Ewing Sarcoma

• Ewing sarcoma is a type of tumor that forms in bone or soft tissue.
• Signs and symptoms of Ewing sarcoma include swelling and pain near the tumor.
• Tests that examine the bone and soft tissue are used to diagnose and stage Ewing sarcoma.
• A biopsy is done to diagnose Ewing sarcoma.
• Certain factors affect prognosis (chance of recovery).

Ewing sarcoma is a type of tumor that forms from a certain kind of cell in bone or soft tissue. Ewing sarcoma may be found in the bones of the legs, arms, feet, hands, chest, pelvis, spine, or skull. Ewing sarcoma also may be found in the soft tissue of the trunk, arms, legs, head and neck, abdominal cavity, or other areas.

Ewing sarcoma is most common in adolescents and young adults.

Ewing sarcoma has also been called peripheral primitive neuroectodermal tumor, Askin tumor (Ewing sarcoma of the chest wall), extraosseous Ewing sarcoma (Ewing sarcoma in tissue other than bone), and Ewing sarcoma family of tumors.

These and other signs and symptoms may be caused by Ewing sarcoma or by other conditions. Check with your child's doctor if your child has any of the following:

• Pain and/or swelling, usually in the arms, legs, chest, back, or pelvis.
• A lump (which may feel soft and warm) in the arms, legs, chest, or pelvis.
• Fever for no known reason.
• A bone that breaks for no known reason.

Procedures that make pictures of the bones and soft tissues and nearby areas help diagnose Ewing sarcoma and show how far the cancer has spread. The process used to find out if cancer cells have spread within and around the bones and soft tissues is called staging.

In order to plan treatment, it is important to know if the cancer is in the area where it first formed or if it has spread to other parts of the body. Tests and procedures to detect, diagnose, and stage Ewing sarcoma are usually done at the same time.

The following tests and procedures may be used to diagnose or stage Ewing sarcoma:

• Physical exam and history: An exam of the body to check general signs of health, including checking for signs of disease, such as lumps or anything else that seems unusual. A history of the patient's health habits and past illnesses and treatments will also be taken.
• MRI (magnetic resonance imaging): A procedure that uses a magnet, radio waves, and a computer to make a series of detailed pictures of areas inside the body, such as the area where the tumor formed. This procedure is also called nuclear magnetic resonance imaging (NMRI).
• CT scan (CAT scan): A procedure that makes a series of detailed pictures of areas inside the body, such as the area where the tumor formed or the chest, taken from different angles. The pictures are made by a computer linked to an x-ray machine. A dye may be injected into a vein or swallowed to help the organs or tissues show up more clearly. This procedure is also called computed tomography, computerized tomography, or computerized axial tomography.
• PET scan (positron emission tomography scan): A procedure to find malignant tumor cells in the body. A small amount of radioactive glucose (sugar) is injected into a vein. The PET scanner rotates around the body and makes a picture of where glucose is being used in the body. Malignant tumor cells show up brighter in the picture because they are more active and take up more glucose than normal cells do. A PET scan and a CT scan are often done at the same time. If there is any cancer, this increases the chance that it will be found.
• Bone scan: A procedure to check if there are rapidly dividing cells, such as cancer cells, in the bone. A very small amount of radioactive material is injected into a vein and travels through the bloodstream. The radioactive material collects in the bones with cancer and is detected by a scanner.
• Bone marrow aspiration and biopsy: The removal of bone marrow and a small piece of bone by inserting a hollow needle into the hipbone. Samples are removed from both hipbones. A pathologist views the bone marrow and bone under a microscope to see if the cancer has spread.
• X-ray: An x-ray is a type of energy beam that can go through the body and onto film, making a picture of areas inside the body, such as the chest or the area where the tumor formed.
• Complete blood count (CBC): A procedure in which a sample of blood is drawn and checked for the following:
  • The number of red blood cells, white blood cells, and platelets.
  • The amount of hemoglobin (the protein that carries oxygen) in the red blood cells.
  • The portion of the blood sample made up of red blood cells.
• Blood chemistry studies: A procedure in which a blood sample is checked to measure the amounts of certain substances, such as lactate dehydrogenase (LDH), released into the blood by organs and tissues in the body. An unusual (higher or lower than normal) amount of a substance can be a sign of disease.

