title: Treatment and outcome of patients with relapsed clear cell sarcoma of the kidney: a combined SIOP and AIEOP study.
abstract: BACKGROUND
  Clear cell sarcoma of the kidney (CCSK) is an uncommon paediatric renal tumour. Relapses occur in about 15% of the patients. Since detailed clinical information on relapsed CCSK is scarce, the current study aims to describe outcome of patients with relapsed CCSK treated according to recent European protocols.
  
  
  METHODS
  We analysed prospectively collected data of all CCSK patients who developed a relapse after complete remission at the end of primary treatment, entered onto SIOP and AIEOP trials between 1992 and 2012.
  
  
  RESULTS
  Thirty-seven of 237 CCSK patients (16%) treated according to SIOP and AIEOP protocols developed a relapse. Median time from initial diagnosis to relapse was 17 months (range, 5.5 months - 6.6 years). Thirt-five out of thirty-seven relapses (95%) were metastatic; the most common sites of relapse were the brain (n=13), lungs (n=7) and bone (n=5). Relapse treatment consisted of chemotherapy (n=30), surgery (n=19) and/or radiotherapy (n=18), followed by high-dose chemotherapy and autologous bone marrow transplantation (ABMT) in 14 patients. Twenty-two out of thirty-seven patients (59%) achieved a second complete remission (CR); 15 of whom (68%) developed a second relapse. Five-year event-free survival (EFS) after relapse was 18% (95% CI: 4%-32%), and 5-year overall survival (OS) was 26% (95% CI: 10%-42%).
  
  
  CONCLUSIONS
  In this largest series of relapsed CCSK patients ever described, overall outcome is poor. Most relapses are metastatic and brain relapses are more common than previously recognised. Intensive treatment aiming for local control, followed by high dose chemotherapy and ABMT, seems to be of benefit to enhance survival. Novel development of targeted therapy is urgently required.
authors.affiliation: Department of Paediatric Haematology and Oncology, Erasmus MC - Sophia Children's Hospital, Dr. Molewaterplein 60, 3015GJ Rotterdam, The Netherlands.
authors.forename: S L
authors.initials: SL
authors.lastname: Gooskens
authors.affiliation: Department of Paediatric Haematology and Oncology, Saarland University, Campus, 66123 Saarbrücken, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Furtwängler
authors.affiliation: Paediatric Oncology Unit, Department of Haematology and Paediatric Onco-Haematology, Fondazione IRCCS Instituto Nazionale dei Tumori, Via Giacomo Venezian,1, 20133 Milano, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Spreafico
authors.affiliation: Department of Statistics, Netherlands Cancer Institute (NKI-AvL), Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands.
authors.forename: H
authors.initials: H
authors.lastname: van Tinteren
authors.affiliation: Department of Paediatric Haematology and Oncology, Academic Medical Center-Emma Children's Hospital, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.
authors.forename: J
authors.initials: J
authors.lastname: de Kraker
authors.affiliation: Department of Pathology, Cardiff University School of Medicine, Heath Park, Cardiff CF14 4XN, UK.
authors.forename: G M
authors.initials: GM
authors.lastname: Vujanic
authors.affiliation: Institute of Pathology, University of Kiel, Christian-Albrechts-Platz 4, 24118 Kiel, Germany.
authors.forename: I
authors.initials: I
authors.lastname: Leuschner
authors.affiliation: Department of Pathology, Hopitaux Universitaires Est Parisien, Trousseau La Roche-Guyon, 26 Avenue du Docteur Arnold Netter, 75012 Paris, France.
authors.forename: A
authors.initials: A
authors.lastname: Coulomb-L'Herminé
authors.affiliation: Department of Emergency Medicine, Medical University of Wroclaw, and Department of Paediatric Surgery, Marciniak Hospital, Slezna 96, 53-111 Wroclaw, Poland.
authors.forename: J
authors.initials: J
authors.lastname: Godzinski
authors.affiliation: Department of Paediatric Oncology and INSERM U830, Institut Curie, 26 Rue d'Ulm, 75005 Paris, France.
authors.forename: G
authors.initials: G
authors.lastname: Schleiermacher
authors.affiliation: Department of Paediatric and Adolescent Oncology, University College Hospital, 235 Euston Rd, London NW1 2BU, UK.
authors.forename: S
authors.initials: S
authors.lastname: Stoneham
authors.affiliation: Department of Paediatrics, Centre Lyon Berard, 28 Promenade Léa et Napoléon Bullukian, 69008 Lyon, France.
authors.forename: C
authors.initials: C
authors.lastname: Bergeron
authors.affiliation: Molecular Haematology and Cancer Biology, Institute of Child Health, University College, Gower St, London WCE1 6BT, UK.
authors.forename: K
authors.initials: K
authors.lastname: Pritchard-Jones
authors.affiliation: Department of Paediatric Haematology and Oncology, Saarland University, Campus, 66123 Saarbrücken, Germany.
authors.forename: N
authors.initials: N
authors.lastname: Graf
authors.affiliation: Department of Paediatric Haematology and Oncology, Erasmus MC - Sophia Children's Hospital, Dr. Molewaterplein 60, 3015GJ Rotterdam, The Netherlands.
authors.forename: M M
authors.initials: MM
authors.lastname: van den Heuvel-Eibrink
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D009367:Neoplasm Staging; D011446:Prospective Studies; D018227:Sarcoma, Clear Cell / Q000188:drug therapy* / Q000473:pathology; D016896:Treatment Outcome