High-Dose Melphalan, Etoposide, Total-Body Irradiation, and Autologous Stem-Cell Reconstitution as Consolidation Therapy for High-Risk Ewing’s Sarcoma Does Not Improve Prognosis

Meyers, Paul A.; Krailo, Mark; Ladanyi, Marc; Chan, Kawah; Sailer, Scott L.; Dickman, Paul S.; Baker, David L.; Jh, Davis; Gerbing, Robert B.; Grovas, Alfred; Herzog, Cynthia E.; Lindsley, Karen; Liu‐Mares, Wen; Nachman, James B.; Sieger, Lance; Wadman, Jean; Görlick, Richard

doi:10.1200/jco.2001.19.11.2812

Cited by 197 publications

(135 citation statements)

References 24 publications

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“…These rates are comparable to published PFS rates after conventional therapy (chemotherapy, surgery and irradiation) in patients with similar disease characteristics though the recent addition of ifosfamide and etoposide to conventional therapy has resulted in higher PFS rates in patients with local disease. 2,4 Further, PFS rates reported in the current study where patients received ASCT at several institutions over a decade are comparable to those reported by others 22,23 and suggest that the results of these smaller prospective trials are generalizable to the results of ASCT as practiced by the North American transplant community. Most patients with recurrent disease prior to transplantation achieved a complete or partial remission prior to ASCT.…”

Section: Discussionsupporting

confidence: 73%

Myeloablative therapy with autologous stem cell rescue for patients with Ewing sarcoma

Gardner

Carreras

Boudreau

et al. 2008

Bone Marrow Transplant

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The aim of this study was to identify risk factors associated with PFS in patients with Ewing sarcoma undergoing ASCT; 116 patients underwent ASCT in 1989-2000 and reported to the Center for International Blood and Marrow Transplant Research. Eighty patients (69%) received ASCT as first-line therapy and 36 (31%), for recurrent disease. Risk factors affecting ASCT were analyzed with use of the Cox regression method. Metastatic disease at diagnosis, recurrence prior to ASCT and performance score o90 were associated with higher rates of disease recurrence/progression. Five-year probabilities of PFS in patients with localized and metastatic disease at diagnosis who received ASCT as first-line therapy were 49% (95% CI 30-69) and 34% (95% CI 22-47) respectively. The 5-year probability of PFS in patients with localized disease at diagnosis, and received ASCT after recurrence was 14% (95% CI 3-30). PFS rates after ASCT are comparable to published rates in patients with similar disease characteristics treated with conventional chemotherapy, surgery and irradiation suggesting a limited role for ASCT in these patients. Therefore, ASCT if considered should be for high-risk patients in the setting of carefully controlled clinical trials.

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Section: Discussionsupporting

confidence: 73%

Myeloablative therapy with autologous stem cell rescue for patients with Ewing sarcoma

Gardner

Carreras

Boudreau

et al. 2008

Bone Marrow Transplant

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“…Some studies suggested an improvement in clinical outcomes, [37][38][39] whereas others did not. 40,41 In the current study, HDC with hematopoietic stem cell rescue failed to improve EFS significantly among high-risk patients. Precise assessment of the utility of HDC for patients with high-risk ESFT will require massive prospective, controlled studies.…”

Section: Discussionmentioning

confidence: 94%

Clinical outcome of patients with Ewing sarcoma family of tumors of bone in Japan

Obata

Ueda

Kawai

et al. 2007

Cancer

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BACKGROUND.Ewing sarcoma family of tumors (ESFT) of bone is extremely rare in Japan. The objectives of the current study were to assess the clinical outcome and prognostic factors of patients with ESFT of bone in Japan and to compare them between Euro‐American and Japanese populations.METHODS.The authors conducted a retrospective analysis of 243 patients who were treated for ESFT of bone in Japan between 1981 and 2003. Local therapy was surgery in 35% of patients, surgery combined with radiotherapy in 40% of patients, radiotherapy alone in 22% of patients, and no local treatment in 3% of patients. All but 3 patients received various regimens of multidrug chemotherapy.RESULTS.The median patient age was 16 years. The primary disease sites were the trunk in 53% of patients and the extremities in 47% of patients. Forty‐one patients had metastases at presentation. The median follow‐up was 66 months. A univariate survival analysis demonstrated that patients who had metastases at presentation, primary site in the trunk, age ≥16 years, tumor size ≥10 cm, tumor that responded poorly to induction chemotherapy, and local treatment with radiotherapy alone had a significantly worse event‐free survival (EFS). A multivariate analysis further verified that the former 3 factors were significant adverse prognostic factors. Of 201 patients with localized disease, 45 patients who received current chemotherapy regimens that included ifosfamide and etoposide had a significantly better 5‐year EFS rate (67.6%) compared with other patients.CONCLUSIONS.The clinical outcome of patients with localized ESFT of bone in Japan has improved markedly with the use of current chemotherapy regimens that include ifosfamide and etoposide and has become comparable to the outcomes observed in other major series of Euro‐American patients. The prognostic factors are also almost identical. Cancer 2007 © 2007 American Cancer Society.

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“…Event-free survival was not improved compared with the literature. In 2001, Meyers et al 17 published a further report focusing on patients with bone or BM metastases. Out of 32 patients with high-risk ET-MBM, 23 patients were transplanted after induction therapy with CY, doxorubicin and VCR alternating with ifosfamide and etoposide and myeloablative therapy with melphalan, etoposide and TBI.…”

Section: Discussionmentioning

confidence: 99%

“…Such limitations are characteristic for many studies in high-risk ET-MBM. 17 Successful treatment of high-risk ET-MBM needs both systemic chemotherapy and local control. Our data suggest that TB-MRI may facilitate precise identification of initial metastases in high-risk ET-MBM and that sufficient ICI may decrease the relapse rate.…”

Section: Discussionmentioning

confidence: 99%

“…A carefully controlled study has recently shown that HDC alone may not improve the prognosis of patients with primary multifocal ET. 17 A study has also shown that total body magnetic resonance imaging (TB-MRI) is more sensitive than the conventionally used 99m technetium methylene diphosphonate bone scintigraphy scan for detection of metastatic bones in primary multifocal ET. 18 On the basis of these findings, we examined the role of TB-MRIgoverned involved compartment irradiation (ICI) followed by melphalan/etoposide (ME)-based HDC in combination with stem cell rescue (SCR) in high-risk ET-MBM patients in a retrospective study.…”

Section: Introductionmentioning

confidence: 99%

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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

Burdach

Thiel

Schöniger

et al. 2009

Bone Marrow Transplant

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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.

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High-Dose Melphalan, Etoposide, Total-Body Irradiation, and Autologous Stem-Cell Reconstitution as Consolidation Therapy for High-Risk Ewing’s Sarcoma Does Not Improve Prognosis

Abstract: Consolidation with high-dose melphalan, etoposide, TBI, and autologous stem-cell support failed to improve the probability of EFS in this cohort of patients with newly diagnosed metastatic ES.

Cited by 197 publications

References 24 publications

Myeloablative therapy with autologous stem cell rescue for patients with Ewing sarcoma

Myeloablative therapy with autologous stem cell rescue for patients with Ewing sarcoma

Clinical outcome of patients with Ewing sarcoma family of tumors of bone in Japan

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

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