Because most patients with apparently localized disease at diagnosis have occult metastatic disease, multidrug chemotherapy as well as local disease control with surgery and/or radiation is indicated in the treatment of all patients.[1,2,3,4,5,6,7,8] Current regimens for the treatment of localized Ewing tumor of bone (ETB) achieve event-free survival (EFS) and overall survival (OS) of approximately 70% at 5 years after diagnosis.
The National Cancer Institute (NCI) provides the PDQ pediatric cancer treatment information summaries as a public service to increase the availability of evidence-based cancer information to health professionals, patients, and the public.
The histiocytic diseases in children and adults include three major classes of disorders of which only one, Langerhans cell histiocytosis (LCH), a dendritic cell disorder, will be discussed. Erdheim-Chester disease (primarily found in adults) and juvenile xanthogranuloma...
Current standard chemotherapy in the United States includes vincristine, doxorubicin, and cyclophosphamide, also known as VAdriaC or VDC, alternating with ifosfamide and etoposide (IE). The combination of IE has shown activity in ETB, and a large randomized clinical trial and a nonrandomized trial demonstrated that outcome was improved when IE was alternated with VAdriaC.[2,9,10] Dactinomycin is no longer used in the United States but continues to be used in the Euro-Ewing studies. Increased doxorubicin dose intensity during the initial months of therapy was associated with an improved outcome. The use of high-dose VAdriaC has shown promising results in small numbers of patients. Forty-four patients treated with high-dose VAdriaC and IE had an 82% 4-year EFS. However, in a trial of the former Children's Cancer Group, which compared a dose-intensified chemotherapy regimen of vincristine, doxorubicin, cyclophosphamide, ifosfamide, and etoposide (VDC/IE) with standard doses of the same regimen, no differences in outcome were observed. This trial did not maintain the dose intensity of alkylating agents for the duration of treatment and did not recapitulate the previously published experience.
In a completed Children's Oncology Group (COG) trial (COG-AEWS0031), 568 patients with newly diagnosed localized extradural Ewing sarcoma family of tumors (ESFT) were randomly assigned to receive chemotherapy (VAdriaC alternating with IE) given every 2 weeks (interval compression) versus every 3 weeks (standard). Patients randomly assigned to the every 2-week interval of treatment had an improved 3-year EFS (76% vs. 65%, P = .028). There was no increase in toxicity observed with the every 2-week schedule.
Local control can be achieved by surgery and/or radiation. Surgery is generally the preferred approach if the lesion is resectable.[15,16] The superiority of resection for local control has never been tested in a prospective randomized trial. The apparent superiority may represent selection bias. In past studies, smaller more peripheral tumors were more likely to be treated by surgery, and larger, more central tumors were more likely to be treated by radiation therapy. An Italian retrospective study showed that surgery improved outcome only in extremity tumors, although the number of patients with central axis ETB who achieve adequate margins is small. In a series of 39 patients treated at St. Jude Children's Research Hospital, who received both surgery and radiation, the 8-year local failure rate was 5% for patients with negative surgical margins and 17% for those with positive margins. If a very young child has an ETB, surgery may be a less morbid therapy than radiation therapy because of the retardation of bone growth caused by radiation. Another potential benefit for surgical resection of the primary tumor is information concerning the amount of necrosis in the resected tumor. Patients with residual viable tumor in the resected specimen have a worse outcome compared with those with complete necrosis. In a French Ewing study (EW88), EFS for patients with less than 5% viable tumor, 5% to 30% viable tumor, and more than 30% viable tumor was 75%, 48%, and 20%, respectively. European investigators are studying whether treatment intensification (i.e., high-dose chemotherapy with stem cell rescue) will improve outcome for patients with a poor histologic response. Radiation therapy should be employed for patients who do not have a surgical option that preserves function and should be used for patients whose tumors have been excised but with inadequate margins. Pathologic fracture at the time of diagnosis does not preclude surgical resection and is not associated with adverse outcome.