Second malignancies after Ewing tumor treatment in 690 patients from a cooperative German/Austrian/Dutch study

Paulussen, Michael; Ahrens, S.; Lehnert, Martin; Taeger, Dirk; Hense, Hans‐Werner; Wagner, Alexandra L.; Dunst, Jürgen; Harms, D.; Reiter, Alfred; Henze, Günter; Niemeyer, Charlotte M.; Göbel, U.; Kremens, Bernhard; Fölsch, Ulrich R.; Aulitzky, Walter E.; Voûte, P. A.; Zoubek, A.; Jürgens, Heribert

doi:10.1023/a:1013148730966

Cited by 88 publications

(55 citation statements)

References 43 publications

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“…[26][27][28] In the present study, one possible case of treatment-related fatal adverse effect and two cases of secondary malignancy (one MDS and one AML) were observed. Treatmentrelated deaths in three out of 21 patients (14%) strongly suggest that such intensive treatment must be restricted to patients with a high risk of mortality.…”

Section: Discussionsupporting

confidence: 50%

High-dose chemotherapy and autologous peripheral blood stem cell transfusion for adult and adolescent patients with small round cell sarcomas

Yamada

Takahashi

Taji

et al. 2007

Bone Marrow Transplant

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The treatment of small-round-cell tumors (SRCT) in adult patients remains a challenge to clinicians. In the present study, we analyzed the feasibility and efficacy of high-dose chemotherapy (HDCT) followed by autologous peripheral blood stem-cell rescue as a consolidation therapy exclusively for patients with good disease control through a single regimen of induction chemotherapy and local therapy. Twenty-one patients (12 females, median age 22.0 years) were analyzed, including seven cases with rhabdomyosarcoma (RMS) and 14 cases with Ewing's family tumors (EFT). Overall, survival was 46% and failure-free survival (FFS) was 33% at 3 years. Patients with EFT had better FFS than those with RMS, with an estimated 3-year FFS of 50% (Po0.01). There was a single case of possible treatment-related death and two cases of secondary malignancies. This study cannot conclusively determine the beneficial effects of HDCT for improving treatment outcomes in adult SRCTs due to the small number of subjects. However, study findings suggest that a subgroup of patients with EFT may obtain prolonged survival benefits from this therapy.

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Section: Discussionsupporting

confidence: 50%

High-dose chemotherapy and autologous peripheral blood stem cell transfusion for adult and adolescent patients with small round cell sarcomas

Yamada

Takahashi

Taji

et al. 2007

Bone Marrow Transplant

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“…A low risk (0.4-2.2%) of secondary neoplasias was reported for patients diagnosed with ESFT and treated with moderatedose combination chemotherapy regimens [4,15]. However, in recent years, the use of protocols that included intensification of alkylators and topoisomerase-II inhibitors has resulted in a significant increase in the incidence of t-AML/MDS [4,7,16].…”

Section: Discussionmentioning

confidence: 99%

Treatment of Ewing sarcoma family of tumors with a modified P6 protocol in children and adolescents

Mora

Torres

Parareda

et al. 2011

Pediatric Blood & Cancer

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INTRODUCTIONEwing sarcoma family of tumors (ESFT) is the second most common bone malignancy in children, accounting for approximately 40% of all bone cancers [1]. ESFT is characterized by a specific balanced chromosomal translocation which fuses the amino-terminal domain of the EWSR1 gene or, in rare cases, the TLS/FUS gene, to the DNA-binding domain of one of five ETS genes [2]. The transcripts resulting from these fusion genes can be detected using the reverse transcriptase-polymerase chain reaction (RT-PCR) technique. RT-PCR provides a higher sensitivity than conventional cytological analysis to detect tumor cells in bone marrow (BM) and peripheral blood (PB). Previous studies have reported that among patients with local-regional ESFT, RT-PCR positivity of BM correlates with a high risk of adverse outcome and significantly poorer disease-free survival rates [3]. Thus, RT-PCR analysis of BM might be useful to classify localized and metastatic patients at diagnosis.Treatment of ESFT has improved over the last two decades with reported durable remissions in 50-70% of non-metastatic patients [4]. In 1995, the group at MSKCC published the P6 protocol showing a successful induction of remission in patients with localregional disease and good initial responses with dose-intensive and short-term chemotherapy in patients with distant metastases [5]. A subsequent and extended outcome data on 68 patients (44 localized) with ESFT treated with the P6 protocol showed a 4-year EFS and OS for patients with localized disease of 82% and 89%, respectively. Patients with detectable metastatic disease at diagnosis had a significantly worse prognosis, with a 4-year EFS rate of 12% and OS rate of 17.8% [6].In 1998, the MSKCC group reported a cumulative incidence of therapy related acute myelogenous leukemias (t-AML) and myelodysplastic syndromes (MDS) at 40 months of 8% in survivors of the P6 protocol [7]. The latest report from the MSKCC group [6] details three patients experiencing secondary MDS/t-AML out of 44 non-metastatic patients, which makes a 7% incidence in the population with longest overall survival. This and other experiences suggested that repetitive use of high-dose alkylating agents given with topoisomerase-II inhibitors is strongly leukemogenic, even with modest cumulative doses of each drug. The two well-described kinds of t-AML/MDS occurred, namely, those associated with topoisomerase-II inhibitors and marked by early emergence of t-AML with translocations of the MLL gene at chromosome band 11q23, and those associated with alkylating agents and marked by an MDS, whole or partial deletions of chromosomes 5 or 7, and a latency period of 2-8 years [8,9].In 2001, we modified the original P6 (hereby mP6) protocol by: (1) reducing the number of chemotherapy cycles down to five, three CDV and two IE, in order to decrease the risk of secondary tumors; (2) using higher doses of ifosfamide (2.8 g/m 2 /day instead of 1.8 g) post-surgery in cases with poor histological response; and (3) using dexrazoxane before doxorubicin t...

