An Italian Retrospective Survey On Bone Metastasis In Melanoma: Impact Of Immunotherapy And Radiotherapy On Survival
Background: We performed a multicenter retrospective observational study to investigate the impact of clinicalpathological features and therapeutic strategies on both the complications and survival of patients with bone metastases from malignant melanoma.
Patients and Methods: A total of 305 patients with melanoma and radiological evidence of BMs were retrospectively enrolled from 19 Italian centers. All patients received conventional treatments in accordance with each own treating physicians practice. Both univariate and multivariate models were used to explore the impact of melanoma features, including skeletal-related events , and different treatments on both overall survival and time-to-SREs. The chi-squared test evaluated the suitability of several parameters to predict the occurrence of SREs.
Based on our results, patients undergoing immunotherapy and palliative RT showed an OS benefit suggestive of a possible additive effect. The apparent protective role of bone targeting agent use on SREs observed in our analysis should deserve prospective evaluation.
Treatments For Cancer In Your Bones
Some treatments shrink the cancer. Others protect your bones from the damage the cancer can cause. And some therapies ease your symptoms to help you feel better.
Targeted therapy. These medicines go after substances that help cancer cells grow and survive. Theyâre designed to kill cancer without harming healthy cells.
Tyrosine kinase inhibitors target proteins that help cancer cells and their blood vessels grow. These drugs include:
Bevacizumab is another type of targeted therapy. It blocks a protein called VEGF, which helps tumors grow new blood vessels.
- Checkpoint inhibitors, such as nivolumab
Radiation. In this treatment, a machine beams high-energy X-rays to kill cancer cells inside your body. It can relieve pain in your bones. It also can prevent weak bones from breaking. If you already have a fracture, killing cancer cells with radiation will help it heal faster.
Surgery to remove cancer from your bone can relieve pain, prevent fractures, and make it easier for you to move around.
Melanoma: How To Prevent Detect It
Melanoma is one of the most common cancers in young adults, especially young women, according to the American Cancer Society.
More than 76,000 new cases will be diagnosed this year in the U.S. and more than 10,000 people will die from the disease, it estimates.
Studies have suggested that the more moles or atypical moles someone has increases skin cancer risk, but new research found that most melanoma patients had few moles and no atypical moles. The study, published Wednesday in JAMA Dermatology, is a reminder that melanoma isn’t always linked to mole count.
Indoor tanning can cause skin cancers including melanoma, the Centers for Disease Control and Prevention warns. Daly used sun beds as a teenager, but as an adult, she was very aware of sun exposure and would always cover up, especially after she had the mole removed, her brother said.
To prevent melanoma and spot it early:
- Protect your skin when youre in the sun.
- Watch your moles and if you ever notice a spot that is changing or that represents an ugly duckling stands out as distinct from others that you have show it to your doctor immediately.
Read Also: Stage 3 Melanoma Survival Rate
Exploring Mechanisms Of Metastasis
In humans, breast cancer can recur in patients more than a decade after the disease has been treated. In most of these cases, the cancer has metastasized to bone.
Our study addresses a difficult clinical problemthe disease can recur in patients who thought they had been cured of breast cancer years earlier, explained Dorothy A. Sipkins, M.D., Ph.D., of the Duke Cancer Institute, who led the research.
Past work had suggested that these late recurrences may be caused by the emergence of breast cancer cells that had previously spread to the boneknown as micrometastasesbut had remained dormant. But the mechanisms involved in the spread of breast cancer to bone are poorly understood.
E-selectin is an adhesion proteina protein that helps cells bind to other cells and to their surroundingsthat is present on the surfaces of cells lining blood vessels. Because the protein has been associated with the homing of hematopoietic stem cells into the bone marrow at certain regions, or niches, where it is highly expressed, the researchers investigated whether breast cancer cells could co-opt E-selectin to also mediate their movement into the bone.
E-selectin is a sticky protein expressed by certain blood vessels that serves as a portal into the bone marrow, explained Cynthia Dunbar, M.D., of the Hematology Branch at the National Heart, Lung, and Blood Institute, who was not involved in the research. The bone marrow seems to provide a protective home for breast cancer cells.
What Else Should I Know About Treatment For Advanced Melanoma
Thanks to research breakthroughs, more patients diagnosed with advanced melanoma are living longer some for years.
Because these breakthrough are relatively recent, its important to:
Work with a team of melanoma specialists.
Ask your melanoma specialists if any of the newer treatments are appropriate for you.
Realize that no one treatment works for everyone, so you may need to try different treatments or combine treatments.
Researchers continue to study advanced melanoma, and next-generation treatments are now being studied in clinical trials. If you want to know whether you are a match for a trial, you can find out if there are any relevant trials at, Clinical Trial Finder.
