title: 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.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department 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.
authors.forename: Uwe
authors.initials: U
authors.lastname: Thiel
authors.affiliation: Department 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.
authors.forename: Angela
authors.initials: A
authors.lastname: Wawer
authors.affiliation: Department 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.
authors.forename: Irene
authors.initials: I
authors.lastname: von Luettichau
authors.affiliation: Department 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.
authors.forename: Hans-Ulrich
authors.initials: HU
authors.lastname: Bender
authors.affiliation: Department 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.
authors.forename: Franziska
authors.initials: F
authors.lastname: Blaeschke
authors.affiliation: Laboratory for Pediatric Sarcoma Biology, Institute of Pathology, LMU, Munich, Germany.
authors.forename: Thomas G P
authors.initials: TG
authors.lastname: Grunewald
authors.affiliation: Department of Radiology, Klinikum Schwabing, Städtisches Klinikum München, Munich, Germany.
authors.forename: Marc
authors.initials: M
authors.lastname: Steinborn
authors.affiliation: Department of Radiation Oncology, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.|Munich Comprehensive Cancer Center, München, Germany.
authors.forename: Barbara
authors.initials: B
authors.lastname: Röper
authors.affiliation: Department of Pediatric Hematology and Oncology, Universitätsklinikum Frankfurt, Frankfurt, Germany.|Department of Transfusion Medicine and Immunohematology, Universitätsklinikum Frankfurt, Frankfurt, Germany.
authors.forename: Halvard
authors.initials: H
authors.lastname: Bonig
authors.affiliation: Department of Pediatric Hematology and Oncology, Universitätsklinikum Frankfurt, Frankfurt, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Klingebiel
authors.affiliation: Department of Pediatric Hematology and Oncology, Universitätsklinikum Frankfurt, Frankfurt, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Bader
authors.affiliation: Department of Pediatric Oncology, Hematology and Immunology, Olgahospital, Klinikum Stuttgart, Stuttgart, Germany.
authors.forename: Ewa
authors.initials: E
authors.lastname: Koscielniak
authors.affiliation: Vestische Kinder- und Jugendklinik, Datteln, Universität Witten/Herdecke, Datteln, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Paulussen
authors.affiliation: Department of Pediatric Hematology and Oncology, Universitätsklinikum Münster, Münster, Germany.
authors.forename: Uta
authors.initials: U
authors.lastname: Dirksen
authors.affiliation: Department of Pediatric Hematology and Oncology, Universitätsklinikum Münster, Münster, Germany.
authors.forename: Heribert
authors.initials: H
authors.lastname: Juergens
authors.affiliation: Department 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.
authors.forename: Hans-Jochem
authors.initials: HJ
authors.lastname: Kolb
authors.affiliation: Department 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.|Munich Comprehensive Cancer Center, München, Germany.
authors.forename: Stefan E G
authors.initials: SE
authors.lastname: Burdach
mesh_terms: D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001853:Bone Marrow / Q000473:pathology*; D001859:Bone Neoplasms / Q000401:mortality / Q000473:pathology* / Q000628:therapy; D002648:Child; D003131:Combined Modality Therapy / Q000379:methods; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D009364:Neoplasm Recurrence, Local / Q000401:mortality / Q000473:pathology* / Q000628:therapy; D011379:Prognosis; D011446:Prospective Studies; D012074:Remission Induction / Q000379:methods; D012512:Sarcoma, Ewing / Q000401:mortality / Q000473:pathology* / Q000628:therapy; D016019:Survival Analysis; D016896:Treatment Outcome; D055815:Young Adult
keywords: Ewing sarcoma; allogeneic stem cell transplantation; bone marrow metastasis; bone metastasis; high-dose chemotherapy