title: Successful treatment of childhood high-risk hepatoblastoma with dose-intensive multiagent chemotherapy and surgery: final results of the SIOPEL-3HR study.
abstract: OBJECTIVE
  The primary objective was to determine the efficacy of a newly designed preoperative chemotherapy regimen in an attempt to improve the cure rate of children with high-risk hepatoblastoma.
  
  
  METHODS
  High risk was defined as follows: tumor in all liver sections (ie, Pretreatment Extension IV [PRETEXT-IV]), or vascular invasion (portal vein [P+], three hepatic veins [V+]), or intra-abdominal extrahepatic extension (E+), or metastatic disease, or alpha-fetoprotein less than 100 ng/mL at diagnosis. Patients were treated with alternating cycles of cisplatin and carboplatin plus doxorubicin (preoperatively, n = 7; postoperatively, n = 3) and delayed tumor resection.
  
  
  RESULTS
  Of the 151 patients (150 evaluable for response) 118 (78.7%) achieved a partial response to chemotherapy. Complete resection of the liver tumor could be achieved in 115 patients (76.2%) either by partial hepatectomy (55.6%) or by liver transplantation (20.6%). In 106 children (70.2%), complete resection of all tumor lesions (including metastases) was achieved. Among the patients with initial lung metastases, 52.2% achieved complete remission of the lung lesions with chemotherapy alone. In half of the patients with initial PRETEXT-IV tumor as the only high-risk feature, the tumor could be completely resected with partial hepatectomy. Event-free (EFS) and overall survival (OS) estimates at 3 years were 65% (95% CI, 57% to 73%) and 69% (95% CI, 62% to 77%) for the whole group. EFS and OS for all patients with PRETEXT-IV tumor were 68% and 69%, respectively, and they were 56% and 62%, respectively, for patients with metastasis.
  
  
  CONCLUSIONS
  The applied treatment rendered a great proportion of tumors resectable, and, in comparison with previously published results, led to an improved survival in patients with high-risk hepatoblastoma.
authors.affiliation: Department of Pediatric Oncology, Emma Children's Hospital Academic Medical Centre, University of Amsterdam, Amsterdam, the Netherlands. j.zsiros@amc.uva.nl
authors.forename: József
authors.initials: J
authors.lastname: Zsíros
authors.forename: Rudolf
authors.initials: R
authors.lastname: Maibach
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Shafford
authors.forename: Laurence
authors.initials: L
authors.lastname: Brugieres
authors.forename: Penelope
authors.initials: P
authors.lastname: Brock
authors.forename: Piotr
authors.initials: P
authors.lastname: Czauderna
authors.forename: Derek
authors.initials: D
authors.lastname: Roebuck
authors.forename: Margaret
authors.initials: M
authors.lastname: Childs
authors.forename: Arthur
authors.initials: A
authors.lastname: Zimmermann
authors.forename: Veronique
authors.initials: V
authors.lastname: Laithier
authors.forename: Jean-Bernard
authors.initials: JB
authors.lastname: Otte
authors.forename: Beatriz
authors.initials: B
authors.lastname: de Camargo
authors.forename: Gordon
authors.initials: G
authors.lastname: MacKinlay
authors.forename: Marcelo
authors.initials: M
authors.lastname: Scopinaro
authors.forename: Daniel
authors.initials: D
authors.lastname: Aronson
authors.forename: Jack
authors.initials: J
authors.lastname: Plaschkes
authors.forename: Giorgio
authors.initials: G
authors.lastname: Perilongo
mesh_terms: D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage; D017024:Chemotherapy, Adjuvant; D002648:Child; D002675:Child, Preschool; D002945:Cisplatin / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D018197:Hepatoblastoma / Q000188:drug therapy* / Q000601:surgery*; D006801:Humans; D007223:Infant; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000601:surgery*; D008297:Male; D011300:Preoperative Care; D011446:Prospective Studies; D012307:Risk Factors; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D004317:Doxorubicin; D016190:Carboplatin; D002945:Cisplatin