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Treatment By Stage

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In this section, you will find information about standard treatments for each stage of melanoma, as well as experimental treatments for which you may be eligible.

 

Stage 0

Stage I

Stage II

Stage III

Stage IV

Brain Metastases

Recurrent Melanoma

 

To learn about stages of melanoma click here.

Stage 0 Treatment

Treatment
Goal
Surgery

To remove any cancer remaining after the biopsy. The procedure is called wide excision.

 

The surgeon removes the rest of the tumor, including the biopsy site, as well as a surgical margin, (a surrounding area of normal-appearing skin), and the underlying subcutaneous tissue, to make certain the whole tumor has been removed.

 

The width of the margin taken depends upon the thickness of the primary tumor.

 

Most surgeons today follow the guidelines adopted and recommended by the National Institutes of Health and the World Health Organization Melanoma Program:

 

  • At least 0.5 centimeter margin in all directions (less than 0.25 inch) 

 

This typically results in a scar at least 4-5 cm (about 2 inches) in length, but it may be longer depending on the location on the skin and the size and orientation of the biopsy site.  Skin grafting may sometimes be required to cover the wound, especially on the face or on the fingers or toes.

 

To learn about surgery click here.

 

To learn about Stage 0 click here.

 

Stage I Treatment

Treatment 

Goal 

Surgery

To remove any cancer remaining after the biopsy. The procedure is called wide local excision.

 

The surgeon removes the rest of the tumor, including the biopsy site, as well as a surgical margin, (a surrounding area of normal-appearing skin), and the underlying subcutaneous tissue, to make certain the whole tumor has been removed.

 

The width of the margin taken depends upon the thickness of the primary tumor.

 

Most surgeons today follow the guidelines adopted and recommended by the National Institutes of Health and the World Health Organization Melanoma Program which call for a 1 cm margin in all directions. This typically results in a scar at least 6 cm (about 2 inches) in length, but it may be longer depending on the location on the skin and the size and orientation of the biopsy site. Skin grafting may sometimes be necessary to cover the wound especially on the face or on the fingers or toes.

Sentinel

Lymph

Node Biopsy

(SLNB)

Sentinel lymph node biopsy is most accurate when the lymph channels around the primary melanoma have not been disturbed by a prior wide excision. Therefore, in general, the sentinel node biopsy and wide excision are done during the same surgery, with the sentinel node biopsy being done first.

 

Recommended for patients with 

  • Ulcerated tumors of any thickness
  • Positive biopsy margins
  • Lymphovascular invasion (seeing cancer cells In the lymphatic channels or blood vessels
  • Young adults with the presence of mitosis (rate at which cells divide)

 

Purpose

  • Determine whether any cancer cells have spread to the sentinel node, the first lymph node to receive drainage from the primary tumor, and the site where melanomas commonly spread to first.
  • Sentinel lymph node biopsy is most accurate when the lymph channels around the primary melanoma have not been disturbed by a prior wide excision. Therefore, in general, the sentinel node biopsy and wide excision are done during the same surgery, with the sentinel node biopsy being done first.
  • Further treatment will depend on whether the lymph node biopsy is positive.

 

To learn about sentinel lymph node biopsy click here.

 

To learn about Stage I click here.

 

Stage II Treatment

TreatmentGoal 

Surgery

To remove any cancer remaining after the biopsy. The procedure is called wide local excision. Surgery is the main treatment for Stage II melanoma.

 

The surgeon removes the rest of the tumor, including the biopsy site, as well as a surgical margin, (a surrounding area of normal-appearing skin) and underlying subcutaneous tissue to make sure the whole tumor has been removed. The width of the margin taken depends upon the thickness of the primary tumor.

 

Most surgeons today follow the guidelines adopted and recommended by the National Institutes of Health and the World Health Organization Melanoma Program:

 

  • Stage IIA & IIB - 2 cm margin - about .75 inch - for tumors between 1.1 mm and 3.99 mm in depth (Breslow Depth)

  • Stage IIC - 2-4 cm margin - about .75 inch to 1.5 inch - for tumors greater than 4 mm; 2 cm margin - about .75 inch - for tumors between 1.1 mm and 3.99 mm in depth (Breslow depth)

 

Recent advances in surgery allow surgeons to take narrower margins than before, so a much greater amount of normal skin is preserved. 

