Makindo Medical Notes.com

Stages

• In situ (non-invasive) melanoma remains confined to the epidermis.
• Thin tumour are less than 1.0 millimetre (mm) in Breslow depth.
• Intermediate tumour are 1.0-4.0 mm.
• Thick melanomas are greater than 4.0 mm.

The presence of microscopic ulceration upgrades a tumour seriousness and can move it into a later stage. Therefore, the physician may consider using a more aggressive treatment than would otherwise be selected. The mitotic rate has been introduced into the staging system based on recent evidence that it is also an independent factor predicting prognosis. The presence of at least one mitosis (cancer cell division) per millimetre squared (mm2) can upgrade a thin melanoma to a later stage at higher risk for metastasis.

Early Melanomas (Clinical Stages I And II) T categories (for Tumour)

• Stage Tis. The tumour is in situ and remains non-invasive in the epidermis.
• Stage T1a. The tumour is invasive but less than or equal to 1.0 mm in Breslow thickness, without ulceration and with a mitotic rate of less than 1/mm2.
• Stage T1b. The tumour is less than or equal to 1 mm thick. It is ulcerated and/or the mitotic rate is equal to or greater than 1/mm2.
• Stage T2a. The tumour is 1.01-2.0 mm thick without ulceration.
• Stage T2b. The tumour is 1.01-2.0 mm thick with ulceration.
• Stage T3a. The melanoma is 2.01-4.0 mm thick without ulceration.
• Stage T3b. The melanoma is 2.01-4.0 mm thick with ulceration.
• Stage T4a. The tumour is thicker than 4.0 mm without ulceration
• Stage T4b. The tumour is thicker than 4.0 mm with ulceration.

Later Stages Stage III and IV

• Stage III. By the time a melanoma advances to Stage III or beyond, an important change has occurred. The Breslow's thickness is by then irrelevant and is no longer included in staging, but the presence of microscopic ulceration continues to be used, as it has an important effect on the progression of the disease. At this point, the tumour has either spread to the lymph nodes or to the skin between the primary tumour and the nearby lymph nodes. (All tissues are bathed in lymph a colourless, watery fluid consisting mainly of white blood cells which drains into lymphatic vessels and lymph nodes throughout the body, potentially carrying cancer cells to distant organs.)
• Stage III if it has metastasized or spread beyond the original tumour site. This can be determined by examining a biopsy of the node nearest the tumour , known as the sentinel node. Such a biopsy is now frequently done when a tumour is more than 1 mm in thickness, or when a thinner melanoma shows evidence of ulceration. As the sentinel node biopsy is not considered necessary in all cases, you may wish to discuss the matter with your physician. In-transit or satellite metastases are also included in Stage III. In this case, the spread is to skin or underlying (subcutaneous) tissue for a distance of more than 2 centimetres (1 cm equals 0.4 inches) from the primary tumour , but not to the regional lymph nodes. In addition, the new staging system includes metastases so tiny they can be seen only through the microscope (micrometastases). Just how advanced the tumour is into Stage III (the category, for nodes) depends on factors such as whether the metastases are in transit or have reached the nodes, the number of metastatic nodes, the number of cancer cells found in them, and whether or not they are micro metastases or can be seen with the naked eye.
• Stage IV. The melanoma has metastasized to lymph nodes distant from the primary tumour or to internal organs, most often the lung, followed in descending order of frequency by the liver, brain, bone, and gastrointestinal tract. The two main factors in determining how advanced the melanoma is into Stage IV (the category, for metastases) are the site of the distant metastases (non-visceral, lung, or any other visceral metastatic sites) and elevated serum lactate dehydrogenase (LDH) level

Management

• Wide local excision
• Lesions > 1 mm need sentinel node biopsy or those with evidence of lymphadenopathy
• Sentinel lymph node biopsy to establish evidence of metastatic spread
• Metastatic disease - Interferon alpha - 2B for 1 year but expensive and side effects +
• Chemotherapy - Dacarbazine (DTIC) and certain combination regimens
• Interleukin 2 but of limited use for visceral metastases and can cause a systemic inflammatory response

