title: Outcome of extracranial malignant rhabdoid tumours in children registered in the European Paediatric Soft Tissue Sarcoma Study Group Non-Rhabdomyosarcoma Soft Tissue Sarcoma 2005 Study-EpSSG NRSTS 2005.
abstract: Extracranial malignant rhabdoid tumours (MRT) are rare lethal childhood cancers that often occur in infants and have a characteristic genetic mutation in the SMARCB1 gene. The European Paediatric Soft Tissue Sarcoma Study Group (EpSSG) conducted a multinational prospective study of registered cases of extracranial MRT to test an intensive multimodal approach of treatment for children with newly diagnosed extracranial MRT.
  
  
  
  Between December 2005 and June 2014, we prospectively registered 100 patients from 12 countries with a diagnosis of MRT tumour at an extracranial site on the EpSSG Non-Rhabdomyosarcoma Soft Tissue Sarcoma 2005 Study (NRSTS 2005). They were all treated on a standard multimodal protocol of surgery, radiotherapy, and chemotherapy over 30 weeks as follows: vincristine, cyclophosphamide, and doxorubicin (VDCy) at weeks 1, 10, 13, 22, and 28; vincristine was also given alone on weeks 2, 3, 11, 12, 14, 15, 23, 24, 29, and 30. Cyclophosphamide, carboplatin, and etoposide (Cy*CE) was given at weeks 4, 7, 16, 19, and 25. Radiotherapy was recommended for all primary tumour sites and all sites of metastatic disease.
  
  
  
  Forty-three patients completed the protocol treatment. Median follow-up for alive patients of the complete cohort was 44.6 months (range 11.5-84.6). For the whole cohort, the 3-year event-free survival (EFS) was 32.3% (95% confidence interval [CI] 23.2-41.6%) with a 3-year overall survival (OS) of 38.4% (95% CI 28.8-47.9%). For localised disease, the 4-year EFS was 39.3% (95% CI 28.2-50.1%) with a 4-year OS of 40.1% (95% CI 28.4-51.5%). For metastatic disease, the 2-year EFS was 8.7% (95% CI 1.5-24.2%) with a 2-year OS of 13.0% (95% CI 3.3-29.7%). Multivariable analysis disclosed that all patients ≤1 year of age were associated with at higher risk of death (hazard ratio [HR]: 2.6; 95% CI 1.0-6.8; p-value = 0.0094). Risk of death was also related with gender in metastatic patients (HR for males: 2.9, 95% CI 1.0-8.0; p-value = 0.0077).
  
  
  
  The EpSSG NRSTS 2005 protocol of intensive therapy can be delivered to extracranial MRT patients, with a possible improvement in outcome. The outcome, however, remains poor for patients who progress or with metastatic disease.
authors.affiliation: Paediatric Oncology, Royal Manchester Children's Hospital, Manchester, UK. Electronic address: Bernadette.brennan@cmft.nhs.uk.
authors.forename: Bernadette
authors.initials: B
authors.lastname: Brennan
authors.affiliation: Clinical Trials and Biostatistics Unit, IRCCS Istituto Oncologico Veneto, Padova, Italy.
authors.forename: Gian Luca
authors.initials: GL
authors.lastname: De Salvo
authors.affiliation: Pediatric, Adolescent, Young Adult Department, Institut Curie, Paris, France.
authors.forename: Daniel
authors.initials: D
authors.lastname: Orbach
authors.affiliation: Clinical Trials and Biostatistics Unit, IRCCS Istituto Oncologico Veneto, Padova, Italy.
authors.forename: Angela
authors.initials: A
authors.lastname: De Paoli
authors.affiliation: Department of Diagnostic Paediatric Histopathology, Royal Manchester Children's Hospital, Manchester, UK.
authors.forename: Anna
authors.initials: A
authors.lastname: Kelsey
authors.affiliation: Department of Pediatric Oncology, University Children's Hospital, Brno, Czech Republic.
authors.forename: Peter
authors.initials: P
authors.lastname: Mudry
authors.affiliation: Department of Pediatrics, CHC-Clinique Esperance, Montegnée, Belgium.
authors.forename: Nadine
authors.initials: N
authors.lastname: Francotte
authors.affiliation: Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands.
authors.forename: Max
authors.initials: M
authors.lastname: Van Noesel
authors.affiliation: Pediatric Hematology and Oncology Division, Padova University, Padova, Italy.
authors.forename: Gianni
authors.initials: G
authors.lastname: Bisogno
authors.affiliation: Fondazione IRCCS Istituto Nazionale Tumori Milano, Milan, Italy.
authors.forename: Michela
authors.initials: M
authors.lastname: Casanova
authors.affiliation: Fondazione IRCCS Istituto Nazionale Tumori Milano, Milan, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Ferrari
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D059186:Chemoradiotherapy, Adjuvant; D002648:Child; D002675:Child, Preschool; D003520:Cyclophosphamide / Q000008:administration & dosage; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D009367:Neoplasm Staging; D011446:Prospective Studies; D018335:Rhabdoid Tumor / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D012509:Sarcoma / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D014750:Vincristine / Q000008:administration & dosage
chemical_list: D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide
keywords: Malignant rhabdoid tumour; Paediatric; Prognostic factors; Prospective registry; Survival