title: Outcome of localised blastemal-type Wilms tumour patients treated according to intensified treatment in the SIOP WT 2001 protocol, a report of the SIOP Renal Tumour Study Group (SIOP-RTSG).
abstract: Blastemal-type Wilms tumour (BT-WT) has been identified as a high risk histological subgroup in WT assessed after pre-nephrectomy chemotherapy in trials of the International Society of Paediatric Oncology (SIOP) Renal Tumour Study Group. Therefore, in SIOPWT2001, post-operative chemotherapy for BT-WT was intensified aiming to improve survival. Survival analysis of all unilateral BT-WT patients (SIOPWT2001) (n=238), was compared with historical BT-WT controls (SIOP93-01) (n=113). 351/4061 (8.6%) unilateral non-metastatic BT-WT patients (SIOP93-01/SIOPWT2001) were studied. Median age at diagnosis was 43 months (Inter Quartile Range (IQR) 24-68 months), stages: I (n=140, 40%), II (n=106, 30%), III (n=105, 30%). BT-WTs were higher staged, showed greater volume decrease after pre-operative chemotherapy and were diagnosed at an older median age compared to other WT patients. Patient characteristics did not differ substantially between SIOP93-01 and SIOPWT2001. Univariate analysis showed a 5-year event-free survival (EFS) of 80% (95% confidence interval (CI): 75-86%) (SIOPWT2001) compared to 67% in SIOP93-01 (95% CI: 59-76%; p=0.006) and overall survival (OS) of 88% (95% CI: 83-93%) (SIOPWT2001) compared to 84% (95% CI: 77-91%; p=0.4) in SIOP93-01. 95% of relapses were distant metastases (SIOP93-01/SIOPWT2001). Treatment protocol, age at diagnosis, tumour stage (III versus I/II) and volume (at surgery), were prognostic variables for EFS (uni- and multivariate Cox regression analysis). Independent prognosticators for OS were age at diagnosis, tumour stage and volume (at surgery). The most significant survival benefit of intensified treatment, was observed in Stage I (EFS 96% in SIOPWT2001 (OS 100%), 71% in SIOP93-01 (OS 90%)). BT-WT derived benefits from more intensive chemotherapy as reflected by a reduction in relapse risk. However, the benefit of the more intensive chemotherapy to improve OS was only observed in stage I BT-WTs, by adding doxorubicin.
authors.affiliation: Department of Pediatric Oncology, Princess Máxima Centre for Paediatric Oncology, Utrecht, The Netherlands; Dutch Childhood Oncology Group, The Hague, The Netherlands. Electronic address: m.m.vandenheuvel-eibrink@prinsesmaximacentrum.nl.
authors.forename: M M
authors.initials: MM
authors.lastname: van den Heuvel-Eibrink
authors.affiliation: Biometrics Department, Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: H
authors.initials: H
authors.lastname: van Tinteren
authors.affiliation: Centre Léon Bérard, Pediatrie, Lyon, France.
authors.forename: C
authors.initials: C
authors.lastname: Bergeron
authors.affiliation: Department of Pathology, Hospital d'Enfants Armand Trousseau, Paris, France.
authors.forename: A
authors.initials: A
authors.lastname: Coulomb-L'Hermine
authors.affiliation: Instituto Nacional do Cancer, Pediatric Hematology Program, Rio de Janeiro, Brazil.
authors.forename: B
authors.initials: B
authors.lastname: de Camargo
authors.affiliation: Kiel Pediatric Tumour Registry, University of Kiel, Kiel, Germany.
authors.forename: I
authors.initials: I
authors.lastname: Leuschner
authors.affiliation: Childhood Cancer Research Unit, Astrid Lindgren Children's Hospital, Karolinska Institutet Stockholm, Stockholm, Sweden.
authors.forename: B
authors.initials: B
authors.lastname: Sandstedt
authors.affiliation: Hospital Materno-Infantil "Carlos Haya", Malaga, Spain.
authors.forename: T
authors.initials: T
authors.lastname: Acha
authors.affiliation: Department of Pediatric Surgery, Marciniak Hospital Wroclaw and Chair of Emergency Medicine, Medical University, Wroclaw, Poland.
authors.forename: J
authors.initials: J
authors.lastname: Godzinski
authors.affiliation: Department of Radiation Oncology, Emma Children's Hospital, Academic Medical Centre, Amsterdam, The Netherlands.
authors.forename: F
authors.initials: F
authors.lastname: Oldenburger
authors.affiliation: Department of Pediatric Oncology, Princess Máxima Centre for Paediatric Oncology, Utrecht, The Netherlands.
authors.forename: S L
authors.initials: SL
authors.lastname: Gooskens
authors.affiliation: Department of Pediatric Oncology-Hematology, Emma Children's Hospital, Academic Medical Centre, Amsterdam, The Netherlands.
authors.forename: J
authors.initials: J
authors.lastname: de Kraker
authors.affiliation: Department of Histopathology, School of Medicine Cardiff University, Cardiff, United Kingdom.
authors.forename: G M
authors.initials: GM
authors.lastname: Vujanic
authors.affiliation: Institute of Child Health, University College London, London, United Kingdom.
authors.forename: K
authors.initials: K
authors.lastname: Pritchard-Jones
authors.affiliation: Department of Pediatric Hematology/Oncology, University Hospital for Children, Homburg, Germany.
authors.forename: N
authors.initials: N
authors.lastname: Graf
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008297:Male; D009367:Neoplasm Staging; D016016:Proportional Hazards Models; D016896:Treatment Outcome; D009396:Wilms Tumor / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology
keywords: Blastemal-type; SIOPWT2001; Survival; Wilms tumour