Ewing's sarcoma

Overview

Ewing's sarcoma occurs in the bone or close to the bone, most often in adolescents between the age of 10 and 20. It occurs in about one teenager in 50,000 and accounts for about 30 percent of bone cancers in children. This cancer most often is found in the arms and legs, particularly the thigh bone. It also may involve muscle and soft tissues surrounding the tumor. Ewing's sarcoma cells can spread or metastasize to other areas of the body, including bone marrow and the lungs.

Prior to adolescence, the number of boys and girls affected by Ewing's sarcoma is equal. After adolescence, however, the number of men with the disease is slightly higher than women. This may be due to the increased rate of growth among males during adolescence.

Signs & symptoms

The following are the most common symptoms of Ewing's sarcoma. Each child, however, may experience symptoms differently.

• Pain around the site of the tumor
• Swelling and redness around the site of the tumor
• Fever
• Weight loss and decreased appetite
• Fatigue
• Paralysis and incontinence if the tumor is in the spinal region
• Symptoms related to nerve compression from a tumor such as numbness, tingling and paralysis

Diagnosis

In addition to a complete medical history and physical examination of your child, diagnostic procedures for Ewing sarcoma will include an X-ray examination of the painful area. There may be multiple diagnostic tests such as:

• Bone scans — A nuclear imaging method to detect bone diseases and tumors and determine the cause of bone pain or inflammation.
• Computed tomography (CT or CAT) scan — With the help of computers, X-rays produce images of thin cross sections of the body to provide more detail than conventional X-rays. CT scans often are used to supplement other diagnostic X-rays. The CT scan of the chest is essential to look for any cancer that may have spread to the lungs.
• Magnetic resonance imaging (MRI) — Magnetic resonance imaging (MRI) uses magnets, rather than X-rays, to produce detailed images of the body. The MRI machine sends radio waves into the body and then measures the response with a computer to produce an image or picture. MRIs are used for certain types of tumors because they can produce a better image than X-rays.
• Blood tests — A complete blood count (CBC) will show abnormalities in the blood. An abnormal CBC result might suggest the spread of cancer to the bone marrow. A blood test for levels of an enzyme called lactate dehydrogenase (LDH) should be obtained. Elevation of the serum LDH level at diagnosis is associated with Ewing's sarcoma and other cancers. The red blood cell sedimentation rate also may be elevated in Ewing's sarcoma.
• Biopsy — Although the results of imaging studies may strongly suggest that cancer is present, a biopsy or tissue test is the only way to be certain. A biopsy is also the only way to distinguish a Ewing's sarcoma from other types of cancer. If the tumor involves bone, a doctor experienced in the treatment of Ewing's sarcoma should perform a biopsy. Proper planning of the biopsy location and technique can prevent later complications and reduce the amount of surgery during treatment.

Biopsies

There are several ways to obtain a sample of the tumor for diagnosis. If the tumor is small and in a good location, the surgeon can completely remove it while your child is under general anesthesia. This is often called an excisional biopsy.

If the tumor is large or cannot be removed without risk to adjacent vital tissue, part of the tumor is removed in an incisional biopsy.

A small sample also can be taken by a needle biopsy, which involves placing a needle through the skin into the tumor. This technique usually isn't used for bone tumors.

If your child is going to have surgery, you may be asked to allow the surgeon to obtain extra tissue for additional studies. No matter what method is used, tissue will be sent to a pathologist, a doctor specializing in diagnosing diseases by laboratory tests.

If your child is going to have general anesthesia for the bone biopsy, the surgeon also may plan other procedures while your child is asleep, to avoid performing more operations than necessary. For example, if your child is thought to have cancer in the chest or elsewhere, the surgeon may want to obtain a biopsy sample of these suspected lumps while your child is still asleep. The pediatric hematologist (blood specialist) and oncologist (cancer specialist) also may perform bone marrow biopsies to determine if the cancer has spread.

At the time of the bone biopsy, a pathologist may examine the tissue under the microscope to determine if it is cancer while your child is still asleep. If it is Ewing's sarcoma, the surgeon can place a central venous access catheter for cancer treatment, an intravenous tube, into the blood vessel of your child's chest during the same operation.

If a biopsy indicates Ewing's sarcoma, additional studies may be performed since Ewing's sarcoma shares some of the same characteristics of other childhood cancers.

• Immunohistochemistry — A portion of the sample is treated with special laboratory antibodies to identify substances that are found in Ewing's sarcoma cells, but not in other types of cancer. Additional chemicals or stains are added so cells containing these substances change color and can be easily recognized under a microscope.
• Cytogenetics — Close examination of chromosomes from Ewing's sarcoma cells usually reveals translocations, which means that part of one chromosome breaks off and attaches to another chromosome. Ewing's sarcoma cells have translocations involving chromosomes 11 and 22 as well as chromosomes 21 and 22. These characteristics can help distinguish Ewing's sarcoma from other types of cancer.
• Reverse transcription polymerase chain reaction (RTPCR) — This test is another way to recognize translocations in Ewing's sarcoma cells. Instead of using a microscope to look for the chromosomal changes as in cytogenetic testing, RTPCR relies on chemical analysis of the RNA, a substance related to DNA, from genes affected by the translocation. RTPCR testing is more sensitive than cytogenetics in detecting translocations in Ewing's sarcoma cells. It can be used to confirm the type of tumor and may prove useful in monitoring for residual or recurrent cancer after treatment.
• Bone Marrow Aspiration and Biopsy — Cells are removed from bone marrow, the spongy network of tissues inside the bones, to check for signs of cancer. Depending upon the diagnosis, this procedure may be done periodically throughout your child's treatment to determine whether cancerous cells have spread to the bone marrow. A bone marrow aspiration and biopsy usually takes 15 to 20 minutes to complete.

