controversies in melanoma

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Controversies in Melanoma Prof Ravi Kant, Dr Ajay Yadav, Dr Vivek Gupta, Dr Vishal Gupta, Ms Tanmya Stuti Ravi

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Controversies in Melanoma. Prof Ravi Kant , Dr Ajay Yadav, Dr Vivek Gupta, Dr Vishal Gupta, Ms Tanmya Stuti Ravi. Controversies in Melanoma. Biology Detection-Computer, USG, RT-PCR Staging- AJCC 2000 +Prognosis SLN Biopsy + ELND Surgical margins Adjuvant treatment + Vaccines Summary. - PowerPoint PPT Presentation

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Page 1: Controversies in Melanoma

Controversies in Melanoma

Prof Ravi Kant, Dr Ajay Yadav, Dr Vivek Gupta, Dr Vishal Gupta, Ms Tanmya Stuti Ravi

Page 2: Controversies in Melanoma

2

Controversies in Melanoma

• Biology• Detection-Computer, USG, RT-PCR• Staging- AJCC 2000 +Prognosis• SLN Biopsy + ELND• Surgical margins• Adjuvant treatment + Vaccines• Summary

Page 3: Controversies in Melanoma

3

Biology of melanoma

development and progression

Page 4: Controversies in Melanoma

4

Biology of melanoma

1. Melanocytes →

2. Nevus →

3. Dysplastic nevus →

4. Radial growth phase →

5. Vertical growth phase →

6. Metastases.

Page 5: Controversies in Melanoma

5

Melanoma & Nevi

• Class I = Precursor

• Class II = Intermediate

• Class III = VGP tumorigenic

VGP = vertical growth phase

Page 6: Controversies in Melanoma

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Cell cycle regulation in melanoma

Page 7: Controversies in Melanoma

7

Expression of defined molecules in melanoma cell

Page 8: Controversies in Melanoma

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Express adhesions receptors,

Integrins, Adherine, and cellular

adhesions molecules

Page 9: Controversies in Melanoma

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• melanoma cells express N-adherine instead of E-adherine.

• E-adherine allows melanocytes to adhere to keratinocytes, while melanoma cells can not adhere to keratinocytes

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10

Page 11: Controversies in Melanoma

11B- catenin pathway

Page 12: Controversies in Melanoma

12

Biology- what is new?

• PTEN pathway = phosphatase and tensin deleted on chromosome 10 →

• IGF-1 → Akt / PKB (Oncogene)+PtdIns(3,4)P2→ P13 kinase →growth factor + adhesion receptor (integrin)

Page 13: Controversies in Melanoma

13

Biology – what is new?

• Ras pathway →Grb2/Sos →ras →Raf →MEK 1,2 →MAPK 1.2 →TCF/SRF/Elk-1 →Proliferation

• As apoptosis is blocked by depriving

• Bad & Caspase-9 from p13 kinase

• Apoptosis turned into growth

Page 14: Controversies in Melanoma

Naevi

Page 15: Controversies in Melanoma

15

Nevus• Proliferative lesion of

melanocytes

• Scattered along basal layer

• Acquired - mostly

• congenital

Page 16: Controversies in Melanoma

16

Naevi : types

1. Lentigo Flat

2. Junctional

3. Compound – slightly elevated

4. Intradermal – papillomatous

Page 17: Controversies in Melanoma

17

Naevi: Lentigo simplex-1• Pigmented macule, <5mm, jet

black color

• In infants & children

• Melanocytic proliferation along basal layer

Page 18: Controversies in Melanoma

18

Naevi: Lentigo simplex-2• Abundant melanocytes along

basal layer

• Associated with Peutz-Jegher syndrome

• P-J syndrome = hamartomatous polypes in GIT +naevi in oral & buccal mucosa

Page 19: Controversies in Melanoma

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Naevi: Junctional • Next stage after lentigo• Macular lesions, < 7mm• Less deeply pigmented than

lentigo• Homogenous brown black areas• Melanocytic proliferation along

basal layer• Highest malignant potential

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Naevi: Compound

• Next stage of maturation of junctional naevi

• In children & adolescent

• Pale brown & papular

• Junctional + dermal component

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Naevi: Intradermal

• Last stage in maturation• Mostly after 30 years of age• Flesh colored papule with little

pigment• Melanocytes confined to

dermis only

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Blue naevi• Benign melanocytic naevi• Slate blue color• Two types : common & cellular

