Results of the EICESS-92 Study: Two Randomized Trials of Ewing's Sarcoma Treatment—Cyclophosphamide Compared With Ifosfamide in Standard-Risk Patients and Assessment of Benefit of Etoposide Added to Standard Treatment in High-Risk Patients

Paulussen, Michael; Craft, Alan; Lewis, Ian; Hackshaw, Allan; Douglas, C; Dunst, Jürgen; Schuck, Andreas; Winkelmann, Winfried; Köhler, Gabriele; Poremba, Christopher; Zoubek, A.; Ladenstein, Ruth; Berg, Henk van den; Hunold, Andrea; Cassoni, Anna; Spooner, D.; Grimer, R. J.; Whelan, Jeremy; McTiernan, Anne; Jürgens, H.

doi:10.1200/jco.2008.16.5720

Cited by 240 publications

(169 citation statements)

References 24 publications

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“…Eleven (37%) of these primary tumors were located in the femur, nine (30%) in the pelvis, six (20%) in the tibia, four (13%) in the fibula. (Neo)adjuvant chemotherapy was given according to recommended protocols (Table 1) [10,20,23].…”

Section: Patientsmentioning

confidence: 99%

“…Ewing's sarcoma differs from osteosarcoma in some respects: the mean age of the patients is younger than those with osteosarcoma and seldom occurs beyond the age of 30 years, local control can be achieved with radiation as well as resection, and the drugs used to treat Ewing's sarcoma are different than those used to treat osteosarcoma [3,20,31]. In addition to adequate local control, the use of aggressive polychemotherapy has remarkably improved the survival of patients with Ewing's sarcoma [10,25,32,37] since adjuvant chemotherapy was first introduced in the 1980s and has led to a growing number of long-term survivors [8,20,23]. However, chemotherapy can result in long-term late effects on the cardiac, pulmonary, and metabolic systems as well as on skeletal muscle [16].…”

Section: Introductionmentioning

confidence: 99%

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Do Patients With Ewing's Sarcoma Continue With Sports Activities After Limb Salvage Surgery of the Lower Extremity?

Hobusch

Lang

Schuh

et al. 2015

Clinical Orthopaedics &Amp; Related Research

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Background Limb salvage surgery has evolved to become the standard method of treating sarcomas of the extremities with acceptable oncologic results. However, little information exists relative to the activity level or ability to participate in sports after tumor reconstructions. Questions/purposes The aims of the study were to answer the following questions: (1) Which sports activity levels and what types of sports can be expected in the long term after tumor reconstruction? (2) Which frequency durations are patients with Ewing's sarcoma able to perform in longterm followup after local control? (3) Do surgical complications affect sports activity level? Methods Thirty patients (13 females, 17 males; mean age, 18 ± 8 years; range, 2-36 years at diagnosis; mean followup 16 ± 6 years [minimum, 5 years]) were included. Tumors were located in the pelvis, femur, tibia, and fibula. Surgical procedures included surgical resections alone (n = 8), surgical resection with biological reconstruction (n = 9), or endoprosthetic reconstruction (n = 13). We assessed UCLA sports activity levels, kinds of sports as well as the frequency per week and the duration of each training unit at long term (minimum followup, 5 years). Results In long-term followup 83% patients (25 of 30) were performing athletic activity regularly. The hours/ week of sports depended on type of surgery and were highest after resections in the pelvis and femur (5.8) and were lowest after megaprosthetic reconstruction of the pelvis (1.0). Patients undergoing biologic reconstructions were able to perform high-impact sports. UCLA sports activity levels were high after joint-preserving vascularized fibula for tibia reconstruction (7.4) and after megaprosthetic reconstruction of the lower extremity (6.3-6.4) and were low after tumors located in the fibula (4.2). Complications during followup did not significantly influence sports activity in long-term survivors.

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Section: Patientsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Do Patients With Ewing's Sarcoma Continue With Sports Activities After Limb Salvage Surgery of the Lower Extremity?

