Clinical Research Papers:
Bone marrow involvement identifies a subgroup of advanced Ewing sarcoma patients with fatal outcome irrespective of therapy in contrast to curable patients with multiple bone metastases but unaffected marrow
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Uwe Thiel1, Angela Wawer1, Irene von Luettichau1, Hans-Ulrich Bender1, Franziska Blaeschke1,Thomas G.P. Grunewald2, Marc Steinborn3, Barbara Röper4,10,*, Halvard Bonig5,6, Thomas Klingebiel5, Peter Bader5, Ewa Koscielniak7, Michael Paulussen8, Uta Dirksen9, Heribert Juergens9, Hans-Jochem Kolb1, Stefan E.G. Burdach1,10
1Department of Pediatrics and Pediatric Oncology Center, Kinderklinik München Schwabing, Städtisches Klinikum München und Klinikum rechts der Isar, Wilhelm Sander Sarcoma Unit, Klinikum rechts der Isar, Technische Universität München, Munich, Germany
2Laboratory for Pediatric Sarcoma Biology, Institute of Pathology, LMU, Munich, Germany
3Department of Radiology, Klinikum Schwabing, Städtisches Klinikum München, Munich, Germany
4Department of Radiation Oncology, Klinikum rechts der Isar, Technische Universität München, Munich, Germany
5Department of Pediatric Hematology and Oncology, Universitätsklinikum Frankfurt, Frankfurt, Germany
6Department of Transfusion Medicine and Immunohematology, Universitätsklinikum Frankfurt, Frankfurt, Germany
7Department of Pediatric Oncology, Hematology and Immunology, Olgahospital, Klinikum Stuttgart, Stuttgart, Germany
8Vestische Kinder- und Jugendklinik, Datteln, Universität Witten/Herdecke, Datteln, Germany
9Department of Pediatric Hematology and Oncology, Universitätsklinikum Münster, Münster, Germany
10Munich Comprehensive Cancer Center, München, Germany
*Present address: Radiation Oncology Clinic, Klinikum Bogenhausen, Städtisches Klinikum München, Munich, Germany
Stefan E.G. Burdach, email: firstname.lastname@example.org
Keywords: Ewing sarcoma, bone metastasis, bone marrow metastasis, allogeneic stem cell transplantation, high-dose chemotherapy
Received: February 08, 2016 Accepted: June 30, 2016 Published: July 29, 2016
Purpose: Advanced Ewing sarcomas have poor prognosis. They are defined by early relapse (<24 months after diagnosis) and/or by metastasis to multiple bones or bone marrow (BM). We analyzed risk factors, toxicity and survival in advanced Ewing sarcoma patients treated with the MetaEICESS vs. EICESS92 protocols.
Design: Of 44 patients, 18 patients were enrolled into two subsequent MetaEICESS protocols between 1992 and 2014, and compared to outcomes of 26 advanced Ewing sarcoma patients treated with EICESS 1992 between 1992 and 1996. MetaEICESS 1992 consisted of induction chemotherapy, whole body imaging directed radiotherapy to the primary tumor and metastases, tandem high-dose chemotherapy and autologous rescue. In MetaEICESS 2007 this treatment was complemented by allogeneic stem cell transplantation. EICESS 1992 comprised induction chemotherapy, local therapy to the primary tumor only followed by consolidation chemotherapy.
Results: In MetaEICESS 8/18 patients survived in complete remission vs. 2/26 in EICESS 1992 (p<0.05). Survival did not differ between MetaEICESS 2007 and MetaEICESS 1992. Three MetaEICESS patients died of complications, all in MetaEICESS 1992. After exclusion of patients succumbing to treatment related complications (n=3), 7/10 patients survived without BM involvement, in contrast to 0/5 patients with BM involvement. This was confirmed in a multivariate analysis. There was no correlation between BM involvement and the number of metastases at diagnosis.
Conclusion: The MetaEICESS protocols yield long-term disease-free survival in patients with advanced Ewing sarcoma. Allogeneic stem cell transplantation was not associated with increased death of complications. Bone marrow involvement is a risk factor distinct from multiple bone metastases.
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