A New International PrognosticStratification System in Hepatoblastoma: Children’s Hepatic tumor International Collaborative Stratification (CHICS)
Rebecka L.Meyers, Beate Haeberle, Eiso Hiyama, Rudolf Maibach, Mark D. Krailo, Yurong Feng, Kenichi Yoshimura, Eugenia Rinaldi, Maurizio Ortali, Arun Rangaswami, Marcio H. Malogolowkin, Giorgio Perilongo, Kenichiro Watanabe, Irene Schmid,Daniel C. Aronson, Dietrich von Schweinitz, Ivo Leuschner, Dolores H. Lopez-Terrada, Yukichi Tanaka, Piotr Czauderna
Purpose: Four major study groups have coordinated clinical research in hepatoblastoma (HB): SIOPEL (International Childhood Liver Tumors Strategy Group), COG (Children’s Oncology Group), GPOH (German Association of Pediatric Hematology and Oncology), and JPLT (Japanese Study Group for Pediatric Liver Tumors). Prognostic risk factor analysis by individual study groups has been statistically limited by small patient numbers. To address this challenge Childhood Hepatic tumors International Collaboration (CHIC) set out to create a shared database in order to develop a common global risk stratification system in hepatoblastoma (CHICS).
Methods: In cooperation with the data management group CINECA, the CHIC steering committee created the International Pediatric Liver Tumors Warehouse, that includes data from all children treated on 9 separate trialsbetween 1989 and 2008: 1605 patients. Univariate analysis was used to identify prognostic variables. They were then included in a backwards elimination multivariate analysis to identify those constellations of factors most predictive of outcome.
Results: Univariate analysis identified the following factors, present at diagnosis,that significantly predicted event-free survival (EFS):Pretreatment Extent of Disease (PRETEXT); AFP<100; AFP 100-1000; metastatic disease; age; macrovascular involvement retrohepatic IVC and/or all three hepatic veins (+V); macrovascular involvement portal bifurcation (+P); contiguous extrahepatic tumor (E); tumor multifocality; and tumor rupture at diagnosis. A hierarchical assessment of these factors led to selection of a prognostic backbone based upon PRETEXT I/II, PRETEXT III, PRETEXT IV, AFP <100, and metastatic disease. Within each of these backbone groups, patients with the presence or absence of the remaining risk factors were further stratified into low risk (EFS>90%), intermediate risk (EFS 70-90%), high risk (EFS 50-70%), and very-high risk (EFS<50%).
Conclusion: CHIC has created the largest database reported to date for a pediatric rare tumor. This new stratification system (CHICS) is an important step towards international collaborative study and individualized treatment in HB.