Ewing's family of tumors (EFT) is a group of cancers that affect the bones or nearby soft tissue. Cancer occurs when cells in the body become abnormal and multiply without control or order. The cells form a growth of tissue, called a tumor. The type of tumors in EFT varies because tumors develop in different places. EFT includes:

• Ewing's tumor of the bones (also called Ewing's sarcoma), the most common type of EFT
  
  
• Extraosseus Ewing's (EOE), a tumor that grows in soft tissues outside the bone
  
  
• Peripheral primitive neuroectodermal tumor (PPNET), a rare cancer found in the bones and soft tissues, including Askin's tumor, which is a PPNET of the chest wall

EFT of the bone occurs most often in the legs, spine, ribs, or pelvis. EFT of the soft tissue is usually found in the thighs, pelvis, spine, chest, or feet.

Statistics

EFT makes up about 1.4% of all childhood cancers. The five-year relative survival rate (the percentage of patients who survive at least five years after the cancer is detected, excluding those who die from other diseases) of patients with EFT is 70% for localized cancer (cancer that has not spread) and 30% for cancer that has metastasized (spread).

About two-thirds (64%) of all people with EFT are between the ages of 10 and 20. EFT is rare in adults older than 30 and in very young children.

EFT is more common among boys than girls. EFT occurs most frequently in white people and is rare in black people in the United States and Africa. These tumors have been reported in Japan but are rare in China.

Cancer survival statistics should be interpreted with caution. These estimates are based on data from thousands of cases of this type of cancer in the United States each year, but the actual risk for a particular individual may differ. It is not possible to tell a person how long he or she will live with EFT. Because the survival statistics are measured in five-year (or sometimes one-year) intervals, they may not represent advances made in the treatment or diagnosis of this cancer.

Statistics adapted from the American Cancer Society and the National Cancer Institute.

A risk factor is anything that increases a person's chance of developing cancer. Some risk factors can be controlled, such as smoking, and some cannot be controlled, such as age and family history. Although risk factors can influence the development of cancer, most do not directly cause cancer. Some people with several risk factors never develop cancer, while others with no known risk factors do.

Doctors and researchers don't know what causes most childhood cancers. Changes in a tumor cell's chromosomes appear to be responsible for EFT, but the disease is not inherited. The genetic changes occur for no known reason. A high percentage of tumor cells have a chromosomal translocation, in which small pieces of genetic material swap places inside the tumor cell. Usually the translocation is between chromosomes 11 and 22. The fusion of these bits of genetic material results in the uncontrolled growth of EFT cells.

Children with EFT may experience the following symptoms. Sometimes, children with EFT do not show any of these symptoms. Or, these symptoms may be caused by a medical condition that is not cancer. If you are concerned about a symptom on this list, please talk with your child's doctor.

• Stiffness, pain, swelling, or tenderness in the bone or in the tissue surrounding the bone (About 85% of children with EFT have pain.)
  
  
• A lump near the surface of the skin that may feel warm and soft to the touch
  
  
• A fever that doesn't go away
  
  
• A broken bone that happens without an injury, as a tumor growing in the bone can cause the bone to weaken or fracture

Doctors use many tests to diagnose cancer and determine if it has metastasized. Some tests may also determine which treatments may be the most effective. For most types of cancer, a biopsy is the only way to make a definitive diagnosis of cancer. If a biopsy is not possible, the doctor may suggest other tests that will help make a diagnosis. Imaging tests may be used to find out whether the cancer has metastasized. Your child’s doctor may consider these factors when choosing a diagnostic test:

• Age and medical condition
• The type of cancer suspected
• Severity of symptoms
• Previous test results

In addition to a physical examination, the following tests may be used to diagnose EFT:

Blood tests. Abnormal levels of white blood cells, red blood cells, and platelets can indicate that cancer has spread. The doctor may also check liver and kidney function and look for high levels of a particular blood enzyme (lactate dehydrogenase, or LDH), which sometimes helps to determine the presence of cancer in the body.

Imaging tests

Three types of imaging tests are commonly used to diagnose EFT:

X-ray. An x-ray is a picture of the inside of the body. Doctors can usually find bone tumors with an x-ray.

