Melanoma
Content
Melanoma
Melvin D. Schursky MD Morristown Memorial Hospital April 28, 2006
Melanoma
• Demographics • Diagnosis & Staging • Treatment • Adjuvant Therapy • Distant Metastasis
Facts
•
• • • •
Cutaneous Neoplasms as a whole are the most commonly diagnosed malignant tumors in the US ~1.4 million new cases annually 1/5 Americans born in 2004 will be diagnosed with skin cancer in the US MC Skin cancer types are Basal and SCC Melanoma accounts for 4% of skin cancer diagnoses but 75% of skin cancer deaths.
Incidence Rates: US, 1975-2000
Incidence (per 100,000)
30 25 20 15 10 5 0 1975 1980 1985 1990 1995 2000
Ries LAG, et al, eds. SEER Cancer Statistics Review, 1975–2000. Bethesda, MD: National Cancer Institute; 2003: Tables XVI-1–9.
White Men All Men Overall Women
• •
Incidence rate has more than tripled from 1980 to 2000 From 2003 to 2004 there was a 4% increase as well
Trends in Cancer Incidence:1950-2000 (whites) Trends in Cancer Incidence:1950-2000 (whites)
Melanoma Liver Lung Multiple Myeloma Prostate NHL Thyroid Kidney Testis CNS Bladder Breast All Sites Larynx Pancreas Leukemia Hodgkin's Disease Colorectal Uterus Esophagus Ovary -31.2
-74.3 -77.6
Oral Stomach Cervix
43 36.5 31.5 21 20.4 18.5 16 15.7
96.9 90.6 88.7
295 294.3 291.6 282.9 252 240.8 196.1 167.6 159.7
619.1
-100
0
100
200
300
400
500
600
700
SEER Data, 1950–2000, Table I–3
% Change
Melanoma Impact: 2004
•
Increasing risk
• • • US: from 1:1,500 (1935) to 1:74 (today) Crosses race and gender lines Highest in white men
• •
High number of productive years lost Most patients diagnosed early Relative survival on the rise
• More than breast, lung, and colorectal cancer • More distant disease at diagnosis among Black population • Early diagnosis, therapy have impact • Recent decrease in Black population
•
Etiology and Risk Factors
• Familial • History of malignant melanoma • Skin type and color (fair complexion) • CDKNRA/p16/MC1R mutation (only found in 0.2%) • Environmental • UV light exposure ∀ ≥ 3 blistering sunburns before age 20 • Outdoor summer jobs for ≥ 3 years in adolescent years • Use of sunlamps, tanning beds
Etiology and Risk Factors
•
Other • Inability to tan • Blue or green eyes • Blond or Red hair • History of Actinic keratosis, elastosis • Marked freckling on upper back • Large number of normal nevi • Atypical dysplastic nevi, congenital giant nevi • More than 100 normal nevi • Immunosuppression • Populations residing closer to equator have higher incidence • Xeroderma Pigmentosa
Question
•
What are the ABCDEs of Melanoma Diagnoses?
The ABCDEs of Melanoma Diagnosis
The ABCDEs of Melanoma Diagnosis
Asymmetry
One half of the lesion is shaped differently than the other
The ABCDEs of Melanoma Diagnosis
Asymmetry
One half of the lesion is shaped differently than the other
Border
The border of the lesion is irregular, blurred, or ragged
The ABCDEs of Melanoma Diagnosis
Asymmetry
One half of the lesion is shaped differently than the other
Border Color
The border of the lesion is irregular, blurred, or ragged
Inconsistent pigmentation, with varying shades of brown and black
The ABCDEs of Melanoma Diagnosis
Asymmetry
One half of the lesion is shaped differently than the other
Border Color
The border of the lesion is irregular, blurred, or ragged
Inconsistent pigmentation, with varying shades of brown and black
Diameter
>6 mm, or a progressive change in size
The ABCDEs of Melanoma Diagnosis
Asymmetry
One half of the lesion is shaped differently than the other
Border Color Evolution
The border of the lesion is irregular, blurred, or ragged
Inconsistent pigmentation, with varying shades of brown and black
Diameter
>6 mm, or a progressive change in size
History of change in the lesion
Question
•
Which of the following growth patterns of melanoma is associated with the highest mortality rate?
