Newly Diagnosed with MelanomaNow What

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• Newly Diagnosed with MelanomaNow What?
• Bret Taback, MD
• Division of Surgical Oncology
• Columbia University Medical Center
• May 10, 2008

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Obtain a Second Opinion

• Ask your
• Internist
• Family members
• Friends
• Colleagues
• Others who may have had melanoma
• Search online

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What to do Before Visiting the Doctors Office

• Make a list of questions before you arrive none
  are foolish
• Bring all records, i.e. path reports and slides,
  any x-ray films/disks and reports, (prior
  surgical records especially operative reports)
• Come with a friend, family member, colleague
  and/or physician
• Bring a pencil and paper take notes (record if
  necessary)
• Ask for their business and call them if you have
  future questions or concerns

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• How did we get here?

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First Description of Melanoma

• 1787
• John Hunter first published account of patient
  with melanoma (recurrence) removal of tumor
  behind the jaw, cancerous fungous excrescence
• 1806
• Laennec first to describe melanoma as a disease
  entity before the Faculty of Medicine in Paris as
  la melanose melanosis

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Historical Aspects

• 1892
• Herbert Snow (1847-1930) Royal Marsden Hospital
• He rejects treatment of the primary tumor
  with irritants i.e. ligature or silver
  nitrate/caustics.
• He recognizes death is due to metastasis
  which he states first involves the nearest lymph
  glands and radical removal of such organs is
  indicated before enlargement takes place ELND

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Handley Presents to The Royal College of Surgeons

• 1907
• William Sampson Handley (1872-1962)
• Senior Surgeon Middlesex Hospital gives two
  Hunterian Lectures to the Royal College of
  Surgeons (Feb 25 and Feb 27)
• The first lecture was pathology of melanoma
• It was based on a single autopsy study - 34 y.o.
  female with advanced metastasis
• Suggested melanoma spread centrifugally through
  the lymphatics first and then through the blood
  (similar to breast cancer)

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• And thus radical primary tumor excision with
  ELND survived for over half a century until the
  1960s

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Primary Tumor

• Wallace H. Clark, Jr.
• 1969 defined anatomic levels of invasion
• Radial and vertical growth phase
• Alexander Breslow
• 1969 recognized tumor thickness as an important
  prognostic factor
• 1975 correlated thickness with survival
• Breslow Thickness (millimeters) 5-Year
  Survival ()
• less than 0.76 97
• 0.76-1.50 92
• 1.51-2.50 762.51-4.0 624.1-8.0 52
• gt 8.0 32

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Melanoma Diagnosis
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Biopsy -gt Diagnosis

• Punch
• Incision
• Excision
• Shave
• Goals
• Make a diagnosis
• Rule out lesions with potentially similar
  features
• Determine depth and level of invasion, ulceration

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Surgical Treatment of Primary Melanoma
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• Surgical Margins

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Prognostic Factors for Primary MelanomaClinically
or Pathologically Staged Patients
Variable P Risk Ratio 95 CI Thickness lt.0000
1 1.558 1.473-1.647 Ulceration lt.00001 1.901 1.73
5-2.083 Age lt.00001 1.101 1.071-1.132 Site lt.000
01 1.338 1.224-1.463 Level of invasion
lt.00001 1.214 1.136-1.297 Sex .001 0.836 0.764-
0.915
J Clin Oncol. 2001193622-3634.
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Wide Excision Prospective Randomized Trials
Surgical Trial
n
Tumor Thickness
Arms
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Surgical Excision for Localized Cutaneous
MelanomaRecommended Margins
Melanoma Thickness
Margin
Melanoma in situ lt1 mm 14 mm gt4 mm
5 mm 1 cm 2 cm gt2 cm
NCCN Practice Guidelines Melanoma.
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Treatment of Primary Lesion Avoid Local
Recurrence
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US Intergroup Trial Results Surgical Margin

• n740 (486 randomized)
• Melanoma 1-4 mm
• 2 cm vs. 4 cm margin
• Median follow up gt10 years
• No difference in local recurrence
• 2.6 (4 cm) vs. 2.1 (2 cm)
• Skin grafts rates
• 46 (4 cm) vs. 11 (2 cm)
• Survival rates
• 77 (4 cm) vs 70 (2 cm) gt PNS
• Risk of LR based on primary tumor not margin

