Originally published as JCO Early Release 10.1200/JCO.2007.15.0466 on February 17 2009

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Cooperative Trial CWS-91 for Localized Soft Tissue Sarcoma in Children, Adolescents, and Young Adults

From the Olgahospital, Pediatrics 5 (Oncology, Hematology, and Immunology), and Katharinenhospital, Department of Radiotherapy, Klinikum Stuttgart; Department of Plastic Surgery and Hand Surgery, Marienhospital, Stuttgart; Institute of Pediatric Pathology, University of Kiel, Kiel; Department of Radiotherapy, University of Regensburg, Regensburg; Department of Pediatric Hematology and Oncology, University Children's Hospital Muenster, Muenster; Department of Pediatric Oncology, University of Tuebingen, Tuebingen; Department of Pediatric Oncology, University of Frankfurt (Main), Frankfurt; Asklepios Kinderklinik, St Augustin; Department of Maxillofacial Surgery, University of Hamburg, Hamburg, Germany; St Anna Kinderspital, Vienna, Austria; Ostschweizer Kinderspital, St Gallen, Switzerland; and the Queen Silvia Children's Hospital, Goeteborg, Sweden.

Corresponding author: Tobias M. Dantonello, MD, Olgahospital, Pediatrics 5 (Oncology, Hematology, and Immunology), Klinikum Stuttgart, Bismarckstrasse 8, D-70176 Stuttgart, Germany; e-mail: tobias.dantonello{at}olgahospital-stuttgart.de.

Purpose To improve risk-adapted therapy for localized childhood soft tissue sarcoma within an international multicenter setting.

Patients and Methods Four hundred forty-one patients younger than 21 years with localized rhabdomyosarcoma and rhabdomyosarcoma-like tumors (ie, extraosseous tumors of the Ewing family, synovial sarcoma, and undifferentiated sarcoma) were eligible. Therapy was stratified according to postsurgical stage, histology, and tumor site. In unresectable tumors, treatment was further adapted depending on response to induction chemotherapy, TN classification, tumor size and second-look surgery. A novel five-drug combination of etoposide, vincristine, dactinomycin, ifosfamide, and doxorubicin (EVAIA) was evaluated for high-risk patients, but cumulative chemotherapy dosage and treatment duration were reduced for the remaining individuals as compared with that of the previous trial CWS-86. Hyperfractionated accelerated radiotherapy (HART) was recommended at doses of either 32 or 48 Gy.

Results At a median follow-up of 8 years, 5-year event-free survival (EFS) and overall (OS) survival for the entire cohort was 63% ± 4% and 73% ± 4%, respectively (all survival rates in this abstract are calculated and displayed with ±95% CI). EFS/OS rates by histology were 60% ± 5%/72% ± 5% in rhabdomyosarcoma, 62% ± 10%/69% ± 10% for Ewing tumors of soft tissues, 84% ± 12%/90% ± 10% for synovial sarcoma, and 67% ± 38%/83% ± 30% for undifferentiated sarcoma, respectively. Response to one cycle of the five-drug combination EVAIA was similar to that of the four-drug combination VAIA used in CWS-86. Two hundred twelve patients with rhabdomyosarcoma underwent radiation (EFS, 66% ± 6%); 53 of those patients had a favorable risk profile and received 32 Gy of HART (EFS, 73% ± 12%). TN classification, tumor site, tumor size, histology, and age were prognostic in univariate analysis.

Conclusion Improved risk stratification enabled decreased therapy intensity for selected patients without compromising survival. Intensified chemotherapy with EVAIA did not improve outcome of localized high-risk rhabdomyosarcoma.

Supported by Grant No. M76/91/Tr2, Project-No. 70456, from the Deutsche Krebshilfe (German Cancer Aid), Bonn and by the Foerderkreis Krebskranke Kinder e.V., Stuttgart, Germany.

For a complete list of contributing centers, see the Appendix (online only).

Presented in part at the 38th Congress of the International Society of Pediatric Oncology, September 17-21, 2006, Geneva, Switzerland.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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