Ewing Sarcoma (children)


Ewing sarcoma is a type of bone cancer that is diagnosed in children and adolescents, and rarely in adults over 30. It was named for James Ewing, the doctor who first described it, and is part of a group cancers sometimes referred to as Ewing sarcoma family of tumors. 

The cells associated with Ewing sarcoma are thought to be a primitive cell type1 – meaning it hasn’t ‘declared’ itself as a specific type of cell like bone cell (osteoblast) or cartilage cell(chondrocyte). These primitive cells are found in bone and soft tissue and if this primitive (stem) cell starts to grow at an abnormal rate it forms a cancerous tumor. If that tumor forms in the bone it is Ewing sarcoma of bone.  Because these primitive cells are also found in the soft tissue around bones, a tumor of primitive cells outside the bone is called an extraosseous Ewing sarcoma (outside bone).   Two other tumors in the Ewing family are neuroectodermal tumor (a brain tumor) and Askin tumor (chest wall sarcoma).

Ewing sarcoma is the second most common bone cancer in kids but it is a rare with only 250 new cases diagnosed each year in the U.S.2  The bones most commonly affected are the thigh (femur), lower leg (tibia or fibula), upper arm (humerus), and the pelvis.
 

Signs and Symptoms of Ewing Sarcoma

  • Pain – the pain experienced with a Ewing sarcoma is typically in the area of the tumor. This is often called local pain.
  • Swelling - there may be inflammation in the area of a tumor leading to swelling.
  • Decreased function – pain and swelling can contribute to a limited ability (or willingness) to use the affected extremity.
  • Fracture – the area of the bone where the tumor is located is weaker and more fragile than normal bone so fractures (called pathologic fracture) can occur in this area of the bone tumor.
  • Fever – a persistent fever with no obvious cause may be present.
  • Weight loss – unexplained weight loss can indicate a disease process.

Cause for Ewing Sarcoma

Ewing sarcoma is caused by a chromosomal change but the cause of the change is not known. Therefore it is considered a genetic cause but not one that is inherited or passed along from parents to kids3.

Diagnostic Tests for Ewing Sarcoma

The first test that raises a suspicion for Ewing sarcoma is an x-ray. It may show an area in the bone that isn’t formed normally.

Once a bone tumor is suspected it is very important that a patient sees an orthopedic oncologist before further testing or biopsy. Because it is a rare condition, bone cancer is best managed by a specialist who has training and experience in diagnosing and treating extremity sarcomas.

      MRI     An MRI enables the doctors to better see the full extent of the tumor. It is important to know if the tumor is ‘invading’ other tissues as treatment plans (such as surgical options) are being considered.
      Biopsy A biopsy is necessary to determine the exact type of tumor as well as its grade (aggressiveness). It is important that the biopsy be done by a specialist experienced in appropriate biopsy of extremity tumors. A biopsy done incorrectly may limit surgical options, and in some cases make amputation the only surgical option.
Bone marrow aspiration If a Ewing sarcoma is suspected a bone marrow aspiration may be done to help with the diagnosis. This is because the types of cells in the bone marrow are similar in type (stem cells) to those that develop Ewing sarcoma so this helps to confirm Ewing sarcoma and with staging.
  Bone scan A bone scan is one of the tests done to help determine the extent of the cancer (staging). This is like an x-ray of your entire skeleton to see if there are any other areas of tumor.
  PET/CT scan This test is another that is necessary for staging of the cancer. It reveals if the cancer has metastasized to the abdomen, brain or other areas of the body.

Ewing Sarcoma Staging

Ewing sarcoma is an aggressive tumor so is automatically considered a high grade tumor. Knowing the stage is important in determining the best treatment options for a child as well as for understanding prognosis. Ewing sarcoma is described in one of three stages:

    Localized tumor This is a sarcoma that is only in the area that it was first found. It usually involves the bone and may involve the soft tissues in the area. The diagnostic tests such as the PET/CT or bone scan won’t show areas that the tumor may have spread to such as the lungs or brain.
    Metastatic tumor This is a sarcoma that has spread to other areas of the body such as the lungs, other bones or even the bone marrow. This indicates a more aggressive form of cancer.
  Recurrent This is the term used for Ewing sarcoma that has come back (recurred) after it has been treated. It may come back in the area where it was first found (local recurrence) or may be in another part of the body.