Sentinel Lymph Node Biopsy

(SLNB)

Sentinel lymph node biopsy is recommended for all Stage II tumors regardless of size.

 

Sentinel node biopsy is most accurate when it is performed before wide local excision, the surgery to remove the tumor and the surrounding skin.

 

Purpose

  • Determine whether any cancer cells have spread to the sentinel node, the first lymph node to receive drainage from the primary tumor, and the site where melanomas commonly spread to first. 
  • Further treatment will depend on whether the lymph node biopsy is positive.
Adjuvant therapy

For patients with Stage IIB or IIC melanoma, adjuvant treatment with medicines may be recommended after sugery.

 

These medicines are systemic therapies that go through the bloodstream in an effort to reach and destroy any remaining cancer cells throughout the body

 

  • Interferon is a protein produced by normal cells to fight viral infections and disease and is used in large doses to treat melanoma as an immunotherapy.

 

Purpose

  • Interferon therapies have been shown to help the body's immune system fight certain diseases more effectively.
  • Several studies indicate that high dose interferon alfa-2b, a manufactured form of interferon, consistently delays relapse/recurrence of melanoma in patients with Stage IIB/C. However, studies have not consistently shown that interferon can extend overall survival.

 

Treatment Side Effects

  • Side effects are common, but can range from mild to severe but are typically reversible.

  • Thus far,  shorter courses of interferon have not been shown to be beneficial. The long-acting, pegylated form of interferon is not FDA approved for the treatment of Stage II melanoma.

 

For more information on high dose interferon alfa-2b click here.
Clinical Trials

Clinical trials are research studies to evaluate new therapies and improve cancer care. These studies are responsible for most of the advances in cancer prevention, diagnosis, and treatment. If you have melanoma, you may be eligible to participate in a clinical trial.

 

Several experimental treatments are currently being tested in Clinical Trials:

 

  • Experimental vaccines, GM-CSF, CTLA4-blocking antibodies, interleukins, and other therapies designed to boost the immune system to fight the return of melanoma
  • Chemotherapy treatments
Except for chemotherapy, all of these treatments are designed to boost the immune system. These therapies have not yet been shown to extend overall survival in any randomized, controlled trials for any stage of melanoma, and in some cases may even worsen survival rates. Scientists are constantly working to improve the efficacy of these treatments.

 

To learn about sentinel lymph node biopsy click here.

 

To learn about Stage II click here.

 

Stage III Treatment

Treatment 
Goal  

Surgery

To remove any cancer remaining after the biopsy of the primary melanoma. The procedure is called a wide local excision. Wide local incision is recommended for small, easily removable recurrent tumors and for patients with a limited number of in-transit tumors.

 

The surgeon removes the tumor, including the biopsy site, as well as a surgical margin, (a surrounding area of normal-appearing skin), and underlying subcutaneous tissue.

 

Most surgeons today follow the guidelines adopted and recommended by the National Institutes of Health and the World Health Organization Melanoma Program.

  • The recommended margins for wide local excision of the primary melanoma ranges from 1-2 cm and is determined by the thickness of the primary melanoma.

Lymph

Node Dissection

When cancerous lymph nodes are found and there is evidence that the melanoma has spread to nearby lymph nodes, an additional surgery to remove the remaining lymph nodes from the area is usually recommended. If your melanoma was found by sentinel lymph node biopsy this is called a complete lymph node dissection (CLND). If your melanoma was found because your lymph nodes were enlarged, this is called a therapeutic lymph node dissection (TLND.

 

The goal of the surgery is to prevent further spread of the disease through the body by way of the lymphatic system. Current studies are underway to determine whether CLND and TLND may also prolong survival.

 

CLND and TLND also play an important role in controlling the pain often caused by untreated lymph node disease.

Sentinel Lymph

Node

Biopsy

(SLNB)

If a patient has already been diagnosed with Stage III melanoma, a sentinel lymph node biopsy is typically recommended only for patients where it is suspected that there might be melanoma in another lymph node basin.

 

The results of the biopsy will guide the course of treatment.

 

For more on sentinel lymph node biopsy click here.

Adjuvant Therapy

Systemic treatment, given after surgery to remove all the melanoma, is often recommended for Stage III melanoma. These systemic therapies go throughout the bloodstream in an effort to reach and destroy any remaining cancer cells throughout the body.