Computed tomography (CT or CAT) scan. A CT scan creates a three-dimensional picture of the inside of the body with an x-ray machine. A computer then combines these images into a detailed, cross-sectional view that shows any abnormalities or tumors. Sometimes, a contrast medium (a special dye) is injected into a vein to provide better detail

Magnetic resonance imaging (MRI). An MRI uses magnetic fields, not x-rays, to produce detailed images of the body. A contrast medium may be injected into a patient’s vein to create a clearer picture.

Surgical tests

Biopsy. A biopsy is the removal of a small amount of tissue for examination under a microscope. An orthopedic oncologist (a doctor who specializes in cancers of the musculoskeletal system) who has experience with EFT should perform the biopsy of a tumor in the arm or leg. The doctor may take a sample of the tumor itself, a sample of the bone marrow, or both. Other tests can suggest that cancer is present, but only a biopsy can make a definite diagnosis. The sample removed from the biopsy is analyzed by a pathologist (a doctor who specializes in interpreting laboratory tests and evaluating cells, tissues, and organs to diagnose disease).

Bone marrow aspiration. For this test, a small amount of bone marrow is removed with a needle from the hip bone and examined under a microscope. The child's skin is numbed with a local anesthetic during the procedure.

Laboratory tests

Using the tissue sample obtained from the biopsy, the doctor can conduct other laboratory tests to learn more about the cancer.

Immunohistochemistry. A test to detect EFT cells in tissue.

Cytogenetics test and reverse transcription polymerase chain reaction test (RT-PCR). Tests to determine if the genetic changes that characterize EFT cells are present in the sample.

To learn about the terms used in this section, read the Cancer.Net Feature: Cancer Terms to Know: Newly Diagnosed.

To learn more about what to expect during common diagnostic tests, read Cancer.Net: Tests and Procedures.

Staging

Staging is a way of describing a cancer, such as where it is located, if or where it has spread, and if it is affecting the functions of other organs in the body. Doctors use diagnostic tests to determine the cancer’s stage, so staging may not be complete until all of the tests are finished. Knowing the stage helps the doctor to decide what kind of treatment is best and can help predict a patient’s prognosis (chance of recovery). There are different stage descriptions for different types of cancer.

While there is no official staging system for EFT, the following criteria help doctors describe EFT:

Localized EFT. The cancer has remained in the bone or tissue where it began or spread only to the nearby tissues.

Metastatic EFT. The cancer has spread from the bone or tissue where it began to other parts of the body, such as the lungs, other bones, or bone marrow. Rarely, the disease spreads to the lymph nodes, brain, or spinal cord. Approximately 25% of patients with EFT will have obvious evidence of tumor spread at the time of diagnosis. Whether the cancer has spread is the most important factor used to determine the treatment options and a patient’s prognosis.

Recurrent EFT. Recurrent EFT is cancer that comes back after treatment. It may recur where it began or in another part of the body.

Clinical trials are the standard of care for the treatment of children with cancer. In fact, more than 60% of children with cancer are treated as part of a clinical trial. Clinical trials are research studies that compare standard treatments (the best treatments available) with newer treatments that may be more effective. Cancer in children is rare, so it can be hard for doctors to plan treatments unless they know what has been most effective in other children. Investigating new treatments involves careful monitoring using scientific methods, and all participants are followed closely to track progress.

To take advantage of these newer treatments, all children with cancer should be treated at a specialized cancer center. Doctors at these centers have extensive experience in treating children with cancer and have access to the latest research. Many times, a team of doctors treats a child with cancer. Pediatric cancer centers often have extra support services for children and their families, such as nutritionists, social workers, and counselors. Special activities for kids with cancer may also be available.

Children and teenagers with EFT should be treated in clinical trials specifically designed for their disease. Therapy for EFT typically consists of systemic therapy (therapies that treat the entire body, such as chemotherapy or stem cell transplantation [SCT]) combined with localized therapy. Localized therapy is therapy to treat the tumor itself, such as surgery and radiation therapy. When more than one treatment is used, it is called combination therapy. Doctors make treatment decisions based on the stage of the disease and the age of the child, while trying to avoid long-term side effects of treatment.