1. 2. 3. 4. 5. Superficial spreading Lentigo Maligna Acral Lentiginous Nodular Juvenile
Question
•
Which of the following growth patterns of melanoma is associated with the highest mortality rate?
1. 2. 3. 4. 5. Superficial spreading Lentigo Maligna Acral Lentiginous Nodular Juvenile
Explanation
•
Nodular melanomas are on average thicker than other growth patterns of melanoma; therefore, they have the highest mortality rate. Growth pattern is not an independent prognostic factor when the tumor thickness and ulceration are taken into account
Question
•
What are the Morphologic Types of Melanoma?
Morphologic Types of Melanoma
Type
Superficial spreading
Frequency
Features
60%-70% Flat during early phase; notching, scalloping, areas of regression Darker and thicker than superficial blue-black or blue-red (5% amelanotic) Enlarge slowly; usually large, flat, tan
Nodular 15%-30% spreading, rapid onset; commonly Lentigo maligna Acral lentiginous Blacks (70%) ~5% or brown
Uncommon On soles, palms, beneath nail beds; Asians (46%), usually large, tan or brown; irregular border; subungual melanoma Rare, locally aggressive, occur
Desmoplastic 1.7% primarily on head and neck in elderly
Biopsy
• •
Histologic confirmation and microstaging Excisional (preferred)
• Small lesions (<1.5 cm)
•
Incisional
• Large lesions (>1.5 cm)
• •
Punch Biopsy an Acceptable Alternative Shave biopsy discouraged (WHY?)
Diagnostic Biopsy in Primary Melanoma
• •
Try to perform a narrow excisional biopsy (1-2 mm) Goals • Rule out lesions with potentially similar features • seborrheic keratosis, pigmented basal cell cancer, solar lentigines, atypical nevi • Determine depth and level of invasion • Identify prognostic features of the 1º lesion
Question
•
Which of the following characteristics of melanoma is not included in staging information?
1. 2. 3. 4. 5. Ulceration Tumor size Tumor thickness Lymph node metastases Distant metastases
Question
•
Which of the following characteristics of melanoma is not included in staging information?
1. 2. 3. 4. 5. Ulceration Tumor size Tumor thickness Lymph node metastases Distant metastases
Explanation
•
The 2002 melanoma staging system is a major advance in the accuracy of melanoma patient staging. Tumor size (diameter of the lesion on the skin) has not been found to be related to prognosis. Tumor thickness, ulceration, lymph node metastases, and distant metastases are all important factors in determining outcome.
Question
•
What is the single variable that most accurately determines therapy and prognosis?
Breslow Level
Thickness 0-0.75 mm 0.75-1.49 mm 1.50-3.00 mm 3.01-4.00 mm > 4 mm Description Thin Intermediate Intermediate Intermediate Thick T Stage (T1) (T2) (T3a) (T3b) (T4)
Clark’s Level
Level I Tis II III IV V
Description Confined to epidermis Into papillary dermis Abuts the reticular dermis Into reticular dermis Into subcutaneous tissue
T Stage T1 T2 T3 T4
Question
•
In a patient with a 0.6 mm thick melanoma arising on the neck, the recommended treatment is wide local excision with a:
1. 2. 3. 4. 0.5 cm margin 1.0 cm margin 1.0 cm margin and sentinel lymph node biopsy 2.0 cm margin and sentinel lymph node biopsy
Question
•
In a patient with a 0.6 mm thick melanoma arising on the neck, the recommended treatment is wide local excision with a:
1. 2. 3. 4. 0.5 cm margin 1.0 cm margin 1.0 cm margin and sentinel lymph node biopsy 2.0 cm margin and sentinel lymph node biopsy
Explanation
•
The guidelines for wide local excision of melanoma are based on a series of randomized trials that show that there is no decrease in survival when margins are reduced. T1 melanomas can be safely excised with a 1 cm margin of surrounding normal skin. SLN biopsy is not performed for T1 tumors because the incidence of occult nodal metastases is less than 1%.
