Total body MRI-governed involved compartment irradiation combined with high-dose chemotherapy and stem cell rescue improves long-term survival in Ewing tumor patients with multiple primary bone metastases

Abstract

We examined the role of total body magnetic resonance imaging (TB-MRI)-governed involved compartment irradiation (ICI) and high-dose chemotherapy (HDC), followed by stem cell rescue (SCR) in patients with high-risk Ewing tumors (ETs) with multiple primary bone metastases (high-risk ET-MBM). Eleven patients with high-risk ET-MBM receiving initial assessment of involved bones by TB-MRI were registered from 1995 to 2000 (group A). In all, 6 patients out of 11 had additional lung disease at initial diagnosis; all had multifocal bone disease with more than three bones involved. After systemic induction with etoposide, vincristine, adriamycin (doxorubicin), ifosfamide, and actinomycin D (EVAIA) or VAIA chemotherapy, ICI of all sites positive by TB-MRI was administered, followed by HDC and SCR. A second group matched for observation period and consisting of 26 patients with more than three involved bones at diagnosis was treated with the European Intergroup Cooperative Ewing Sarcoma Study-92 (EICESS-92) protocol (group B). These patients did not receive TB-MRI and consequently did not receive TB-MRI-governed ICI, or HDC and SCR. Survival in group A vs group B was 45 vs 8% at 5 years and 27 vs 8% at 10 years after diagnosis (log rank and Breslow: Po0.005). We conclude that TB-MRIgoverned ICI followed by HDC and SCR in ET-MBM is feasible and warrants further evaluation in prospective studies.

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

“…more than one) or bone marrow (BM) [3, 4]. Overall survival of advanced Ewing sarcoma after ten years is ≤10% [4–6], warranting the study of intensified treatment modalities [6–19]. Moreover, the distinct contribution of BM involvement vs. multiple bone metastases to the dismal prognosis is not defined.…”

Consolidation of first-line therapy with busulphan and melphalan, and autologous stem cell rescue in children with Ewing’s sarcoma

“…In patients with multifocal bone metastases, implementation of total body magnetic resonance imaging governing the compartment irradiation was reported to be more effective than high-dose chemotherapy alone. 13 A different approach of the new therapies was to utilize the graft versus tumour effect after allogeneic transplantation in relapsed patients; 14 however, the optimal intensity of conditioning regimen and optimal donor have not been determined yet. 15,18 Other experimental therapies included immunotherapy with tumour-derived T-cells or dendritic cells 16 or monoclonal Abs against insulin-like growth factor type 1 receptor.…”

DKK2 Mediates Osteolysis, Invasiveness, and Metastatic Spread in Ewing Sarcoma

“…For the analysis of in vivo tumor growth and metastatic potential, 1.5 Â 10 6 to 3 Â 10 6 Ewing sarcoma cells and derivates were injected in a volume of 0.2 mL into immunodeficient Rag2…”

“…Although prognosis of patients with localized disease has markedly improved in past decades, metastatic disease-present in about 25% of patients with Ewing sarcoma at diagnosisis usually associated with fatal outcome (5,6). Especially the development of metastases in bones is a catastrophic event in the clinical course of patients with Ewing sarcoma (5, 7).…”