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Welcome to Dr. Hamid Sanatinia's Virtual Headquarters
Melanoma

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Should we treat or not???
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Staging & Prognosis
Treatment Approaches
Immunotherapy/Chemotherapy for Melanoma
Subtypes of Melanoma
Link to National Cancer Institute PDQ web site
Other Skin Cancers



Stage vs 5-yr survival (1992 data)
STAGE I (T1 or T2 N0M0): <.75 mm or 0.76-1.50 mm 5-YR survival 90%
STAGE II (T3 or T4 N0M0): 1.51-4.0 or >4.0 5-YR survival 70%
STAGE III (any T, N1-N2, M0): 5-YR survival 35%
STAGE IV: (any T, any M, M1a-M1b): 5-YR survival: <2

PROGNOSTIC FACTORS:
1. Tumor size (depth)
2. Number of lymph nodes involved
3. Melanomas in radial growth phase have a good prognosis regardless of all other factors.
4. Nodular growth pattern has been shown (multivariate analysis) to be an unfavorable prognostic feature.


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TREATMENT OPTIONS

SURGICAL TREATMENT:
***Excision margins:
Lesions < 1 mm in thickness, the recommended excision margin is 1 cm.
Lesions 1-4 mm in thickness require a 2-cm margin.
Lesions > 4 mm in thickness require at least a 2-cm margin.
Note:If the anatomic location of the primary precludes excision of the desired margin (for example, on the hands/feet or the face), a 1 cm margin may be acceptable as long as the margins are negative.

***Lymph node dissection:

In patients with clinically enlarged lymph nodes & no evidence of distant disease ie stage III, a complete regional lymph node dissection is recommended. Depending on the number of positive lymph nodes found, the prognosis for long-term survival is approximately 20%-40%.

Sentinel Lymph Node Biopsy
** A negative SLN should rule out nodal disease in over 95% of patients.

Selective lymphadenectomy
In patients with clinically negative nodes, selective lymphadenectomy is the management of choice for patients with intermediate & thick melanomas who are found to have involved sentinel lymph nodes.


Treatment according to Stage:
Stage I: Wide Excision
Stage II: Wide excision +/- sentinel lymph node dissection. If positive then total lymphadenopathy & further treatment per stage III
Stage III: Following surgery, adjuvant IFNa-2b recommended.
Stage IV: IFNa-2b, DTIC, temazolamide, clinical trials with vaccines, biochemotherapy, etc.
A phase III trial of sequential biochemotherapy vs chemotherapy alone (CVD regimen) found the overall response rate was almost double & the CR was significantly higher with the combination than with CVD alone; OS improvement was only borderline.



___________________________________________________________________

TREATMENT OPTIONS

SURGICAL TREATMENT:
***Excision margins:
Lesions < 1 mm in thickness, the recommended excision margin is 1 cm.
Lesions 1-4 mm in thickness require a 2-cm margin.
Lesions > 4 mm in thickness require at least a 2-cm margin.
Note:If the anatomic location of the primary precludes excision of the desired margin (for example, on the hands/feet or the face), a 1 cm margin may be acceptable as long as the margins are negative.

***Lymph node dissection:

In patients with clinically enlarged lymph nodes & no evidence of distant disease ie stage III, a complete regional lymph node dissection is recommended. Depending on the number of positive lymph nodes found, the prognosis for long-term survival is approximately 20%-40%.



Chemotherapy & Immunotherapy
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HIGH-DOSE INTERFERON ALPHA-2b
20 million units/m2/day IV for 5-7 days every week X 4 weeks,
Then 10 million units/m2/day subcutaneously 3X a week Qweek X48 weeks.

REF:
Journal of Clinical Oncology 14(1): 7-17, 1996.
Journal of Clinical Oncology 18(12): 2444-2458, 2000.
Journal of Clinical Oncology 19: 2370-2380, 2001

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LOW-DOSE INTERFERON
3 million units per day given subcutaneously 3X a week Qweek X104 weeks.
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TEMADAR
Temazolamide 150-200 mg/m2 QD X 5 days Q28 days.

Relatively active in melanoma. It also penetrates blood-brain barrier.

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Dacarbazine (DTIC) 10-15% response noted
Carmustine (BCNU)
Lomustine (CCNU),
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GMCSF 125 ug/m2 SC QD X 14 days Q 28 days. Treatment cycles continued for 1 year or until disease recurrence!!!