Chemotherapy

Chemotherapy is the use of drugs to kill cancer cells. Systemic chemotherapy is delivered through the bloodstream, targeting cancer cells throughout the body. The doctor may use surgery or radiation therapy (see below) first and then give chemotherapy to eliminate any remaining EFT cells.

Chemotherapy for EFT is usually injected into a vein or muscle; it is rarely given by mouth. Patients with EFT may receive vincristine (Oncovin), cyclophosphamide (Cytoxan, Neosar), and doxorubicin (Adriamycin, Rubex), ifosfamide (Ifex), and etoposide (VePesid, Etopophos). People with metastatic disease may also be treated with the above medications and dactinomycin (Cosmegen).

The side effects of chemotherapy depend on the individual and the dose used, but can include fatigue, risk of infection, nausea and vomiting, loss of appetite, and diarrhea. These side effects usually go away once treatment is finished.

The medications used to treat cancer are continually being evaluated. Talking with your child's doctor is often the best way to learn about the medications prescribed for your child, their purpose, and their potential side effects or interactions with other medications. Learn more about prescriptions through Cancer.Net's Drug Information Resources, which provides links to searchable drug databases.

Surgery

When it is possible, surgical removal of the tumor should be performed after chemotherapy (neoadjuvant chemotherapy). The doctor may perform surgery to remove the cancer and some surrounding tissue. Surgery may also be needed to remove any remaining cancer cells after chemotherapy or radiation therapy.

Often a tumor can be removed without causing disability. If the cancer occurs in the arm or leg, surgery to remove much of the bone may affect the limb's ability to function.

Bone grafts from other parts of the body may help to reconstruct a limb. A prosthesis (artificial limb) made of metal or plastic bones or joints can replace lost tissue. Physical therapy after surgery can help the child learn to use the limb again.

Radiation therapy

Radiation therapy is the use of high-energy x-rays or other high-energy particles to kill cancer cells. Radiation therapy is used in patients when surgery is not possible or did not remove all cancer cells, as well as in cases when chemotherapy was not effective. The most common type of radiation treatment is called external-beam radiation therapy, which is radiation given from a machine outside the body. When radiation therapy is given using implants, it is called internal radiation therapy or brachytherapy. Intraoperative radiation therapy (radiation given inside the body during surgery) is being studied in clinical trials.

Side effects from radiation therapy may include fatigue, mild skin reactions, upset stomach, and loose bowel movements. Most side effects go away soon after treatment is finished. In the long term, radiation therapy can also interfere with normal bone growth and is associated with the development of a secondary cancer.

Stem cell transplantation/bone marrow transplantation

Some children's best treatment option may be SCT. This is an experimental approach that is still under evaluation.

A stem cell transplant is a medical procedure in which diseased bone marrow is replaced by highly specialized cells, called hematopoietic stem cells. Hematopoietic stem cells are found both in the bloodstream and in the bone marrow. Today, this procedure is more commonly called a stem cell transplant, rather than bone marrow transplant, because blood stems cells are typically what is being transplanted, not the actual bone marrow tissue.

There are two types of stem cell transplantation depending on the source of the replacement blood stem cell: allogeneic (ALLO) and autologous (AUTO). AUTO transplantations are used to treat EFT.

In an AUTO transplant, the patient’s own stem cells are used. The stem cells are obtained from the patient when he or she is in remission from previous treatment. The stem cells are frozen until they are needed, usually after the high-dose treatment (explained below) is completed.

The goal of transplantation is to destroy cancer cells in the marrow, blood, and other parts of the body and have replacement blood stem cells create healthy bone marrow. In most stem cell transplants, the patient is treated with high doses of chemotherapy and/or radiation therapy to destroy as many cancer cells as possible. This also destroys the patient’s bone marrow tissue and suppresses the patient’s immune system. After the high-dose treatment is given, blood stem cells are infused into the patient’s vein to replace the bone marrow and restore normal blood counts.

