title: The Children's Hepatic tumors International Collaboration (CHIC): Novel global rare tumor database yields new prognostic factors in hepatoblastoma and becomes a research model.
abstract: BACKGROUND
  Contemporary state-of-the-art management of cancer is increasingly defined by individualized treatment strategies. For very rare tumors, like hepatoblastoma, the development of biologic markers, and the identification of reliable prognostic risk factors for tailoring treatment, remains very challenging. The Children's Hepatic tumors International Collaboration (CHIC) is a novel international response to this challenge.
  
  
  METHODS
  Four multicenter trial groups in the world, who have performed prospective controlled studies of hepatoblastoma over the past two decades (COG; SIOPEL; GPOH; and JPLT), joined forces to form the CHIC consortium. With the support of the data management group CINECA, CHIC developed a centralized online platform where data from eight completed hepatoblastoma trials were merged to form a database of 1605 hepatoblastoma cases treated between 1988 and 2008. The resulting dataset is described and the relationships between selected patient and tumor characteristics, and risk for adverse disease outcome (event-free survival; EFS) are examined.
  
  
  RESULTS
  Significantly increased risk for EFS-event was noted for advanced PRETEXT group, macrovascular venous or portal involvement, contiguous extrahepatic disease, primary tumor multifocality and tumor rupture at enrollment. Higher age (≥ 8 years), low AFP (<100 ng/ml) and metastatic disease were associated with the worst outcome.
  
  
  CONCLUSIONS
  We have identified novel prognostic factors for hepatoblastoma, as well as confirmed established factors, that will be used to develop a future common global risk stratification system. The mechanics of developing the globally accessible web-based portal, building and refining the database, and performing this first statistical analysis has laid the foundation for future collaborative efforts. This is an important step for refining of the risk based grouping and approach to future treatment stratification, thus we think our collaboration offers a template for others to follow in the study of rare tumors and diseases.
authors.affiliation: Department of Surgery and Urology for Children and Adolescents, Medical University of Gdansk, Poland. Electronic address: czauderna.p@gmail.com.
authors.forename: Piotr
authors.initials: P
authors.lastname: Czauderna
authors.affiliation: Department of Paediatric Surgery, University of Munich, Germany.
authors.forename: Beate
authors.initials: B
authors.lastname: Haeberle
authors.affiliation: Department of Pediatric Surgery, Hiroshima University, Japan.
authors.forename: Eiso
authors.initials: E
authors.lastname: Hiyama
authors.affiliation: Department of Pediatric Hematology Oncology, Stanford University, USA.
authors.forename: Arun
authors.initials: A
authors.lastname: Rangaswami
authors.affiliation: Children's Oncology Group, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Krailo
authors.affiliation: IBCSG, Bern, Switzerland.
authors.forename: Rudolf
authors.initials: R
authors.lastname: Maibach
authors.affiliation: CINECA, Bologna, Italy.
authors.forename: Eugenia
authors.initials: E
authors.lastname: Rinaldi
authors.affiliation: Children's Oncology Group, USA.
authors.forename: Yurong
authors.initials: Y
authors.lastname: Feng
authors.affiliation: Queen Elisabeth's Central Hospital University of Malawi, Blantyre, Malawi.
authors.forename: Daniel
authors.initials: D
authors.lastname: Aronson
authors.affiliation: Medical College of Wisconsin, USA.
authors.forename: Marcio
authors.initials: M
authors.lastname: Malogolowkin
authors.affiliation: Innovative Clinical Research Center (iCREK), Kanazawa University Hospital, Japan.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Yoshimura
authors.affiliation: Institute of Pathology, University of Kiel, Germany.
authors.forename: Ivo
authors.initials: I
authors.lastname: Leuschner
authors.affiliation: Department of Pathology & Immunology, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Dolores
authors.initials: D
authors.lastname: Lopez-Terrada
authors.affiliation: Department of Pediatric Surgery, Chiba University Hospital, Japan.
authors.forename: Tomoro
authors.initials: T
authors.lastname: Hishiki
authors.affiliation: Department of Pediatrics, University of Padova, Italy.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Perilongo
authors.affiliation: Department of Paediatric Surgery, University of Munich, Germany.
authors.forename: Dietrich
authors.initials: D
authors.lastname: von Schweinitz
authors.affiliation: Department of Pediatric Oncology and Hematology, University of Munich, Germany.
authors.forename: Irene
authors.initials: I
authors.lastname: Schmid
authors.affiliation: Department of Pediatrics, Kyoto University, Japan.
authors.forename: Kenichiro
authors.initials: K
authors.lastname: Watanabe
authors.affiliation: CINECA, Bologna, Italy.
authors.forename: Marisa
authors.initials: M
authors.lastname: Derosa
authors.affiliation: Department of Surgery, University of Utah, Salt Lake City, USA.
authors.forename: Rebecka
authors.initials: R
authors.lastname: Meyers
mesh_terms: D000293:Adolescent; D000367:Age Factors; D002648:Child; D002675:Child, Preschool; D003299:Cooperative Behavior; D016208:Databases, Factual / Q000706:statistics & numerical data; D018572:Disease-Free Survival; D005260:Female; D018197:Hepatoblastoma / Q000175:diagnosis / Q000401:mortality / Q000628:therapy; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007391:International Cooperation; D008113:Liver Neoplasms / Q000175:diagnosis / Q000401:mortality / Q000628:therapy; D008297:Male; D018570:Risk Assessment; D012307:Risk Factors; D016019:Survival Analysis; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
keywords: Chemotherapy; Hepatoblastoma; Pathology; Risk stratification