Risk of subsequent gliomas and meningiomas among 69,460 5-year survivors of childhood and adolescent cancer in Europe: the PanCareSurFup study.

BACKGROUND: Childhood cancer survivors are at risk of subsequent gliomas and meningiomas, but the risks beyond age 40 years are uncertain. We quantified these risks in the largest ever cohort. METHODS: Using data from 69,460 5-year childhood cancer survivors (diagnosed 1940-2008), across Europe, standardized incidence ratios (SIRs) and cumulative incidence were calculated. RESULTS: In total, 279 glioma and 761 meningioma were identified. CNS tumour (SIR: 16.2, 95% CI: 13.7, 19.2) and leukaemia (SIR: 11.2, 95% CI: 8.8, 14.2) survivors were at greatest risk of glioma. The SIR for CNS tumour survivors was still 4.3-fold after age 50 (95% CI: 1.9, 9.6), and for leukaemia survivors still 10.2-fold after age 40 (95% CI: 4.9, 21.4). Following cranial radiotherapy (CRT), the cumulative incidence of a glioma in CNS tumour survivors was 2.7%, 3.7% and 5.0% by ages 40, 50 and 60, respectively, whilst for leukaemia this was 1.2% and 1.7% by ages 40 and 50. The cumulative incidence of a meningioma after CRT in CNS tumour survivors doubled from 5.9% to 12.5% between ages 40 and 60, and in leukaemia survivors increased from 5.8% to 10.2% between ages 40 and 50. DISCUSSION: Clinicians following up survivors should be aware that the substantial risks of meningioma and glioma following CRT are sustained beyond age 40 and be vigilant for symptoms.

IT-Related Barriers and Facilitators to the Implementation of a New European eHealth Solution, the Digital Survivorship Passport (SurPass Version 2.0): Semistructured Digital Survey.

BACKGROUND: To overcome knowledge gaps and optimize long-term follow-up (LTFU) care for childhood cancer survivors, the concept of the Survivorship Passport (SurPass) has been invented. Within the European PanCareSurPass project, the semiautomated and interoperable SurPass (version 2.0) will be optimized, implemented, and evaluated at 6 LTFU care centers representing 6 European countries and 3 distinct health system scenarios: (1) national electronic health information systems (EHISs) in Austria and Lithuania, (2) regional or local EHISs in Italy and Spain, and (3) cancer registries or hospital-based EHISs in Belgium and Germany. OBJECTIVE: We aimed to identify and describe barriers and facilitators for SurPass (version 2.0) implementation concerning semiautomation of data input, interoperability, data protection, privacy, and cybersecurity. METHODS: IT specialists from the 6 LTFU care centers participated in a semistructured digital survey focusing on IT-related barriers and facilitators to SurPass (version 2.0) implementation. We used the fit-viability model to assess the compatibility and feasibility of integrating SurPass into existing EHISs. RESULTS: In total, 13/20 (65%) invited IT specialists participated. The main barriers and facilitators in all 3 health system scenarios related to semiautomated data input and interoperability included unaligned EHIS infrastructure and the use of interoperability frameworks and international coding systems. The main barriers and facilitators related to data protection or privacy and cybersecurity included pseudonymization of personal health data and data retention. According to the fit-viability model, the first health system scenario provides the best fit for SurPass implementation, followed by the second and third scenarios. CONCLUSIONS: This study provides essential insights into the information and IT-related influencing factors that need to be considered when implementing the SurPass (version 2.0) in clinical practice. We recommend the adoption of Health Level Seven Fast Healthcare Interoperability Resources and data security measures such as encryption, pseudonymization, and multifactor authentication to protect personal health data where applicable. In sum, this study offers practical insights into integrating digital health solutions into existing EHISs.

Late Adverse Effects after Treatment for Childhood Acute Leukemia.

The aim of this review is to raise awareness and knowledge among healthcare professionals and policymakers about late adverse effects in survivors of childhood leukemia. With contemporary treatment, over 90% of children with acute lymphoblastic leukemia (ALL) and over 60% with acute myeloid leukemia (AML) are cured. Large cohort studies demonstrate that 20% of ALL and most AML survivors have at least one chronic health condition by 20-25 years after diagnosis. These are life-changing or threatening in some survivors and contribute to increased premature mortality. We describe the frequency, causes, clinical features, and natural history of the most frequent and severe late adverse effects in childhood leukemia survivors, including subsequent malignant neoplasms, metabolic toxicity, gonadotoxicity and impaired fertility, endocrinopathy and growth disturbances, bone toxicity, central and peripheral neurotoxicity, cardiotoxicity, psychosocial late effects, accelerated ageing and late mortality. The wide range of late effects in survivors of haemopoietic stem cell transplant is highlighted. Recent developments informing the approach to long-term survivorship care are discussed, including electronic personalized patient-specific treatment summaries and care plans such as the Survivor Passport (SurPass), surveillance guidelines and models of care. The importance of ongoing vigilance is stressed given the increasing use of novel targeted drugs with limited experience of long-term outcomes. CONCLUSION: It is vital to raise awareness of the existence and severity of late effects of childhood leukemia therapy among parents, patients, health professionals, and policymakers. Structured long-term surveillance recommendations are necessary to standardize follow-up care.

