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Applying a Hypoxia-Incorporating TCP Model to Experimental Data on Rat Sarcoma.
MedLine Citation:
PMID:  22270163     Owner:  NLM     Status:  Publisher    
PURPOSE: To verify whether a tumor control probability (TCP) model which mechanistically incorporates acute and chronic hypoxia is able to describe animal in vivo dose-response data, exhibiting tumor reoxygenation. METHODS AND MATERIALS: The investigated TCP model accounts for tumor repopulation, reoxygenation of chronic hypoxia, and fluctuating oxygenation of acute hypoxia. Using the maximum likelihood method, the model is fitted to Fischer-Moulder data on Wag/Rij rats, inoculated with rat rhabdomyosarcoma BA1112, and irradiated in vivo using different fractionation schemes. This data set is chosen because two of the experimental dose-response curves exhibit an inverse dose behavior, which is interpreted as due to reoxygenation. The tested TCP model is complex, and therefore, in vivo cell survival data on the same BA1112 cell line from Reinhold were added to Fischer-Moulder data and fitted simultaneously with a corresponding cell survival function. RESULTS: The obtained fit to the combined Fischer-Moulder-Reinhold data was statistically acceptable. The best-fit values of the model parameters for which information exists were in the range of published values. The cell survival curves of well-oxygenated and hypoxic cells, computed using the best-fit values of the radiosensitivities and the initial number of clonogens, were in good agreement with the corresponding in vitro and in situ experiments of Reinhold. The best-fit values of most of the hypoxia-related parameters were used to recompute the TCP for non-small cell lung cancer patients as a function of the number of fractions, TCP(n). CONCLUSIONS: The investigated TCP model adequately describes animal in vivo data exhibiting tumor reoxygenation. The TCP(n) curve computed for non-small cell lung cancer patients with the best-fit values of most of the hypoxia-related parameters confirms previously obtained abrupt reduction in TCP for n < 10, thus warning against the adoption of severely hypofractionated schedules.
Ruggero Ruggieri; Nadejda Stavreva; Stefania Naccarato; Pavel Stavrev
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-1-21
Journal Detail:
Title:  International journal of radiation oncology, biology, physics     Volume:  -     ISSN:  1879-355X     ISO Abbreviation:  -     Publication Date:  2012 Jan 
Date Detail:
Created Date:  2012-1-24     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7603616     Medline TA:  Int J Radiat Oncol Biol Phys     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2012 Elsevier Inc. All rights reserved.
Department of Radiation Oncology, S. Cuore-don Calabria Hospital, Negrar (VR), Italy.
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