Page 23: Controversies in Melanoma

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Common Blue naeviMostly in scalp & dorsum of hand, feet1. Dermal collection of spindle

melanocytes2. F > M , max. in 4th decade

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Blue naevi: Cellular type

1. Uncommon

2. F > M

3. > 50% in sacrococcygeal area& buttock

4. < 1% under go malignancy

5. Rx : simple excision

Page 25: Controversies in Melanoma

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Nevus

• Common

• Atypical

• Congenital

• Spitz

• Familial

Page 26: Controversies in Melanoma

26

Malignant Melanoma

• Arises from transformed melanocytes of epidermis

• Accounts for almost all deaths from skin cancer

• 4 fold increase in incidence in Australia

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Melanoma : Risk Factors-1

• Congenital naevi >5% BSA, 1000X

• Previous melanoma

• Family history

• 5 naevi > 5mm (Common nevi)

• 50 naevi > 2mm (Common nevi)

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Melanoma : Risk Factors-2

• Dysplastic nevi, Atypical= 2X for single; 12X for >10

• Family history Atypical =37-148X

• Dysplatic naevi syndrome

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Melanoma : Risk factors-3

• White race,• Red hair, • Blond hair, • Blue eyes• Poor tanning ability, • Sunburns during childhood• Albinism

Page 30: Controversies in Melanoma

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Melanoma : Risk factors-4

• Freckles

• Equatorial latitude

• Xeroderma pigmentosa

• Psoralen sunscreen

• Tanning salons

• Junctional naevi

Page 31: Controversies in Melanoma

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Melanoma : Risk factors-5

• Spitz Nevi= benign except when>10 y age+ulceration>1cmInvolve subcut fatMitotic activity >6/mm2

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Melanoma : Risk factors-6

• Familial syndromes

• B-K nevus syndromes

• Atypical nevus

• CDKN2A mutation

• CDK4 mutation

Page 33: Controversies in Melanoma

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DD

• Pigmented Basal cell CA

• Seborrheic keratitis

• Solar lentigines

• Atypical nevi

Page 34: Controversies in Melanoma

34

MM: Clinical features

• Lentigo maligna : Hutchinson's freckle (7-15%)

• Superficial spreading : most common (60-70%)

• Nodular : 12-25%

• Acral lentiginous

• Amelanotic

Page 35: Controversies in Melanoma

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1. Superficial spreading Melanoma

• Most common type 70%

• Occur any where on skin except hands & feet

• Usually > 5 mm , flat

• Variegated color pattern

• Irregular edge with areas of regression

• Long radial growth phase

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36

2. Nodular Melanoma

• Most malignant

• Younger age group

• Any part of the body

• raised and always palpable with sharp irregular border

• Blue, black or gray color

• Lack of radial growth phase

Page 37: Controversies in Melanoma

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2. Nodular Melanoma

• Second most common 15-30 %

• Rapid onset

• ♂>♀

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3. Lentigo maligna Melanoma

• Hutchinsons melanotic freckle

• Least common type 5%

• Most commonly on face of elderly

• Begins as irregularly pigmented ,flat, brown macule

• quite large at the time of diagnosis late invasive growth phase

• Good prognosis

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4. Acral lentiginous

• Uncommon 1-3%

• Palm, sole, heel & subungual

• More common in dark skin persons

• Subungual –common in big toe or thumb

• Poor prognosis , 29%@20Y

• 70% ulcerate, 74% >1.5 mm

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4. Acral lentiginous-risk factor