REF: Journal of Clinical Oncology 18(8): 1614-1621, 2000
N=48, Stage III or IV melanoma. OS & DFS were significantly prolonged in patients who received GM-CSF compared with matched historical controls. The median survival duration was 37.5 months in the study patients versus 12.2 months in the matched controls (P < .001)


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THALIDOMIDE
Thalidomide 100-200 mg po Qhs
REF= case report 1 patient with complete resolution of intracranial & scalp lesions. NEJM 345(16):1214; October 18, 2001
REF= Br J Cancer 2000;82:812-817. Continuous low dose thalidomide:a phase II study in advanced melanoma, renal cell, ovarian and breast cancer. No response seen in melanoma patients. However, it was tolerated well. Used 100 mg Qhs. Better sleep!!

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THALIDOMIDE + TEMADAR

JCO 20(11):2610, 2002
Unresectable stage III or IV melanoma without brain metastases: 4 treatment cohorts: level 1, temozolomide 50 mg/m2/d X 6 weeks followed by a 4-week break; levels 2, 3, & 4, temozolomide 75 mg/m2/d for 6 weeks followed, respectively, by breaks of 4, 3, & 2 weeks. Thalidomide was started at 200 mg/d, and escalated to a maximum dose of 400 mg/d. Safety was assessed at weeks 2 and 4 and every 4 weeks thereafter; tumor response was evaluated every 8 to 10 weeks.

N= 12; 3 on each cohort. Therapy was well tolerated on all of the treatment schedules. Thalidomide at a dose of 400 mg/d was well tolerated in patients <70, & 200 mg/d was well tolerated in older patients.
The most common adverse events were grade 2 - 3 constipation & neuropathy, which were attributed to thalidomide. Five major responses (1 CR, 4 PR) were documented, all at dose levels 2 - 4. 3 of 5 responding pts were in the over-70 age group. The median duration of response = 6 months (range, 4 - 17+ months), & the median overall survival :12.3 months (range, 4 to 19+ months).

CONCLUSION: The combination of temozolomide and thalidomide was well tolerated and had antitumor activity in patients with advanced melanoma, including elderly patients over 70 years old


HISTOLOGIC SUB-TYPES
1. SUPERFICIAL SPREADING MELANOMA The most common type of cutaneous melanoma. Often arises within a preexisting nevus & is typically surrounded by a zone of atypical melanocytes that may extend beyond the visible borders of the lesion.

2. NODULAR MELANOMA 10%-15% of cutaneous melanomas. Dark blue-black & more symmetrical & uniform in coloration than other melanomas. Amelanotic nodular melanomas also occur & are frequently misdiagnosed.

3. LENTIGO MALIGNA MELANOMA. 10%-15% of cutaneous melanomas. Typically occur on the sun-exposed areas of the head/neck & the hands. Clinically, they are large (often > 3 cm in diameter), flat, tan lesions with areas of dark brown or black coloration. These lesions arise from a precursor lesion known as lentigo maligna, or Hutchinson?s freckle.

4. ACRAL-LENTIGINOUS MELANOMA. A distinct variant of melanoma that occurs in equal frequency among whites & darker-pigmented races. Because of the high incidence of other types of cutaneous melanoma in whites, acral-lentiginous melanomas account for only 2%-8% of melanomas in whites vs 40%-60% of melanomas in African Americns, Hispanics, & Asians. Acral-lentiginous melanomas occur on the palms, soles, & subungual locations.
Subungual melanomas can easily be confused with subungual hematomas; the presence of pigmentation in the paronychial skin is indicative of melanoma.

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Link to NCI PDQ on melanoma





Other Skin Cancers:
1. BASAL CELL CARCINOMA
2. SQUAMOUS CELL CARCINOMA
3. BOWEN'S DISEDASE --name given to squamous cell carcinoma in situ involving the skin.
4. MERKEL?S CELL CANCER -- rare & aggressive skin cancer, presumably arising from the neuroendocrine cells of the skin.
5. SARCOMAS Dermatofibrosarcoma protuberans is the most common primary sarcoma affecting the skin. Leiomyosarcoma, angiosarcoma, & malignant fibrous histiocytoma can also arise entirely within the skin.