Document Detail

Delay differential equations and the dose-time dependence of early radiotherapy reactions.
MedLine Citation:
PMID:  17022249     Owner:  NLM     Status:  MEDLINE    
The dose-time dependence of early radiotherapy reactions impacts on the design of accelerated fractionation schedules--oral mucositis, for example, can be dose limiting for short treatments designed to avoid tumor repopulation. In this paper a framework for modeling early reaction dose-time dependence is developed. Variation of stem cell number with time after the start of a radiation schedule is modeled using a first-order delay differential equation (DDE), motivated by experimental observations linking the speed of compensatory proliferation in early reacting tissues to the degree of tissue damage. The modeling suggests that two types of early reaction radiation response are possible, stem cell numbers either monotonically approaching equilibrium plateau levels or overshooting before returning to equilibrium. Several formulas have been derived from the delay differential equation, predicting changes in isoeffective total radiation dose with schedule duration for different types of fractionation scheme. The formulas have been fitted to a wide range of published animal early reaction data, the fits all implying a degree of overshoot. Results are presented illustrating the scope of the delay differential model: most of the data are fitted well, although the model struggles with a few datasets measured for schedules with distinctive dose-time patterns. Ways of extending the current model to cope with these particular dose-time patterns are briefly discussed. The DDE approach is conceptually more complex than earlier descriptive dose-time models but potentially more powerful. It can be used to study issues not addressed by simpler models, such as the likely effects of increasing or decreasing the dose-per-day over time, or of splitting radiation courses into intense segments separated by gaps. It may also prove useful for modeling the effects of chemoirradiation.
John D Fenwick
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Medical physics     Volume:  33     ISSN:  0094-2405     ISO Abbreviation:  Med Phys     Publication Date:  2006 Sep 
Date Detail:
Created Date:  2006-10-06     Completed Date:  2006-11-20     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0425746     Medline TA:  Med Phys     Country:  United States    
Other Details:
Languages:  eng     Pagination:  3526-40     Citation Subset:  IM    
Department of Medical Physics, Clatterbridge Centre for Oncology, Clatterbridge Road, Wirral CH63 4JY, United Kingdom.
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MeSH Terms
Apoptosis / radiation effects*
Cell Survival / radiation effects*
Computer Simulation
Dose Fractionation
Dose-Response Relationship, Radiation
Models, Biological*
Radiation Dosage
Stem Cells / cytology*,  physiology,  radiation effects*
Time Factors

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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