 

Interferon is a protein produced by normal cells to fight viral infections and disease. There are now two types of interferon that have been approved by the Food and Drug Administration (FDA) for Stage III melanoma: high-dose interferon (brand name: Intron A) and pegylated interferon (brand name: Sylatron).

 

Purpose and Effectiveness
  • Interferon therapies have been shown to help the body's immune system fight disease more effectively.
  • High- dose interferon alfa-2b significantly prolongs disease-free survival in patients with Stage III melanoma. It has not been shown to prolong overall survival. The drug has to be administered frequently, over a period of a year, at a very high doses in order to be effective. Pegylated interferon alfa-2b is designed to provide high levels of interferon in the blood when given by subcutaneous injection once a week for at least one year, and up to 5 years. This has shown to prolong disease-free survival but has not been shown to prolong overall survival.

Treatment Side Effects
Other Treatment Options

Clinical trials - There are several clinical trials evaluating different treatments in the adjuvant therapy of melanoma. This includes medicines that are already FDA-approved for more advanced melanoma, such as ipilimumab, dabrafenib, vemurafenib and trametinib.

 

FOR UNRESECTABLE STAGE III MELANOMA:

 

A)     Ipilimumab (brand name: Yervoy) is a monoclonal antibody that has been approved by the FDA for the treatment of unresectable or metastatic melanoma. Unresectable melanoma is such that all sites of melanoma tumors cannot be completely removed surgically.

 

  • Ipilimumab is designed to restore and strengthen the immune system by successfully activating T-cells (T lymphocytes), a critical component of the immune system, with the hope to sustain an active immune response to fight the cancer cells for a long time.
  • Studies indicate that it improves overall median survival by 4 months.


Treatment Side
Effects

 

B)     Vemurafenib (brand name: Zelboraf) and Dabrafenib (brand name: Tafinlar) are tyrosine kinase inhibitors that have been approved by the FDA for the treatment of patients with unresectable or metastatic melanoma that have a BRAF V600E mutation.

 

Purpose and Effectiveness

  • The BRAF gene and protein is normally involved in regulating cell growth, but is mutated in about half of patients with melanoma. vemurafenib and dabrafenib work by blocking the function of the V600E-mutated BRAF protein.
  • In a trial comparing vemurafenib to dacarbazine (chemotherapy) in patients with the BRAF V600E mutation, the dacarbazine group had a response rate (shrinkage rate of 5% with 64% still living at 6 months. In the vemurafenib group, the response rate was 48% with 84% still living at 6 months.
  • In a trial comparing dabrafenib to dacarbazine (chemotherapy) in patients with the BRAF V600E mutation, the dabrafenib group had progression free survival (the time a patient lives without cancer growing or spreading) of 5.1 months compared to 2.7 months for those on dacarbazine.

 

Treatment Side Effects

 

C)    Trametinib (brand name: Mekinist) is a kinase inhibitor that inhibits another protein, named MEK, and has been approved by the FDA for the treatment of patients with unresectable or metastatic melanoma that have a BRAF V600E or BRAF V600K mutation.  Trametinib has not shown benefit when used by patients who have already taken a BRAF inhibitor and their melanoma is no longer sensitive.

 

Purpose and Effectiveness

  • The BRAF protein is normally involved in regulating cell growth, but is mutated in about half of the patients with late-stage melanomas. Mekinist works by blocking the function of the MEK protein, which is overactive inV600E-mutated or V600K-mutated melanoma.
  • In a trial comparing trametinib to chemotherapy (dacarbazine or paclitaxel) in patients with metastatic melanoma with a BRAF V600E or BRAF V600K mutation, the trametinib group had improved overall survival compared with chemotherapy.

 

Treatment Side Effects

 

D)     Dabrafenib in combination with Trametinib

 

Purpose and Effectiveness

  • In a phase I/II trial comparing dabrafenib alone to dabrafenib with trametinib in patients with BRAF V600E or V600K mutations, the combination group had a response rate (tumor shrinkage rate) of 76% which lasted for 10.5 months versus a response rate of 54% that lasted for 5.6 months in the dabrafenib only group. There is an ongoing phase III study to evaluate the combination treatment versus single agent dabrafenib but the results are still pending at this time. The FDA granted accelerated approval for the use of combination therapy.