• Needle biopsy: For a needle biopsy, tissue is removed using a needle. This type of needle biopsy may be done if it's possible to remove tissue samples large enough to be used for testing.
• Incisional biopsy: For an incisional biopsy, a sample of tissue is removed through an incision in the skin.
• Excisional biopsy: The removal of an entire lump or area of tissue that doesn't look normal.

The specialists (pathologist, radiation oncologist, and surgeon) who will treat the patient usually work together to decide where the needle should be placed or the biopsy incision should be made. This is done so that the biopsy doesn't affect later treatment such as surgery to remove the tumor or radiation therapy.

If there is a chance that the cancer has spread to nearby lymph nodes, one or more lymph nodes may be removed and checked for signs of cancer.

The following tests may be done on the tissue that is removed:

• Cytogenetic analysis: A laboratory test in which cells in a sample of tissue are viewed under a microscope to look for certain changes in the chromosomes.
• Immunohistochemistry: A test that uses antibodies to check for certain antigens in a sample of tissue. The antibody is usually linked to a radioactive substance or a dye that causes the tissue to light up under a microscope. This type of test may be used to tell the difference between different types of cancer.
• Flow cytometry: A laboratory test that measures the number of cells in a sample, the percentage of live cells in a sample, and certain characteristics of cells, such as size, shape, and the presence of tumor markers on the cell surface. The cells are stained with a light-sensitive dye, placed in a fluid, and passed in a stream before a laser or other type of light. The measurements are based on how the light-sensitive dye reacts to the light.

The factors that affect prognosis (chance of recovery) are different before and after treatment.

Before treatment, prognosis depends on:

• Whether the tumor has spread to lymph nodes or distant parts of the body.
• Where in the body the tumor started.
• Whether the tumor formed in the bone or in soft tissue.
• How large the tumor is at when the tumor is diagnosed.
• Whether the LDH level in the blood is higher than normal.
• Whether the tumor has certain gene changes.
• Whether the child is younger than 15 years.
• The patient's sex.
• Whether the child has had treatment for a different cancer before Ewing sarcoma.
• Whether the tumor has just been diagnosed or has recurred (come back).

After treatment, prognosis is affected by:

• Whether the tumor was completely removed by surgery.
• Whether the tumor responds to chemotherapy or radiation therapy.

If the cancer recurs after initial treatment, prognosis depends on:

• Whether the cancer came back more than two years after the initial treatment.
• Where in the body the tumor came back.
• The type of initial treatment given.

The process used to find out if cancer has spread from where it began to other parts of the body is called staging. There is no standard staging system for Ewing sarcoma. The results of the tests and procedures done to diagnose and stage Ewing sarcoma are used to group the tumors into localized or metastatic.

Ewing sarcoma is described based on whether the cancer has spread from the bone or soft tissue in which the cancer began.

Ewing sarcoma is described as either localized or metastatic.

Localized Ewing sarcoma

The cancer is found in the bone or soft tissue in which it began and may have spread to nearby tissue, including nearby lymph nodes.

Metastatic Ewing sarcoma

The cancer has spread from the bone or soft tissue in which it began to other parts of the body. In Ewing tumor of bone, the cancer most often spreads to the lung, other bones, and bone marrow.

Cancer can spread through tissue, the lymph system, and the blood:

• Tissue. The cancer spreads from where it began by growing into nearby areas.
• Lymph system. The cancer spreads from where it began by getting into the lymph system. The cancer travels through the lymph vessels to other parts of the body.
• Blood. The cancer spreads from where it began by getting into the blood. The cancer travels through the blood vessels to other parts of the body.

Cancer may spread from where it began to other parts of the body.

When cancer spreads to another part of the body, it is called metastasis. Cancer cells break away from where they began (the primary tumor) and travel through the lymph system or blood.

• Lymph system. The cancer gets into the lymph system, travels through the lymph vessels, and forms a tumor (metastatic tumor) in another part of the body.
• Blood. The cancer gets into the blood, travels through the blood vessels, and forms a tumor (metastatic tumor) in another part of the body.

The metastatic tumor is the same type of cancer as the primary tumor. For example, if Ewing sarcoma spreads to the lung, the cancer cells in the lung are actually Ewing sarcoma cells. The disease is metastatic Ewing sarcoma, not lung cancer.

Recurrent Ewing sarcoma is cancer that has recurred (come back) after it has been treated. The cancer may come back in the tissues where it first started or in another part of the body.

