Melanoma

WHAT IS MELANOMA?

Melanoma is a disease in which malignant (cancer) cells form in the skin cells called melanocytes (cells that color the skin).

Melanocytes are found throughout the lower part of the epidermis. They produce melanin, the pigment that gives skin its natural color. When skin is exposed to the sun, melanocytes produce more pigment, causing the skin to tan, or darken.

The skin is the body’s largest organ. It protects against heat, sunlight, injury, and infection. The skin has 2 main layers: the epidermis (upper or outer layer) and the dermis (lower or inner layer).

Melanoma occurs when melanocytes (pigment cells) become malignant. Most pigment cells are in the skin; when melanoma starts in the skin, the disease is called cutaneous melanoma. Melanoma may also occur in the eye (ocular melanoma or intraocular melanoma). Rarely, melanoma may arise in the meninges, the digestive tract, lymph nodes, or other areas where melanocytes are found.

Melanomais the most serious type of cancer of the skin. In some parts of the world, especially among Western countries, melanoma is becoming more common every year. In the United States, for example, the percentage of people who develop melanoma has more than doubled in the past 30 years.

Melanoma can occur anywhere on the body.

In men, melanoma is often found on the trunk (the area from the shoulders to the hips) or the head and neck. In women, melanoma often develops on the arms and legs. Melanoma usually occurs in adults, but it is sometimes found in children and adolescents.



WHAT ARE RISK FACTORS OF MELANOMA?

Unusual moles, exposure to sunlight, and health history can affect the risk of developing melanoma.

Risk factors include the following:

Unusual moles.
Exposure to natural sunlight.
Exposure to artificial ultraviolet light (tanning booth).
Family or personal history of melanoma.
Being white and older than 20 years.
Red or blond hair.
White or light-colored skin and freckles.
Blue eyes.

HOW TO DIAGNOSE MELANOMA?

Possible signs of melanoma include a change in the appearance of a mole or pigmented area.

The following presentations suggest melanoma.

A mole that:
changes in size, shape, or color.
has irregular edges or borders.
is more than 1 color.
is asymmetrical (if the mole is divided in half, the 2 halves are different in size or shape).
itches.
oozes, bleeds, or is ulcerated (a hole forms in the skin when the top layer of cells breaks down and the underlying tissue shows through).
Change in pigmented (colored) skin.
Satellite moles (new moles that grow near an existing mole).
Tests that examine the skin are used to detect (find) and diagnose melanoma.

If a mole or pigmented area of the skin changes or looks abnormal, the following tests and procedures can help diagnose melanoma:

Skin examination: To examine the skin to look for moles, birthmarks, or other pigmented areas that look abnormal in color, size, shape, or texture.
Biopsy: A local excision is done to remove as much of the suspicious mole or lesion as possible. A pathologist then looks at the tissue under a microscope to check for cancer cells.
There are 4 major types of melanoma according to mass features:

Superficial spreading melanoma is the most common type of melanoma (70% of cases). It is usually flat and irregular in shape and color with varying shades of black and brown. It may occur at any age or site and is most common in Caucasians.
Nodular melanoma (15% of cases) usually starts as a raised area that is dark black-blue or bluish-red, however some can lack color.
Lentigo maligna melanoma (5% of cases) usually occurs in the elderly. It is most common in sun damaged skin on the face, neck, and arms. The abnormal skin areas are usually large, flat, and tan with intermixed areas of brown.
Acral lentiginous melanoma is the least common form of melanoma. It usually occurs on the palms, soles, or under the nails. It is more common in African Americans.
Stages of Melanoma

The following stages are used for melanoma:

Stage 0: In stage 0, the melanoma cells are found only in the outer layer of skin cells and have not invaded deeper tissues.
Stage I: Melanoma in stage I is thin:
The tumor is no more than 1 millimeter (1/25 inch) thick. The outer layer (epidermis) of skin may appear scraped. (This is called an ulceration).
Or, the tumor is between 1 and 2 millimeters (1/12 inch) thick. There is no ulceration.
The melanoma cells have not spread to nearby lymph nodes.

Stage II: The tumor is at least 1 millimeter thick:
The tumor is between 1 and 2 millimeters thick. There is ulceration.
Or, the thickness of the tumor is more than 2 millimeters. There may be ulceration.
The melanoma cells have not spread to nearby lymph nodes.

Stage III: The melanoma cells have spread to nearby tissues:
The melanoma cells have spread to one or more nearby lymph nodes.
Or, the melanoma cells have spread to tissues just outside the original tumor but not to any lymph nodes.
Stage IV: The melanoma cells have spread to other organs, to lymph nodes, or to skin areas far away from the original tumor.
Recurrent: Recurrent disease means that the cancer has come back (recurred) after it has been treated. It may have come back in the original site or in another part of the body.


