Background: Radiation therapy normal tissue dose constraints are critical when treating pediatric patients. However, there is limited evidence supporting proposed constraints which has led to variations in constraints over the years. In this study we identify these variations in dose constraints within pediatric trials both in the United States (US) and in Europe used in the past 30 years. Procedure: All pediatric trials from the Children’s Oncology Group website were queried from inception until January 2022 and a sampling of European studies was included. Dose constraints were identified and built into an organ-based interactive web application with filters to display data by organs-at-risk (OARs), protocol, start date, dose, volume, and fractionation scheme. Dose constraints were evaluated for consistency over time and compared between pediatric US trials and European trials Results: One hundred and five closed trials were included—93 US trials and 12 European trials. Thirty-eight separate OARs were found with high dose constraint variability. Across all trials, nine organs had greater than 10 different constraints (median 16, range 11-26), including serial organs. When comparing US versus European dose tolerances, US constraints were higher for seven OARs, lower for one, and identical for five. No OARs had constraints change systematically over the last 30 years. Conclusion: Review of pediatric dose-volume constraints in clinical trials showed substantial variability for all OARs. Continued efforts focused on standardization of OAR dose constraints and risk profiles are essential to increase consistency of protocol outcomes and ultimately to reduce radiation toxicities in the pediatric population.

Background Childhood cancer survivors face late health problems; despite advances in research, details on risk remain unclear. We describe the methodological aspects of the Dutch Childhood Cancer Survivor Study (DCCSS) cross-sectional clinical study (LATER 2 study). Procedure From the multi-center DCCSS LATER cohort of 6,165 five-year survivors diagnosed 1963-2001, we invited 4,735 eligible in 2016, as well as siblings and parents of survivors. Gaps in evidence identified during development of surveillance guidelines were translated into clinical research questions for 16 outcome-specific sub-projects. The regular care visit to the LATER outpatient clinic forms the backbone of outcome assessment complemented with research-defined measurements (physical examination, diagnostic tests, questionnaires). Furthermore, blood/saliva samples were taken for DNA extraction. Results In total, 2519 (53.2%) survivors participated in the LATER 2 study. Of those participating survivors, 49.3% was female. Median time since childhood cancer diagnosis was 26.9 years (range 14.8 to 54.7 years) and median attained age was 34.4 years (range 15.4 to 66.6 years). Conclusions The high-quality data generated in the LATER 2 study will provide valuable insights into risks of and risk factors for clinical and (psychosocial) health outcomes and factors for early recognition of (psychosocial) health outcomes in long-term childhood cancer survivors. This will contribute to fill in important gaps in knowledge and improve the quality of life and care for childhood cancer survivors.