Related AAD resources
ReferencesChukwueke U, Batchelor T, et al. Management of brain metastases in patients with melanoma. J Oncol Pract. 2016 12:536-42.
Emory Medical Center. A year in the life: Jimmy Carter shares his cancer experience. Posted July 11, 2016. Last accessed March 26, 2018.
Podlipnik S, Carrera C, et al. Performance of diagnostic tests in an intensive follow-up protocol for patients with American Joint Committee on Cancer stage IIB, IIC, and III localized primary melanoma: A prospective cohort study. J Am Acad Dermatol. 2016 75:516-24.
Nordmann N, Hubbard M, et al. Effect of gamma knife radiosurgery and programmed cell death 1 receptor antagonists on metastatic melanoma. Cureus. 2017 9: e1943.
You May Like: Well Differentiated
How Can Melanoma Spread To The Brain
While melanoma normally begins in the skin, cancer cells sometimes grow and break away from the place where the cancer began. The cells that break away often travel to nearby:
Once in the blood or lymph , the melanoma cells often travel to the lungs, liver, spleen, or brain.
Cancer cells growing bigger than normal cells
Cancer cells can grow, break off, and spread.
Amelanotic Melanoma Risk Factors
Though these risk factors dont mean someone will develop melanoma, they are linked with increased risk of all forms of the cancer, including amelanotic melanoma.
Exposure to UV rays: Damage to DNA in your skin cells, from exposure to UV rays , is the No. 1 risk factor for all types of melanoma. Both natural sunlight and artificial tanning lamps increase the risk of developing this type of skin cancer. Getting many sunburns during childhood also has been associated with the development of melanoma on the chest, back and legs.
Moles: If you have a lot of moles or have atypical moles, youre at greater risk of developing melanoma. Additionally, patients with the inherited condition dysplastic nevus syndrome are at a high risk of developing melanoma during their lifetime.
Fair skin: People who have light-colored, freckled skin and blond or red hair with blue or green eyes are at a greater risk of developing melanoma. This is especially true if your skin tends to burn as opposed to tanning when exposed to UV rays.
Race: Melanoma is 20 times more likely for white people than it is for black people, according to the American Society of Clinical Oncology .
Family and personal history: If your close relatives have a history of melanoma, youre at increased risk. If youve previously had melanoma or another type of skin cancer, the chance of developing it again is also greater.
You May Like: Is Stage 3 Melanoma Curable
How Is Melanoma Treated When It Spreads To The Brain
Scientists have learned that attacking this cancer with different types of treatment can improve how well each individual treatment works.
According to the Emory Medical Center, doctors used this approach to treat Mr. Carter. His treatment began with surgery. This was followed by radiation therapy and immunotherapy .
Keep all of your follow-up appointments
Research shows that the earlier melanoma is found in the brain, the more effective treatment can be.
When melanoma spreads to the brain, the treatment plan may include:
Surgery: Doctors may recommend surgery to:
Remove the tumor.
Reduce the size of a tumor. This can make other treatments more effective.
Take out some of the tumor so that it can be examined. This allows your doctors to choose the medication most likely to help.
Relieve symptoms, such as headaches.
While surgery can remove existing tumors, other treatment often follows. This approach helps to kill cancer cells that surgery cannot remove.
Following surgery, you may be treated with radiation, medication, or both.
Radiation therapy: Radiation therapy helps to kill cancer cells that are too small to be seen. It may also be a treatment option when several tumors have formed in the brain or surgery is too risky.
Two types of radiation therapy are used to treat melanoma in the brain:
The type of radiation used depends on many considerations, including the number of tumors and where they appear in the brain.
Supportive care can:
Drugs To Treat Bone Metastases
The drugs used most often for treating bone problems in people with bone metastases are the bisphosphonate drugs pamidronate and zoledronic acid and the drug denosumab . These drugs are given intravenously or subcutaneously . Most patients are treated once a month at first, but may be able to be treated less often later on if they are doing well. Treatment with one of these drugs can help prevent further bone damage and events related to weakened bones such as fractures, hypercalcemia, and spinal cord compression.
These treatments can have a rare but serious side effect called osteonecrosis of the jaw . Patients complain of pain and doctors find that part of the jawbone has died. This can lead to an open sore that doesnt heal or tooth loss in that area. The jawbone can also become infected. Having jaw surgery or having a tooth removed can trigger this problem. It is best to avoid these procedures while you are taking one of these medicines. One way to avoid these dental procedures is to maintain good oral hygiene by flossing, brushing, making sure that dentures fit properly, and having regular dental checkups. Any tooth or gum infections should be treated right away. If ONJ does occur, the doctor will stop the bone medicine.