Surgical Excision for Localized Cutaneous Melanoma
Melanoma Thickness
≤ 1 mm 1.01–2.00 mm 2.01–4.00 mm >4 mm
Margin
1 cm 1–2 cm† 2 cm 2 cm
The Reconstructive Ladder
Complex Distant Flap Skin Graft Local Flap Direct Closure Simple
Question
•
Sentinel lymph node biopsy for melanoma:
1. 2. 3. 4. Improves the accuracy of staging Prolongs survival for node-positive patients Should be performed for all T1 patients Should be followed by adjuvant chemotherapy 5. Reduces the incidence of in-transit metastases
Question
•
Sentinel lymph node biopsy for melanoma:
1. 2. 3. 4. Improves the accuracy of staging Prolongs survival for node-positive patients Should be performed for all T1 patients Should be followed by adjuvant chemotherapy 5. Reduces the incidence of in-transit metastases
Explanation
•
Sentinel lymph node (SLN) biopsy improves the accuracy of staging by detecting occult nodal metastasis. These variables are included in the 2002 AJCC staging system. It is not yet known whether early detection of nodal metastases will result in improved survival. Patients with T1 melanoma (<1.0 mm thickness) are not candidates for SLN biopsy unless there is ulceration of the primary tumor. Adjuvant chemotherapy is an option for stage III patients but has not been proven to be of benefit. SLN biopsy does not affect the incidence of in-transit metastases.
Sentinel Lymph Node (SLN) Mapping and Biopsy
•
• •
Lymphatic metastases from tumor spread first through afferent channels SLN is first node along those channels SLNs are immunosuppressed and proven to be sites of early metastases
Question
•
A patient with a 1.8 mm thick melanoma arising on the mid upper back undergoes lymphatic mapping. The lymphoscintigram shows radionuclide uptake first in the left axilla and 10 minutes later in the right axilla. Which of the following is recommended in the management of this patient? 1. Cancel the sentinel node biopsy procedure and observe at 6-month intervals 2. Repeat the study to see if the left side always appears first 3. First identify and biopsy the left sentinel node, perform a frozen section, and biopsy the right side only if the left side is positive 4. Identify and biopsy the sentinel nodes in both axillae. 5. Perform bilateral axillary lymph node dissections.
Question
•
A patient with a 1.8 mm thick melanoma arising on the mid upper back undergoes lymphatic mapping. The lymphoscintigram shows radionuclide uptake first in the left axilla and 10 minutes later in the right axilla. Which of the following is recommended in the management of this patient? 1. Cancel the sentinel node biopsy procedure and observe at 6-month intervals 2. Repeat the study to see if the left side always appears first 3. First identify and biopsy the left sentinel node, perform a frozen section, and biopsy the right side only if the left side is positive 4. Identify and biopsy the sentinel nodes in both axillae. 5. Perform bilateral axillary lymph node dissections.
Explanation
•
Lymphatic mapping defines the lymphatic basin(s) receiving lymph flow from the primary tumor site. If the study shows flow to more than one basin, the sentinel nodes in each basin are potential sites for occult nodal metastases and should therefore be excised and analyzed.
