Ewing sarcoma gets its name from the physician who first described it in 1921, Dr. James Ewing. He noted that this bone cancer was different from osteosarcoma, because it was particularly sensitive to radiation. For several years it was felt that Ewing’s sarcoma occurred only within the bone; however, other similar tumors were found within soft tissues. These tumors include extraosseous Ewing sarcoma (EES), Askin’s tumor, and peripheral primitive neuroectodermal tumor (PPNET). Together, these four malignancies are called the Ewing sarcoma family of tumors (ESFT).

Who gets ESFT?

Each year, about 250 children and adolescents in the United States are diagnosed with an ESFT malignancy. Ewing sarcoma of the bone accounts for 87 percent of these diagnoses.

Most ESFT occur in young people between the ages of 10 and 20, and the median age of children diagnosed with Ewing sarcoma is 15. Only 27 percent of ESFT cases are diagnosed in children younger than age 10, but Ewing sarcoma has been diagnosed in infants and small children. Boys are diagnosed with this disease more often than girls, and there is a much higher incidence in White children compared with those of other ethnic groups (93% of all Ewing sarcoma of the bone and 85% of EES are diagnosed in White children).

Ewing sarcoma most commonly arises in the legs (41%) and the pelvis (26%), but it can also occur in the chest wall (16%), the arm bones (9%), the spine (6%), the hands and feet (3%), and the skull (2%).

Genetic factors

ESFT aren’t typically associated with other childhood congenital diseases. However, when scientists look at the genetic material (DNA in chromosomes) of an ESFT tumor, more than 90 percent of the tumor cells have a translocation between chromosomes 11 and 22 called t(11:22). This shifts a portion of one chromosome to the other and produces a new protein from the fusion of the two chromosomes. Scientists are studying this protein to try to learn more about ESFT.

Environmental factors

No environmental factors have been associated with development of ESFT.

ESFT signs and symptoms

The signs and symptoms of ESFT depend on the location of the disease. Almost all children diagnosed with Ewing sarcoma of the bone have pain, and more than half have swelling of the affected area. Approximately 16 percent have a fracture at the site of disease, and 20 percent have a fever. Children or teens with metastatic disease (disease that has spread to other parts of the body) may be tired and have unexplained weight loss. If the cancer has spread to areas around the spine, symptoms may include back pain or paralysis.

A diagnosis is sometimes delayed because the symptoms of ESFT tumors can be very similar to those of trauma, growing pains, or an infection. Diagnosis commonly occurs months after symptoms begin.

Diagnosis of ESFT

Any child or teen with a suspected ESFT should be seen by an orthopedic oncologist (a surgeon) and a pediatric oncologist with experience treating these diseases. The oncologist will obtain the child’s medical history and perform a complete physical examination. Several blood tests will be ordered, including a complete blood count (CBC) and differential (see Appendix A, Blood Tests and What They Mean). Other laboratory studies include the measurement of lactate dehydrogenase (LDH). If there is suspicion that the disease may be neuroblastoma, a urinalysis may be ordered to measure catecholamine levels.

Once the oncology team makes a diagnosis, other tests are done to determine whether the disease has spread. This process is called staging. CT and MRI of the chest, abdomen, and pelvis are usually done to provide detailed images that help define the extent of the disease. Radionuclide scanning, also called scintigraphy, is used to determine the size of the primary tumor and whether the disease has spread. The orthopedic or pediatric oncologist will perform bone marrow biopsies and aspirates in each hip to check whether the disease has spread to the bone marrow.

There are two stages for ESFT tumors:

•  Localized. The tumor has not spread to distant sites.

•  Metastatic. The tumor has spread to other parts of the body, such as the lungs, bones, and bone marrow.

Prognosis

Treatment for childhood ESFT has steadily improved over the last four decades. In the 1960s, virtually all children with ESFT died, but today, the majority of children and teens with localized disease who receive optimal treatment are cured.

Like many cancers, the most important prognostic factor for ESFT is whether the disease has spread. With localized tumors, the location of the primary site also has prognostic significance. Increased serum lactate dehydrogenase (LDH) levels are associated with larger tumors or metastases.

Girls and younger patients have a somewhat better prognosis than boys and children older than age 10.

Treatment of ESFT

At diagnosis, many parents do not know how to find experienced doctors and the best treatments for their child. State-of-the-art care is available from physicians who participate in the Children’s Oncology Group (COG). This study group includes pediatric surgeons and oncologists, radiation oncologists, researchers, and nurses. COG conducts studies to discover better therapies and supportive care for children with cancer. You can learn more about COG and find a list of its member treatment centers at www.childrensoncologygroup.org.

The goals of ESFT treatment are to cure the child, maintain as much function of the affected area as possible, and minimize the possible long-term effects of treatment. Treatment for an ESFT tumor includes chemotherapy plus surgery and/or radiation. If the tumor is completely removed with good margins of normal tissue, radiation is generally not given.

Surgery

It is essential that the surgeon who will remove the tumor has experience with ESFT. The type of surgery depends on the location of the mass and the impact surgery will have on the function of the affected part of the body (see Chapter 14, Surgery).

During the operation, the surgeon removes all or some of the tumor and then takes samples from surrounding tissues. The pathologist determines whether the entire tumor has been removed, or whether some cells remained behind. If the surgeon is able to remove the entire tumor, it is referred to as a total gross resection. If there is evidence of remaining disease, it is referred to as residual disease. If the residual disease is visible to the naked eye or can be felt by the surgeon’s hand, it is called gross residual disease. If it is only visible under the microscope, it is called microscopic residual disease.

Before the development of limb-salvage surgery, most children with extremity tumors had the affected limb amputated and received high-dose radiation therapy. Many children now have limb-salvage procedures using autologous grafts, allografts, an endoprosthesis, or rotationplasty (see pages 17 to 20 for descriptions of these surgeries) or targeted radiation therapy to treat their tumor.

Radiation

Radiation is often needed to treat children diagnosed with ESFT. Radiation is used for tumors that cannot be completely removed with clear margins. The entire prechemotherapy tumor area, with 2 centimeter margins, is usually included in the radiation field. Children or teens with gross residual disease are usually given a total dose of 5,580 cGy. For those with microscopic residual disease, the standard dose is 5,040 cGy. Radiation is given over a period of 4 to 6 weeks. No radiation therapy is recommended for children who have no evidence of microscopic residual disease following surgery. For more information, see Chapter 17, Radiation Therapy.

Research to evaluate the potential benefits of proton beam radiation and intensity modulated radiation therapy is ongoing. These types of more focused radiation therapy decrease the dose of radiation to healthy tissue around the tumor. However, it will be a number of years before enough information is available to determine whether either proton radiation or intensity modulated radiation therapy might allow for greater function and reduce the risk of secondary cancers.

Chemotherapy

Before chemotherapy became a standard way to treat ESFT in the 1960s, very few children survived. Chemotherapy reduces the size of the tumor before surgery, kills microscopic cancer cells, and improves the long-term survival rate. All children or teens with Ewing sarcoma receive chemotherapy as part of treatment.

Current standard chemotherapy includes vincristine, doxorubicin, and cyclophosphamide, alternating with ifosfamide and etoposide (also called VP-16). For more information about these medications, see Chapter 15, Chemotherapy.