title: Improved 6-year overall survival in AT/RT - results of the registry study Rhabdoid 2007.
abstract: Atypical teratoid rhabdoid tumors (AT/RT) are characterized by mutations and subsequent inactivation of SMARCB1 (INI1, hSNF5), a predilection for very young children and an unfavorable outcome. The European Registry for rhabdoid tumors (EU-RHAB) was established to generate a common European database and to establish a standardized treatment regimen as the basis for phase I/II trials. Thus, genetic analyses, neuropathologic and radiologic diagnoses, and a consensus treatment regimen were prospectively evaluated. From 2005 to 2009, 31 patients with AT/RT from four countries were recruited into the registry study Rhabdoid 2007 and treated with systemic and intraventricular chemotherapy. Eight patients received high-dose chemotherapy, 23 radiotherapy, and 17 maintenance therapy. Reference evaluations were performed in 64% (genetic analyses, FISH, MLPA, sequencing) up to 97% (neuropathology, INI1 stain). Germ-line mutations (GLM) were detected in 6/21 patients. Prolonged overall survival was associated with age above 3 years, radiotherapy and achievement of a complete remission. 6-year overall and event-free survival rates were 46% (±0.10) and 45% (±0.09), respectively. Serious adverse events and one treatment-related death due to insufficiency of a ventriculo peritoneal shunt (VP-shunt) and consecutive herniation were noted. Acquisition of standardized data including reference diagnosis and a standard treatment schedule improved data quality along with a survival benefit. Treatment was feasible with significant but manageable toxicity. Although our analysis is biased due to heterogeneous adherence to therapy, EU-RHAB provides the best available basis for phase I/II clinical trials.
authors.affiliation: Children's Hospital Augsburg, Swabian Children's Cancer Center, Stenglinstr. 2, 86156, Augsburg, Germany.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Bartelheim
authors.affiliation: Children's Hospital Augsburg, Swabian Children's Cancer Center, Stenglinstr. 2, 86156, Augsburg, Germany.
authors.forename: Karolina
authors.initials: K
authors.lastname: Nemes
authors.affiliation: Children's Hospital Augsburg, Swabian Children's Cancer Center, Stenglinstr. 2, 86156, Augsburg, Germany.
authors.forename: Angela
authors.initials: A
authors.lastname: Seeringer
authors.affiliation: Department of Pediatric Hematology and Oncology, University Children's Hospital Münster, Albert-Schweitzer-Str. 33, 48149, Münster, Germany.
authors.forename: Kornelius
authors.initials: K
authors.lastname: Kerl
authors.affiliation: Department of Pediatrics, University Hospital of North-Norway, Tromsø, Norway.|Department of Pediatric Medicine, Oslo University Hospital Rikshospitalet, P.O. Box 4950 Nydalen, N-0424, Oslo, Norway.
authors.forename: Jochen
authors.initials: J
authors.lastname: Buechner
authors.affiliation: Department of Pediatric Hematology and Oncology, University Children's Hospital Münster, Albert-Schweitzer-Str. 33, 48149, Münster, Germany.
authors.forename: Joachim
authors.initials: J
authors.lastname: Boos
authors.affiliation: Department of Pediatric Hematology and Oncology, University of Saarland, Gebäude 9, 66421, Homburg, Germany.
authors.forename: Norbert
authors.initials: N
authors.lastname: Graf
authors.affiliation: Department of Pediatric Hematology and Oncology, University Mannheim, Theodor-Kutzer-Ufer 1-3, 68167, Mannheim, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Dürken
authors.affiliation: Institute of Biostatistics and Clinical Research, University of Münster, Schmeddingstraße 56, 48149, Münster, Germany.
authors.forename: Joachim
authors.initials: J
authors.lastname: Gerss
authors.affiliation: Institute of Neuropathology, University Hospital Münster, Pottkamp 2, 48149, Münster, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Hasselblatt
authors.affiliation: Department of Radiooncology, University of Leipzig, Stephanstraße 9a, 04103, Leipzig, Germany.
