Guidelines Summary
Guidelines Contributor: Mrinal M Gounder, MD Attending Physician in Medical Oncology, Sarcoma and Developmental Therapeutics Service, Memorial Sloan-Kettering Cancer Center
Guidelines for the management of Ewing sarcoma have been published by the following organizations:
Diagnosis
National Comprehensive Cancer Network (NCCN) guidelines recommend that all patients younger than 40 years of age with abnormal radiographs be referred to an orthopedic oncologist for further workup that includes biopsy. For patients 40 years old or older, the recommended workup includes the following [25] :
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Computed tomography (CT) of the chest, abdomen and pelvis
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Bone scan
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Mammogram and other imaging studies as clinically indicated
Findings of other lesions indicates a non-bone primary tumor. If no other lesions are found, the patient should be referred to an orthopedic oncologist for a biopsy. [25]
European Society for Medical Oncology (ESMO) guidelines recommend followup of an abnormal radiograph with magnetic resonance imaging (MRI) of the whole compartment with adjacent joints. CT scan is recommended only in the case of diagnostic problems or doubt, to provide clearer visualization of calcification, periosteal bone formation, or cortical destruction. [26]
Both guidelines agree that biopsy is required to confirm the diagnosis prior to any surgical procedure and should be performed at a specialized center that will provide the definitive treatment. [25, 26]
Classification
ESMO guidelines recommend specifying the tumor type and subtype according to the 2013 World Health Organization (WHO) classification. [26] Under the WHO classification system, tumors are further classified as benign, intermediate or malignant. Bone sarcomas are classified by group (eg, chondrogenic, osteogenic, fibrohistiocytic, Ewing sarcoma) and further subtyped within each group. [27]
NCCN guidelines recommend that the final pathologic evaluation include assessment of surgical margins as well as the size/dimensions of tumors. [25]
Grading and Staging Systems
A number of staging systems are used for bone tumors. The ESMO guidelines do not provide a specific recommendation for which system should be followed. [26] NCCN follows both the tumor-node-metastasis (TNM) classification of the American Joint Cancer Committee/Union for International Cancer Control (AJCC/UICC) [28] and the Surgical Staging System from the Musculoskeletal Tumor Society (MTS) [29] for staging. [25]
Treatment
NCCN recommendations for treatment of Ewing sarcoma are as follows [25] :
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Enrollment in a clinical trial should be considered when available; in addition, whenever possible patients should be referred to a tertiary care center with expertise in sarcoma, for treatment by a multidisciplinary team
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Multi-agent chemotherapy for at least 12 weeks followed by local control therapy and adjuvant treatment; longer duration of initial chemotherapy can be considered for patients with metastatic disease, based on response
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VAC/IE (vincristine, doxorubicin [Adriamycin], and cyclophosphamide alternating with ifosfamide and etoposide) is the preferred regimen for localized disease
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VAC (vincristine, doxorubicin, and cyclophosphamide) is the preferred regimen for patients with metastatic disease
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Restaging following chemotherapy
ESMO recommends a treatment protocol of three to six cycles of multi-agent chemotherapy (doxorubicin, cyclophosphamide, ifosfamide, vincristine, dactinomycin, and etoposide), followed by local therapy and another six to 10 cycles of chemotherapy. Wide resection is preferred over radiation therapy for local control. [26]
For patients with stable or improved disease after restaging, the NCCN recommends the following [25] :
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Wide excision or definitive radiation therapy with chemotherapy, or amputation in selected cases.
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Postoperative chemotherapy for 28-49 weeks, depending on the type of regimen and the dosing schedule (category 1 for wide excision)
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Postoperative radiation therapy in addition to chemotherapy if surgical margins are positive or very close
For patients with progressive disease after restaging the NCCN recommends radiation therapy with or without surgery for local control and palliation, followed by chemotherapy or best supportive care. Treatment options for relapsed or refractory disease include enrollment in clinical trials or chemotherapy with or without radiation therapy. [25]
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Radiograph of an 11-year-old boy with a large Ewing sarcoma in the right pelvic area. Destruction of the bone structure resulted from tumor involvement.
