Comparing Metastatic Melanoma Cells In Lymph Versus Blood
Most studies of cancer cell metastasis in people have focused on cells circulating in the blood. Thats because its much easier to collect patient blood samples than it is to collect samples of lymph, the clear fluid that carries immune cells through vessels of the lymphatic system, Dr. Morrison said.
Dr. Morrisons team found that human melanoma cells injected into lymph nodes in the mice were more likely to form distant tumors than melanoma cells injected into blood.
To study the role of lymph in metastasis, lead investigator Jessalyn Ubellacker, Ph.D., a postdoctoral researcher in Dr. Morrisons lab, figured out how to collect melanoma cells from lymph in mice. This allowed the team to do the first side-by-side comparison of melanoma cells spreading through lymph and through blood in the same animal, Dr. Morrison said.
Next the team found that melanoma cells in lymph experienced less oxidative stress than melanoma cells in blood. That offered a potential explanation for why melanoma cells from lymph nodes were surviving better and better able to form a tumor, Dr. Morrison said.
Further experiments showed that melanoma cells in blood are vulnerable to ferroptosisa form of cell death that occurs when lipids damaged by oxidative stress build up in the outer membrane of a cell. By contrast, melanoma cells from lymph nodes were protected from ferroptosis.
Treating Stage I Melanoma
Stage I melanoma is typically treated by wide excision . The width of the margin depends on the thickness and location of the melanoma. Most often, no other treatment is needed.
Some doctors may recommend a sentinel lymph node biopsy to look for cancer in nearby lymph nodes, especially if the melanoma is stage IB or has other characteristics that make it more likely to have spread. You and your doctor should discuss this option.
If the SLNB does not find cancer cells in the lymph nodes, then no further treatment is needed, although close follow-up is still important.
If cancer cells are found on the SLNB, a lymph node dissection might be recommended. Another option might be to watch the lymph nodes closely by getting an ultrasound of the nodes every few months.
If the SLNB found cancer, adjuvant treatment with an immune checkpoint inhibitor or targeted therapy drugs might be recommended to try to lower the chance the melanoma will come back. Other drugs or perhaps vaccines might also be options as part of a clinical trial.
How Is Melanoma Staged
Melanoma stages are assigned using the TNM system.
The stage of the disease indicates how much the cancer has progressed by taking into account the size of the tumor, whether its spread to lymph nodes, and whether its spread to other parts of the body.
A doctor can identify a possible melanoma during a physical exam and confirm the diagnosis with a biopsy, where the tissue is removed to determine if its cancerous.
But more sophisticated technology, such as PET scans and sentinel lymph node biopsies, are necessary to determine the cancers stage or how far its progressed.
There are five stages of melanoma. The first stage is called stage 0, or melanoma in situ. The last stage is called stage 4. Survival rates decrease with later stages of melanoma.
Its important to note that survival rates for each stage are just estimates. Each person with melanoma is different, and your outlook can vary based on a number of different factors.
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Stage : Melanoma In Situ
The earliest stage of melanoma is stage 0, also known as melanoma in situ or carcinoma in situ. In situ is a Latin phrase that means in position, and this diagnosis means that the cancer cells are present only in the epidermisthe bodys most superficial layer of skinand nowhere else.
This diagnosis has a very good prognosis, Noelani González, MD, an instructor of dermatology at the Mount Sinai Icahn School of Medicine in New York City, tells Health. People with localized melanomas who are treated quickly have a 5-year survival rate of 97%meaning they are, on average, about 97% as likely to still be alive in five years as people who dont have these cancers.
Treatment for this stage cancer involves a wide excision surgery, where the affected skin is cut away and the wound is stitched and bandaged. The skin will be removed with margins, explains Dr. González. That means that some normal skin will also be removed around the edges to make sure there arent any cancer cells left over.
The removed skin is then looked at under a microscope to ensure that all of the cancer was removed with clean margins, says Dr. González. Because stage 0 cancer has not spread to any other tissues or organs, no further treatment is required.
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Taking Care Of Yourself
Hearing that your cancer has spread is scary, but a lot of research is underway to find new treatments. And there are treatments available to try to stop the disease from spreading, so you can live longer.
It’s important to have support and to talk about your fears and feelings, too. Your doctor can help you find a cancer support group.
These tips may help you feel better during melanoma treatment:
- If you lose your appetite, eat small amounts of food every 2 to 3 hours instead of bigger meals. A dietitian can give you other tips on nutrition and eating during your cancer treatment. Ask your doctor for a referral.
- Exercise can help you feel better overall and fight fatigue. But listen to your body, and balance rest and activity.
- Get the kind of emotional support that’s right for you. It could be from family, friends, your cancer support group, or a religious group.
