Overview

Localized Ewing’s sarcoma affects only the bone in which it developed and the tissues next to the bone, such as muscle and tendon. There is no detectable spread of the cancer to other areas of the body as detected by computed tomography (CT) or magnetic resonance imaging (MRI) scans.

The following is a general overview of treatment for localized Ewing’s sarcoma. Treatment may consist of surgery, radiation therapy, chemotherapy, or all three modalities. Multi-modality treatment is treatment using two or more techniques; this is increasingly recognized as an important approach for increasing a patient’s chance of cure or prolonging survival. In some cases, participation in a clinical trial utilizing new, innovative therapies may provide the most promising treatment. Circumstances unique to each patient’s situation may influence how these general treatment principles are applied and whether the patient decides to receive treatment. The potential benefits of multi-modality care, participation in a clinical trial, or standard treatment must be carefully balanced with the potential risks. The information on this website is intended to help educate patients about their treatment options and to facilitate a mutual or shared decision-making process with their treating cancer physician.

The multi-modality approach to treatment for Ewing’s sarcoma requires that patients be treated by a multi-disciplinary team consisting of the primary care physician, an orthopedic surgeon experienced in bone tumors, a pathologist, radiation oncologists, pediatric oncologists, rehabilitation specialists, pediatric nurse specialists, social workers, and others. An experienced team is best found in specialty cancer centers that treat many patients with Ewing’s sarcoma. Engaging a multidisciplinary team at one of these centers helps ensure that the patient receives treatment, supportive care, and rehabilitation that will achieve optimal survival and quality of life. The primary cooperative group evaluating Ewing’s sarcoma treatment in the U.S. is the Children’s Cancer Study Group.

Treatment of Localized Ewing’s Sarcoma

Effective treatment of localized Ewing’s sarcoma requires both local and systemic therapy. Local therapy consists of surgery alone, radiation therapy alone or both radiation and surgery. Surgery and Radiation are directed at eradication of the primary tumor. Systemic therapy is treatment directed at eliminating cancer cells throughout the body, and usually consists of a combination of chemotherapy drugs.

The delivery of systemic therapy in addition to local treatment is necessary to maximize a patient’s chance of cure. Most patients diagnosed with localized Ewing’s sarcoma actually have micrometastases that are undetectable by current procedures. Micrometastases are cancer cells that have spread beyond the area of the original cancer. The presence of micrometastases may cause Ewing’s sarcoma recurrence following local treatment with surgery alone, radiation alone or surgery plus radiation. Thus, systemic therapy is nearly always given to patients with Ewing’s sarcoma to treat undetectable micrometastases. Typically, patients undergo chemotherapy before (neoadjuvant) and after (adjuvant) surgery with or without radiation.

Surgery

The ultimate goal of surgery for localized Ewing’s sarcoma is to remove the cancer without amputation. The specific type of surgery a patient undergoes depends on the location and extent of the cancer. For surgery to be successful, the cancer and a large margin of healthy tissue surrounding the cancer must be removed. Even with the advent of chemotherapy as systemic treatment and radiation as local treatment, surgery is still an important component of treatment for Ewing’s sarcoma. For more details go to: The Role of Surgery in Ewing’s Sarcoma.

Radiation Therapy

Radiation Therapy is used to prevent local recurrences following complete or incomplete surgery. Even with complete surgical resection some patients will have a local recurrence without the administration of large doses of radiation therapy and chemotherapy. Radiation therapy is also given to patients who cannot undergo surgery because of the location or in an attempt to avoid amputation. For more details go to: The Role of Radiation Therapy for Ewing’s Sarcoma.

Combined Modality Therapy

The main improvement in the treatment of localized Ewing’s sarcoma over the past 30 years has been the advent of combination chemotherapy. Chemotherapy is often delivered before surgery or radiation therapy (neoadjuvant chemotherapy) and after surgery or radiation therapy (adjuvant therapy).

Surgery, Radiation Therapy and Chemotherapy for Localized Ewing’s Sarcoma: The most common approach for the treatment of localized Ewing’s sarcoma is to remove as much tumor as possible surgically, deliver local radiation to eradicate microscopic tumor not removed by surgery and to administer systemic combination chemotherapy to eradicate micrometastases. Researchers from St Jude Children Research Center have reported the outcomes of 39 patients with localized Ewing’s sarcoma treated with definitive surgery, radiation therapy and chemotherapy.1 Chemotherapy consisted of vincristine, actinomycin D, cyclophosphamide, and doxorubicin with alternating cycles of ifosfamide and etoposide. Five-year survival was 90 percent, and only 11 percent of patients experienced a recurrence in the area where the cancer originated (local recurrence). Patients who had positive surgical margins (evidence of cancer at the edge of the tissue that was removed) had a local recurrence rate of 17 percent compared to 5.2 percent for those with no tumor in the surgical margins. This study shows that multimodality therapy is very effective for treating favorable risk patients. In a more recent publication these same authors reported five- and 10-year survival rates of 84.5 percent and 75.8 percent, respectively.2 Patients with disease originating in bone had better survival than patients with disease originating in soft tissue.