Techniques in SLN Mapping and Biopsy
•
Preoperative injection of radiocolloid + intraoperative blue dye improves accuracy of lymphatic mapping
• Identification of SLN occurs both by sight and with a handheld gamma probe • Lymphatic drainage does not always match classic anatomical patterns
•
Excision of primary lesion
• Should be performed at the time of SLN biopsy • Recent studies have shown no significant decrement in ability to identify SLN when mapping and biopsy are performed after wide excision
Potential Candidates for SLN Biopsy
•
• • •
•
Risk of nodal metastasis varies with tumor thickness • <5% for tumors ≤ 1 mm w/o ulceration, other adverse factors • 20% for tumors 1–4 mm • 35% for tumors ≥ 4 mm SLN biopsy should be discussed with all patients with invasive melanoma Patients with primary melanomas ≥ 1 mm are appropriate candidates for SLN biopsy Some patients with thinner primary melanomas may also be appropriate candidates for SLN biopsy • Ulceration, Clark level IV invasion, truncal location, and mitoses should be considered Evaluate each patient individually
Prognostic Factors for Primary Melanoma
Variable
Thickness Ulceration Age Site Level of invasion Sex
P Risk Ratio95% CI
<.000011.558 <.000011.901 <.000011.101 <.000011.338 <.000011.214 .001 0.836 1.473-1.647 1.735-2.083 1.071-1.132 1.224-1.463 1.136-1.297 0.764-0.915
J Clin Oncol. 2001;19:3622-3634.
Adjuvant IFN-α 2b in High-Risk Melanoma: Efficacy Summary
•
• •
High Dose Interferon Therapy • Only FDA-approved adjuvant therapy for high-risk melanoma • Significantly prolongs relapse-free survival (RFS) • 26% reduction in risk (P2= 0.00009) • Overall survival (OS) improved in 2 randomized trials • 15% reduction (P2 = 0.06) Low-dose therapy is less effective Ongoing studies • Modified dosing regimens • Intermediate and high-risk melanoma • Define mechanism of action
Oncology. 2002;16:1177-1187. Ann Surg Oncol. 2001:8(9 Suppl):38s-40s. J Clin Oncol.1996;14:7-17. J Clin Oncol. 2000;18:2444-2458. J Clin Oncol. 2001;19:2370-2380. Ann Surg Oncol. 2001;8:41S-43S. Canc Treat Rev. 2003;29:241-252.
Question
•
A 40 year old woman develops a solitary right upper lobe pulmonary metastasis 4 years after resection of a primary melanoma on her back. Which of the following treatments is associated with the highest disease-free survival rate?
1. 2. 3. 4. 5. Dacarbazine (DTIC) Biochemotherapy Pulmonary resection Radiation therapy Interferon – alpha 2b
Question
•
A 40 year old woman develops a solitary right upper lobe pulmonary metastasis 4 years after resection of a primary melanoma on her back. Which of the following treatments is associated with the highest disease-free survival rate?
1. 2. 3. 4. 5. Dacarbazine (DTIC) Biochemotherapy Pulmonary resection Radiation therapy Interferon – alpha 2b
Explanation
•
In most cases, metastatic melanoma appears simultaneously at multiple sites. In these instances, systemic therapy is given. When an isolated metastasis appears at an extirpatable site, resection is recommended. Several reports have shown that there is a 10% to 15% long-term disease-free survival rate associated with metastasectomy. Some recent reports have shown this to be true for the resection of multiple simultaneous visceral metastases in highly selected patients.
Metastatic Disease
• •
•
•
All Stage III disease need full lymph node dissection 5 year survival rate for patients who undergo lymphadenectomy for clinically positive involved nodes ranges from 25% to 70% If the Sentinel lymph node is positive for melanoma, regional therapeutic lymphadenectomy is indicated based on potential survival and clinical benefit. Axillary node melanoma with no other primary – complete axillary node dissection
Metastatic Disease
• • • •
Resection of metastases has provided some patients with long disease-free interval and is the best chance for cure. Isolated metastases that can be resected with a low-risk procedure should probably undergo resection. Most common sites of recurrence are skin subcutaneous tissues, and distant lymph nodes, followed by visceral sites. Common visceral sites of metastasis, in order of decreasing occurrence, are lung, liver, brain, bone, and GI tract.
