Approach Considerations
Treatment lasts 6-9 months and consists of alternating courses of 2 chemotherapeutic regimens: (1) vincristine, doxorubicin, and cyclophosphamide and (2) ifosfamide and etoposide. [4] Chemotherapy can be administered on an inpatient or outpatient basis, depending on patient tolerance and proximity to the hospital.
Patients often develop episodes of fever while neutropenic, resulting in 3- to 7-day hospitalizations between cycles of chemotherapy.
In a pilot study in which standard chemotherapy for newly diagnosed metastatic Ewing sarcoma was combined with low-dose antiangiogenic therapy, Felgenhauer et al found the combination treatment to be “feasible according to protocol definitions” but also determined that it tended to cause toxicity in areas that had received radiation therapy, limiting the protocol’s usefulness. Although 24-month event-free survival in the study was better for patients with isolated pulmonary metastases than it was for historical controls, the investigators pointed out that the study used only a small number of patients and did not include contemporaneous controls. [16]
Chemotherapy interval compression from the standard 3-week therapy to 2 weeks improves outcomes for localized Ewing sarcoma, without increased toxicity, according to a study by the Children's Oncology Group. [17, 18] According to the investigators, patients who received interval compression chemotherapy every 2 weeks had a 5-year event-free survival rate of 73%, compared with 65% in patients who received chemotherapy every 3 weeks. The doses of chemotherapy were similar between the groups and both groups of patients received granulocyte-colony stimulating factor (G-CSF) to support adequate neutrophil counts. No significant increase in therapy-related toxicity due to the extra intensification was reported. [17, 18]
Currently, an open study within the Children’s Oncology Group (AEWS1031) is evaluating the efficacy of adding vincristine, topotecan, and cyclophosphamide to the interval compressed 5-drug backbone for patients with nonmetastatic Ewing sarcoma (NCT01231906). [19]
Obtaining informed consent is required before therapy if the patient will be enrolled in a clinical trial. If no appropriate trial is accruing patients, the oncologist refers to the most recent clinical trial to determine the best therapeutic regimen. A consent form that includes the recommended agents and their adverse effects should be strongly considered in these circumstances.
Surgery and radiation therapy
Management of the primary tumor site is critical to long-term cure. Definitive surgical margins are desirable (eg, removal of fibula, limb salvage with extensive margins). Any surgery should be performed under the supervision of experienced oncologic surgeons specializing in the area of the body where the tumor is found. The specific surgery is highly patient dependent. [20, 21]
In the absence of a minimally morbid surgical procedure, local control may be achieved with radiation therapy. Doses to the tumor and fractionation are site dependent. [22]
Recurrent disease
There are no standardized second-line treatment plans for relapsed or refractory Ewing sarcoma. Considerations need to be made depending on site(s) of disease recurrence and prior therapy. Chemotherapy combinations such as vincristine/irinotecan/temozolomide [23] or gemcitabine/docetaxel [24] have been considered in recurrent Ewing sarcoma. Radiation and/or surgery may have a role for local control and disease palliation. Identification and development of targeted therapies for Ewing sarcoma are underway in early clinical trial settings.
Diet
Patients require close monitoring of their caloric intake during treatment. The services of a dietitian are often needed, although no special diets are required for treatment.
Activity
Activity limitations depend on the location of primary and metastatic lesions. No general restrictions are indicated.
Treatment Team
Medical therapy varies slightly among European and North American pediatric oncologists. Patients should be treated under the supervision of a pediatric oncologist; staff at a comprehensive pediatric oncology center should direct care. (Medical therapy varies slightly among European and American pediatric oncologists.)
A multidisciplinary team should evaluate and treat the patient. The team may include, along with pediatric oncologists and in-house infectious disease specialists, the following personnel:
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Radiation oncologists
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Surgeons
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Radiologists
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Pathologists
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Nurses
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Social workers
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Occupational and/or physical therapists
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Blood bank specialists
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Psychologists
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School tutors
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Pharmacists
The primary care physician should be kept informed about the patient's progress and complications. After therapy is completed, the primary physician should increase his or her involvement in patient care.
Consultations
The following specialists may be consulted:
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Orthopedic surgeon - If the patient has a lesion close to bone that is potentially resectable, consultation with an orthopedic oncologist is required before biopsy; biopsy planning is critical because an inappropriately conducted procedure can contaminate tissue planes
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Neurologist - Lesions close to nerve roots, ganglia, or plexuses may result in neurologic symptoms
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Pathologist - When a mass is resected from a pediatric patient, a pathologist should be aware of the procedure and the differential diagnosis; this information and involvement is critical in order for appropriate diagnostic studies to be performed.
Chemotherapeutic Care
Most patients require red blood cell (RBC) and platelet support during therapy. Although granulocyte colony-stimulating factor (G-CSF) is given for neutrophil support, patients most often require a minimum of weekly laboratory evaluations.
A full physical examination is required before each cycle of chemotherapy and any time suspicious signs or symptoms arise between cycles. Suspicious signs include those similar to the signs observed at presentation, as well as unexplained fever or pain.
Follow-up
Primary and metastatic sites are evaluated approximately every 10-12 weeks during therapy and every 3-4 months during the first year after therapy.
Reevaluations are spaced out gradually for 5-6 years after the completion of therapy. After 5 years of disease-free remission, no further scanning is indicated; however, the patient should have annual follow-up visits to monitor the function of the primary site and late effects of therapy, preferably in a late-effects clinical setting.
Other posttreatment considerations include the following:
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Late effects from chemotherapy require regular follow-up with a provider trained to evaluate such sequelae
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Recurrence of primary disease is the major risk in the first 10 years after diagnosis.
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A second malignancy occurs in approximately 1-2% of patients beginning 5 years after diagnosis; the most common second malignancy is acute myeloid leukemia.
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Therapeutic toxicities to the heart and kidneys, to the nervous and endocrine systems, and to mental status should be monitored in patients who suffered acute toxicity and in those who developed symptoms after therapy.
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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.