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Treatment Of Stage Iii Melanoma That Cannot Be Removed By Surgery Stage Iv Melanoma And Recurrent Melanoma
For information about the treatments listed below, see the Treatment Option Overview section.
Treatment of stage III melanoma that cannot be removed by surgery, stage IV melanoma, and recurrentmelanoma may include the following:
- Radiation therapy to the brain, spinal cord, or bone.
Treatments that are being studied in clinical trials for stage III melanoma that cannot be removed by surgery, stage IV melanoma, and recurrent melanoma include the following:
- Immunotherapy alone or in combination with other therapies such as targeted therapy.
- For melanoma that has spread to the brain, immunotherapy with nivolumab plus ipilimumab.
- Targeted therapy, such as signal transduction inhibitors, angiogenesis inhibitors, oncolytic virus therapy, or drugs that target certain genemutations. These may be given alone or in combination.
- Surgery to remove all known cancer.
- Systemic chemotherapy.
Use our clinical trial search to find NCI-supported cancer clinical trials that are accepting patients. You can search for trials based on the type of cancer, the age of the patient, and where the trials are being done. General information about clinical trials is also available.
You May Have A Genetic Mutation
Its very likely that your melanoma tumor will have a DNA mutation. These mutations turn off tumor-suppressor genes, allowing cancers to grow out of control, according to the American Cancer Society. Discovering which mutation you have through genetic profiling can help your doctor determine the best course of treatment. Research has shown that about 50% of melanomas contain the BRAF mutation, while others may contain MEK mutations or the less common C-KIT mutation. Most people will only have only one of these mutations.
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Youll Have A Team On Your Side
Once your physician finds out where your stage 4 melanoma has spread, youll be referred to more doctors for treatment. If your tumors are operable, youll be referred to a surgical oncologist, who will perform the surgery. Youll also have a medical oncologist, who will determine your ideal type of treatment, or combination of treatments. Treatments for stage 4 melanoma include immunotherapy, targeted drugs, chemotherapy, and radiation.
Treatment Options For Stage 4 Cancer
Stage 4 cancer is challenging to treat, but treatment options may help control the cancer and improve pain, other symptoms and quality of life. Systemic drug treatments, such as targeted therapy or chemotherapy, are common for stage 4 cancers.
Often, a clinical trial may be an option, offering new treatments to help you fight stage 4 cancer.
Below are the prevailing treatment options for the five most common cancers.
Treatment of stage 4 breast cancer: For cancer that has spread beyond the breast and nearby lymph nodes, systemic drug treatments are typically used. These include:
- Hormone therapy
- Chemotherapy
- Immunotherapy
They may be used alone or in combination, and they may also be determined by the hormone receptor and the HER2 status of the cancer.
Surgery and radiation may be treatment options in specific cases to help improve symptoms caused by a growing tumor, not to get rid of the cancer. The tumor may be removed with surgery or shrunk by radiation therapy if, for example, its:
- Blocking a blood vessel
- Causing a wound
- Affecting the spinal cord
Treatment of stage 4 lung cancer: In general, stage 4 lung cancer is also treated with systemic drug therapies.
Stage 4 lung cancer that has spread to one distant area tends to be treated differently than lung cancer that has spread more widely. For stage 4A cancers, treatment tends to focus on the one site where the cancer has spread.
There may also be clinical trials assessing new treatments for stage 4 melanoma.
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Mouse Models Mimic Metastasis Of Human Melanoma
Metastasis is a highly inefficient process in that the vast majority of cancer cells that try to migrate die before they ever have an opportunity to form a tumor, Dr. Morrison said.
Dr. Morrisons team found previously that one factor limiting the survival of melanoma cells circulating in the blood is that the cells experience a high level of oxidative stress. Oxidative stressan imbalance between free radicals and antioxidants in the bodycauses chemical reactions that can damage proteins, DNA, and lipids in cells and disrupt normal cell processes. However, precisely how oxidative stress kills circulating melanoma cells was not known.
For their studies, the team used a mouse model of metastasis created by transplanting melanoma cells from humans beneath the skin of specially bred mice with weakened immune systems. These mice were used to avoid having the transplanted human cells seen as foreign and attacked by the immune system. The team also used a second mouse model created by transplanting mouse melanoma cells into mice with normal immune systems.
Comparing these two mouse models let the researchers control for potential effects of the immune system on the spread of melanoma, Dr. Salnikow explained.
The study was supported in part by NCIs Patient-Derived Models of Cancer program, which promotes the development of animal models that more closely mirror how tumor cells behave in humans.
Treating Stage 4 Melanoma
If melanoma comes back or spreads to other organs it’s called stage 4 melanoma.
In the past,;cure from stage 4 melanoma was very rare but new treatments, such as immunotherapy and targeted treatments, show encouraging results.