• >50 y age

• >3mm width, variegated border

• Extension of pigment in to nail bed/ nail fold

• Dark complexioned patient

Page 41: Controversies in Melanoma

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5. Amelanotic Melanoma

• Desmoplastic, 1.7%

• H&N

• Pink, reveal some pigment on close inspection; Stain+ with S-100

• Worse prognosis

• Often present with regional lymph nodes metastases

Page 42: Controversies in Melanoma

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5. Amelanotic Melanoma

• Locally aggressive

• Known for local recurrences

• Stain ► S-100

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MM : spread

• Local extension

• Blood stream : lung, liver, brain, skin

• Lymphatic :

– embolisation, permeation

– satellite nodule

– in-transit nodule

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Controversies in Melanoma

• Biology• Detection-Computer, USG, RT-PCR• Staging- AJCC 2000 +Prognosis• SLN Biopsy + ELND• Surgical margins• Adjuvant treatment + Vaccines• Summary

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MM : Diagnosis

• Signs of transformation of mole in to MM

• Major

–Change in size, shape, color• Minor

–Inflammation, itching

–Crusting or bleeding

– > 5mm diameter

Page 46: Controversies in Melanoma

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MM: Diagnosis

• A : Asymmetry

• B : irregular border

• C : color variegation

• D : diameter > 5 mm

• E : enlargement or evolution

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Detection- Vision

• A = asymmetry

• B = border irregularity

• C = color variegation

• D =diameter > 6mm

• E = elevation, enlargement, evolutionary changes

• F= any funny change

Page 48: Controversies in Melanoma

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Detection- Vision

1. Change in size2. Change in shape3. Change in Color4. Inflammation5. Crusting / bleeding6. Sensory change7. > 7mm in size enlargement

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Detection- Digital Vision

• Epiluminescence microscopy

• Dermatoscopy

• Surface microscopy

• Incident light microscopy

• Can see the dermis, epidermo-dermal junction

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Epiluminescence microscopy-ominous signs

• Melanin pigment network

• Black dots

• Globules

• Streaks

• Radial streaming

• Blue-white milky veils

• Pseudopods

• Pseudo network

• Structure less area

• Melanin reticulum

• Epidermo-dermal junction

• Multiple brown dots

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Epiluminescence microscopy-good signs

• Axial symmetry of pigmentation

• Presence of one color only

• Sensitivity 92%

• Specificity 71%

Page 52: Controversies in Melanoma

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Detection-digital vision

• Computer based Dermatoscopy

• Spectrophotometric image analysis

• Reflectance spectroscopy

• Computer aided image analysis Topodermatographic

• USG, MR and OCT = in vivo histology

• Virtual histology

Page 53: Controversies in Melanoma

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USG for Regional LN

• 7.5-20 mhZ for LN : 20-100 for Virtual• USG B scan-LN• Vassallo index<2 (Long:Trans)• Hypoechoic central area• Color Doppler-peripheral perfusion• USG Guided FNAC +RT-PCR Tyro• USG guided anchor wire for mets

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Screening

Dermatologist

or

non-Dermatologists?

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Screening

Dermatologist

• sensitivity 89% - 97%

• positive predictive value - 17-75%

• specificity - 97%

Page 56: Controversies in Melanoma

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PET vs CTSensitive

%

Specificity %

FDG PET 94-100 83 -94

CT 55-84 68-84

Holder

Ann Surg 1998

Rinne

Cancer 1998

Page 57: Controversies in Melanoma

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FDG PET >CT

• regional and mediastinum lymph nodes

• abdominal visceral and soft tissue metastasis

Page 58: Controversies in Melanoma

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Lung mets

87 vs 70 %

CT>PET

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MRI for brain

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A single whole body PET scan could replace all other imaging modalities in melanoma.

