Treatment of Ewing sarcoma family of tumors: Current status and outlook for the future

BACKGROUND: The Ewing sarcoma family of tumors (ESFT) comprises a group of well-characterized neoplasms with aggressive behavior. Despite significant progress with the use of intensive multiagent chemotherapy and local control measures, a significant proportion of patients die of disease progression. Chemotherapy dose intensification and autologous hematopoietic stem cell transplant (HSCT) have been explored by many institutions without obvious benefit in high-risk patients. Our current understanding in the biology and treatment of ESFT suggests that a more rational approach to the development of risk-adapted therapy should be undertaken. PROCEDURE: We performed a review of the most relevant data regarding the current status in the treatment of ESFT. The results of the major American and European cooperative groups were analyzed, including the treatment strategies used and the prognostic factors identified for both localized and metastatic ESFT. RESULTS: The intensification of alkylating agents and topoisomerase-II inhibitors is feasible and has resulted in some survival improvement for selected patients. This benefit seems to be restricted to patients with localized disease, and a proportion of survivors are at risk of developing treatment-related hematologic malignancies. Nevertheless, these advances have resulted in a re-definition of prognostic factors, which may help to define risk groups based on tumor load parameters as well as biologic factors (type of fusion transcript and histologic response to chemotherapy). Patients with advanced metastatic disease may benefit from HSCT. New strategies such as immunotherapy and the use of biologic modifiers may have a role in the treatment of ESFT. CONCLUSIONS: Future treatment for ESFT should consider risk-adapted strategies and the inclusion of newer therapies such as biologic modifiers for the minimal residual disease. A modified risk-adapted therapy is proposed.