Survival of AJC Clinical stage I and II melanoma patients relative to tumor location
7.5 – Year Survival Rate (%)
Thickness (mm) Extremities Hands or Feet Head and Neck Trunk BANS
<0.85 0.85-1.69 1.7-3.64 >3.65
100 100 86 83
100 100 60 0
100 100 64 65
100 97 77 12
98 78 58 33
Melvin D. Schursky MD Morristown Memorial Hospital April 28, 2006
Melanoma
• Demographics • Diagnosis & Staging • Treatment • Adjuvant Therapy • Distant Metastasis
Facts
•
• • • •
Cutaneous Neoplasms as a whole are the most commonly diagnosed malignant tumors in the US ~1.4 million new cases annually 1/5 Americans born in 2004 will be diagnosed with skin cancer in the US MC Skin cancer types are Basal and SCC Melanoma accounts for 4% of skin cancer diagnoses but 75% of skin cancer deaths.
Incidence Rates: US, 1975-2000
Incidence (per 100,000)
30 25 20 15 10 5 0 1975 1980 1985 1990 1995 2000
Ries LAG, et al, eds. SEER Cancer Statistics Review, 1975–2000. Bethesda, MD: National Cancer Institute; 2003: Tables XVI-1–9.
White Men All Men Overall Women
• •
Incidence rate has more than tripled from 1980 to 2000 From 2003 to 2004 there was a 4% increase as well
Trends in Cancer Incidence:1950-2000 (whites) Trends in Cancer Incidence:1950-2000 (whites)
Melanoma Liver Lung Multiple Myeloma Prostate NHL Thyroid Kidney Testis CNS Bladder Breast All Sites Larynx Pancreas Leukemia Hodgkin's Disease Colorectal Uterus Esophagus Ovary -31.2
-74.3 -77.6
Oral Stomach Cervix
43 36.5 31.5 21 20.4 18.5 16 15.7
96.9 90.6 88.7
295 294.3 291.6 282.9 252 240.8 196.1 167.6 159.7
619.1
-100
0
100
200
300
400
500
600
700
SEER Data, 1950–2000, Table I–3
% Change
Melanoma Impact: 2004
•
Increasing risk
• • • US: from 1:1,500 (1935) to 1:74 (today) Crosses race and gender lines Highest in white men
• •
High number of productive years lost Most patients diagnosed early Relative survival on the rise
• More than breast, lung, and colorectal cancer • More distant disease at diagnosis among Black population • Early diagnosis, therapy have impact • Recent decrease in Black population
•
Etiology and Risk Factors
• Familial • History of malignant melanoma • Skin type and color (fair complexion) • CDKNRA/p16/MC1R mutation (only found in 0.2%) • Environmental • UV light exposure ∀ ≥ 3 blistering sunburns before age 20 • Outdoor summer jobs for ≥ 3 years in adolescent years • Use of sunlamps, tanning beds
Etiology and Risk Factors
•
Other • Inability to tan • Blue or green eyes • Blond or Red hair • History of Actinic keratosis, elastosis • Marked freckling on upper back • Large number of normal nevi • Atypical dysplastic nevi, congenital giant nevi • More than 100 normal nevi • Immunosuppression • Populations residing closer to equator have higher incidence • Xeroderma Pigmentosa
Question
•
What are the ABCDEs of Melanoma Diagnoses?
The ABCDEs of Melanoma Diagnosis
The ABCDEs of Melanoma Diagnosis
Asymmetry
One half of the lesion is shaped differently than the other
The ABCDEs of Melanoma Diagnosis
Asymmetry
One half of the lesion is shaped differently than the other
Border
The border of the lesion is irregular, blurred, or ragged
The ABCDEs of Melanoma Diagnosis
Asymmetry
One half of the lesion is shaped differently than the other
Border Color
The border of the lesion is irregular, blurred, or ragged
Inconsistent pigmentation, with varying shades of brown and black
The ABCDEs of Melanoma Diagnosis
Asymmetry
One half of the lesion is shaped differently than the other
Border Color
The border of the lesion is irregular, blurred, or ragged
Inconsistent pigmentation, with varying shades of brown and black
Diameter
>6 mm, or a progressive change in size
The ABCDEs of Melanoma Diagnosis
Asymmetry
One half of the lesion is shaped differently than the other
Border Color Evolution
The border of the lesion is irregular, blurred, or ragged
Inconsistent pigmentation, with varying shades of brown and black
Diameter
>6 mm, or a progressive change in size
History of change in the lesion
Question
•
Which of the following growth patterns of melanoma is associated with the highest mortality rate?