Chemotherapy and Radiation Therapy: Patients with Ewing’s sarcoma who have inoperable tumors or tumors in sites not suitable for surgery are generally treated with radiation therapy and chemotherapy. Researchers at St Jude Children’s Research Center have reported the outcomes of 79 patients with Ewing’s sarcoma treated with low-dose or high-dose radiation and chemotherapy with vincristine, actinomycin D, and cyclophosphamide with alternating cycles of ifosfamide and etoposide.3 The local recurrence rate was 30 percent and the overall survival was 65 percent. Patients who were older or who had larger tumors were more likely to experience a local recurrence. Patients who had received radiation doses below 40 Gy were also more likely to experience a local recurrence, suggesting that high-dose radiation may help to eradicate the cancer.

Researchers from Italy have reported that neoadjuvant and adjuvant chemotherapy may improve outcomes of patients with localized Ewing’s sarcoma.4 They treated 157 patients with localized Ewing’s with neoadjuvant vincristine, doxorubicin, and cyclophosphamide followed by ifosfamide and actinomycin. Patients were then treated with surgery, surgery plus radiation, or radiation only. After surgery and/or radiation therapy, all patients received adjuvant chemotherapy. Five-year survival without a cancer recurrence was 71 percent, which as better than previous results achieved without neoadjuvant chemotherapy.

Intensive Chemotherapy: Researchers from Memorial Sloan-Kettering have reported that a high-dose, short-term chemotherapy regimen improves outcomes of patients with localized Ewing’s sarcoma.5 The drugs used in this intensive regimen were cyclophosphamide, doxorubicin, ifosfamide and etoposide. The researchers reported a four-year event-free survival of 89 percent in patients with localized disease. There was no apparent improvement in patients with metastatic disease using this more intensive regimen.

Strategies to Improve Treatment

The development of more effective cancer treatments requires that new and innovative therapies be evaluated with cancer patients. Clinical trials are studies that evaluate the effectiveness of new drugs or treatment strategies. Future progress in the treatment of localized Ewing’s sarcoma will result from the continued evaluation of new treatments in clinical trials. Participation in a clinical trial may offer patients access to better treatments and advance the existing knowledge about treatment of this cancer. Patients who are interested in participating in a clinical trial should discuss the risks and benefits of clinical trials with their physician. Areas of active exploration to improve the treatment of localized Ewing’s sarcoma include the following:

Improvement in Identifying Prognostic Factors: Combination chemotherapy has significantly improved the outcomes of patients with localized Ewing’s sarcoma. However, there is room for improvement in high risk patients. It is important to identify patients with localized Ewing’s sarcoma who can be cured with current treatment regimens and those who cannot be cured. Patients identified as high risk for recurrence should be treated on innovative protocols investigating new treatment regimens or strategies. For other types of cancer, there has been progress in using gene-expression profiling to identify poor, average and good risk groups of patients; similar studies need to be done in patients with localized Ewing’s sarcoma.

Autologous Stem Cell Transplantation: Ewing’s sarcoma is generally responsive to chemotherapy, and it’s possible that high-risk patients will benefit from increased doses of chemotherapy. High-dose chemotherapy followed by autologous stem cell transplantation is being evaluated in patients with relapsed Ewing’s sarcoma and high-risk patients with metastatic disease with some success,6 and studies of this approach in selected patients with high-risk, localized Ewing’s sarcoma are warranted.

Supportive Care: Neupogen^® (filgrastim) and Neulasta^® (pegfilgrastim) have been used to shorten the duration of severe neutropenia and to decrease the incidence of febrile neutropenia in patients with Ewing’s sarcoma receiving chemotherapy.78

Radiation Therapy: Ewing’s sarcoma is a radiosensitive cancer and many of the more modern radiation therapy techniques may improve outcomes.

Targeted Therapies: New drugs are being developed which target enzyme pathways necessary for cancer survival. One such enzyme system is the tyrosine kinase pathway. This enzyme pathway has been targeted by a drug called Gleevec^® (imatinib), which has been used successfully to treat patients with chronic myeloid leukemia (CML).Preclinical studies suggest that Gleevec may also be effective against Ewing’s sarcoma cells since they rely on the same enzyme as CML cells. Clinical trials of Gleevec for the treatment of Ewing’s sarcoma should begin in the near future. Another targeted therapy, Iressa^® (gefitinib), has produced a partial response in at least one patient with refractory Ewing’s sarcoma.9 Researchers are looking at a number of molecular targets for the development of other targeted therapies.10

References

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