Childhood Cancer Survivorship Passport Challenges in the European Health Data Space.

Innovation in cancer therapy has increased childhood cancer survival rates. However, survivors are still at risk of developing late effects. In the digital transformation of the health sector, the Survivorship Passport (SurPass) can support long-term follow-up care plans. Gaps in seamless connectivity among hospital departments, primary care, combined with the time of health professionals required to collect and fill-in health data in SurPass, are barriers to its adoption in daily clinical practice. The PanCareSurPass (PCSP) project was motivated to address these gaps by a new version of SurPass (v2.0) that supports semi-automatic assembly from organizational Electronic Health Record (EHR) systems of the treatment summary data using HL7 FHIR, to create SurPass, and to link it to regional or national digital health infrastructures in six European countries. In this paper we present the methodology used to develop the SurPass technical implementation strategy with special focus on the European Health Data Space (EHDS). The recently provisionally approved EHDS regulation instruments a digital health data ecosystem with opportunities for cost-effective SurPass implementation across Europe. Moving forward, a European HL7 FHIR SurPass Implementation Guide along with synthetic data sets, and validation tools can enrich the European Electronic Health Record Exchange Format (EEHRxF) with use cases on health & wellness of childhood cancer survivors.

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.

Radiation Doses Received by Major Organs at Risk in Children and Young Adolescents Treated for Cancer with External Beam Radiation Therapy: A Large-scale Study from 12 European Countries.

PURPOSE: Childhood cancer survivors, in particular those treated with radiation therapy, are at high risk of long-term iatrogenic events. The prediction of risk of such events is mainly based on the knowledge of the radiation dose received to healthy organs and tissues during treatment of childhood cancer diagnosed decades ago. We aimed to set up a standardized organ dose table to help former patients and clinicians in charge of long-term follow-up clinics. METHODS AND MATERIALS: We performed whole body dosimetric reconstruction for 2646 patients from 12 European countries treated between 1941 and 2006 (median, 1976). Most plannings were 2- or 3-dimensional. A total of 46% of patients were treated using Cobalt 60, and 41%, using a linear accelerator. The median prescribed dose was 27.2 Gy (IQ1-IQ3, 17.6-40.0 Gy). A patient-specific voxel-based anthropomorphic phantom with more than 200 anatomic structures or substructures delineated as a surrogate of each subject's anatomy was used. The radiation therapy was simulated with a treatment planning system based on available treatment information. The radiation dose received by any organ of the body was estimated by extending the treatment planning system dose calculation to the whole body, by type and localization of childhood cancer. RESULTS: The integral dose and normal tissue doses to most of the 23 considered organs increased between the 1950s and 1970s and decreased or plateaued thereafter. Whatever the organ considered, the type of childhood cancer explained most of the variability in organ dose. The country of treatment explained only a small part of the variability. CONCLUSIONS: The detailed dose estimates provide very useful information for former patients or clinicians who have only limited knowledge about radiation therapy protocols or techniques, but who know the type and site of childhood cancer, sex, age, and year of treatment. This will allow better prediction of the long-term risk of iatrogenic events and better referral to long-term follow-up clinics.

Assessment of HL7 FHIR Interoperability Between EHR Systems and the Survivorship Passport v2.0 Platform to Generate Treatment Summaries for Childhood Cancer Survivors in Six Clinics: Preliminary Testing Results.

The Survivorship Passport (SurPass) for childhood cancer survivors provides a personalized treatment summary together with a care plan for long-term screening of possible late effects. HL7 FHIR connectivity of Electronic Health Record (EHR) systems with the SurPass has been proposed to reduce the burden of collecting and organizing the relevant information. We present the results of testing and validation efforts conducted across six clinics in Austria, Belgium, Germany, Italy, Lithuania, and Spain. We also discuss ways in which this experience can be used to reduce efforts for the SurPass integration in other clinics across Europe.