 

Treatment Side Effects

  • coming soon

Radiation Therapy

Radiation therapy in the adjuvant setting has been shown to improve local control (control melanoma in the lymph node basin) but has not been proven to improve overall survival (keep melanoma from coming back elsewhere in the body) in randomized, controlled studies.

 

For more information on radiation therapy click here.

Clinical

Trials

Clinical trials are research studies to evaluate new therapies and improve cancer care. These studies are responsible for most of the advances in cancer prevention, diagnosis, and treatment. If you have melanoma, you may be eligible to participate in a clinical trial.

 

See the section on clinical trials in the Stage IV melanoma section for more information.

 

For more information on clinical trials click here.

 

To learn about lymph node dissection click here.

 

To learn about Stage III click here.

 

Stage IV Treatment

Once your stage of melanoma has been determined, your doctor will discuss a plan of treatment with you. Several new drugs, including Ipilimumab (Yervoy), Vemurafenib (Zelboraf), Dabrafenib (Tafinlar), Trametinib (Mekinist), and Dabrafenib in combination with Trametinib have been FDA approved, and have shown  improvements in survival.

 

Many experimental treatments are under investigation and may be available by enrolling in a clinical trial.

 

TreatmentGoal 
Surgery

To remove the cancerous tumors or lymph nodes that have metastasized or spread to other areas of the body, if they are few in number and/or are causing symptoms

 

For more information on surgery click here.
Treatment Options

Treatment given in addition to a primary cancer treatment (such as surgery) is recommended for Stage IV Melanoma. These are systemic therapies that go through the bloodstream to reach and affect cancer cells throughout the body. The goal of systemic treatment is to try and control the melanoma and treat symptoms. Treatments can be divided into immune or biologic therapies, molecularly targeted therapies, or chemotherapies.

 

A)     Immunotherapies

 

1)      Ipilimumab (brand name: Yervoy) is a monoclonal antibody that has been approved by the Federal Drug Administration (FDA) for the treatment of unresectable or metastatic melanoma.

 

Purpose and Effectivenss

  • Ipilimumab is designed to restore and strengthen the immune system by specifically activating T-cells against melanoma; T cells are, a critical component of the immune system. The hope is that the immune therapy will cause a sustained and active immune response that will continue to fight the cancer cells even after the medication dosing has stopped.
  • Studies indicate that it improves overall median survival by 4 months compared to a vaccine treatment.

 

Treatment Side Effects

 

2)      High Dose Interleukin-2 (brand name: HD IL-2) is a cytokine therapy approved by the FDA for the treatment of advanced metastatic melanoma. It appears to benefit approximately 16% of patients with disease shrinkage, of which 6% appear to derive long term durable responses.

 

Purpose and Effectivenss

  • HD Interleukin-2 is designed to restore and strengthen the immune system.
  • This treatment requires that the person is in very good health with no other significant health problems, including no heart problems. Not everyone is a candidate for HD Il-2 and it is administered by trained physicians and clinical staff inside a hospital.

 

Treatment Side Effects

 

B)     Targeted Therapies

 

1)      Vemurafenib (brand name: Zelboraf) and Dabrafenib (brand name: Tafinlar) are oral kinase inhibitors that interfere with the action of mutated BRAF and have been approved by the FDA for the treatment of patients with the BRAF V600E/K mutation with unresectable or metastatic melanoma.

 

Purpose and Effectiveness

  • The BRAF protein is normally involved in regulating cell growth, but is mutated (abnormal) in about half of patients with late-stage melanomas. Vemurafenib and dabrafenib work by blocking the function of the V600E-mutated BRAF protein.
  • In a trial comparing vemurafenib to dacarbazine (chemotherapy) in patients with the BRAF V600E mutation, the dacarbazine group had a median survival time of 9.7 months, with 44% still living at one year. Median survival time in the Vemurafenib group was 13.6 months, with 56% still living at one year.
  • In a trial comparing dabrafenib to dacarbazine (chemotherapy) in patients with the BRAF V600E mutation, the dabrafenib group had progression free survival (the time a patient lives without cancer growing or spreading) of 6.9 months compared to 2.7 months for those on dacarbazine. Median overall survival in the dabrafenib group has been reported at 18.2 months, compared with 15.6 months in the dacarbazine group.