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“…However, as primary site was an important prognostic factor associated with tumour burden, and trials were open for patients with both localised and metastatic disease, this seems unlikely. There was a maximum interval of 3 weeks between diagnosis and starting treatment for patients to be eligible for EICESS-92 (Paulussen et al, 2001), but no maximum period between diagnosis and starting treatment was specified for the two earlier trials Craft et al, 1998). Patients with any primary site and those with metastatic disease at diagnosis were eligible for all three trials.…”

Section: Discussionmentioning

confidence: 99%

Patterns of care and survival for patients aged under 40 years with bone sarcoma in Britain, 1980–1994

et al. 2005

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The purpose of the study was to calculate population-based survival rates for osteosarcoma (OS) and Ewing's sarcoma (ES) in Great Britain during 1980 -1994, determine proportions of patients treated at specialist centres or entered in national and international clinical trials, and investigate effects of these factors on survival. Data on a population-based series of 1349 patients with OS and 849 with ES were compiled from regional and national cancer registries, UK Children's Cancer Study Group, regional bone tumour registries and clinical trials. Follow-up was through population registers. Survival was analysed by actuarial analysis with log-rank tests and by Cox's proportional hazards analysis. Five-year survival rates during 1980 -1984, 1985 -1989 and 1990 -1994 were 42% (95% CI: 37, 46), 54% (95% CI: 50, 59) and 53% (95% CI: 48, 57), respectively, for OS and 31% (95% CI: 26, 37), 46% (95% CI: 40, 51) and 51% (95% CI: 45, 57) for ES. Proportions of patients treated at a supraregional bone tumour centre or a paediatric oncology centre in the three quinquennia were 36, 56 and 67% for OS and 41, 60 and 69% for ES. In 1983 -1992, 48% of OS patients were entered in a national trial; for ES, 27% were entered in 1980 -1986 and 54% in 1987 -1994. Survival was similar for trial and nontrial patients with OS. For ES, trial patients had consistently higher 5-year survival than nontrial patients : 1980 -1986 1987 1993-1994 , 54 vs 43%. During 1985-1994, patients with OS or ES whose main treatment centre was a nonteaching hospital had lower survival rates. In multivariate analyses of patients diagnosed during 1985 -1994 that also included age, sex, primary site, surgical treatment centre, the results relating to main treatment centre for both OS and ES retained significance but the survival advantage of trial entry for ES became nonsignificant. For both OS and ES diagnosed since 1985, patients whose main treatment centre was a nonspecialist hospital had a lower survival rate.

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Second malignancies after Ewing tumor treatment in 690 patients from a cooperative German/Austrian/Dutch study

Abstract: The second cancder risk observed was in the range to be expected in cancer survivors. High-dose therapy, and less markedly, etoposide, may contribute to the overall second cancer risk.

Cited by 88 publications

References 43 publications

High-dose chemotherapy and autologous peripheral blood stem cell transfusion for adult and adolescent patients with small round cell sarcomas

High-dose chemotherapy and autologous peripheral blood stem cell transfusion for adult and adolescent patients with small round cell sarcomas

Treatment of Ewing sarcoma family of tumors with a modified P6 protocol in children and adolescents

Patterns of care and survival for patients aged under 40 years with bone sarcoma in Britain, 1980–1994

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