PET

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1. Cost

2. Limited availability

3. Lack of sufficient data

Limitations of PET

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Controversies in Melanoma

• Biology• Detection-Computer, USG, RT-PCR• Staging- AJCC 2000 + Prognosis• SLN Biopsy + ELND• Surgical margins• Adjuvant treatment + Vaccines• Summary

Page 63: Controversies in Melanoma

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Prognostic factors

Tumor thickness = Breslow

Vs

Level of invasion = Clark level

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Thickness vs. Level

54 multivariate analysis of

prognostic factors using data from 48 papers

Vollmer

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Thickness vs. Level

Tumor thickness significant

in 42 of 54 studies

Vollmer

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Thickness vs. Level

Level of invasion important

prognostic factor in only 8 of 48

Studies

Vollmer

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Thickness vs. Level

• Tumor thickness

• 1 , 2, & 4 mm

• Best for survival data

• Adopted in 2002 AJCCButtner

Buzaid

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Thickness vs. Level- conclusion• Clark level of invasion is a minor

prognostic factor

• cutoffs of tumor thickness such as 1mm, 2mm and 4mm provide better prognostic information

• 2002 AJCC staging of melanoma

Page 69: Controversies in Melanoma

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Ulceration: prognostic significance

Significant prognostic factor

Vollmer - multivariate analysis in

7 of 11 studies

Page 70: Controversies in Melanoma

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Ulceration: prognostic significance

strongest predictors of outcome

Balch - meta-analysis that

included 15,798 patients with

localized melanoma

Page 71: Controversies in Melanoma

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Ulceration: prognostic significance

• Ulceration has the most significant impact on survival.

• Buzaid : influence of ulceration according to the tumor thickness

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Ulceration

• Acantholysis

• Shows autocrine and paracrine pathways are active

• Adverse prognosis

Page 73: Controversies in Melanoma

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Ulceration: prognostic significance

• Independent prognostic factor

• Included in AJCC 2002 staging

• Upstage patients compared

with those having tumor of

same thickness

Page 74: Controversies in Melanoma

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Satellites vs. In-transit metastases

• In transit and satellite metastases

common manifestations of

intralymphatic metastasis

• associated with poor prognosis

Page 75: Controversies in Melanoma

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Satellites vs. In-transit metastases

prognosis of patient with satellites is usually worse than that of patient with in-transit or nodal metastasis (stage III)

Buzaid J Clin Oncol 1997

Haffner Br J Cancer 1992

Cascinelli J Surg Oncol 1986

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Satellites vs. In-transit metastases

• Satellites =

• pT4b (1997) N2c / N3 (2002)

• Stage II stage III

Page 77: Controversies in Melanoma

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Lymph node size vs. number-Prognostic value

Size not a significant prognostic

factor even after stratification

according to cutoff size

Drepper Cancer 1993

Buzaid J Clin Oncol 1995

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Lymph node size vs. number-Prognostic value

Number of LN most consistent prognostic factor by multivariate analysis

Buzaid J Clin Oncol 1997

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Author Pt No OS %

Survival % by LN no

1 2-4 5 or ↑Buzaid 95 442 42 55 34 25Drepper

93112 39 47 31 20

Singletary

92264 NS 45 31

Balch 92 234 NS 40 28 18Coit 91 449 32 40 40 19

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Lymph node number-Prognostic value

• number of positive nodes has replaced size of lymph node mass

Current 2002 AJCC staging system.

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Lymph node number-Prognostic value

N1 = 1 LN

N2 = 2 or 3 LNs

N3 = 4 LNs

AJCC 2002 staging

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Prognostic Value of Biochemical & serologic markers

Significant prognostic factor in melanoma

• LDH

• S-100-B

• melanoma inhibitory activity serum markers

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Prognostic Value of Biochemical & serologic markers

After logistic regression analysis,

LDH is found to be the only

statistically significant marker

for progressive disease and the

most relevant overall parameter

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Prognostic Value of Biochemical & serologic markers

• AJCC staging 2002 includes LDH

• Distant metastases + elevated serum LDH = M1c category

• Two or more reports = > 24 hrs apart.

