Improving Pediatric Normal Tissue Radiation Dose-Response Modeling in Children With Cancer: A PENTEC Initiative

The development of normal tissue radiation dose-response models for children with cancer has been challenged by many factors, including small sample sizes; the long length of follow-up needed to observe some toxicities; the continuing occurrence of events beyond the time of assessment; the often complex relationship between age at treatment, normal tissue developmental dynamics, and age at assessment; and the need to use retrospective dosimetry. Meta-analyses of published pediatric outcome studies face additional obstacles of incomplete reporting of critical dosimetric, clinical, and statistical information. This report describes general methods used to address some of the pediatric modeling issues. It highlights previous single- and multi-institutional pediatric dose-response studies and summarizes how each PENTEC taskforce addressed the challenges and limitations of the reviewed publications in constructing, when possible, organ-specific dose-effect models.