Ewing’s sarcoma, now often referred to as Ewing’s Family of Tumors (EFST), is a small blue round cell sarcoma of bone, but it also can occur exclusively in the soft tissues. It most commonly occurs in the second decade of life, although it can occur in younger and older patients. It is a rare tumor, with less than 500 cases diagnosed annually in the United States. Thus patients should seek treatment at major cancer centers where there is likely to be some experience with the treatment of this disease. This tumor is most common in Caucasians, and is quite rare among those of African descent. The tumor most often occurs in the extremities, although 40% occur centrally in the pelvis, vertebrae and chest wall. Extremity tumors appear to have a better prognosis than do central axis tumors. The origin of the cell type giving rise to ESFT is thought to be a very primitive mesenchymal cell, perhaps with some neural features. The tumor is now most clearly identified by the presence of a characteristic chromosomal abnormality and confirmation of the presence of the abnormality should be included in all diagnostic evaluations.
As noted above, ESFT is an exceedingly rare tumor, with annual incidence rates among Caucasian children less than 21 years being in the range of 2-3 cases per million in the U.S. There are no known predisposition syndromes, although there may be some association with genitourinary developmental abnormalities (undescended testis, replication of the renal collecting system). The reason underlying the predilection of this tumor for Caucasians remains unknown at the present time.
Since this tumor is so rare and usually occurs in previously healthy teenagers and young adults, there is often a considerable delay in diagnosis, with one study showing an average of three months from the onset of symptoms until diagnosis. The most common presenting signs and symptoms are pain and swelling at the site of the primary tumor. Fevers accompanying these symptoms are also quite common, which reflects the systemic nature of this tumor, even when confined to a single primary tumor site. Thus the presentation of a young patient with a bony abnormality on x-ray and fever can easily be confused with an infection of the bone, and a biopsy is the only way to establish the diagnosis. It is important to stress that the biopsy should be done only in close cooperation with an orthopedic oncologist, since position of the biopsy is critical for later surgical resection if the biopsy should turn out to be positive for a malignancy of bone.
ESFT is highly sensitive to chemotherapy and radiation therapy, and all patients are treated with chemotherapy coupled with surgery and/or radiation therapy to the primary tumor site. Once the diagnosis is made and prior to initiation of treatment, patients need to be properly staged to search for the extent of the primary tumor and the presence or absence of metastases that will determine the ultimate approach to treatment. This staging evaluation includes bone scan, CT and MRI exam of the primary tumor and CT of the chest. In addition, many centers will include a bone marrow evaluation. Once the staging evaluation is completed, treatment usually begins with chemotherapy given every three weeks for around three months. Following the three months of “induction chemotherapy,” patients will undergo either surgery or radiation therapy or both to the site of the primary tumor. If surgery is undertaken, chemotherapy will restart following recovery from the surgery usually within a week or two following surgery. If radiation alone is used, chemotherapy is usually given together with the radiation, although certain drugs are not given together with the radiation. The choice of surgery or radiation therapy depends on numerous factors including the resectability of the primary tumor, likely side effects and the local expertise available. Treatment usually includes 10-14 cycles of chemotherapy. Once therapy is completed, patients are usually followed closely (every several months) with scans for the first year following completion of treatment, and then less frequently in subsequent years. Currently, depending on size, location and age, the majority of patients can be cured of localized ESFTs.
The most common sites of metastases are the lungs, bone and bone marrow. Although the prognosis for metastatic disease is inferior to localized disease, the site and extent of metastatic disease impacts on prognosis. Patients with metastases to the lung only generally fare better than those with bone and bone marrow disease. Treatment of patients with metastatic disease includes similar chemotherapy to those with localized tumors. Surgery is done less frequently, and most patients receive radiation treatment to their primary tumor site as well as to metastatic sites of disease when feasible. Patients with lung metastases often receive whole lung radiation at some point during treatment or sometimes it is given at the end of chemotherapy. The challenge for patients with metastatic disease remains the high rate of recurrence, although most patients respond initially to treatment. High-dose chemotherapy with peripheral blood stem cell rescue has been used for patients with metastatic disease although results have generally not been superior to standard treatment without high-dose therapy. Clearly new treatment approaches are necessary to improve on the overall survival of patients with metastatic ESFTs, and ongoing clinical trials are necessary to test such new approaches.
No specific targeted therapies currently exist for the treatment of ESFTs. However, as noted above, this tumor type is associated with a very specific chromosomal abnormality that we now know leads to the expression of a tumor-specific factor that appears to regulate the expression of a variety of proteins. Current work is aimed at determining which of these proteins are critical for the malignant behavior of these tumors, with the hope than once identified, these proteins can be the targets for new therapies.
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