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Prognostic Markers-1

• Micro stage• Breslow 1,2,4• Clark levels• Ulceration• Mitotic figures• Inflammatory

regression• Micro satellites

• Vertical growth fraction

• Tumor infiltrating lymphocytes

• Molecular markers

• Micro staging approaches

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Prognostic Markers-2

• S phase fraction• Mitotic index• Ulceration

• RT-PCR +• Tyrosinase or• MelanA or• MART1 m rna

• Integrins: β3 subunit of vitronectin-receptor for Vertical growth phase

• Β1integrin for LN mets

Page 87: Controversies in Melanoma

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Prognostic Markers-3

• MMP-2 ↑=☼• VEGF ↑=☼• Mitf=

Microphtalmia transcription factor ↑=☺

• CD 40 + =☼

• CD 40 L+ CD 40 = worse prognosis

Page 88: Controversies in Melanoma

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Prognostic Markers-4

• Mutation in Codon 12 or 61 of N-ras = ☼ = ↓ OS

• Mutation in Codon 18 of N-ras exon 1 = ☺

(No mets)

• Transcription factor = Activator Protein-2=AP-2

• Regulates gene in cell cycle and growth control

• ↓ AP-2= ↓ p21=

↓ RFS & ↓OS

Page 89: Controversies in Melanoma

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MM : prognostic factors

• Depth of invasion (BRESLOW)

• Ulceration

• High mitotic rate

• Anatomic location

• Histologic type

• Lymphoid & dendritic cell infiltration

• regression

Page 90: Controversies in Melanoma

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Depth of invasion in mm: Breslow

I 1

II 1-2

III 2-4

IV >4

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Depth of invasion : Clark

• I : superficial to basement membrane

• II : papillary dermis

• III : papillary/reticular dermis junction

• IV : reticular dermis

• V : subcutaneous fat

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Controversies in Melanoma

• Biology• Detection-Computer, USG, RT-PCR• Staging- AJCC 2000 +Prognosis• SLN Biopsy + ELND• Surgical margins• Adjuvant treatment + Vaccines• Summary

Page 93: Controversies in Melanoma

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Elective LN dissection

Persistent area of controversy

Micro metastases in Clinically N-

= 14% -20%

Page 94: Controversies in Melanoma

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Arguments for Elective LN dissection

retrospective + prospective studies

GoldsmithMemorial hospital1552 patients5 yr survival 78% vs. 68%

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Melanoma Inter-group Trial 1996

• 700 patients

• Prospective study

• Significantly improved survival rates with ELND in a subgroup = <60 years, non-ulcerated 1-4 mm

Balch : Ann Surg 1996

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Balch Cancer 1979

At 5 Year Distant Metastases

Survival

ELND 15% 83%

TLND 78% 37%

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Survival advantage ?

Positive nodes after ELND 16%

Slingluff Ann Surg 1994

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Elective LN dissection: no benefit

WHO 1998 Prospective

Intergroup Melanoma 1996

Prospective

Mayo Clinic, 1986 Prospective

WHO, 1977 Prospective

Sydney melanoma, 1995 Retrospective

Duke university, 1994 Retrospective

University of Pennsylvania,1985

Retrospective

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Elective LN dissection: benefitRomple, 1995 Retrospective

Drepper, 1993 Retrospective

Sydney melanoma unit, 1985

Retrospective

Duke university, 1983

Retrospective

University of Alabama, 1982

Retrospective

Memorial, 1975 Retrospective

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ELND

or

Sentinel LN biopsy ?

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Sentinel Lymph Node Biopsy

Sensible approach

In view of low occult metastasis - 12-15% ; It allows upto 85% of patients with melanoma to be spared a formal lymph node dissection, thus avoiding complication associated with that procedure

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SLN biopsy

• 100% sensitive

• 97% specific

Pu Plast Reconstruct Surg 1999

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• No decrease in survival compared with patients undergoing ELND

• Therapeutically equivalent but prognostically more accurate than ELND

Essner Ann Surg Oncol 1999

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SLN Indications:

• 5-10% risk of mets to Node

• Candidate for High dose interferon alfa-2b

• Melanoma < 1mm thickness but Clarke level III or ↑ (10% risk of recurrence)

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• Primary tumors between 1mm

and 4mm thickness

• up to 45% incidence of occult

nodal metastases

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SLN: Contraindication-1

1. < 1 mm thickness melanoma

(< 2% N or M)

