Ewing Sarcoma

Excerpt

Ewing sarcoma is an aggressive tumor of adolescents and young adults, constituting 10% to 15% of all bone sarcomas. James Ewing first described this condition in 1921. Ewing sarcoma represents 'classic' Ewing sarcoma of bone, extra-skeletal Ewing sarcoma, malignant small cell tumor of the chest wall (Askin tumor), and soft tissue-based primitive neuroectodermal tumors. Due to their similar histologic and immunohistochemical characteristics, these sarcomas originate from unique mesenchymal progenitor cells.

Ewing sarcoma family tumors are characterized by non-random chromosomal translocations producing fusion genes that encode aberrant transcription factors. The t(11;22)(q24;q12) translocation is associated with 85% of tumors and leads to EWS-FLI-1 formation, whereas t(21;12)(22;12) and other less common translocations induced EWS-ERG fusion comprises the remaining 10% to 15% of cases. The most commonly affected anatomical sites include the pelvis, axial skeleton, and femur; however, Ewing sarcoma may occur in almost any bone or soft tissue. Typically, patients present with pain and swelling over the site of involvement.

Over the last 40 years, both local therapy and multiagent adjuvant chemotherapy have achieved considerable progress in the treatment of localized disease that improved the 5-year survival rate from less than 20% to greater than 70%, but the recurrence rate remains high. However, most present locally, and subclinical metastatic disease is present in almost all cases. Approximately 25% of patients with initially localized disease ultimately relapse. No standard therapy exists for relapsed and refractory Ewing sarcoma, with survival rates being less than 30% in those with isolated lung metastases and less than 20% in those with bone and bone marrow involvement. Given the considerations of toxicity and suboptimal survival from metastatic disease, there is an urgent unmet need to develop novel therapies for Ewing sarcoma.