HOW TO TREAT MELANOMA?

Traditional therapies

Patient with melanoma may have surgery, chemotherapy, biological therapy, or radiation therapy andcombination of abovetreatments.

At any stage of disease, patient with melanoma may have treatment to control pain and other symptoms of the cancer, to relieve the side effects of therapy, and to ease emotional and practical problems. This kind of treatment is called symptom management, supportive care, or palliative care.

Surgery

Surgery is the usual treatment for melanoma. The surgeon removes the tumor and some normal tissue around it. This procedure reduces the chance that cancer cells will be left in the area. The width and depth of surrounding skin that needs to be removed depends on the thickness of the melanoma and how deeply it has invaded the skin.

Lymph nodes near the tumor may be removed because cancer can spread through the lymphatic system. If the pathologist finds cancer cells in the lymph nodes, it may mean that the disease has also spread to other parts of the body. Two procedures are used to remove the lymph nodes:Sentinel lymph node biopsyand Lymph node dissection.

Adjuvant therapymay be given after surgery to kill cancer cells that remain in the body. The patient may receive biological therapy.

In such cases, whose melanoma that has spread to other parts of the body. use other methods of treatment, such as chemotherapy, biological therapy, radiation therapy, or a combination of these methods may be used..

Chemotherapy

Patient with melanoma may receive chemotherapy in one of the following regimen with response rates of 19% to 55%

CBDTCisplatin,25mg/m2 per day i.v. for 3 days,day
1-3(total dose/cycle,75mg/m2)

Carmustine,150mg/m2 i.v.,day 1 on every 43 days(total dose/two cycle,150mg/m2)

Dacarbazine,220 mg/m2 per day i.v. for 3 days,day 1-3(total dose/cycle,660mg/m2)

Tamoxifen,10mg twice daily p.o. during the therapy

Cycle repeats every 21 days

CVDCisplatin,20mg/m2 per day i.v. for 4 days,days
2-5(total dose/cycle,80mg/m2)

Vinblastine,1.6mg/m2 per day i.v.,for 5 days,days 1-5(total dose/cycle,8mg/m2)

Dacarbazine,800mg/m2 i.v. on day 1(total dose/cycle,800mg/m2)

Cycle repeats every 21 days

Biological Therapy

Biological therapy for melanoma uses substances called cytokines. The body normally produces cytokines in small amounts in response to infections and other diseases. Using modern laboratory techniques, scientists can produce cytokines in large amounts. In some cases, biological therapy given after surgery can help prevent melanoma from recurring. For patients with metastatic melanoma or a high risk of recurrence, interferon alpha and interleukin-2 (also called IL-2 or aldesleukin) may be recommended after surgery.

Interferon-a(IFN-a):The agent was the first recombinant cytokine investigated in phase Ⅰ/Ⅱtrials,in the metastatic melanoma,based on its antiproliferative as well as immunomodulatory effects.The response rate induced by IFN-α is around 15%,and up to one third of the responses are complete and durable.Responses can be observed up to 6 months after initiation of the therapy.Patients with small tumor volume have better therapeutic effects compared with patients with large-volume tumors.

Following regimens were recommended:

(a)IFN-a-2a,20 million U/m2 per dose i.v.,5 days/week for 4 weeks

(total dose/week,100 million U/m2),THEN

IFN-a-2b,10 million U/m2 s.c.,3 times per week for 48 weeks

(total dose/week,30 million U/m2)

(b)IFN-a-2b,20 million U/m2 per dose i.v.,5 days/week for 4 weeks

(total dose/week,100 million U/m2),THEN

IFN-a-2b, 10 million U/m2 s.c.,3 times per week for 48 weeks

(total dose/week,30 million U/m2)

(c)IFN-a-2a,3 million U/m2 s.c. 3 times per week for 2 years

(total dose/week,9 million/m2)

Dendritic cells (DCs) vaccine: Preliminary data from dendritic cell vaccination trials, mainly of advanced melanoma, show unequivocal evidence of immunization and of the first clinical responses.



Seventeen patients with stage IV melanoma were treated with a fully autologous immunotherapy consisting of monocyte-derived DC, matured after culture with irradiated tumour cells. 12 patients received a complete priming phase of six cycles of either 0.9x106 or 5x106 DC/intradermal injection, at 2-weekly intervals.The remaining five patients could not complete priming, due to progressive disease. Three of the 12 patients who completed priming have durable complete responses (average duration 35 months), three had partial responses, and the remaining six had progressive disease. The treatment had minimal side-effects and was well tolerated by all patients. The result shows that mature, monocyte-derived DC preparations exposed to appropriate tumour antigen sources can be reliably produced for patients with advanced metastatic melanoma, and in a subset of those patients with lower volume disease their repeated administration results in durable complete responses.