Before recommending transplantation, doctors will talk with the patient about the risks of this treatment and consider several other factors, such as the type of cancer, results of any previous treatment, and patient’s age and general health.

In SCT, replacement cells engraft (begin to make new blood cells) and turn into healthy, blood-producing tissue in two to three weeks. Destroying the patient’s own marrow reduces the body’s natural defenses, temporarily leaving the patient at an increased risk of infection. Until the patient’s immune system is back to normal, patients may need antibiotics and blood transfusions.

In an AUTO transplant, there is little risk of tissue rejection because the replacement stem cells are the patient’s own cells. However, there is a risk in an autologous transplant that some of the cells that are put back into the patient could still be cancerous.

Learn more by reading the Cancer.Net Feature series Understanding Bone Marrow and Stem Cell Transplantation.

Recurrent EFT

For recurrent EFT, the treatment depends on where and when the cancer recurred and how it was initially treated. The doctor may use chemotherapy and radiation treatment and may surgically remove new tumors. SCT may also be recommended in this setting.

New drugs that are being tested for effectiveness against EFT may also be used.

Doctors and scientists are always looking for better ways to treat children with EFT. A clinical trial is a way to test a new treatment to prove that it is safe, effective, and possibly better than a standard treatment. People who participate in clinical trials are among the first to receive new treatments before they are widely available. However, there is no guarantee that the new treatment will be safe, effective, or better than a standard treatment.

People decide to participate in clinical trials for many reasons. For some people, a clinical trial is the best treatment option available. Because standard treatments are not perfect, people are often willing to face the added uncertainty of a clinical trial in the hope of a better result. Other people volunteer for clinical trials because they know that this is the only way to make progress in treating EFT, such as finding new drugs. Even if they do not benefit directly from the clinical trial, their participation may benefit future children with EFT.

In order to join a clinical trial, people must complete a learning process known as informed consent. During informed consent, the doctor should list all of the person's options, so that the person understands the standard treatments and how the new treatment differs from the standard treatment. The doctor must also list all of the risks of the new treatment, which may or may not be different than the risks of standard treatment. Finally, the doctor must explain what will be required of each person in order to participate in the clinical trial, including the number of doctor visits, tests, and the schedule of treatment. Learn more about clinical trials, including patient safety, phases of a clinical trial, deciding to participate in a clinical trial, questions to ask the research team, and links to find cancer clinical trials.

Cancer and its treatment can cause a variety of side effects. However, doctors have made major strides in recent years in reducing pain, nausea and vomiting, and other physical side effects of cancer treatments. Many treatments used today are less intensive but as effective as treatments used in the past. Doctors also have many ways to provide relief to patients when such side effects do occur.

Fear of treatment side effects is common after a diagnosis of cancer, but it may be helpful to know that preventing and controlling side effects is a major focus of your child’s health-care team. Before treatment begins, talk with your child’s doctor about possible side effects of the specific treatments your child will be receiving. The specific side effects that can occur depend on a variety of factors, including the type of cancer, its location, the individual treatment plan (including the length and dosage of treatment), and the person’s overall health.

Ask your doctor which side effects are most likely to happen (and which are not), when side effects are likely to occur, and how they will be addressed by the health-care team if they do happen. Also, be sure to communicate with your doctor about side effects your child experiences during and after treatment. For more information on the most common side effects of cancer and different treatments, along with ways to prevent or control them, visit Cancer.Net’s section on Managing Side Effects, based on ASCO’s curriculum.

In addition to physical side effects, there may be psychosocial (emotional and social) effects as well. Learn more about the importance of addressing these needs in Cancer.Net’s section on Caring for the Whole Patient.

For more information on late effects or long-term side effects, please read the After Treatment section or talk with your child’s doctor.

After treatment for EFT ends, talk with your child’s doctor about developing a follow-up care plan. This plan may include regular physical examinations and/or medical tests to monitor your child’s recovery for the coming months and years. All children treated for cancer, including EFT, should have life-long, follow-up care.

Follow-up care includes bone scans (a small amount of radioactive material is injected into a vein where it collects in areas of the bone and is detected by a scanner), CT scans, MRI, and x-rays.

