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Melanoma Treatment Information for Professionals

Different factors play a role in the management of melanoma, including the tumor's extent, the advancement of the disease, the patient's age and general health and many other. The treatment of malignant melanoma therefore must be chosen individually. The following enumeration lists different stages of melanoma with possible therapeutic procedures.

Primary tumor treatment

As far as possible, all melanomas should be surgically removed with a resection margin depending on the tumor thickness.

- Tumor thickness < 1mm: A horizontal and vertical resection margin of 1 cm is recommended.
- Tumor thickness > or = 1 mm: The resection margin should comprise 2 - 3 cm, depending on the anatomic conditions.
The patients should also be considered for sentinel node biopsy. (This procedure involves injecting blue dye or a radiolabelled colloid into the skin at the site of the melanoma, opening the skin surgically over the relevant draining lymph-node basin, and biopsying the node into which the dye or radiolabelled colloid first drains.)If the sentinel node is free of tumor, it is unlikely that there will be tumor cells in other nodes. If the node is positive, a full lymph-node dissection is recommended.
- Tumor thickness > 1,5 mm: Some centers recommend an adjuvant therapy with alpha- interferon (e.g. Roferon A). During the treatment phase, alpha-interferon 2A is applied daily subcutaneously for 3 weeks in a dose of 3 million I.U. During the following 49 weeks, the substance is applied only three times a week in the same dosage.
If surgical treatment of primary melanoma is not possible, radiotherapy is recommended.

Treatment of in-transit-metastases

Cutaneous in-transit-metastases should be surgically removed as far as possible. If this procedure is not an option, the following therapeutical measures should be considered:
- If the metastases are localized on an extremity, an intraarterial hyperthermal cytostatic drug perfusion as well as a regional lymph-node dissection are possible therapeutical strategies.
- If hyperthermal drug perfusion is not an option, radiotherapy is a possible treatment.
- Other possibilities include a combination of local sensitization with DNCB (production of an allergic contact dermatitis over superficial cutaneous metastases) and cytostatic dacarbazine, immune therapy with tumor vaccines, and an adjuvant therapy with alpha-interferon 2B according to the protocol of the EORTC Melanoma Cooperative Group.

Treatment of lymph node metastases

- Radical lymph-node dissection is recommended as far as possible. Postoperative radiotherapy may follow. Adjuvant interferon therapy in the context of a clinical trial may be an option after surgical removal of the metastases.

- If surgical treatment is not possible, radiotherapy alone may give good palliative results. Several melanoma vaccines are in the course of evaluation for patients with inoperable lymph node metastases.

Treatment of distant metastases

It is advisable that patients with advanced disease should be treated in specialized centers by a multidisciplinary team. Several treatment options as well as clinical trials of therapy are available depending on the affected organs, the number of metastases and the patient's general health.

In case of an operable solitary metastasis (neuro)surgical procedures are recommended. Palliative surgery may be necessary in case of perforation, abscess formation and internal bleeding.

Radiotherapy is indicated in case of brain metastases when surgical procedures are not possible or advisable. Stereotactic radiation is applied in case of up to 2 brain metastases. When more than 2 metastases have been detected, radiation of the whole brain is a common procedure. Stereotactic radiation with a gamma-knife may be applied even in case of more than 2 brain metastases. Palliative radiotherapy is advisable in case of bone metastases.

Inoperable remote metastases without brain involvement
In this case several treatment options and clinical trials of therapy are available, including
- Dacarbazine. Studies have shown partial of complete remission in 20 - 40% of treated patients.
- Polychemotherapy combining cisplatin, dacarbazine, BCNU and tamoxifene, or Polychemoimmunotherapy with interleukin-2 and alpha-interferon added.
- Chemoimmunotherapy combining temozolomide with alpha-interferon (clinical trial)
- Currently only as second-line therapy in case of ineffective first-line chemotherapy: several tumor vaccines, chemotherapy with paclitaxel and carboplatin.

Inoperable brain metastases

- Chemotherapy with fotemustine

- Chemotherapy with temozolomide, eventually in combination with radiation

Isolated multiple liver metastases

- Intraarterial chemotherapy into the A. hepatica propria with fotemustine.
- Local hyperthermy.

After surgical removal of all metastases or successful chemotherapy a postjuvant immunotherapywith interleukin-2 and alpha-interferon may be possible in the context of a clinical trial.

This listing of possible therapeutical options does not claim to be complete. Besides established treatments, it includes experimental chemo- and immuno(chemo)therapies which are being applied in specialized centers and whose efficacy is still being investigated. Uni Heidelberg