Treatment of Ewing Sarcoma

Once the diagnosis of bone cancer has been made and staging of the tumor is completed, treatment is started. Through many years of research, specialists have determined that the most effective course of treatment involves chemotherapy before surgery (neoadjuvant chemotherapy), followed by surgical resection of the tumor, and followed by a course of post-operative chemotherapy (adjuvant chemotherapy).

Chemotherapy – “Chemo” is the use of medications to kill cancer cells. A course of chemotherapy before surgery usually includes multiple weeks of chemotherapy infusions into the blood stream. This course of chemo is directed at killing the primary Ewing sarcoma and any tumor cells that might not have been detected yet. Another course of chemo is given after surgery to further treat for undetected spread and minimize the chance of recurrence.

Surgery – once the chemotherapy course is completed surgery is necessary to remove the tumor. It is very important that the entire tumor is removed in order to minimize the possibility that it will return; therefore, the surgeon will remove a small amount of normal tissue around the tumor to better assure that no cancerous cells are left. Very careful surgical planning is necessary to accomplish complete removal (resection) of the sarcoma and maintenance of the patient’s best function.

Options can include:

  Resection Removal of the tumor without “rebuilding” the area that it was removed.
  Resection with reconstruction – removal of the tumor and “rebuilding” with metal implants and/or bone allografts; soft tissue reconstruction may also be necessary.
  Amputation Removing the extremity at a level above the tumor.

Radiation therapy – Ewing sarcoma is radiosensitive so radiation is used in some situations to treat Ewing sarcoma. If chemotherapy wasn’t effective in killing the primary tumor radiation is considered after surgery. Or, if the tumor is in a location that it can’t be removed surgically then radiation is utilized with chemo to treat the disease. It is also considered for treatment of recurrent Ewing sarcoma.

There are risks of giving radiation to treat any type of cancer. These include changes to the skin around the radiated area which can have an effect on surgery, and radiation sarcoma which is a cancer that can develop later in life. Therefore, radiation is not the preferred treatment for tumors that able to be removed by surgery.

Prognosis

Prognosis means ‘chance of recovery’ and is often the first question asked after a child has been diagnosed with a bone cancer. There are a number of factors that contribute to an individual child’s prognosis:

Tumor site – the location of the tumor and whether there are tumors in more than one bone. Tumors in more than one bone indicate a later stage of the cancer which decreases the long term survival.

Size of the tumor – larger tumors have a worse prognosis.

Presence of metastatic disease – the stage of cancer at the time of diagnosis contributes to prognosis. If disease has spread to the lungs or other sites the prognosis is not as good.

Response to initial chemotherapy – when the tumor is resected during surgery it is tested to determine how much of the tumor died (indicating that the chemotherapy was effective). The greater the percentage of tumor death the better the prognosis.

Prognosis is better when the tumor is at the end of the bone that it is located in (therefore farther from the body) and there is no metastatic disease (the cancer hasn’t spread). Younger children tend to have a better prognosis than young adults. Prognosis of Ewing sarcoma is poor when the tumor is located in a bone closer to the body, or if there is metastatic disease at the time of diagnosis 4.


References
1. Tirode F, Laud-Duval K, Prieur A, et al.: Mesenchymal stem cell features of Ewing tumors. Cancer Cell 11 (5): 421-9, 2007
2. Jawad MU, Cheung MC, Min ES, et al.: Ewing sarcoma demonstrates racial disparities in incidence-related and sex-related differences in outcome: an analysis of 1631 cases from the SEER database, 1973-2005. Cancer 115 (15): 3526-36, 2009
3. Bailly RA1, Bosselut R, Zucman J, Cormier F, Delattre O, Roussel M, Thomas G, Ghysdael J.; DNA-binding and transcriptional activation properties of the EWS-FLI-1 fusion protein resulting from the t(11;22) translocation in Ewing sarcoma.; Mol Cell Biol. 1994 May;14(5):3230-41
4. Bacci G, Longhi A, Ferrari S, et al.: Prognostic factors in non-metastatic Ewing's sarcoma tumor of bone: an analysis of 579 patients treated at a single institution with adjuvant or neoadjuvant chemotherapy between 1972 and 1998. Acta Oncol 45 (4): 469-75, 2006