Hobusch

Lang

Schuh

et al. 2015

Clinical Orthopaedics &Amp; Related Research

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“…20,21,23,36 The 7-year EFS of 61%, achieved with the ETC conditioning regimen, seems encouraging, especially considering the survival reported in studies with conventional chemotherapy [18][19][20][21] in which the EFS was always o40%. Nevertheless, Paulussen et al 22 recently reported a 5-year EFS of 55% in high-risk ESFT using an intensive induction chemotherapy (EVAIA regimen) without HDC/ASCT, confirming that the effect of HDC/ASCT remains controversial.…”

Section: Discussionmentioning

confidence: 99%

Toxicity of high-dose chemotherapy with etoposide, thiotepa and CY in treating poor-prognosis Ewing's sarcoma family tumors: the experience of the Bambino Gesù Children's Hospital

Ilari

Ioris

Milano³

et al. 2010

Bone Marrow Transplant

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We report the toxicity of high-dose chemotherapy (HDC) based on etoposide, thiotepa and CY (ETC) in children with poor-prognosis Ewing's sarcoma family tumors (ESFTs). A total of 26 patients with high-risk ESFT (metastasis or axis localization or tumor volume 4200 ml or necrosis o95%) were reviewed. The conditioning was based on etoposide (600 mg/m 2 ), thiotepa (750 mg/m 2 ) and CY (120 mg/kg) followed by autologous BM or PBSC rescue. The conditioning regimen was well tolerated, without any toxic deaths. The median time from transplant to a neutrophil count of 40.5 Â 10 9 /l was 10 days (range 6-27) and 22.5 days (range 9-114) for a plt count of 450 Â 10 9 /l. Oral mucositis was recorded in 20 patients, grade 1/2 in 19 and grade 3 in the last patient. Diarrhea grade 1/2 was recorded in four patients and grade 1/2 liver toxicity in four patients. Sepsis was documented in four cases and skin toxicity in three. Lung and tubular toxicity, respectively, were reported in one patient each. We conclude that the ETC regimen presented a limited and manageable toxicity. Further studies would confirm the role of ETC in high-risk ESFT.

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“…21 The median OS was 1 year (range 0.5-14 years). Out of 26 patients, 2 were alive at the end of the follow-up period and 24 patients had died, of whom 22 patients succumbed to DFD and 2 patients succumbed to DFC.…”

Section: Resultsmentioning

confidence: 99%

“…19,20 In group B, 26 patients with more than three bones involved at diagnosis (aged 6-37 years; median: 17 years) were registered from 1992 to 1996 and treated according to the European Intergroup Cooperative Ewing Sarcoma Study 92 protocol (EICESS 92) for high-risk ET-MBM, as previously described. 21 In all, 1 out of 26 patients had LN metastases and 10 out of 26 patients had lung disease at initial diagnosis. Group B patients did not receive TB-MRI at staging, and thus did not receive TB-MRI-governed ICI.…”

Section: Patient Characteristicsmentioning

confidence: 99%

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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Results of the EICESS-92 Study: Two Randomized Trials of Ewing's Sarcoma Treatment—Cyclophosphamide Compared With Ifosfamide in Standard-Risk Patients and Assessment of Benefit of Etoposide Added to Standard Treatment in High-Risk Patients

Abstract: Cyclophosphamide seemed to have a similar effect on EFS and OS as ifosfamide in SR patients but was associated with increased toxicity. In HR patients, the addition of etoposide seemed to be beneficial.

Cited by 240 publications

References 24 publications

Do Patients With Ewing's Sarcoma Continue With Sports Activities After Limb Salvage Surgery of the Lower Extremity?

Do Patients With Ewing's Sarcoma Continue With Sports Activities After Limb Salvage Surgery of the Lower Extremity?

Toxicity of high-dose chemotherapy with etoposide, thiotepa and CY in treating poor-prognosis Ewing's sarcoma family tumors: the experience of the Bambino Gesù Children's Hospital

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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