell depletion (CD4+ T cells)

• Associated with skin cancer

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11/8/2014 3 Impaired Immunity Organ Transplant

• Drug Related

– Cyclosporin, azathioprin, tacrolimus – Varies with transplant type

• Incidence increases with time after transplant

– 10% at 10 years – 40% at 20 years

• SCC is predominant cancer
• Highly aggressive tumors

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Why vary with transplant type?

• Heart transplant requires more

immunosuppression

• Renal transplant performed in older patients

– Less time to develop skin ca

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Organ Transplant

• Increased risk of NMSC
• Onset of cancer at a

younger age

• More aggressive tumors

with increased morbidity and mortality

• Some patients develop

multiple tumors

Increased risk of developing NMSC

Population-based Standard Incidence Ratios of Skin Cancer in Transplant Patients Skin Cancer Increased Incidence in Transplant Patients SCC 65 to 250 fold SCC of lip 20 fold BCC 10 fold Melanoma 1.6 to 3.4 fold Kaposi’s Sarcoma 84 fold

Scandinavian population-based registries Jensen JAAD 1999;40:17 Hartevelt Transplantation 1990;49:506; Lindelof BJD 2000;143;513

11/8/2014 4 More aggressive tumors with increased morbidity and mortality

• Tumors are more aggressive than in non-transplant

patients

• Cincinnati Transplant Tumor Registry
• 5.2% of individuals with skin cancer died of their

tumors

• More died from SCC than melanoma

Risk Factors for Skin Cancer with Organ Transplant Increased

General Population Transplant Population Increasing age ++ ++++ Fair skin, light hair, light eyes ++ ++++ Sun exposure ++ ++++ History of previous skin cancer 50% risk of 2nd cancer >70% risk of 2nd skin cancer

Precursors lesions?

• SCCA

– Actinic Keratosis – Bowen’s Disease (CIS)

• BCCA

– No precursors

15 Image Wikipedia Bowen’s Disease

BCCA Types

• Nodular Ulcerative –most common
• Superficial – Least aggressive
• Pigmented
• Morhpeaform (sclerosing) – aggressive

insidious growth

• Basosquamous-features of SCCA

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11/8/2014 5 High Risk Features for SCCA

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Current Opinion in Otolaryngology & Head & Neck Surgery: April 2011 - Volume 19 - Issue 2 - p 99–105

High Risk Lesions: Aggressive Biologic Behavior SCCA

• Histology
• Thickness in mm
• Depth in Clark’s level
• Perineural involvement
• Size >2cm
• Etiology
• Immune status
• Anatomic site

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Anatomic Site

• Higher Rate Recurrence and

Lymphatic Met

– Ear – Lip – Direct invasion parotid (>50% metastatic)

• High Rate Recurrence

– Nasolabial crease – Periorbital – Preauricular

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The H Zone of the face along embryonic fusion planes

Factors Associated with Metastases

• SCC arising in scar, ulcer,

burn

• Large neglected tumors
• Hx of ionizing radiation,

PUVA therapy, arsenic ingestion or immunosuppression

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11/8/2014 6 Mortality From SCCA

• BCCA

– Rare – Pts refused treatment

• SCCA

– Is 2nd most common cause after melanoma – Most common if lymphatic spread (>50%) – Not hx of refused treatment

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Who dies from NMSC?

• Elderly
• Suppressed immune system

– HIV – Organ Transplant

• Refused Treatment

– Upset about a positive margin in medial canthus 20 years prior.

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America Cancer Society Fact Sheet

Treatment: Early Stage

• Cryotherapy (Actinic Keratosis)
• Electrocautery and Curretage (<.5cm)
• Diffuse Treatments : 5FU, chemical/laser peel
• Surgical Excision (Moh’s, WLE)
• Radiation

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Surgical Excision

• Moh’s

– H zone lesion (high risk) – Recurrent, indistinct boarders, cosmetically important areas, aggressive histologies, priorly radiated, immunosuppressed, basal nevus

• Wide Local Excision

– When Moh’s no longer adequate – Recurrent lesions

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11/8/2014 7 Radiation therapy

• IS effective for BCC/SCC but not often used as

primary treatment

– 95% cure rate small lesions – 80% cure rate for large lesions (w high risk features)

• Radiation is generally reserved for

– High risk SCC/BCC – Poor surgical candidates – Recurrence after surgery – Manage nodal disease prophylactically