2. > 4mm thickness melanoma,

Clinically N-

(as 60-70% N & occult M 70%)

Page 107: Controversies in Melanoma

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SLN: Contraindication-2

• FNAC + LN

• Prior wide excision of primary

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SLN Micromets: Significance

Gershenwald 1999 J Clin Oncol

+SLN= 23% rec rate; 16% death rate

- SLN=9% recurrence rate, 35% death

Clary 2001, Ann Surg 233:250-258

+SLN=40% recurrence, 58%DFS@3y

-SLN=14% recurrence, 75%DFS@3y

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SLN Micromets: Significance

Short term DFS ↑ : HE-, IH-, RT PCR+

Short term DFS ↓ : HE-, IH-, RT PCR+

Page 110: Controversies in Melanoma

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SLN

Method Success in %

Blue dye 70-82

Isotope 84-94

Both 96-98

False +

in %

False-

in %

0,5, 27

Page 111: Controversies in Melanoma

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Blue dye for SLN

• Patent blue V & Isosulfan blue

• Anaphylaxis in 3 / 406 cases

• Incidence with Isosulfan blue =1%

• Prepared for anaphylaxis treatment

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Blue dye for SLN

• 2-5 ml of 1% Isosulfan blue into the dermis (not sub cut) around the intact tumor + Exercise+ 5-15 minutes wait

• Clears from SLN within 45 minutes

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Isotope

• Tc 99m labeled sulfur colloid• 100 μm filtered Tc 99m labeled sulfur

colloid- even better• 99m Tc DTPA mannosyl-dextran →

affinity for lymph node; avoid distal lymph node imaging

• 3 hours prior injection, intradermally around the tumor

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Isotope

• Allows dissection down to the LN without need to create flaps

• Keep hand held array at an angle= avoid “Shine Through”

• If ↑ 3:1 resection bed : background ratio = search more SLN

Page 115: Controversies in Melanoma

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SLN

• H/E stain

• Immunohistochemistry to S-100 protein, HMB-45 antigen,

• RT-PCR Tyrosinase, Mel A

• 14% are HE – and + by IH

• 20-30% are HE-, IH- but RT-PCR+

• Cell culture technique

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Controversies in Melanoma

• Biology• Detection-Computer, USG, RT-PCR• Staging- AJCC 2000 +Prognosis• SLN Biopsy + ELND• Surgical margins• Adjuvant treatment + Vaccines• Summary

Page 117: Controversies in Melanoma

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• In situ 5 mm

• <2mm 1cm

• >2mm 2cmSober AJ : J Am Acad Dermatol 2001

Current recommendations for surgical margins: primary

cutaneous melanoma : thickness based decision

Page 118: Controversies in Melanoma

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Diameter, Location & Surgical Margins : Zitelli 1997

Location

Head & Neck, Hand

Trunk & Extremity

Size in cm ↓

Margin in cm ↓ Margin in cm ↓

< 2 1.5 1

>2 2.5 1.5

Page 119: Controversies in Melanoma

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Surgical margins

No significant difference in survival for excision margin 2 cm or 4 cm for tumor between 1mm and 4mm

Balch Ann Surg 1993

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Tumor thickness =1-2 mm

Margin 1cm or 3cm

OS same

Margin: WHO Melanoma group

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No significant difference in survival for margins 2 or 5 cm for tumors between 0.6 mm to 2mm

Swedish melanoma group.

Cancer 1998

Margin 2 or 5 cm

Page 122: Controversies in Melanoma

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Mohs Micrographically controlled Surgery

• In situ fixation- earlier by ZnO

• Now micrography-sectioned and inked and oriented=mapped

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Controversies in Melanoma

• Biology• Detection-Computer, USG, RT-PCR• Staging- AJCC 2000 +Prognosis• SLN Biopsy + ELND• Surgical margins• Adjuvant treatment + Vaccines• Summary

Page 124: Controversies in Melanoma

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No Role of prophylactic

(adjuvant)

Isolated Limb Perfusion

Page 125: Controversies in Melanoma

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EORTC

WHO

North American Perfusion Group

No improvement in survival

Isolated Limb Perfusion

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Therapeutic isolated limb perfusion

• Better DFS

• No significant change in OS

Hafstrom J Clin Oncol 1991

Page 127: Controversies in Melanoma

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Who are candidates for ILP?

