Ewing's Sarcoma and Primitive Neuroectodermal Family of Tumors

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Epidemiology and clinical features

ES is the second most common primary malignancy of bone. It is a disease primarily of children and young adults and is rarely seen in older adults. In the United States, approximately 300 cases of ES are diagnosed in children and adolescents under the age of 20 each year. There is a slight male predominance, with an average annual rate of 3.3 per million in men and 2.6 per million in women [8]. The peak incidence in men is between the ages of 10 and 14 years, whereas in women it is between the

Genetic and molecular characterization

Over 85% of analyzed cases of ES are characterized by a t(11;22)(q24;q12) translocation [2], [34], [35], [36], [37]. This translocation is also seen in pPNET [38], reflecting the common histogenesis shared with ES. The result of this translocation is the fusion of the ews gene, which encodes for an RNA-binding protein of unknown function and is located at 22q12, with the human homolog of the murine FLI1 gene, a member of the ETS family of transcription factors that is located at 11q24 [39]. The

Treatment of localized Ewing's sarcoma family of tumors

Before the development of effective chemotherapy, local control measures alone were used for the treatment of localized ESB with 5-year survival rates of 10% to 20% [49], [50], [51], [52], [53], [54]. Subclinical metastatic disease is now assumed to be present in nearly all patients because of the significant relapse rate seen in patients who have undergone local treatment without systemic chemotherapy. Micrometastatic disease in the bone marrow has been detected by reverse

Treatment of metastatic disease

Approximately 20% to 25% of patients who have EFT have overt metastases at the time of diagnosis [24], [27], [112], [113]. Patients who present with metastatic disease continue to have a poor prognosis with a 5-year relapse free survival (RFS) rate of 30% [27]. There is a trend toward better survival for those with lung involvement alone as compared with those with bone metastases or a combination of lung and bone disease [114]. Many patients who have metastatic disease at diagnosis respond

Treatment of progressive and relapsed disease

The outcome is poor once patients have relapsed, particularly for those relapsing within 2 years of diagnosis [27]. A recent study from SJCRH revealed a 17% 5-year postrecurrence survival. Those who had relapse more than 2 years after diagnosis, those who had local recurrence alone that could be treated with radical surgery and intensive chemotherapy, and those who had isolated pulmonary metastases treated with WLI fared better [119].

Studies performed in the early 1980s found significant

Stem cell transplantation in the treatment of Ewing's sarcoma family of tumors

In an effort to improve outcome, particularly for high-risk patients, the role high-dose myeloablative therapy followed by stem cell rescue has been investigated. It was hoped that increased dose-intensity would increase the fraction of tumor cells destroyed, thus leading to an increased probability of long-term EFS. Several small series and case reports suggested improved clinical outcomes with stem cell transplantation (SCT) [113], [127], [128], [129], [130], [131], [132], [133], [134], [135]

Risk for secondary malignancy after curative therapy

Treatment-related acute myeloblastic leukemia and myelodysplastic syndrome (t-AML/MDS) have been reported in 1% to 2% of survivors of EFT [158], [159], [160]. These secondary malignancies occur most commonly between 2 and 5 years following diagnosis [159], [160]. The advent of protocols that include intensification of alkylators and topoisomerase-II inhibitors has resulted in a significant increase in the incidence of t-AML/MDS [144]. The cumulative incidence of t-AML/MDS was 8% in survivors of

Current clinical trials and prospects for future studies

The prognosis for patients who have EFT has improved dramatically with the advent of combined modality therapy [62], [63], [64], [65]. Despite these advancements in therapy, a significant proportion of patients develop recurrent disease and eventually succumb to their disease. Therefore, continued investigation of novel treatment strategies is important to further improve the outcome of these patients.

Immunohistochemical studies performed on EFT have shown that approximately 70% of samples

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