Different types of treatments are available for children with Ewing sarcoma. Some treatments are standard (the currently used treatment), and some are being tested in clinical trials. A treatment clinical trial is a research study meant to help improve current treatments or obtain information on new treatments for patients with cancer. When clinical trials show that a new treatment is better than the standard treatment, the new treatment may become the standard treatment.

Because cancer in children is rare, taking part in a clinical trial should be considered. Some clinical trials are open only to patients who have not started treatment.

Treatment will be overseen by a pediatric oncologist, a doctor who specializes in treating children with cancer. The pediatric oncologist works with other health care providers who are experts in treating children with Ewing sarcoma and who specialize in certain areas of medicine. These may include the following specialists:

• Pediatrician.
• Surgical oncologist or orthopedic oncologist.
• Radiation oncologist.
• Pediatric nurse specialist.
• Social worker.
• Rehabilitation specialist.
• Psychologist.

Side effects from cancer treatment that begin after treatment and continue for months or years are called late effects. Late effects of cancer treatment may include the following:

• Physical problems.
• Changes in mood, feelings, thinking, learning, or memory.
• Second cancers (new types of cancer). Patients treated for Ewing sarcoma have an increased risk of acute myeloid leukemia and myelodysplastic syndrome. There is also an increased risk of sarcoma in the area treated with radiation therapy.

Some late effects may be treated or controlled. It is important to talk with your child's doctors about the effects cancer treatment can have on your child.

Five types of standard treatment are used:

Chemotherapy

Chemotherapy is a cancer treatment that uses drugs to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. When chemotherapy is taken by mouth or injected into a vein or muscle, the drugs enter the bloodstream and can reach cancer cells throughout the body (systemic chemotherapy). When chemotherapy is placed directly into the cerebrospinal fluid, an organ, or a body cavity such as the abdomen, the drugs mainly affect cancer cells in those areas (regional chemotherapy). Combination chemotherapy is treatment using more than one anticancer drug.

Systemic chemotherapy is part of the treatment for all patients with Ewing tumors. It is often the first treatment given and lasts for about 6 to 12 months. Chemotherapy is often given to shrink the tumor before surgery or radiation therapy and to kill any tumor cells that may have spread to other parts of the body.

Radiation Therapy

Radiation therapy is a cancer treatment that uses high-energy x-rays or other types of radiation to kill cancer cells or keep them from growing. There are two types of radiation therapy:

• External radiation therapy uses a machine outside the body to send radiation toward the cancer.
• Internal radiation therapy uses a radioactive substance sealed in needles, seeds, wires, or catheters that are placed directly into or near the cancer.

External radiation therapy is used to treat Ewing sarcoma.

Radiation therapy is used when the tumor cannot be removed by surgery or when surgery to remove the tumor will affect important body functions or the way the child will look. It may be used to make the tumor smaller and decrease the amount of tissue that needs to be removed during surgery. It may also be used to treat any tumor that remains after surgery and tumors that have spread to other parts of the body.

Surgery

Surgery is usually done to remove cancer that is left after chemotherapy or radiation therapy. When possible, the whole tumor is removed by surgery. Tissue and bone that are removed may be replaced with a graft, which uses tissue and bone taken from another part of the patient's body or a donor. Sometimes an implant, such as artificial bone, is used.

Even if the doctor removes all of the cancer that can be seen at the time of the operation, chemotherapy or radiation therapy may be given after surgery to kill any cancer cells that are left. Chemotherapy or radiation therapy given after surgery to lower the risk that the cancer will come back is called adjuvant therapy.

Targeted Therapy

Targeted therapy is a type of treatment that uses drugs or other substances to identify and attack specific cancer cells without harming normal cells.

Monoclonal antibody therapy is a type of targeted therapy used in the treatment of recurrent Ewing sarcoma. It is being studied for the treatment of metastatic Ewing sarcoma. Monoclonal antibodies are made in the laboratory from a single type of immune system cell. These antibodies can identify substances on cancer cells or normal substances that may help cancer cells grow. The antibodies attach to the substances and kill the cancer cells, block their growth, or keep them from spreading. Monoclonal antibodies are given by infusion. They may be used alone or to carry drugs, toxins, or radioactive material directly to cancer cells.

New types of targeted therapy are being studied.

• Kinase inhibitor therapy is another type of targeted therapy. Kinase inhibitors are drugs that block a protein needed for cancer cells to divide. They are being studied in the treatment of recurrent Ewing sarcoma.
• PARP inhibitor therapy is another type of targeted therapy. PARP inhibitors are drugs that block DNA repair and may cause cancer cells to die. They are being studied in the treatment of recurrent Ewing sarcoma.

