Journal
ONCOTARGET
Volume 7, Issue 43, Pages 70959-70968Publisher
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.10938
Keywords
Ewing sarcoma; bone metastasis; bone marrow metastasis; allogeneic stem cell transplantation; high-dose chemotherapy
Categories
Funding
- Wilhelm Sander-Stiftung [2006.109.1]
- Else Kroner-Fresenius-Stiftung [P31/08//A123/07]
- Deutsche Kinderkrebsstiftung [DKS 2010.07]
- Federal Ministry of Education and Research Germany [TranSarNet 01GM1104B]
- Deutsche Krebshilfe
- Daimler and Benz Foundation
- Reinhard Frank Foundation
- LMU Munich's Institutional Strategy LMUexcellent within German Excellence Initiative
- Mehr LEBEN fur krebskranke Kinder - Bettina-Brau-Stiftung
- Deutsche Krebshilfe [DKH-108128, DKS 50-2635]
- Federal Ministry of Education and Research Germany
- BMBF [TranSaRNet 01GM0869]
- PROVABES ERA-Net-TRANSCAN [01KT1310]
- EEC [602856-2]
- Cura Placida Children's Cancer Research Foundation
- PanCareLife [602030-2 EU-FP7]
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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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