A comprehensive review of 30 years of pediatric clinical trial radiotherapy dose constraints

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 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 (OAR), protocol, start date, dose, volume, and fractionation scheme. Dose constraints were evaluated for consistency over time and compared between pediatric US and European trials Results One hundred five closed trials were included—93 US trials and 12 European trials. Thirty‐eight separate OAR 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, the United States constraints were higher for seven OAR, lower for one, and identical for five. No OAR had constraints change systematically over the last 30 years. Conclusion Review of pediatric dose‐volume constraints in clinical trials showed substantial variability for all OAR. 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.