Treatment of advanced Ewing tumors by combined radiochemotherapy and engineered cellular transplants.

This review will focus primarily on own recent work on the treatment of advanced Ewing tumors (AETs) and will attempt, in addition, to give a comprehensive overview of novel developments. The field under review has been shaped by investigators from both Europe and the United States of America in a scientific debate evolving over more than a decade at the meetings of the International Society of Pediatric Oncology and other scientific meetings. In the light of this debate, most oncologists will agree that patients with AETs are facing the worst prognosis of all patients with this disease and include both: (i) patients with primary metastatic disease with the worst prognosis as well as (ii) patients with relapse with the worst prognosis. The contributions of various investigators have lead to the identification of specific risk stratification criteria to overcome the heterogeneity of patients within the conventionally defined clinical stages of localized metastatic and relapsed disease. This review will address the following issues of treatment of AETs: (i) a definition of AET; (ii) risks and benefits of allogeneic vs. autologous stem cell transplantation; (iii) the role of total body irradiation; (iv) the number of involved bones as a risk factor in multifocal bone disease in AET; (v) the development of immunogene therapy in AET; (vi) the matching of radiochemo- and immunotherapy in AET; (vii) the future perspective of functional genomics and targeted therapy.