1. 2. 3. 4. 5. Superficial spreading Lentigo Maligna Acral Lentiginous Nodular Juvenile
Question
•
Which of the following growth patterns of melanoma is associated with the highest mortality rate?
1. 2. 3. 4. 5. Superficial spreading Lentigo Maligna Acral Lentiginous Nodular Juvenile
Explanation
•
Nodular melanomas are on average thicker than other growth patterns of melanoma; therefore, they have the highest mortality rate. Growth pattern is not an independent prognostic factor when the tumor thickness and ulceration are taken into account
Question
•
What are the Morphologic Types of Melanoma?
Morphologic Types of Melanoma
Type
Superficial spreading
Frequency
Features
60%-70% Flat during early phase; notching, scalloping, areas of regression Darker and thicker than superficial blue-black or blue-red (5% amelanotic) Enlarge slowly; usually large, flat, tan
Nodular 15%-30% spreading, rapid onset; commonly Lentigo maligna Acral lentiginous Blacks (70%) ~5% or brown
Uncommon On soles, palms, beneath nail beds; Asians (46%), usually large, tan or brown; irregular border; subungual melanoma Rare, locally aggressive, occur
Desmoplastic 1.7% primarily on head and neck in elderly
Biopsy
• •
Histologic confirmation and microstaging Excisional (preferred)
• Small lesions (<1.5 cm)
•
Incisional
• Large lesions (>1.5 cm)
• •
Punch Biopsy an Acceptable Alternative Shave biopsy discouraged (WHY?)
Diagnostic Biopsy in Primary Melanoma
• •
Try to perform a narrow excisional biopsy (1-2 mm) Goals • Rule out lesions with potentially similar features • seborrheic keratosis, pigmented basal cell cancer, solar lentigines, atypical nevi • Determine depth and level of invasion • Identify prognostic features of the 1º lesion
Question
•
Which of the following characteristics of melanoma is not included in staging information?
1. 2. 3. 4. 5. Ulceration Tumor size Tumor thickness Lymph node metastases Distant metastases
Question
•
Which of the following characteristics of melanoma is not included in staging information?
1. 2. 3. 4. 5. Ulceration Tumor size Tumor thickness Lymph node metastases Distant metastases
Explanation
•
The 2002 melanoma staging system is a major advance in the accuracy of melanoma patient staging. Tumor size (diameter of the lesion on the skin) has not been found to be related to prognosis. Tumor thickness, ulceration, lymph node metastases, and distant metastases are all important factors in determining outcome.
Question
•
What is the single variable that most accurately determines therapy and prognosis?
Breslow Level
Thickness 0-0.75 mm 0.75-1.49 mm 1.50-3.00 mm 3.01-4.00 mm > 4 mm Description Thin Intermediate Intermediate Intermediate Thick T Stage (T1) (T2) (T3a) (T3b) (T4)
Clark’s Level
Level I Tis II III IV V
Description Confined to epidermis Into papillary dermis Abuts the reticular dermis Into reticular dermis Into subcutaneous tissue
T Stage T1 T2 T3 T4
Question
•
In a patient with a 0.6 mm thick melanoma arising on the neck, the recommended treatment is wide local excision with a:
1. 2. 3. 4. 0.5 cm margin 1.0 cm margin 1.0 cm margin and sentinel lymph node biopsy 2.0 cm margin and sentinel lymph node biopsy
Question
•
In a patient with a 0.6 mm thick melanoma arising on the neck, the recommended treatment is wide local excision with a:
1. 2. 3. 4. 0.5 cm margin 1.0 cm margin 1.0 cm margin and sentinel lymph node biopsy 2.0 cm margin and sentinel lymph node biopsy
Explanation
•
The guidelines for wide local excision of melanoma are based on a series of randomized trials that show that there is no decrease in survival when margins are reduced. T1 melanomas can be safely excised with a 1 cm margin of surrounding normal skin. SLN biopsy is not performed for T1 tumors because the incidence of occult nodal metastases is less than 1%.