authors.forename: Rolf-Dieter
authors.initials: RD
authors.lastname: Kortmann
authors.affiliation: Children's Hospital Medical Center, Technische Universität, Munich, Kölner Platz 1, 80804, München, Germany.
authors.forename: Irene
authors.initials: I
authors.lastname: Teichert von Luettichau
authors.affiliation: Institute of Human Genetics, Christian-Albrechts-University Kiel & University Hospital Schleswig- Holstein, Campus Kiel, Arnold-Heiler-Str. 3, 24105, Kiel, Germany.
authors.forename: Inga
authors.initials: I
authors.lastname: Nagel
authors.affiliation: Department for Children and Adolescents, Section for Pediatric Hematology/Oncology, St Olav's Hospital, University Hospital of Trondheim, 7006, Trondheim, Norway.
authors.forename: Randi
authors.initials: R
authors.lastname: Nygaard
authors.affiliation: Department of Pediatric Hematology and Oncology, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246, Hamburg, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Oyen
authors.affiliation: Department of Pediatric Oncology, Hospital Infantil Virgen del Rocio, AVDA Manuel Siurot S/N, 41013, Sevilla, Spain.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Quiroga
authors.affiliation: Department of Pediatric Hematology and Oncology, University Würzburg, Josef-Schneider-Str. 2, 97080, Würzburg, Germany.
authors.forename: Paul-Gerhardt
authors.initials: PG
authors.lastname: Schlegel
authors.affiliation: Department of Pediatric Hematology and Oncology, Ludwig-Maximilian-University Munich, Lindwurmstr. 4, 80337, München, Germany.
authors.forename: Irene
authors.initials: I
authors.lastname: Schmid
authors.affiliation: Department of Pediatric Hematology and Oncology, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246, Hamburg, Germany.
authors.forename: Reinhard
authors.initials: R
authors.lastname: Schneppenheim
authors.affiliation: Institute of Human Genetics, Christian-Albrechts-University Kiel & University Hospital Schleswig- Holstein, Campus Kiel, Arnold-Heiler-Str. 3, 24105, Kiel, Germany.
authors.forename: Reiner
authors.initials: R
authors.lastname: Siebert
authors.affiliation: Department of Pediatric Oncology, Hospital Infantil Virgen del Rocio, AVDA Manuel Siurot S/N, 41013, Sevilla, Spain.
authors.forename: Palma
authors.initials: P
authors.lastname: Solano-Paez
authors.affiliation: Particle Therapy Clinic at West German Proton Therapy, University Hospital Essen, Hufelandstr. 55, 45147, Essen, Germany.
authors.forename: Beate
authors.initials: B
authors.lastname: Timmermann
authors.affiliation: Department of Neuroradiology, University Hospital Würzburg, Josef-Schneider-Str. 11, 97080, Würzburg, Germany.
authors.forename: Monika
authors.initials: M
authors.lastname: Warmuth-Metz
authors.affiliation: Children's Hospital Augsburg, Swabian Children's Cancer Center, Stenglinstr. 2, 86156, Augsburg, Germany.
authors.forename: Michael Christoph
authors.initials: MC
authors.lastname: Frühwald
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use; D001932:Brain Neoplasms / Q000235:genetics / Q000401:mortality / Q000628:therapy*; D002648:Child; D002675:Child, Preschool; D003131:Combined Modality Therapy; D005060:Europe / Q000453:epidemiology; D005260:Female; D018095:Germ-Line Mutation; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D053208:Kaplan-Meier Estimate; D008297:Male; D011379:Prognosis; D020266:Radiotherapy, Conformal / Q000009:adverse effects / Q000379:methods; D012042:Registries; D018335:Rhabdoid Tumor / Q000175:diagnosis / Q000235:genetics / Q000401:mortality / Q000628:therapy*; D017211:Treatment Failure; D016896:Treatment Outcome
keywords: AT/RT; EU-RHAB Registry; Rhabdoid 2007; pediatric brain tumor