Ewing Sarcoma – Causes, Symptoms, Treat,ment

Ewing sarcoma (ES) is a highly malignant tumor composed of small round cells. The origin of this tumor was unclear until recently, when electron microscopic and immunohistochemical analyses suggested that it is of neurogenic origin [1–3]. ES tumors often express a balanced translocation involving the EWS gene on chromosome 22 and a member of the ETS family of transcription factors [4, 5]. With the development of diagnostic radiological techniques such as magnetic resonance imaging (MRI), extraskeletal masses can be depicted clearly and the tumor area can be accurately evaluated. Due to improvements in intensive chemotherapy, the prognosis of ES patients has improved markedly [6–16]. The current chemotherapy protocols used to treat ES include various combinations of the following six drugs: doxorubicin (DOX), cyclophosphamide (CPM), vincristine (VCR), actinomycin-D (ACT-D), ifosfamide (IFO), and etoposide (ETO). Local ES lesions are usually treated via surgical excision or radiotherapy, or a combination of both. In cases in which surgical excision is not possible due to the large size of the tumor, its anatomical location, or the fact that the acquired surgical margin is not sufficient to achieve local control, pre- or postoperative radiotherapy is usually selected [14].

Ewing sarcoma is a type of tumor that forms in bone or soft tissue.

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, neck, retroperitoneum (area in the back of the abdomen behind the tissue that lines the abdominal wall and covers most of the organs in the abdomen), or other areas.

Ewing sarcoma is most common in adolescents and young adults (teens through mid-20s).

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.

Undifferentiated round cell sarcoma may also occur in the bone or soft tissue.

Undifferentiated round cell sarcoma usually occurs in the bones or the muscles that are attached to bones and that help the body move. There are three types of undifferentiated round cell sarcoma that are treated like Ewing sarcoma:

• Undifferentiated round cell sarcoma with BCOR-CCNB3 rearrangements. This type of bone tumor usually forms in the pelvis, arms, or legs. It may spread to other parts of the body. In this type of round cell sarcoma, the BCOR gene is joined to the CCNB3 gene. To diagnose round cell sarcoma, the tumor cells are checked for this gene change.
• Undifferentiated round cell sarcoma with CIC-DUX4 rearrangements. This type of soft tissue tumor usually forms in the trunk, arms, or legs. It is most common in males and in young adults between 21 and 40 years of age. In this type of round cell sarcoma, the CIC gene is joined to the DUX4 gene. To diagnose round cell sarcoma, the tumor cells are checked for this gene change.
• Undifferentiated round cell sarcoma with CIC-NUTM1 rearrangements. This type of soft tissue tumor usually forms in the central nervous system, but it can also form in the trunk. It is most common in younger patients.

Signs and symptoms of Ewing sarcoma include swelling and pain near the tumor.

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.

Tests that examine the bone and soft tissue are used to diagnose and stage Ewing sarcoma.

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

To plan treatment, it is important to know whether the cancer 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 health 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).

  

  Magnetic resonance imaging (MRI) of the abdomen. The child lies on a table that slides into the MRI scanner, which takes pictures of the inside of the body. The pad on the child’s abdomen helps make the pictures clearer.

• 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.

  

  Computed tomography (CT) scan of the abdomen. The child lies on a table that slides through the CT scanner, which takes x-ray pictures of the inside of the abdomen.

• 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.

  

  Positron emission tomography (PET) scan. The child lies on a table that slides through the PET scanner. The head rest and white strap help the child lie still. A small amount of radioactive glucose (sugar) is injected into the child’s vein, and a scanner makes a picture of where the glucose is being used in the body. Cancer cells show up brighter in the picture because they take up more glucose than normal cells do.

• 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 scan. A small amount of radioactive material is injected into the child’s vein and travels through the blood. The radioactive material collects in the bones. As the child lies on a table that slides under the scanner, the radioactive material is detected and images are made on a computer screen.

• 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.

  

  Bone marrow aspiration and biopsy. After a small area of skin is numbed, a bone marrow needle is inserted into the child’s hip bone. Samples of blood, bone, and bone marrow are removed for examination under a microscope.

• 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.

A biopsy is done to diagnose Ewing sarcoma.

Tissue samples are removed during a biopsy so they can be viewed under a microscope by a pathologist to check for signs of cancer. It is helpful if the biopsy is done at the same center where treatment will be given.

• Needle biopsy: For a needle biopsy, tissue is removed using a needle. This type of 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 the best site to place the needle or biopsy incision. The selection of the biopsy site is important. A biopsy site that is not properly selected may result in more extensive surgery to remove the tumor or a larger area that is treated with 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 the chromosomes of cells in a sample of tissue are counted and checked for any changes, such as broken, missing, rearranged, or extra chromosomes. Changes in certain chromosomes may be a sign of cancer. Cytogenetic analysis is used to help diagnose cancer, plan treatment, or find out how well treatment is working.
• Immunohistochemistry: A laboratory test that uses antibodies to check for certain antigens (markers) in a sample of a patient’s tissue. The antibodies are usually linked to an enzyme or a fluorescent dye. After the antibodies bind to a specific antigen in the tissue sample, the enzyme or dye is activated, and the antigen can then be seen under a microscope. This type of test is used to help diagnose cancer and to help tell one type of cancer from another type 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 the cells, such as size, shape, and the presence of tumor (or other) markers on the cell surface. The cells from a sample of a patient’s blood, bone marrow, or other tissue are stained with a fluorescent dye, placed in a fluid, and then passed one at a time through a beam of light. The test results are based on how the cells that were stained with the fluorescent dye react to the beam of light.

Certain factors affect prognosis (chance of recovery).

The factors that affect prognosis are different before and after treatment.

Before any treatment is given, 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 when the tumor is diagnosed.
• Whether the tumor has caused any broken bones.
• Whether the LDH level in the blood is higher than normal.
• Whether the tumor has certain gene changes.
• Whether tumor DNA has been found in the blood.
• Whether the patient is younger than 15 years.
• The patient’s sex.
• Whether the patient has had treatment for a different cancer.
• Whether the tumor has just been diagnosed or has recurred (come back).

After treatment is given, prognosis is affected by:

• Whether the tumor was completely removed by surgery.
• Whether the tumor responded 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.
• Whether the cancer came back where it first formed or in other parts of the body.

The results of diagnostic and staging tests are used to find out if cancer cells have spread.

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 describe the tumors as localized or metastatic.

Ewing sarcoma is described as localized, metastatic, or recurrent.

Ewing sarcoma is described as localized, metastatic, or recurrent.

There are three ways that cancer spreads in the body.

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.

There are different types of treatment for children with Ewing sarcoma.

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

Children with Ewing sarcoma should have their treatment planned by a team of health care providers who are experts in treating cancer in children.

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.

Four types of standard treatment are used:

New types of treatment are being tested in clinical trials.

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

Treatment for Ewing sarcoma may cause side effects.

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.

Patients may want to think about taking part in a clinical trial.

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.

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 (coming back) 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 NCI’s clinical trials search webpage. Clinical trials supported by other organizations can be found on the ClinicalTrials.gov website.

Follow-up tests may be needed.

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.