Bone Marrow Aspiration and Biopsy

Understandably, bone marrow aspirations may be frightening to you and your child. A local quick-acting anesthetic is injected deep under the skin to numb the puncture site and help control pain. Whenever possible, we give you the option of having the procedure performed under general anesthesia. In the aspiration, a sample of the liquid part of bone marrow is removed.

Immediately following a bone marrow aspiration, your child also may undergo a bone marrow biopsy to remove a small core of bone marrow. This procedure may be necessary to confirm the presence of cancer since the liquid may not contain enough cells.

A bone marrow biopsy usually is performed at the same site as the aspirate. Although the biopsy needle may look frightening, only a very small sample of the spongy bone marrow is removed, using a procedure similar to bone marrow aspiration. The difference is that a side-to-side motion of the needle is used to take out a small sample of the spongy marrow, which is the most painful part of the procedure.

Staging of Ewing's Sarcoma

There are two primary stages of Ewing's sarcoma:

• Localized tumor — A localized tumor is confined to the tissue where it developed and may also include nearby tissues, such as muscle or tendons. An Ewing's sarcoma is considered localized only after appropriate imaging studies, such as X-rays, CT and MRI scans, and the bone marrow biopsy and aspirate do not detect distant spread to other organs. Even when imaging studies do not show metastases, most patients are assumed to have micrometastases or small areas of cancer that have spread and can be found only by examining tissue samples under the microscope.
• Metastatic tumor — A metastatic tumor has spread from its original location to other parts of the body, such as the lungs or to other bones and bone marrow not directly connected to the bone where the tumor started. Less common sites of Ewing's sarcoma metastases include the liver and lymph nodes.

Treatment

A treatment program for Ewing's sarcoma may include several approaches such as surgery, radiation and chemotherapy.

Surgery

Surgery is used to remove a tumor or remove any tumor left after chemotherapy, which typically lasts about nine weeks. Surgery is performed if complete removal of the tumor is possible without damage to vital tissue or organs.

Radiation Therapy

Radiation therapy is a painless procedure similar to X-rays. During therapy, a machine aims beams of high-energy X-rays at the cancer site to kill tumor cells. Some normal cells are damaged as well, but healthy cells have a greater ability to repair damage than do tumor cells. The goal is to damage normal cells as little as possible, while injuring tumor cells so they die or are unable to repair or reproduce themselves. Radiation therapy is used in combination with chemotherapy and sometimes surgery. Radiation for these tumors usually is external radiation from outside the body. Studies are evaluating the effectiveness of radiation implanted in the body during surgery.

Chemotherapy

Chemotherapy uses drugs to kill cancer cells. These drugs may be taken by pill, or injected in a vein or muscle. Chemotherapy is called a systemic treatment because the drug enters the blood stream, travels through the body and can kill cancer cells throughout the body. When more than one drug is used, the treatment is called combination chemotherapy. For treating the Ewing's family of tumors, surgery or radiation often is used to remove the local tumor and chemotherapy is used to kill any cancer cells that remain in the body.

Myeloablative Therapy

A supplement to the treatment options listed above is myeloablative therapy with stem cell support. This usually is reserved for patients who have resistant disease, recurrence of disease or widely disseminated disease. Myeloablative therapy is a very intense regimen of chemotherapy to destroy all cells that divide rapidly. These cells include some blood cells and hair cells, as well as cancer cells. Stem cells are self-renewing cells that create all of the other various types of blood cells. Stem cell support involves enriching the stem cells to increase the number of these important cells circulating in the blood after the chemotherapy has been given to kill the remaining tumor cells.

Treatment Based on Tumor Characteristics

Treatment for the Ewing's tumors depends on where the cancer is located, how far the cancer has spread, the stage of the disease, and the age and general health of the patient.

Localized Tumors

Treatment for localized Ewing's tumors may be one of the following:

• Combination chemotherapy followed by surgery
• Radiation therapy or surgery in combination with radiation therapy
• A clinical trial of intensified chemotherapy
• Chemotherapy after surgery with or without stem cell transplant

Metastatic Tumors

Treatment for metastatic Ewing's tumors may be one of the following:

• Combination chemotherapy followed by radiation therapy or surgery
• High-dose chemotherapy with or without radiation therapy plus additional stem cell support
• A clinical trial of intensive chemotherapy with multiple chemotherapy drug combinations

Recurrent Tumors

For recurrent tumors, treatment depends on where the cancer has recurred, how the cancer was treated before and the specific medical condition of each child. Chemotherapy may be used for children who did not previously receive chemotherapy. Radiation treatment may be given to reduce symptoms. Surgery may be used to remove tumors that have spread to the lungs or other organs. Clinical trials are testing new treatments.