New Immune modulating therapies

• Ipilimumab: Ipilimumab is recommended by NICE as a treatment for people with previously treated or untreated advanced melanoma that's spread or can't be removed using surgery. It's given by injection over a 90-minute period, every three weeks for a total of four doses. Common side effects include diarrhoea, rash, itching, fatigue, nausea, vomiting, decreased appetite and abdominal pain.
• Nivolumab: Nivolumab is recommended by NICE for treating advanced cases of melanoma in adults that have spread or can't be removed using surgery. It's given directly into a vein (intravenously) over a 60-minute period, every two weeks. Treatment is continued for as long as it has a positive effect or until it can no longer be tolerated. Nivolumab can be used either on its own or in combination with ipilimumab. In clinical trials, the most common side effects were tiredness, rash, itching, diarrhoea and nausea.
• Pembrolizumab: Pembrolizumab is recommended by NICE to treat advanced melanoma in adults that have spread or can't be treated with surgery. It's given by injection for 30 minutes, every three weeks. In clinical trials, the most common side effects were diarrhoea, nausea, itching, rash, joint pain and fatigue.
• Talimogene laherparepvec: Talimogene laherparepvec is recommended by NICE for treating melanoma that's spread or can't be removed with surgery, where treatment with other immunotherapies isn't suitable. It's injected directly into the skin, sometimes with the help of ultrasound guidance. In clinical trials, the most common side effects were flu-like symptoms, reactions at the injection site and cellulitis (infection of the deeper layers of skin and underlying tissue).

Targeted treatments

• Around 40 to 50 in every 100 people with melanoma have changes (mutations) in certain genes, which cause cells to grow and divide too quickly. If gene mutations have been identified, medication can be used to specifically target these gene mutations to slow or stop cancer cells from growing. Possible targeted treatments include:
• Vemurafenib Vemurafenib is a medication that blocks the activity of a cancerous gene mutation known as BRAF V600. It's recommended by NICE as a treatment for people who've tested positive for the mutation and have locally advanced melanoma or melanoma that's spread. Common side effects include joint pain, tiredness, rash, sensitivity to light, nausea, hair loss and itching. Vemurafenib can also be used with another medication called cobimetinib for treating people with the BRAF V600 mutation melanoma that's spread or can't be removed with surgery.
• Dabrafenib: Dabrafenib also blocks the activity of BRAF V600. It's recommended by NICE for treating adults with the BRAF V600 mutation who have melanoma that's spread or can't be removed with surgery. Common side effects include decreased appetite, headache, cough, nausea, vomiting, diarrhoea, rash and hair loss. Read the NICE guidance about dabrafenib for treating BRAF V600 mutation-positive melanoma that's spread or can't be removed using surgery.
• Trametinib: Trametinib blocks the activity of the abnormal BRAF protein, slowing the growth and spread of cancer. It's recommended by NICE either for use on its own or with dabrafenib for treating people with melanoma with a BRAF V600 mutation that's spread or can't be removed with surgery. Common side effects include tiredness, nausea, headache, chills, diarrhoea, rash, joint pain, high blood pressure and vomiting. Read the NICE guidance about trametinib in combination with dabrafenib for treating melanoma that's spread or can't be removed with surgery.

Radiotherapy and chaemotherapy

• You may have radiotherapy after an operation to remove your lymph nodes, and it can also be used to help relieve the symptoms of advanced melanoma. Controlled doses of radiation are used to kill cancerous cells.
• If you have advanced melanoma, you may have a single treatment or a few treatments. Radiotherapy after surgery usually consists of a course of five treatments a week (one a day from Monday to Friday) for a number of weeks. There's a rest period over the weekend.
• Common side effects associated with radiotherapy include: tiredness, nausea, loss of appetite, hair loss, sore skin.
• Many side effects can be prevented or controlled with prescription medicines, so tell your treatment team if you experience any. The side effects of radiotherapy should gradually reduce once treatment has finished.
• Chemotherapy is now rarely used to treat melanoma. Targeted treatments and immunotherapy (as described above) are the preferred treatment options.

Melanoma vaccines

• Research is underway to produce vaccines for melanoma, either to treat advanced melanoma or to be used after surgery in people with a high risk of the melanoma returning. They're currently only given as part of a clinical trial.