You May Like: Prognosis For Skin Cancer
What Are The Symptoms Of Melanoma That Has Spread
Melanoma that has spread from the skin to other areas of the body is known as metastatic melanoma. However, since melanoma often first presents itself as an abnormal mole, many people with this malignancy can receive a diagnosis before the cancer has spread. This mole may be asymmetrical, have an uneven border, have an inconsistent color, be large or change over time. A melanoma may also appear as a sore or itchy bump, a tender nodule or a patch of skin that is scaly or bleeding. In some cases, early signs of melanoma are not present. For example, if the cancer starts in a mucous membrane rather than on the skin, a mole may not be present.
Red Flag #: Abdominal Pain And Tenderness
Early on, there may be no noticeable symptoms that melanoma has spread to the liver. When symptoms do show up, they commonly include an enlarged, hard, or tender liver and pain in the upper right area of your abdomen, just below your ribs. Other signs cancer has spread to the liver are similar to symptoms of liver disease: fluid buildup in the belly and yellowing of the skin and eyes .
Also Check: What Is Stage 2 Squamous Cell Carcinoma
What Is Amelanotic Melanoma
Amelanotic melanoma is an aggressive type of skin cancer that doesn’t produce the pigment melanin, which gives most melanomas their dark appearance. As a result, they dont look like other melanomas. Instead, they may appear skin-colored, pink or even reddish, with gray or brownish edges.
Amelanotic melanomas may be easily confused with basal or squamous cell carcinomas, or misidentified as harmless scars or moles, which is dangerous, because they often spread faster than the more easy-to-recognize melanomas.
Solitary Bone Metastases Of Melanoma
Bone is a common site of melanoma metastatic spread, but usually occurs in patients who already have widespread metastases thus, it is a late site of metastasis. In most clinical series, bone metastases from malignant melanoma are less frequent than liver or brain metastases, ranging from 11 to 17% 23. Nevertheless, the autopsy series have shown that skeletal involvement is more common than it has been published in most clinical series 2426. In the literature, it has been reported that only in 3.7% of patients bone was found to be the first and only site of disease and there is limited literature on solitary bone metastasis arising from malignant melanoma that has been confirmed pathologically, as in our study. Studies have shown that 80% of bone metastases from malignant melanoma are found in the axial skeleton 27. When a lesion of malignant melanoma is encountered within bone, two possibilities are considered for its origin: skeletal metastasis of malignant melanoma or direct bone invasion of malignant melanoma of soft parts. However, in a small subset of patients, it can represent the first site of metastatic recurrence 27,28.
For our knowledge, this is the largest case series of solitary bone metastases arising from malignant melanoma that has been confirmed pathologically.
You May Like: What Type Of Skin Cancer Spreads The Fastest
Red Flag #: Swollen Lymph Nodes
If melanoma spreads, it often goes to the lymph nodes first, says Melinda L. Yushak, M.D., assistant professor of hematology and medical oncology at Emory University School of Medicine in Atlanta. The cancer cells will first travel to the nodes closest to the original tumor, she says. Lymph nodes are located throughout your entire body, but large clusters are found in the neck, underarms, chest, abdomen, and groin. If the cancer has made its way to the lymph nodes, it usually wont be painful, but theyll feel swollen or even hard to the touch, Dr. Zaba says.
What Symptoms Develop When Melanoma Spreads To The Brain
Many patients feel the same. They dont have any symptoms that would indicate the cancer has spread.
If your doctor thinks that you are at risk for melanoma spreading to your brain, you may need an MRI. An MRI can find cancer in the brain before you have symptoms. Not everyone who has melanoma needs to have an MRI.
When melanoma spreads to the brain and symptoms occur, they may include:
Paralysis on one side of your body
Problems with your eyesight
Symptoms tends to occur when the cancer has spread to more than one area of the brain. A large tumor can also cause symptoms.
Recommended Reading: Life Expectancy Metastatic Melanoma
Staging For Basal Cell And Squamous Cell Carcinoma
Basal cell and squamous cell carcinoma usually do not spread to other parts of the body. On rare occasions, a persons lymph node may be removed to find out if the cancer has spread, which is called metastasis. Lymph nodes are bean-shaped organs that help fight infection. The doctor may recommend other tests to determine the extent of the disease, including blood tests, chest x-rays, and imaging scans of the lymph nodes and nerves, liver, bones, and brain, but this is uncommon.
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.
Don’t Miss: Melanoma Bone Cancer Symptoms
Symptoms Of Metastatic Melanoma Other Than A Mole
Other symptoms of this type of cancer may not appear until a later stage, when the melanoma has metastasized to another area of the body. Metastatic melanoma most often spreads to the lymph nodes, brain, bones, liver or lungs, and the additional symptoms experienced at this late stage will depend on where the melanoma has spread. For example:
- Lungs A persistent cough or shortness of breath
- Brain Headaches or seizures
- Lymph nodes Swelling of the lymph nodes
- Liver Loss of appetite or unexplained weight loss
- Bone Bone pain or unusual fractures