Conclusion
Review of pediatric dose-volume constraints in clinical trials showed substantial variability for all OARs, both for US trials and for European relative to US trials. None of the OARs had constraints systematically change over time, indicating that the variations seen were not due to the application of new dose-response information, but more likely due to a lack of both robust dose-response data and consensus by protocol committee members who establish the constraints. 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.