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High-Dose Therapy for Patients With Primary Multifocal and Early Relapsed Ewing’s Tumors: Results of Two Consecutive Regimens Assessing the Role of Total-Body Irradiation

S. Burdach, A. Meyer-Bahlburg, H.J. Laws, R. Haase, B. van Kaik, B. Metzner, A. Wawer, R. Finke, U. Göbel, J. Haerting, H. Pape, H. Gadner, J. Dunst, H. Juergens

From the Division of Pediatric Hematology and Oncology, Departments of Pediatric Surgery and Radiation Oncology, and Clinical Studies Coordination Center, University of Halle-Wittenberg, Halle; Departments of Pediatric Hematology/Oncology and Radiation Oncology, University of Düsseldorf, Düsseldorf; Department of Hematology/Oncology, City Hospital Oldenburg, Oldenburg; Department of Pediatric Oncology, University of Münster, Münster, Germany; and St Anna Kinderspital, Vienna, Austria.

Address reprint requests to Stefan Burdach, MD, PhD, Martin-Luther-University Halle-Wittenberg, Children’s Cancer Research Center, and Division of Pediatric Hematology/Oncology, 06097 Halle, Germany; email: meta-eicess{at}medizin.uni-halle.de.

Purpose: Risk stratification of metastatic and relapsed Ewing’s tumors (ETs) has been a matter of debate during the last decade. Patients with bone or bone marrow metastases or early or multiple relapses constitute the worst risk group in ET and have a poorer prognosis than patients with primary lung metastases or late relapses. In this article, the results of the present Meta European Intergroup Cooperative Ewing Sarcoma Study (MetaEICESS) (tandem melphalan/etoposide [TandemME]) were compared with the result of the previous study (hyper melphalan/etoposide [HyperME]), both at 5 years, in a patient population within the same high-risk stratum to determine toxicity.

Patients and Methods: Among 54 eligible patients, 26 were treated according to the HyperME protocol, and 28 were treated according to TandemME protocol. Patients received six cycles of the Cooperative Ewing Sarcoma Study treatment in HyperME and six cycles of the EICESS treatment in TandemME as induction chemotherapy. Patients also received involved-compartment irradiation for local intensification and myeloablative systemic intensification consolidation with hyperfractionated total-body irradiation (TBI) combined with melphalan/etoposide in HyperME or two times the melphalan/etoposide in TandemME followed by autologous stem-cell transplantation.

Results: The event-free survival (EFS) rate ± SD in HyperME and TandemME was 22% ± 8% and 29% ± 9%, respectively. The dead of complication rate was 23% in HyperME and 4% in TandemME.

Conclusion: TandemME offers a decent, albeit still not satisfactory, rate of long-term remissions in most advanced ETs (AETs), with short-term treatment and acceptable toxicity. TBI was not required to maintain EFS level in this setting but was associated with a high rate of toxic death. Future prospective studies in unselected patients are warranted to evaluate high-dose therapy in an unselected group of patients with AET.

This study was supported by grant No. KKS Halle 01GH0105 from the German Federal Ministry of Education and Research, a grant from the Elterninitiative Kinderkrebsklinik Düsseldorf e.V., grant No. 83 25 from AMGEN Ltd, and grant No. 85 18 from Nexell International.

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