Treatment for stage 4 melanoma is given in the hope that it can slow the cancer’s growth, reduce symptoms, and extend life expectancy.
You may be offered surgery to remove other melanomas that have grown away from the original site. You may also be able to have other treatments to help with your symptoms, such as radiotherapy;and medicine.
If you have advanced melanoma, you may decide not to have treatment if it’s unlikely to significantly extend your life expectancy, or if you do not have symptoms that cause pain or discomfort.
It’s entirely your decision and your treatment team will respect it. If you decide not to receive treatment, pain relief and nursing care will be made available when you need it. This is called palliative care.
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Metastatic Melanoma Life Expectancy
The 5-year survival rate for a metastatic melanoma is about 15% to 20% 7). The 10-year survival is about 10% to 15% 8). The outlook is better if the spread is only to distant parts of the skin or distant lymph nodes rather than to other organs, and if the blood level of lactate dehydrogenase is normal.
- The survival differences among M categories will be useful for clinical trial stratification; however, the overall prognosis of all patients with stage IV melanoma remains poor, even among patients with M1a. For this reason, the Melanoma Staging Committee recommended no stage groupings for stage IV.
Table 2. American Joint Committee on Cancer TNM system for Stage 4 Melanoma
| M |
|---|
- A sore that doesnt heal
- Spread of pigment from the border of a spot into surrounding skin
- Redness or a new swelling beyond the border of the mole
- Change in sensation, such as itchiness, tenderness, or pain
- Change in the surface of a mole scaliness, oozing, bleeding, or the appearance of a lump or bump
Be sure to show your doctor any areas that concern you and ask your doctor to look at areas that may be hard for you to see. Its sometimes hard to tell the difference between melanoma and an ordinary mole, even for doctors, so its important to show your doctor any mole that you are unsure of.
Metastatic melanoma in the brain
Figure 2. Metastatic melanoma in the brain
Recurrence In Other Parts Of The Body
Melanoma can also come back in distant parts of the body. Almost any organ can be affected. Most often, the melanoma will come back in the lungs, bones, liver, or brain. Treatment for these recurrences is generally the same as for stage IV melanoma . Melanomas that recur on an arm or leg may be treated with isolated limb perfusion/infusion chemotherapy.
Melanoma that comes back in the brain can be hard to treat. Single tumors can sometimes be removed by surgery. Radiation therapy to the brain may help as well. Systemic treatments might also be tried.
As with other stages of melanoma, people with recurrent melanoma may want to think about taking part in a clinical trial.
The treatment information given here is not official policy of the American Cancer Society and is not intended as medical advice to replace the expertise and judgment of your cancer care team. It is intended to help you and your family make informed decisions, together with your doctor. Your doctor may have reasons for suggesting a treatment plan different from these general treatment options. Don’t hesitate to ask him or her questions about your treatment options.
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Treating Stage 1 To 2 Melanoma
Treating stage 1 melanoma involves surgery to remove the melanoma and a small area of skin around it. This is known as surgical excision.
Surgical excision;is usually;done;using local anaesthetic, which means you’ll be awake, but the area around the melanoma will be numbed, so you will not feel pain. In some cases, general anaesthetic is used, which means you’ll be unconscious during the procedure.
If a surgical excision is likely to leave a significant scar, it may be done in combination with a skin graft. However, skin flaps are now more commonly used because the scars are usually less noticeable than those resulting from a skin graft.
Read more about flap surgery.
In most cases, once the melanoma has been removed there’s little possibility of it returning and no further treatment should be needed. Most people are monitored for 1 to 5 years and are then discharged with no further problems.
Unusual Moles Exposure To Sunlight And Health History Can Affect The Risk Of Melanoma
Anything that increases your risk of getting a disease is called a risk factor. Having a risk factor does not mean that you will get cancer; not having risk factors doesn’t mean that you will not get cancer. Talk with your doctor if you think you may be at risk.
Risk factors for melanoma include the following:
- Having a fair complexion, which includes the following:
- Fair skin that freckles and burns easily, does not tan, or tans poorly.
- Blue or green or other light-colored eyes.
- Red or blond hair.
Being White or having a fair complexion increases the risk of melanoma, but anyone can have melanoma, including people with dark skin.
See the following PDQ summaries for more information on risk factors for melanoma:
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Patients Can Enter Clinical Trials Before During Or After Starting Their Cancer Treatment
Some clinical trials only include patients who have not yet received treatment. Other trials test treatments for patients whose cancer has not gotten better. There are also clinical trials that test new ways to stop cancer from recurring or reduce the side effects of cancer treatment.
Clinical trials are taking place in many parts of the country. Information about clinical trials supported by NCI can be found on NCIs clinical trials search webpage. Clinical trials supported by other organizations can be found on the ClinicalTrials.gov website.