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Margins Matter
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Prognostic Factors for Primary Melanoma Patients
Staged after Node Dissection
Variable P Risk Ratio 95 CI Nodal status
lt.00001 2.239 1.913-2.621 Thickness lt.00001
1.583 1.433-1.749 Ulceration
lt.00001 1.938 1.674-2.242 Site
lt.00001 1.483 1.281-1.716 Age
.0002 1.095 1.044-1.147 Sex .1705
0.900 0.774-1.046 Level of invasion .9082 1.007
0.896-1.131
J Clin Oncol. 2001193622-3634.
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• Lymph node status is the single most important
  prognostic factor in patients diagnosed with
  melanoma

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• Elective Lymph Node Dissection

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Elective Lymph Node Dissection (ELND)
Prospective Randomized Trials
Surgical Trial
n
Criteria Survival
Issues
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Disadvantage of Routine ELND

• 80 of patients do not have lymph node metastasis
  at the time of melanoma diagnosis
• No survival advantage
• Complete lymphadenectomy is associated with
  considerable morbidity1

Complication No () Lymphedema 32
(29) Seroma 11 (13) Wound Flap
Prob 7 (6) Hematoma 1 (1)
1Sim et al Cancer 1978, 41948-956-630
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• Sentinel Lymph Node Biopsy

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Sentinel Lymph Node (SLN)Mapping and Biopsy

• Lymphatic metastases from tumor spread first
  through afferent channels
• Lymph node spread occurs in an orderly
  progression
• SLN is first node along those channels

Ann Surg. 1999230453465.
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Sentinel Lymph Node Studies
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Prognostic Implications of SLN Status on
Disease-Specific Survival
Disease-Specific Survival
Prognostic Factor
HR
95 CI
P value

• 6.53 3.39 12.58 lt.00001
• 1.23 1.10 1.38 .0004
• 2.32 1.03 5.23 .04
• 1.62 0.85 3.08 .14
• 1.72 0.85 3.45 .13
• 1.01 0.98 1.01 .57
• 1.11 0.45 1.82 .78

SLN status Tumor thickness Clark level
gtIII Ulceration Axial location Age Sex
HR Hazard ratio CI Confidence interval
J Clin Oncol. 199917976983.
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MSLT Results

• Randomized trial WLE SLNB (w/ LND if ) vs.
  WLE Observation
• Inclusion Intermediate Thickness (1.2-3.5 mm),
  no clinical LAD
• Accrual 1994-2002, 1269 patients, analysis w/
  median 60 mo follow-up
• LN evaluated by HE and IHC for S100, HMB45,
  (later MART-1 or Melan-A)
• 16 SLN
• False negative rate (recurrence in same bed)
  5-10, decreased w/ center volume and surgeon
  experience

Morton et al 2006 3351307-1317
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Disease-free Survival and Melanoma-Specific
Survival, According to the Type of Treatment and
the Tumor Status of the Sentinel Node
Morton D et al. N Engl J Med 20063551307-1317
Morton et al 2006 3351307-1317
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Baseline Characteristics of MSLT Patients
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Rationale for Lymphadenectomy

• Improve regional disease control
• Enhance accuracy of staging
• Improve odds of survival ?

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Surgical Management of Clinical Stage I and II
Melanoma
SLN identified
Evaluate by hematoxylin/eosin
immunohistochemistry, stepped sections
Node negative
Node positive
Observation
En bloc dissection
Adjuvant therapy
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Follow-up Staging Studies

• CXR
• CBC/Chem/LFTs (LDH)
• Stage III/IV
• CT scan chest/abdomen/pelvis (oral and IV
  contrast)
• PET scan
• MRI brain

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Summary

• Prevention
• Avoid sun burning, protective clothing, sun block
• Detection
• Skin checks, Dermatology exam, Mole mapping
• Surgical treatment
• Biopsy -gt Melanoma Center appropriate surgery
  (WLE, LM, SLNB, CLND)
• Adjuvant therapy (stage III)
• Interferon
• Therapy for stage IV
• IL-2, Chemotherapy, Biochemotherapy, Surgery,
• Clinical trials
• Peptides
• Protein
• DNA/RNA
• Ganglioside
• Lysate
• Shed antigen
• Whole cells IFA
• Dendritic Cells