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Therapeutic

Patients with in transit disease confined to a limb, with no

signs of distant metastases at presentation.

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Drugs for ILP

• DTIC + Others

• Melphalan +others

• TNF ά

• Interferon

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Palliative

Bulky regional disease with limited systemic metastases

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• identified by prognostic factors or

• identified by sentinel lymph node biopsy.

Clark : J Natl Cancer Inst 1989

Adjuvant Indications:↑risk for metastatic disease

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High risk melanoma: Interferon

• Thickness >4mm• Mitotic index• Location• Gender• Ulceration• +SLN• AP-2 index

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Interferon 2b

• √ US FDA for high risk melanoma

• ↓Recurrence

• Interferon alpha2b ▲DFS , ▲ OS by EOCG HDI 1684, EOCG1690 and French LDI Grob 2000- in selected cases

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• high dose interferon alpha 2b

• tamoxifen,

• cisplatin, and

• Vindesine

• GM CSF

• Levamisole.

Adjuvant ?

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• TNF• Interleukin-2• Biochemotherapy• Cytokines• Ab3• Peptide based vaccines• MAGE tumor specific shared ag

Adjuvant ?

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What are New Options

• Biochemotherapy

• DTIC or temozolomide+Nitrosureas

• Interferon = antiproliferative and immunomodulatory

• Interleukin-2 =Immunostimulatory cytokine ►NK cells

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Vaccines

• Vaccines-ganglioside GM2• MAGE Tumor specific antigens• Ab3 a cytokine• Antibody based vaccines• HLA based• Cell based vaccines• Peptide vaccines• Recombinant viruses

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Controversies in Melanoma

• Biology• Detection-Computer, USG, RT-PCR• Staging- AJCC 2000 +Prognosis• SLN Biopsy + ELND• Treatment margins• Adjuvant treatment + Vaccines• Summary

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Major changes in AJCC classification in 2002 -1

• √ Thickness

• X not levels

• √ Ulceration

• √ Number of LN

• X size of LN

• √ LDH

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Major changes in AJCC classification in 2002-2

• √ Upstaging with ulceration

• √ Merge micro satellite & in-transit mets into stage III

• √ Include SLN into staging

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Major changes

• Ultrasound of LN

• RT-PCR Tyrosinase of SLN

• 1→ 106–109

• Detect 1 cancer cell out of 106 – 109

normal cells

• Thin margins

• Adjuvant interferon +/-

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• In situ 5 mm

• <2mm 1cm

• >2mm 2cmSober AJ : J Am Acad Dermatol 2001

Current recommendations for surgical margins: primary

cutaneous melanoma

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Summary

• No role of wide margins

• No role of ELND

• No role of Prophylactic ILP

• Role of SLN

• Interferon alpha2b ▲DFS , ▲ OS

→ EOCG HDI 1684, EOCG1690

& French LDI Grob 2000- in selected cases

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Summary Rx

• Primary surgical

• Surgical principles

Complete surgical excision

Minimum margin 1.0 cm

Maximum margin 2.0 cm

Do not excise beyond deep fascia

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MM :– management of lymph nodes

• Biopsy : FNAC preferred

• Elective dissection : for

1. Clinically involved nodes,

2. Satellitosis,

3. Lymphatic invasion

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Sentinel lymph node biopsy

• Detects micrometastasis in lymph nodes

• Inrtadermal injection of radioactive colloid around lesion

• Lymph node identified by gamma probe

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Sentinel lymph node biopsy

• Intraoperative identification by using patent blue dye

• Identify patients appropriate for elective dissection

• Identify patients among high risk for adjuvant interferon.

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Thank You