Children treated with chemotherapy will need to be monitored for potential problems with their sexual development and fertility (ability to have children). Your child may need to be referred to an endocrinologist (a doctor who specializes in problems with glands and the endocrine system) for evaluation in these areas.

Based on the type of treatment the child received, the doctor will determine what examinations and tests are needed to check for long-term side effects and the possibility of secondary cancers. Your child’s doctor can recommend the necessary screening tests. Follow-up care should also address the child’s quality of life, including any developmental or emotional concerns. Learn more about Childhood Cancer Survivorship.

The child’s family is encourage to organize and keep a record of the child’s medical information so that as the child enters adulthood, he or she has a clear, written history of the diagnosis and the details of the treatment given. The doctor’s office can help you compile this, and it should include recommendations from the doctor about the schedule for follow-up care. This information will be valuable to doctors who care for your child during his or her lifetime.

Children who have had cancer can also enhance the quality of their future by following established guidelines for good health into and through adulthood, including not smoking, maintaining a healthy weight, eating a balanced diet, and participating in regular physical activity. Talk with the doctor about developing a plan that is best for your child’s needs.

To learn about the terms used in this section, read the Cancer.Net Feature: Cancer Terms to Know: After Treatment.

Research for EFT is ongoing. The following advances may still be under investigation in clinical trials and may not be approved or available at this time. Always discuss all diagnostic and treatment options with your child's doctor.

Positron-emission tomography (PET) scan. A PET scan is a way to create pictures of organs and tissues inside the body. A small amount of a radioactive substance is injected into a patient’s body and absorbed by the organs or tissues being studied. This substance gives off energy that is detected by a scanner, which produces the images. The fluorodeoxyglucose (FDG) PET scan is being evaluated for its effectiveness in the staging of EFT.

Chemotherapy. Giving chemotherapy more frequently, such as every two weeks, is being compared to the standard way of giving it every three weeks. By giving the chemotherapy more frequently, the intensity of the chemotherapy is increased. Researchers are comparing the outcome of patients who were treated each way to see if one way is better than the other way for preventing the tumor from coming back.

Allogeneic SCT. In an allogeneic (ALLO) SCT, the person is treated with high doses of chemotherapy and/or radiation therapy to kill as many cancer cells as possible and to prevent the person's immune system from rejecting the donated stem cells. After the high-dose therapy is given, stem cells obtained from a healthy donor (usually a sibling) are infused into the patient's bloodstream. Allogeneic SCTs combined with sirolimus (Rapamune, Rapamycin) and other agents have shown to inhibit growth of Ewing's cells in the laboratory.

Bilateral lung radiation. The effectiveness of bilateral lung radiation is being examined in patients with metastatic Ewing's sarcoma. In this treatment, radiation therapy is given to the lungs after completion of chemotherapy and, in some cases, autologous (AUTO) stem cell transplant is recommended. Another study is looking at combining anti-angiogenic therapy (the use of drugs that block the formation of new blood vessels that are needed for a tumor to grow and spread) with standard treatment in patients with newly diagnosed metastatic Ewing's sarcoma.

Regular communication with your child's doctor is important in making informed decisions about his or her health care. Consider asking the following questions of your child's doctor:

• What type of EFT has been diagnosed?
  
  
• Can you explain my child’s pathology report to me?
  
  
• What treatment options are there?
  
  
• What treatment do you recommend? Why?
  
  
• What clinical trials are open to my child?
  
  
• What chemotherapy will my child receive? How long and how frequently?
  
  
• Will my child receive radiation therapy?
  
  
• How can I best prepare my child for each treatment?
  
  
• What are the possible side effects of this treatment, both in the short term and the long term?
  
  
• How long will my child stay in the hospital?
  
  
• How will this treatment affect my child’s daily life? Will he or she be able to go to school and perform his or her usual activities?
  
  
• Are there options to preserve my child's fertility prior to starting treatment, such as sperm storage (for boys)? Should we consult a fertility specialist?
  
  
• What follow-up tests will my child need, and how often will he or she need them?
  
  
• What support services are available to my child? To my family?