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A Survey of 30 years of Pediatric Clinical Trial Radiotherapy Dose Constraints
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  • April Vassantachart,
  • Arthur Olch,
  • Marjorie Jones,
  • Christophe Marques,
  • Cecile Ronckers,
  • Louis Constine,
  • John Maduro,
  • Charlotte de Boer,
  • Kenneth Wong
April Vassantachart
Los Angeles County University of Southern California Medical Center

Corresponding Author:[email protected]

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Arthur Olch
University of Southern California Keck School of Medicine
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Marjorie Jones
Children's Hospital Los Angeles
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Christophe Marques
Ochsner Lafayette General
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Cecile Ronckers
Prinses Maxima Centrum voor Kinderoncologie
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Louis Constine
University of Rochester
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John Maduro
Prinses Maxima Centrum voor Kinderoncologie
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Charlotte de Boer
Amsterdam Universitair Medische Centra
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Kenneth Wong
University of Southern California Keck School of Medicine
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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.
10 Nov 2022Submission Checks Completed
10 Nov 2022Assigned to Editor
10 Nov 2022Submitted to Pediatric Blood & Cancer
11 Nov 2022Review(s) Completed, Editorial Evaluation Pending
14 Nov 2022Reviewer(s) Assigned
27 Dec 2022Editorial Decision: Revise Minor
23 Jan 20231st Revision Received
23 Jan 2023Submission Checks Completed
23 Jan 2023Assigned to Editor
27 Jan 2023Review(s) Completed, Editorial Evaluation Pending
27 Jan 2023Reviewer(s) Assigned
06 Feb 2023Editorial Decision: Accept