{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T08:47:42Z","timestamp":1787647662790,"version":"build-2736575974"},"reference-count":39,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2023,10,9]],"date-time":"2023-10-09T00:00:00Z","timestamp":1696809600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pediatric Blood &amp; Cancer"],"published-print":{"date-parts":[[2024,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Outcome of primary metastatic rhabdomyosarcoma (RMS) is poor. Certain risk factors as fusion status, Oberlin score, and local treatment of primary tumor are known to influence prognosis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Procedure<\/jats:title><jats:p>Patients with metastatic RMS were treated according to Cooperative Weichteilsarkom Studiengruppe (CWS) guidance with chemotherapy (CHT), radiotherapy (RT) excluding total lung irradiation (TLI), complete resection of the primary tumor, and metastasectomy if possible. Kaplan\u2013Meier estimators and Cox proportional hazard models were used to examine event\u2010free survival (EFS) and overall survival (OS) involving also landmark analyses.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In the European Soft Tissue Sarcoma Registry SoTiSaR (2009\u20132018), 211 patients were analyzed. Many patients had fusion\u2010positive alveolar RMS (<jats:italic>n<\/jats:italic>\u00a0=\u00a083; 39%). Median age was 9.4\u00a0years [0.1\u201319.7\u00a0years]. Treatment primarily consisted of CHT with CEVAIE (carboplatin, epirubicine, vincristine, actinomycin\u2010D, ifosfamide, etoposide: 86%, other regimens: 14%), RT (71%), resection of primary tumor (37%), metastasectomy (19%), and lymph node sampling\/dissection (21%). Maintenance treatment (MT) (oral trofosfamide, idarubicin, etoposide) was added in 74% of patients. Oberlin factors, fusion status, and MT were predictive for EFS and OS. MT with O\u2010TIE was not improving outcome when adjusting for the immortal time bias. Local treatment of the primary tumor and radical irradiation (except TLI) improved EFS, not OS, when adjusting for the Oberlin score. Patients with fusion\u2010negative alveolar RMS (<jats:italic>n<\/jats:italic>\u00a0=\u00a09) had an excellent outcome with a 5\u2010year EFS and OS of 100%, compared to patients with embryonal RMS (49%\/62%), PAX7\u2010 (22%\/47%) and PAX3\/FOXO1\u2010positive ARMS (10\/13%), respectively (<jats:italic>p<\/jats:italic>\u00a0&lt;\u00a0.001).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Prognosis of metastatic RMS primarily depends on fusion status and Oberlin score. Fusion status needs to be considered in future trials to optimize treatment outcome. The role of radical irradiation needs further investigation.<\/jats:p><\/jats:sec>","DOI":"10.1002\/pbc.30707","type":"journal-article","created":{"date-parts":[[2023,10,12]],"date-time":"2023-10-12T02:39:39Z","timestamp":1697078379000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Significance of fusion status, Oberlin risk factors, local and maintenance treatment in pediatric and adolescent patients with metastatic rhabdomyosarcoma: Data of the European Soft Tissue Sarcoma Registry SoTiSaR"],"prefix":"10.1002","volume":"71","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3472-9679","authenticated-orcid":false,"given":"Amadeus T.","family":"Heinz","sequence":"first","affiliation":[{"name":"Department of Pediatric Hematology and Oncology University Children\u00b4s Hospital Tuebingen  Tuebingen Germany"},{"name":"Stuttgart Cancer Center Zentrum f\u00fcr Kinder\u2010, Jugend\u2010 und Frauenmedizin (Olgahospital), P\u00e4diatrie 5 (P\u00e4diatrische Onkologie, H\u00e4matologie, Immunologie) Klinikum der Landeshauptstadt Stuttgart  Stuttgart Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anton","family":"Sch\u00f6nstein","sequence":"additional","affiliation":[{"name":"Network Aging Research Heidelberg University  Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Ebinger","sequence":"additional","affiliation":[{"name":"Department of Pediatric Hematology and Oncology University Children\u00b4s Hospital Tuebingen  Tuebingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00f6rg","family":"Fuchs","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery and Urology University Children's Hospital  Tuebingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beate","family":"Timmermann","sequence":"additional","affiliation":[{"name":"Department of Particle Therapy, West German Proton Therapy Centre Essen (WPE) University Medical Center Essen, West German Cancer Center (WTZ) German Cancer Consortium (DKTK)  Essen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guido","family":"Seitz","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery and Urology University Hospital Giessen\u2010Marburg  Marburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Vokuhl","sequence":"additional","affiliation":[{"name":"Section of Pediatric Pathology Department of Pathology  Bonn Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc","family":"M\u00fcnter","sequence":"additional","affiliation":[{"name":"Stuttgart Cancer Center Department of Radiation Oncology Klinikum der Landeshauptstadt Stuttgart  Stuttgart Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristian W.","family":"Pajtler","sequence":"additional","affiliation":[{"name":"Hopp Children's Cancer Center Heidelberg (KiTZ) Heidelberg University  Heidelberg Germany"},{"name":"Division of Pediatric Neurooncology German Cancer Research Center (DKFZ) and German Cancer Consortium (DKTK) Heidelberg University  Heidelberg Germany"},{"name":"Department of Pediatric Oncology, Hematology, and Immunology Heidelberg University Hospital  Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabine","family":"Stegmaier","sequence":"additional","affiliation":[{"name":"Stuttgart Cancer Center Zentrum f\u00fcr Kinder\u2010, Jugend\u2010 und Frauenmedizin (Olgahospital), P\u00e4diatrie 5 (P\u00e4diatrische Onkologie, H\u00e4matologie, Immunologie) Klinikum der Landeshauptstadt Stuttgart  Stuttgart Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thekla","family":"von Kalle","sequence":"additional","affiliation":[{"name":"Stuttgart Cancer Center, Zentrum f\u00fcr Kinder\u2010, Jugend\u2010 und Frauenmedizin (Olgahospital), Department of Radiology Klinikum der Landeshauptstadt Stuttgart  Stuttgart Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian P.","family":"Kratz","sequence":"additional","affiliation":[{"name":"Pediatric Hematology and Oncology Hannover Medical School  Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gustaf","family":"Ljungman","sequence":"additional","affiliation":[{"name":"Department of Women's and Children's Health Children's University Hospital University of Uppsala  Uppsala Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanna","family":"Juntti","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Adolescence Oulu 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