Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2023 May;70(5):e30270.
doi: 10.1002/pbc.30270. Epub 2023 Mar 7.

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

April Vassantachart  1 , Arthur J Olch  2   3 , Marjorie Jones  4   5 , Christophe Marques  6 , Cécile Ronckers  7   8 , Louis S Constine  9 , John H Maduro  7   10 , Charlotte de Boer  11 , Kenneth Wong  2   3
Affiliations
Review

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

April Vassantachart et al. Pediatr Blood Cancer. 2023 May.

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 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.

Keywords: constraints; oncology; pediatric; radiotherapy.

PubMed Disclaimer

Figures

FIGURE 1
FIGURE 1
Representative plots of the (A) spinal cord, (B) brainstem, and (C) optic chiasm constraints based on the number of trials and treatment modality.
See this image and copyright information in PMC

References

    1. Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer statistics, 2021. CA Cancer J Clin. 2021;71(1):7–33. 10.3322/caac.21654 - DOI - PubMed
    1. Geenen MM, Cardous-Ubbink MC, Kremer LCM, et al. Medical assessment of adverse health outcomes in long-term survivors of childhood cancer. J Am Med Assoc. 2007;297(24):2705–2715. 10.1001/jama.297.24.2705 - DOI - PubMed
    1. Oeffinger KC, Mertens AC, Sklar CA. Chronic health conditions in adult survivors of childhood cancer. Oncol Times. 2007;29(1):26. 10.1097/01.cot.0000265629.30194.8e - DOI - PubMed
    1. Bhakta N, Liu Q, Ness KK, et al. The cumulative burden of surviving childhood cancer: an initial report from the St Jude Lifetime Cohort Study (SJLIFE). Lancet. 2017;390(10112):2569–2582. 10.1016/S0140-6736(17)31610-0 - DOI - PMC - PubMed
    1. Steinmeier T, Schulze Schleithoff S, Timmermann B. Evolving radiotherapy techniques in paediatric oncology. Clin Oncol. 2019;31(3):142–150. 10.1016/j.clon.2018.12.005 - DOI - PubMed

Publication types