Surgical Excision for Localized Cutaneous Melanoma
Melanoma Thickness
≤ 1 mm 1.01–2.00 mm 2.01–4.00 mm >4 mm
Margin
1 cm 1–2 cm† 2 cm 2 cm
The Reconstructive Ladder
Complex Distant Flap Skin Graft Local Flap Direct Closure Simple
Question
•
Sentinel lymph node biopsy for melanoma:
1. 2. 3. 4. Improves the accuracy of staging Prolongs survival for node-positive patients Should be performed for all T1 patients Should be followed by adjuvant chemotherapy 5. Reduces the incidence of in-transit metastases
Question
•
Sentinel lymph node biopsy for melanoma:
1. 2. 3. 4. Improves the accuracy of staging Prolongs survival for node-positive patients Should be performed for all T1 patients Should be followed by adjuvant chemotherapy 5. Reduces the incidence of in-transit metastases
Explanation
•
Sentinel lymph node (SLN) biopsy improves the accuracy of staging by detecting occult nodal metastasis. These variables are included in the 2002 AJCC staging system. It is not yet known whether early detection of nodal metastases will result in improved survival. Patients with T1 melanoma (<1.0 mm thickness) are not candidates for SLN biopsy unless there is ulceration of the primary tumor. Adjuvant chemotherapy is an option for stage III patients but has not been proven to be of benefit. SLN biopsy does not affect the incidence of in-transit metastases.
Sentinel Lymph Node (SLN) Mapping and Biopsy
•
• •
Lymphatic metastases from tumor spread first through afferent channels SLN is first node along those channels SLNs are immunosuppressed and proven to be sites of early metastases
Question
•
A patient with a 1.8 mm thick melanoma arising on the mid upper back undergoes lymphatic mapping. The lymphoscintigram shows radionuclide uptake first in the left axilla and 10 minutes later in the right axilla. Which of the following is recommended in the management of this patient? 1. Cancel the sentinel node biopsy procedure and observe at 6-month intervals 2. Repeat the study to see if the left side always appears first 3. First identify and biopsy the left sentinel node, perform a frozen section, and biopsy the right side only if the left side is positive 4. Identify and biopsy the sentinel nodes in both axillae. 5. Perform bilateral axillary lymph node dissections.
Question
•
A patient with a 1.8 mm thick melanoma arising on the mid upper back undergoes lymphatic mapping. The lymphoscintigram shows radionuclide uptake first in the left axilla and 10 minutes later in the right axilla. Which of the following is recommended in the management of this patient? 1. Cancel the sentinel node biopsy procedure and observe at 6-month intervals 2. Repeat the study to see if the left side always appears first 3. First identify and biopsy the left sentinel node, perform a frozen section, and biopsy the right side only if the left side is positive 4. Identify and biopsy the sentinel nodes in both axillae. 5. Perform bilateral axillary lymph node dissections.
Explanation
•
Lymphatic mapping defines the lymphatic basin(s) receiving lymph flow from the primary tumor site. If the study shows flow to more than one basin, the sentinel nodes in each basin are potential sites for occult nodal metastases and should therefore be excised and analyzed.