 

Treatment Side Effects

 

2)     Trametinib (brand name: Mekinist) is an oral kinase inhibitor that that interfere with the action of MEK and has been approved by the FDA for the treatment of patients with the BRAF V600E or BRAF V600K mutation with unresectable or metastatic melanoma.  Trametinib cannot be used by patients who have already used a BRAF inhibitor.

 

Purpose and Effectiveness

  • The BRAF protein is normally involved in regulating cell growth, but is mutated in about half of the patients with late-stage melanomas. Trametinib works by blocking the function of MEK, a protein that is in the same pathways as BRAF and has shown the most benefit in patients with a V600E-mutated or V600K-mutated BRAF protein.
  • In a trial comparing trametinib to dacarbazine or paclitaxel (chemotherapy) in patients with the BRAF V600E or BRAF V600K mutation, the trametinib group had progression free survival (the time a patient lives without cancer growing or spreading) of 4.8 months compared to 1.5 months for those on chemotherapy.

 

Treatment Side Effects

 

3)     Dabrafenib in combination with Trametinib

 

Purpose and Effectiveness

  • In a phase I/II trial comparing dabrafenib alone to dabrafenib with trametinib in patients with BRAF V600E or V600K mutations, the combination group had a response rate (tumor shrinkage rate) of 76% which lasted for 10.5 months versus a response rate of 54% that lasted for 5.6 months in the dabrafenib only group. There is an ongoing phase III study to evaluate the combination treatment versus single agent dabrafenib but the results are still pending at this time. The FDA granted accelerated approval for the use of combination therapy.

 

Treatment Side Effects

  • coming soon

 

C.    Chemotherapy

 

1)     Dacarbazine (brand name: DTIC) is approved by the FDA for the treatment of advanced metastatic melanomas. It appears to benefit approximately 5-15% of patients with disease shrinkage. It has not been shown to change overall survival.

 

Purpose and Effectiveness

  • Chemotherapy uses toxic drugs to destroy cancer cells. These are established and experimental systemic therapies that ago through the bloodstream to reach and affect cancer cells throughout the body.
  • Other chemotherapy medicines are also used to treat advanced melanoma.

 

Treatment Side Effects

 

To learn more about chemotherapy click here.

Radiation Therapy

Radiation is used in some situations to slow tumor growth or shrink a tumor in organs where surgery is not possible or is not recommended, and for relieving symptoms that a particular tumor in causing, such as in the  brain or bone.

 

Radiation therapy uses x-rays to kill cancer cells.

 

For more on radiation therapy click here.

Clinical Trials

Clinical trials are research studies to evaluate new therapies and improve cancer care. These studies are responsible for most of the advances in cancer prevention, diagnosis, and treatment. If you have melanoma, you may be eligible to participate in a clinical trial.

 

Several experimental treatments are currently being tested in clinical trials.
  • Immunotherapies: designed to boost the body's immune response to tumors. Ongoing clinical trials include antibodies against CTLA4, PD1, and PD-L1, as well as other immunotherapies.
  • Vaccines
  • Adoptive Cell Transfer [ACT]: the transfer of immune cells that have been selected or engineered to attack tumors, particularly with tumor infiltrating lymphocytes [TIL].
  • Targeted Therapies: designed to inhibit mutations and pathways that promote the growth and survival of tumor cells. Some clinical trials are designed for patients with specific mutations in their tumors (for example, BRAF), and thus require testing to determine if patients are appropriate for a given therapy.
  • Chemotherapy
  • Combinations: trials to combine different systemic treatments, as well as trials to test whether combining systemic treatments with surgery, radiation, and other therapies can improve outcomes in patients.

 

In addition to performing clinical trials to test the safety and effectiveness of new treatments, many investigators are also working to determine why therapies work in some patients but not in others, as well as why they sometimes stop working after initial success.  This research depends on the participation of patients in clinical trials, and sometimes in parallel studies that allow researchers to analyze samples of blood, tumor tissue, or other materials.  Some studies have the potential to help patients with melanoma currently, but also to help melanoma patients in the future.

 

For more information on clinical trials click here.

 

To learn about radiation therapy click here.

 

To learn about Stage IV click here.

