Abstract
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.