title: Prognostic stratification for children with hepatoblastoma: the SIOPEL experience.
abstract: OBJECTIVE
  To identify factors relevant to long-term outcome in newly diagnosed hepatoblastoma, and define subgroups for clinical research on tailoring treatment to the individual patient.
  
  
  METHODS
  Between 1995 and 2006 the SIOPEL group conducted two clinical trials which established risk-adapted therapy for hepatoblastoma patients. Patients were stratified into high-risk (AFP < 100 ng/mL and/or PRETEXT IV and/or vascular invasion and/or extra-hepatic intra-abdominal disease (V+/P+/E+) and/or metastases) and standard-risk (all others). The hierarchy of these factors plus multifocality, PRETEXT III, AFP > 1,200,000 ng/mL, patient age, platelet count and histology were further explored. The outcome measure was event-free survival (EFS).
  
  
  RESULTS
  In 541 patients, reduced EFS correlated significantly with AFP < 100 ng/ml (hazard ratio [HR] 4.09, 95% confidence interval 2.16-7.75), AFP ≥ 1.2 × 10(6)ng/mL (2.48, 1.47-4.17), metastatic disease (3.02, 2.05-4.44), PRETEXT IV (2.15, 1.19-3.87), multifocality (1.59, 1.01-2.50), age > 5 years (2.76, 1.68-4.53); borderline with small cell undifferentiated (SCU) histology (2.29, 95% confidence interval 0.91-5.77); but not with PRETEXT III, age 30-60 months, platelet count or V+/P+/E+. By using the significant factors and SCU to stratify the population, we have identified three distinct prognostic groups: PRETEXT I/II/III, and no other factors, have 3 year EFS of 90%, PRETEXT IV and/or multifocal tumour and/or age> 5 years and/or AFP > 1.2 × 10(6) have 3 year EFS of 71% and SCU and/or AFP < 100 ng/mL and/or metastatic have a 3year EFS of 49%.
  
  
  CONCLUSIONS
  Prognostic stratification for clinical research on newly diagnosed hepatoblastoma should take into consideration PRETEXT, metastatic disease, AFP, multifocality, age and SCU histology.
authors.affiliation: IBCSG Coordinating Center, Berne, Switzerland. rudolf.maibach@ibcsg.org
authors.forename: Rudolf
authors.initials: R
authors.lastname: Maibach
authors.forename: Derek
authors.initials: D
authors.lastname: Roebuck
authors.forename: Laurence
authors.initials: L
authors.lastname: Brugieres
authors.forename: Michael
authors.initials: M
authors.lastname: Capra
authors.forename: Penelope
authors.initials: P
authors.lastname: Brock
authors.forename: Patrizia
authors.initials: P
authors.lastname: Dall'Igna
authors.forename: Jean-Bernard
authors.initials: JB
authors.lastname: Otte
authors.forename: Beatriz
authors.initials: B
authors.lastname: De Camargo
authors.forename: Jozsef
authors.initials: J
authors.lastname: Zsiros
authors.forename: Arthur
authors.initials: A
authors.lastname: Zimmermann
authors.forename: Daniel
authors.initials: D
authors.lastname: Aronson
authors.forename: Margaret
authors.initials: M
authors.lastname: Childs
authors.forename: Marcelo
authors.initials: M
authors.lastname: Scopinaro
authors.forename: Bruce
authors.initials: B
authors.lastname: Morland
authors.forename: Jack
authors.initials: J
authors.lastname: Plaschkes
authors.forename: Piotr
authors.initials: P
authors.lastname: Czauderna
authors.forename: Giorgio
authors.initials: G
authors.lastname: Perilongo
mesh_terms: D000293:Adolescent; D000367:Age Factors; D002648:Child; D002675:Child, Preschool; D018572:Disease-Free Survival; D005260:Female; D018197:Hepatoblastoma / Q000175:diagnosis* / Q000473:pathology* / Q000628:therapy; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D011379:Prognosis; D016016:Proportional Hazards Models; D012306:Risk; D013997:Time Factors; D016896:Treatment Outcome