 

Treatments for Brain Metastases

Currently, treatment options for brain metastases depend on the number of metastases, their size and location, the presence of extracranial metastases (melanoma outside of the brain and spinal cord), and the performance status of the patient.

 

Treatment Goal Comments
Surgery

Well-established and a standard treatment for melanoma brain metastases.

Is potentially curative.

Usually reserved for patients with < 3 brain metastases. Patients with many tumors or tumors in critical areas of the brain are usually not candidates for surgery.
Radiation SRS (stereotactic radiosurgery) focuses on certain spots in the brain. One newer type, gamma knife, is able to treat metastases more quickly than previous radiation machines. SRS can result in long-term control of brain metastases for some patients. An alternative to surgery for patients with <3 brain metastases. At some centers, gamma is used to treat more than 3 brain metastases.
WBXRT (whole-brain radiation treatment) treats brain metastases that can be seen as well as tumor cells that are too small to be identified by MRI or CT scans. WBXRT is likely to slow the growth of tumors, but it is generally not thought to be curative. Typically used in patients who have too many brain metastases to be suitable for surgery or SRS.
Chemotherapy Drugs such as fotemustine and temozolomide are able to get into the brain tissue and may be used to treat patients with brain metastases.

 

While these therapies may provide dramatic responses in some patients, they can only slow the growth of tumors in the brain; they are not curative. The majority of tumors will eventually start to grow again.

Most standard chemotherapy drugs cannot penetrate the blood-brain-barrier and therefore have no effect on brain tumors.
Targeted Therapy For most patients with BRAF V600 mutations, certain BRAF inhibitors (for example, dabrafenib and vemurafenib) can cause, significant shrinkage of brain metastases. These BRAF inhibitors are usually not curative, although, they can slow tumor growth. In a phase II clinical trial of Tafinlar in patients with a BRAF V600E mutation, 18% of the patients showed a shrinkage in their brain metastases.
Immunotherapy Immunotherapies (for example, ipilimumab) can sometimes result in the shrinkage of brain metastases.  Initial data from clinical trials suggests that in some patients the control of the brain metastases can be durable (> 2 years).
The existing data suggests that ipilimumab has the greatest chance of producing clinical benefit when brain metastases are relatively small and patients do not require steroids to controls symptoms.  Additional trials with other immunotherapies will be needed to test/define their appropriate use.
Supportive Care Designed to reduce pain, confusion, and/or seizures but not intended to slow or eliminate the growth of the tumors. Steroids (ie dexamethasone) are frequently used to reduce swelling in the brain caused by metastases, which may help ease symptoms of pain and confusion.

Often used when the physician feels that active treatment will do more harm than good, or it is the patients' preference not to be treated.

Recurrent Melanoma

Treatment of recurrent melanoma depends on the stage of the original melanoma, the initial treatment and the type of recurrence. Patients with distant recurrences have the same treatment options as those with Stage IV melanoma.

 

Treatment
Goal
Surgery
In general, isolated local (skin) recurrence may be treated by surgical approaches similar to that recommended for a primary melanoma.

Therapeutic
Lymph
Node
Dissection
(TLND)

Lymph node recurrence, when isolated, may be treated by therapeutic lymph node dissection (TLND).

 

Surgery to remove all regional lymph nodes from the area where cancerous lymph nodes were found. If your melanoma was found by SLNB, then no additional testing is necessary.

 

The goal of the surgery is to prevent further spread of the disease through the lymphatic system. Current studies are underway to show whether TLND may also prolong survival.

TLND also plays an important role in controlling the pain often caused by untreated lymph node disease.

 

To learn about the recurrence of melanoma click here.



IMPORTANT!

All Stage IV patients should be tested for the BRAF, NRAS, and C-KIT mutations, in order to find out if they are eligible for targeted therapy or a clinical trial using targeted therapy.

FAST FACTS

  • After you receive a diagnosis of melanoma, your doctor will discuss a course of action based on a number of factors including your age, general health, and the location, type, and stage of your disease.
  • Treatments are available for all people with melanoma, regardless of the stage of disease.
  • The decision on whether to start treatment, or which treatment to use should be made by discussion with your doctor, based on your specific needs and melanoma.
  • If you have questions about your treatment plan you should seek a second opinion from a melanoma expert.