The importance of age as prognostic factor for the outcome of patients with hepatoblastoma: Analysis from the Children's Hepatic tumors International Collaboration (CHIC) database.

PURPOSE: Treatment outcomes for hepatoblastoma have improved markedly in the contemporary treatment era, principally due to therapy intensification, with overall survival increasing from 35% in the 1970s to 90% at present. Unfortunately, these advancements are accompanied by an increased incidence of toxicities. A detailed analysis of age as a prognostic factor may support individualized risk-based therapy stratification. METHODS: We evaluated 1605 patients with hepatoblastoma included in the CHIC database to assess the relationship between event-free survival (EFS) and age at diagnosis. Further analysis included the age distribution of additional risk factors and the interaction of age with other known prognostic factors. RESULTS: Risk for an event increases progressively with increasing age at diagnosis. This pattern could not be attributed to the differential distribution of other known risk factors across age. Newborns and infants are not at increased risk of treatment failure. The interaction between age and other adverse risk factors demonstrates an attenuation of prognostic relevance with increasing age in the following categories: metastatic disease, AFP < 100 ng/mL, and tumor rupture. CONCLUSION: Risk for an event increased with advancing age at diagnosis. Increased age attenuates the prognostic influence of metastatic disease, low AFP, and tumor rupture. Age could be used to modify recommended chemotherapy intensity.

Risk-stratified staging in paediatric hepatoblastoma: a unified analysis from the Children's Hepatic tumors International Collaboration.

BACKGROUND: Comparative assessment of treatment results in paediatric hepatoblastoma trials has been hampered by small patient numbers and the use of multiple disparate staging systems by the four major trial groups. To address this challenge, we formed a global coalition, the Children's Hepatic tumors International Collaboration (CHIC), with the aim of creating a common approach to staging and risk stratification in this rare cancer. METHODS: The CHIC steering committee-consisting of leadership from the four major cooperative trial groups (the International Childhood Liver Tumours Strategy Group, Children's Oncology Group, the German Society for Paediatric Oncology and Haematology, and the Japanese Study Group for Paediatric Liver Tumours)-created a shared international database that includes comprehensive data from 1605 children treated in eight multicentre hepatoblastoma trials over 25 years. Diagnostic factors found to be most prognostic on initial analysis were PRETreatment EXTent of disease (PRETEXT) group; age younger than 3 years, 3-7 years, and 8 years or older; α fetoprotein (AFP) concentration of 100 ng/mL or lower and 101-1000 ng/mL; and the PRETEXT annotation factors metastatic disease (M), macrovascular involvement of all hepatic veins (V) or portal bifurcation (P), contiguous extrahepatic tumour (E), multifocal tumour (F), and spontaneous rupture (R). We defined five clinically relevant backbone groups on the basis of established prognostic factors: PRETEXT I/II, PRETEXT III, PRETEXT IV, metastatic disease, and AFP concentration of 100 ng/mL or lower at diagnosis. We then carried the additional factors into a hierarchical backwards elimination multivariable analysis and used the results to create a new international staging system. RESULTS: Within each backbone group, we identified constellations of factors that were most predictive of outcome in that group. The robustness of candidate models was then interrogated using the bootstrapping procedure. Using the clinically established PRETEXT groups I, II, III, and IV as our stems, we created risk stratification trees based on 5 year event-free survival and clinical applicability. We defined and adopted four risk groups: very low, low, intermediate, and high. INTERPRETATION: We have created a unified global approach to risk stratification in children with hepatoblastoma on the basis of rigorous statistical interrogation of what is, to the best of our knowledge, the largest dataset ever assembled for this rare paediatric tumour. This achievement provides the structural framework for further collaboration and prospective international cooperative study, such as the Paediatric Hepatic International Tumour Trial (PHITT). FUNDING: European Network for Cancer Research in Children and Adolescents, funded through the Framework Program 7 of the European Commission (grant number 261474); Children's Oncology Group CureSearch grant contributed by the Hepatoblastoma Foundation; Practical Research for Innovative Cancer Control and Project Promoting Clinical Trials for Development of New Drugs and Medical Devices, Japan Agency for Medical Research; and Swiss Cancer Research grant.

Prevalence and incidence of rheumatoid arthritis in Italy.

Aim of the study was to estimate the prevalence and incidence of rheumatoid arthritis (RA) from an administrative cohort consisting of 2,268,514 males and 2,446,769 females, aged ≥ 18 years, from 32 Italian Health Districts. The diagnosis of RA was certified by a qualified specialist and confirmed by ≥3 prescriptions of "specific drugs" (corticosteroids, DMARDs or "biological" agents) during 2011. Patients on "specific drugs" qualified as "active RA"; those who never had more than 4 prescriptions in the past were classified as "unlikely RA," and those previously on chronic treatment but who discontinued therapy for >1 year were classified as "remission RA." The patients with a diagnosis of RA were 22,801 (0.48 %) with a prevalence of "active RA," "remission RA" and "confirmed RA" (Active + Remission RA) of 0.32, 0.09 and 0.41 % (95 % CI 0.38-0.44), respectively. The classification criteria tested in a fifth of the study population by direct analysis yielded >90 % accuracy and precision. The yearly incidence of "active RA" per 100,000 subjects was 48 (95 % CI 40-57) and 20 (95 % CI 10-30) for women and men, respectively. The peak for both prevalence and incidence was around the eighth decade of life. The female/male ratios for both prevalence and incidence were ca. 2.6 before the fifth decade of life, but approached unity in the ninth decade of life. The overall prevalence and incidence of RA in a large sample of the Italian population is only marginally lower than that reported from a similar administrative database of Sweden. With advancing age, the female/male ratio declines to about one.

The Children's Hepatic tumors International Collaboration (CHIC): Novel global rare tumor database yields new prognostic factors in hepatoblastoma and becomes a research model.

INTRODUCTION: 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. CONCLUSION: 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.

Use of psychotropic medications in Italian children and adolescents.

INTRODUCTION: The evidence of psychotropic drug safety and efficacy in the pediatric population is scant and widely debated. Yet, the prescription prevalence and incidence are increasing. A drug utilization study, based on a multiregional prescription database was therefore carried out in a sample of 1,484,770 Italian children and adolescents younger than 18 years during the year 2004. Furthermore, the trend of psychotropic prescription prevalence was evaluated from 1998 to 2004. During 2004, 4,316 children and adolescents received psychotropic drugs (2.91 per thousand youths). Antidepressants were prescribed to 3,503 youths (2.36 per thousand), antipsychotics to 1,005 (0.68 per thousand), and lithium to 73 (0.05 per thousand). A total of 265 youths received drugs from more than one psychotropic class. The prevalence rate of psychotropic drug prescriptions increased with increasing age, with a statistically significant trend ([Formula: see text]; p<0.0001), and it increased in the period 1998-2004 with a statistically significant trend ([Formula: see text]; p<0.0001), reaching its highest value in 2002 (3.08 per thousand). The trend for antidepressants was similar ([Formula: see text]; p<0.0001), while the prevalence of antipsychotics did not increase. CONCLUSION: Even though the prevalence of psychotropic drug prescriptions in Italian children is lower than that reported in other countries (e.g. United States, Canada, Netherlands, UK), the increase in antidepressant prescriptions raises some concerns. Data concerning safety and efficacy of these antidepressants in pediatrics are still limited and further studies are needed to guarantee evidence based therapeutic approaches in children, adolescents and their families.