Combination of chemotherapy with biologic agents

A study showed a response rate of 53% and median survival of 17.6 months with IFN-α2b combined with dacarbazine compared with a response rate of 20% and median survival of 9.6% months with dacarbazine alone.The following regimens can be used:

(a) Dacarbazine, 200mg/m2 i.v. for 5 days,start every week 4

IFN-a-2b,15 million U/m2 i.v. daily for 5 days per week for 3 weeks,and then,10 million U/m2 s.c. 3 times per week.

Cycle repeats every 28 days.

(b)Cisplatin, 20mg/m2 per day i.v. for 4 days,days 2-5 (total dose/cycle,80 mg/m2)

Vinblastine,1.6 mg/m2 per day i.v. for 5 days,days 1-5(total dose/cycle,8mg/m2)

Dacarbazine,800 mg/m2 i.v. on day 1(total dose/cycle,800 mg/m2)

PLUS

Interleukin-2, 9 million U/m2 per day continuous i.v. infusion for 4 days,day 6-9(total dose/cycle,36 million U/m2)

Interferon-a, 5 million U/m2 per dose s.c. for 5 days,days 6-10 (total dose/cycle, 25 million U/m2)

The therapy schedule with the biologic agents either immediately procedes or follows the chemical agents.Cycle repeats every 21 days

(c)Cysplatin, 25mg/m2 i.v. 2-hour infusion on days 1-3 and 22-25 (total dose/cycle, 175mg/m2)

Carmustine, 150mg/m2 i.v. 1-hour infusion on day 1(total dose/cycle, 150mg/m2)

Dacarbazine, 220mg/m2 i.v.2-hour infusion on day 1-3 and 22-25(total dose/cycle,1 540mg/m2)

Tamoxifen, 10-mg tablet orally twice a day for 6 weeks and begin on day 1

Interleukin-2, 1.5 million U/m2 administered i.v. every 8 hours,starting day 4 for 15 doses, day 4-8 and 17-21(total dose/cycle,45 million U/m2)

PLUS

Interferona-2b, 6 million U/m2 per day s.c. for 10 days,day 4-8 and 17-21 (total dose/cycle,60 million U/m2)

Cycle repeats every 6 weeks

Radiation Therapy

Radiation therapy (also called radiotherapy) uses high-energy rays to kill cancer cells. A large machine directs radiation at the body. The patient usually has treatment at a hospital or clinic, five days a week for several weeks. Radiation therapy may be used to help control melanoma that has spread to the brain, bones, and other parts of the body. It may shrink the tumor and relieve symptoms

Treatment Choices by Stage

The following are brief descriptions of the treatments most often used for each stage. (Other treatments may sometimes be appropriate.)

Stage 0

Patients with Stage 0 melanoma may have minor surgery to remove the tumor and some of the surrounding tissue.

Stage I

Patient with Stage I melanoma may have surgery to remove the tumor. The surgeon may also remove as much as 2 centimeters (3/4 inch) of tissue around the tumor. T

Stage II or Stage III

Patient with Stage II or Stage III melanoma may have surgery to remove the tumor. The surgeon may also remove as much as 3 centimeters (1 1/4 inches) of nearby tissue. Sometimes removes nearby lymph nodes may be removed..

Stage IV

Patient with Stage IV melanoma often receive palliative care. The goal of palliative care is to help the patient feel better—physically and emotionally. This type of treatment is intended to control pain and other symptoms and to relieve the side effects of therapy (such as nausea), rather than to extend life.Biological therapy may be used.

Recurrent Melanoma

Treatment for recurrent melanoma depends on where the cancer came back, which treatments the patient has already received, and other factors. As with Stage IV melanoma, treatment usually cannot cure melanoma that recurs. Palliative care is often an important part of the treatment plan. Many patients have palliative care to ease their symptoms while they are getting anticancer treatments to slow the progress of the disease. Some receive only palliative care to improve their quality of life by easing pain, nausea, and other symptoms.



WHAT ARE FACTORS WHICH AFFECT PROGNOSIS?

The prognosis and treatment options depend on the following:

The stage of melanoma (whether cancer is found in the outer layer of skin only, or has spread to the lymph nodes, or to other places in the body.
Whether there was bleeding or ulceration at the primary site.
The location and size of the tumor.
The patient’s general health.
Although many people are successfully treated, melanoma can recur.