A New International Prognostic Stratification 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 trials between 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 1001000; 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.