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Drawbacks to Radiotherapy

• Lack of histological margins

– Subepithelial spread can be several cm – RT Avoided in poorly defined lesion

• Side effects/Scarring with radiation can be

significant

• Significant commitment and access to an skilled

radiotherapist can be an issue

• Recurrence of NMSC after RT may be more

aggressive

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Chemotherapy

• SCC

– Topical 5 FU – Chemoprevention retinoids

• BCC

– Topical

• 5 FU
• Imiquimod

– Intravascular

• Vismodegib

(erivedge)

– FDA 2012

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Hedgehog signaling is normally active in embryonic development (GDC-0499)

In BCC Activation of Smoothened (SMO) protein

• r functional loss of PTCH in >90 % of BCC

Erivedge inhibits SMO

H N O C l N C l S O O

vismodegib

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Teh et al., Cancer Res 2005:

11/8/2014 8 Hedgehog Inhibitor Phase I trial

• 15 patients with advanced disease
• 13 had clinical response

– Overall “response rate”= 60%

• 2 had complete response
• 4 had stable disease 9 months
• FDA approved 2012
• (Trial carried out in part at UCSF)

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Von Hoff 2009 NEJM Phase 1 trial

Vismodegib in locally advanced BCC

Week 20

Week 16: no BCC on biopsy

Baseline Week 8

30 Slide Courtesy Sarah Arron, UCSF Department of Dermatology

Vismodegib

• Indications

– “inappropriate for surgery”

• Signifcant responses
• 50% discontinued
• Adverse events

– 25% serious – 100% mild

• When and where to use

not firmly established – Generally well tolerated – Duration of response? (“9.5mo progression free survival”) – Cost $7500/mo x 10mo

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Sekuklic et al NEJM 2012

Updates

• Changes in Staging System
• Surgical Management of T4 recalcitrant lesions

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11/8/2014 9 Changes in AJCC Staging

• T1

<2cm with less than 2 high risk features

• T2

>2cm or any size with 2 HR features

• T3

Invades maxilla, mandible, orbit, t bone

• T4

invades skeleton or perineural invasion skull base

• N1

single node 3cm or less

• N2a-c same as head and neck
• N3

>6cm

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Advanced Cutaneous Skin Cancer

• Changes in AJCC
• Unresectable “Advanced”

T Staging

• 6th Edition
• T:1:</=2cm
• T2:2-5cm
• T3:>5cm
• 7th Edition
• T1: Same
• T2: >2cm
• Lack of evidence

to support 5cm threshold

Extradermal Invasion

• 6th ed
• Used to

determine T4

• 7th ed
• Eliminated

– Lack of data

11/8/2014 10 Histopathologic Grade

• 6th Edition
• Not included
• 7th Edition
• Now included

– Degree of differentiation reported as risk factor

Anatomic Site

• 6th ed
• Not used for T or

final stage

• 7th ed
• Added as high

risk feature

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Cranial or facial bone involvement

• 6th ed
• Included as T4,

invasion of extradermal structure

• 7th ed
• T3: invasion

maxilla, mandible,

• rbit, T bone
• Correlates w HN

Ca staging

Invasion skull base or axial skeleton

• 6th ed
• Included as T4
• 7th ed
• T4 redefined as

tumor involving skull base or axial skeleton

• Or perinueral

skull base invasion

11/8/2014 11 N staging

• 6th ed
• N0 Absence node
• N1 Presence node
• 7th ed
• N0-N3 based on

size and number of mets

• Congruent with HN

Staging

• Data shows

decreased survival with size and # nodes

Distant Metastases

• No Change

High Risk Lesions: Patient Approach

• Resectable?
• Radiotherapy?
• Medical Therapy?
• Patient compliance?

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Recall T4 Lesions

• Invades skeleton or

perineural invasion skull base

• Direct Extension

through skull

• Perineural skull base

– V1,2,3 – Facial nerve – Auriculotemporal nerve

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11/8/2014 12 Therapeutic Interventions of T4

• Radiation ?
• Consider wide local excision

– If + margins, can they be reirradiated?

• Reduce immunosuppression/ adequate HIV

meds

• Medical therapy?:

– Hedge hog inhibitor for BCC

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• Massive lesions
• Failed Radiation
• Prior surgeries
• Immunosuppressed
• High Met rate
• Invading critical structures
• Invading unresectable intracranial sites

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Considerations Considerations

• Massive lesions

– Size by itself is not a determinant – Are socially isolating – Impetus to treat if even for palliation – How big defect to close?

