Scaling up and implementing the digital Survivorship Passport tool in routine clinical care - The European multidisciplinary PanCareSurPass project.

BACKGROUND: Childhood cancer survivors (CCS), of whom there are about 500,000 living in Europe, are at an increased risk of developing health problems [1-6] and require lifelong Survivorship Care. There are information and knowledge gaps among CCS and healthcare providers (HCPs) about requirements for Survivorship Care [7-9] that can be addressed by the Survivorship Passport (SurPass), a digital tool providing CCS and HCPs with a comprehensive summary of past treatment and tailored recommendations for Survivorship Care. The potential of the SurPass to improve person-centred Survivorship Care has been demonstrated previously [10,11]. METHODS: The EU-funded PanCareSurPass project will develop an updated version (v2.0) of the SurPass allowing for semi-automated data entry and implement it in six European countries (Austria, Belgium, Germany, Italy, Lithuania and Spain), representative of three infrastructure healthcare scenarios typically found in Europe. The implementation study will investigate the impact on person-centred care, as well as costs and processes of scaling up the SurPass. Interoperability between electronic health record systems and SurPass v2.0 will be addressed using the Health Level Seven (HL7) International interoperability standards. RESULTS: PanCareSurPass will deliver an interoperable digital SurPass with comprehensive evidence on person-centred outcomes, technical feasibility and health economics impacts. An Implementation Toolkit will be developed and freely shared to promote and support the future implementation of SurPass across Europe. CONCLUSIONS: PanCareSurPass is a novel European collaboration that will improve person-centred Survivorship Care for CCS across Europe through a robust assessment of the implementation of SurPass v2.0 in different healthcare settings.

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.

The 'Survivorship Passport' for childhood cancer survivors.

BACKGROUND: Currently, there are between 300,000 and 500,000 childhood cancer survivors (CCSs) in Europe. A significant proportion is at high risk, and at least 60% of them develop adverse health-related outcomes that can appear several years after treatment completion. Many survivors are unaware of their personal risk, and there seems to be a general lack of information among healthcare providers about pathophysiology and natural history of treatment-related complications. This can generate incorrect or delayed diagnosis and treatments. METHOD: The Survivorship Passport (SurPass) consists of electronic documents, which summarise the clinical history of the childhood or adolescent cancer survivor. It was developed by paediatric oncologists of the PanCare and SIOPE networks and IT experts of Cineca, together with parents, patients, and survivors' organisations within the European Union-funded European Network for Cancer research in Children and Adolescents. It consists of a template of a web-based, simply written document, translatable in all European languages, to be given to each CCS. The SurPass provides a summary of each survivor's clinical history, with detailed information about the original cancer and of treatments received, together with personalised follow-up and screening recommendations based on guidelines published by the International Guidelines Harmonization Group and PanCareSurFup. RESULTS: The SurPass data schema contains a maximum of 168 variables and uses internationally approved nomenclature, except for radiotherapy fields, where a new classification was defined by radiotherapy experts. The survivor-specific screening recommendations are mainly based on treatment received and are automatically suggested, thanks to built-in algorithms. These may be adapted and further individualised by the treating physician in case of special disease and survivor circumstances. The SurPass was tested at the Istituto Giannina Gaslini, Italy, and received positive feedback. It is now being integrated at the institutional, regional and national level. CONCLUSIONS: The SurPass is potentially an essential tool for improved and more harmonised follow-up of CCS. It also has the potential to be a useful tool for empowering CCSs to be responsible for their own well-being and preventing adverse events whenever possible. With sufficient commitment on the European level, this solution should increase the capacity to respond more effectively to the needs of European CCS.

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.

Standardized data sharing in a paediatric oncology research network--a proof-of-concept study.

Data that has been collected in the course of clinical trials are potentially valuable for additional scientific research questions in so called secondary use scenarios. This is of particular importance in rare disease areas like paediatric oncology. If data from several research projects need to be connected, so called Core Datasets can be used to define which information needs to be extracted from every involved source system. In this work, the utility of the Clinical Data Interchange Standards Consortium (CDISC) Operational Data Model (ODM) as a format for Core Datasets was evaluated and a web tool was developed which received Source ODM XML files and--via Extensible Stylesheet Language Transformation (XSLT)--generated standardized Core Dataset ODM XML files. Using this tool, data from different source systems were extracted and pooled for joined analysis in a proof-of-concept study, facilitating both, basic syntactic and semantic interoperability.