Techniques in SLN Mapping and Biopsy
•
Preoperative injection of radiocolloid + intraoperative blue dye improves accuracy of lymphatic mapping
• Identification of SLN occurs both by sight and with a handheld gamma probe • Lymphatic drainage does not always match classic anatomical patterns
•
Excision of primary lesion
• Should be performed at the time of SLN biopsy • Recent studies have shown no significant decrement in ability to identify SLN when mapping and biopsy are performed after wide excision
Potential Candidates for SLN Biopsy
•
• • •
•
Risk of nodal metastasis varies with tumor thickness • <5% for tumors ≤ 1 mm w/o ulceration, other adverse factors • 20% for tumors 1–4 mm • 35% for tumors ≥ 4 mm SLN biopsy should be discussed with all patients with invasive melanoma Patients with primary melanomas ≥ 1 mm are appropriate candidates for SLN biopsy Some patients with thinner primary melanomas may also be appropriate candidates for SLN biopsy • Ulceration, Clark level IV invasion, truncal location, and mitoses should be considered Evaluate each patient individually
Prognostic Factors for Primary Melanoma
Variable
Thickness Ulceration Age Site Level of invasion Sex
P Risk Ratio95% CI
<.000011.558 <.000011.901 <.000011.101 <.000011.338 <.000011.214 .001 0.836 1.473-1.647 1.735-2.083 1.071-1.132 1.224-1.463 1.136-1.297 0.764-0.915
J Clin Oncol. 2001;19:3622-3634.
Adjuvant IFN-α 2b in High-Risk Melanoma: Efficacy Summary
•
• •
High Dose Interferon Therapy • Only FDA-approved adjuvant therapy for high-risk melanoma • Significantly prolongs relapse-free survival (RFS) • 26% reduction in risk (P2= 0.00009) • Overall survival (OS) improved in 2 randomized trials • 15% reduction (P2 = 0.06) Low-dose therapy is less effective Ongoing studies • Modified dosing regimens • Intermediate and high-risk melanoma • Define mechanism of action
Oncology. 2002;16:1177-1187. Ann Surg Oncol. 2001:8(9 Suppl):38s-40s. J Clin Oncol.1996;14:7-17. J Clin Oncol. 2000;18:2444-2458. J Clin Oncol. 2001;19:2370-2380. Ann Surg Oncol. 2001;8:41S-43S. Canc Treat Rev. 2003;29:241-252.
Question
•
A 40 year old woman develops a solitary right upper lobe pulmonary metastasis 4 years after resection of a primary melanoma on her back. Which of the following treatments is associated with the highest disease-free survival rate?
1. 2. 3. 4. 5. Dacarbazine (DTIC) Biochemotherapy Pulmonary resection Radiation therapy Interferon – alpha 2b
Question
•
A 40 year old woman develops a solitary right upper lobe pulmonary metastasis 4 years after resection of a primary melanoma on her back. Which of the following treatments is associated with the highest disease-free survival rate?
1. 2. 3. 4. 5. Dacarbazine (DTIC) Biochemotherapy Pulmonary resection Radiation therapy Interferon – alpha 2b
Explanation
•
In most cases, metastatic melanoma appears simultaneously at multiple sites. In these instances, systemic therapy is given. When an isolated metastasis appears at an extirpatable site, resection is recommended. Several reports have shown that there is a 10% to 15% long-term disease-free survival rate associated with metastasectomy. Some recent reports have shown this to be true for the resection of multiple simultaneous visceral metastases in highly selected patients.
Metastatic Disease
• •
•
•
All Stage III disease need full lymph node dissection 5 year survival rate for patients who undergo lymphadenectomy for clinically positive involved nodes ranges from 25% to 70% If the Sentinel lymph node is positive for melanoma, regional therapeutic lymphadenectomy is indicated based on potential survival and clinical benefit. Axillary node melanoma with no other primary – complete axillary node dissection
Metastatic Disease
• • • •
Resection of metastases has provided some patients with long disease-free interval and is the best chance for cure. Isolated metastases that can be resected with a low-risk procedure should probably undergo resection. Most common sites of recurrence are skin subcutaneous tissues, and distant lymph nodes, followed by visceral sites. Common visceral sites of metastasis, in order of decreasing occurrence, are lung, liver, brain, bone, and GI tract.
Survival of AJC Clinical stage I and II melanoma patients relative to tumor location
7.5 – Year Survival Rate (%)
Thickness (mm) Extremities Hands or Feet Head and Neck Trunk BANS
<0.85 0.85-1.69 1.7-3.64 >3.65
100 100 86 83
100 100 60 0
100 100 64 65
100 97 77 12
98 78 58 33