• Failed Radiation
• Prior surgeries
• Immunosuppressed
• High Met rate
• Invading critical structures
• Invading unresectable intracranial sites

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• Massive lesions
• Failed Radiation

– How much radiation was given? – Where was radiation given (is there a field miss?) – If you resect, can more be given to critical sites?

• Prior surgeries
• Immunosuppressed
• High Met rate
• Invading critical structures
• Invading unresectable intracranial sites

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Considerations

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• Massive lesions
• Failed Radiation
• Prior surgeries

– Were they inadequate? – Do they impede flap reconstruction?

• Immunosuppressed
• High Met rate
• Invading critical structures
• Invading unresectable intracranial sites

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Considerations

• Massive lesions
• Failed Radiation
• Prior surgeries
• Immunosuppressed

– HIV? Are they on adequate meds yet? – Organ Tx: can meds be decreased?

• High Met rate
• Invading critical structures
• Invading unresectable intracranial sites

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Considerations

• Massive lesions
• Failed Radiation
• Prior surgeries
• Immunosuppressed
• High Met rate

– Image and address nodal basin

• Invading critical structures
• Invading unresectable intracranial sites

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Considerations

• Massive lesions
• Failed Radiation
• Prior surgeries
• Immunosuppressed
• High Met rate
• Invading critical structures

– Orbit, nose, ear, Facial nerve

• Invading unresectable intracranial sites

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Considerations

11/8/2014 14 Considerations

• Massive lesions
• Failed Radiation
• Prior surgeries
• Immunosuppressed
• High Met rate
• Invading critical structures
• Invading unresectable intracranial sites

– Cavernous sinus? – Dura- where?

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Case: Recurrent BCC

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All prior scar must be included in resection

Wide Local Excision

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Perineural invasion leads to cav sinus

46 yo HIV+ male Rec SCC Maxilla and Orbit to Cav L Cav Sinus Involved

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11/8/2014 15 Stable at 7 years after Total maxillectomy, Orbit Exent, RT

Rectus flap stable Cav sinus stable

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SCC Multiple Prior Resections

• Moh’s x 3
• ver 2 years
• 1 Course of

RT

• Rec Lesion

4 months in nonhealing ulcer

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Wide Local Excision with margins

• n skin

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Gross Tumor on Sagittal Sinus discovered intraopertively

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MRI, MRV Image guidance Tumor on Sag Sinus (Blue ink marks sinus)

11/8/2014 16 Preoperative Assesment MRV

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Tumor on Sagital sinus

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Tumor Debrided by neurosurgeon. Plan for re irradiation protocol of residual

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WLE re-irradiation 7,000cGy, Erbitux. Local control Ultimately passed away from metastatic SCC.

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55yo renal transplant patient, 8 years post Tp in 2002 developed SCC r forehead treated with WLEx2. 2004 developed a recurrence, txed with MMS and 5600cGy. 2006- second recurrence treated with MMS, noted muscular and perineural invasion of supraorbital nerve- reexcision x2,

11/8/2014 17 SCCA Preoperative CSF Leak

• 7 yr hx rec scc
• Multiple mohs
• 1 yr hx painful

lesion

• CSF evident

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Treated WLE and Local Advancement flaps

• Underlying

hematologic disorder, hypercoagulable

• Necrosed

advancement flap, taken back for free flap excellent result

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Post Op: Some Successes 55yo renal tx recipient Rec SCCA scalp invading dura with dural resection

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Scalp and Skull Lesions

• Limited data available for outcomes
• Several small series
• Reconstruction

– Free tissue transfer common (lat, scapular, RFFF)

• Defect bone,dura
• >10cm2

– 15-20% complication rate

• Wound infection assoc with implant

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Shonka et al Laryngoscope 2011

11/8/2014 18 Tips for Advanced disease

• 1) Get negative margins on skin and bone
• 2)Reirradiate residual margins when possible-
• ften can, many cases of radiation failure are

associated with field miss

• 3) Calvarial implants are associated with

infection in about 20% of cases

• 4)Evaluate neck for metastases in high risk

lesion

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Conclusion

• Advanced Skin Cancer require multidisciplinary

care

– Skilled facility – Evaluate reirradiation – Consider resection of “unresectable” lesions for local control and possible long term control – Optimize patient status (immunesuppression?)

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