High-Dose Chemotherapy With Stem Cell Rescue

High-dose chemotherapy with stem cell rescue is a way of giving high doses of chemotherapy to treat Ewing sarcoma and then replacing blood -forming cells destroyed by cancer treatment. Stem cells (immature blood cells) are removed from the blood or bone marrow of the patient and are frozen and stored. After chemotherapy is completed, the stored stem cells are thawed and given back to the patient through an infusion. These reinfused stem cells grow into (and restore) the body's blood cells. Chemotherapy with stem cell rescue is used to treat recurrent Ewing sarcoma.

This summary section describes treatments that are being studied in clinical trials. It may not mention every new treatment being studied.

Chimeric Antigen Receptor (CAR) T-Cell Therapy

CAR T-cell therapy is a type of immunotherapy that changes the patient's T cells (a type of immune system cell) so they will attack certain proteins on the surface of cancer cells. T cells are taken from the patient and special receptors are added to their surface in the laboratory. The changed cells are called chimeric antigen receptor (CAR) T cells. The CAR T cells are grown in the laboratory and given to the patient by infusion. The CAR T cells multiply in the patient's blood and attack cancer cells. CAR T-cell therapy is being studied in the treatment of Ewing sarcoma that has recurred.

For some patients, taking part in a clinical trial may be the best treatment choice. Clinical trials are part of the cancer research process. Clinical trials are done to find out if new cancer treatments are safe and effective or better than the standard treatment.

Many of today's standard treatments for cancer are based on earlier clinical trials. Patients who take part in a clinical trial may receive the standard treatment or be among the first to receive a new treatment.

Patients who take part in clinical trials also help improve the way cancer will be treated in the future. Even when clinical trials do not lead to effective new treatments, they often answer important questions and help move research forward.

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 (coming back) or reduce the side effects of cancer treatment.

Clinical trials are taking place in many parts of the country.

Some of the tests that were done to diagnose the cancer or to find out the stage of the cancer may be repeated. Some tests will be repeated in order to see how well the treatment is working. Decisions about whether to continue, change, or stop treatment may be based on the results of these tests.

Some of the tests will continue to be done from time to time after treatment has ended. The results of these tests can show if your child's condition has changed or if the cancer has recurred (come back). These tests are sometimes called follow-up tests or check-ups.

Standard treatments for localized Ewing sarcoma include:

• Chemotherapy.
• Surgery and/or radiation therapy.

These treatments and the order they are given depend on the following:

• Where in the body the tumor started.
• How large the tumor is when the cancer is diagnosed.
• Whether the tumor was completely removed by surgery.
• The child's age and general health.
• Whether the treatment will affect important body functions or the way the child will look.

Treatments being studied for localized Ewing sarcoma include:

High-dose chemotherapy with stem cell rescue.

Standard treatments for metastatic Ewing sarcoma include:

• Chemotherapy.
• Surgery.
• Radiation therapy.

These treatments and the order they are given depend on the following:

• Where in the body the tumor started.
• Where the tumor has spread.
• How large the tumor is.
• Whether the treatment will affect important body functions or the way the child will look.
• The child's age and general health.

Treatments being studied for metastatic Ewing sarcoma include the following:

• Combination chemotherapy with or without targeted therapy. Radiation therapy is given to areas of bone where cancer has spread.
• High-dose chemotherapy with stem cell rescue.

There is no standard treatment for recurrent Ewing sarcoma but treatment options may include the following:

• Combination chemotherapy.
• Radiation therapy to bone tumors, as palliative therapy to relieve symptoms and improve the quality of life.
• Radiation therapy that may be followed by surgery to remove tumors that have spread to the lungs.
• High-dose chemotherapy with stem cell rescue.
• Targeted therapy with a monoclonal antibody.

These treatments and the order they are given depend on the following:

• Where in the body the tumor came back.
• The initial treatment given.

Treatment options being studied for recurrent Ewing sarcoma include the following:

• Checking a sample of the patient's tumor for certain gene changes. The type of targeted therapy that will be given to the patient depends on the type of gene change.
• Targeted therapy with a monoclonal antibody.
• Chimeric antigen receptor (CAR) T-cell therapy.
• Targeted therapy with a PARP inhibitor and chemotherapy.