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Article: Dynamic optimization of a linear-quadratic model with incomplete repair and volume-dependent sensitivity and repopulation

TitleDynamic optimization of a linear-quadratic model with incomplete repair and volume-dependent sensitivity and repopulation
Authors
Issue Date2000
PublisherElsevier Inc. The Journal's web site is located at http://www.elsevier.com/locate/ijrobp
Citation
International Journal of Radiation Oncology - Biology - Physics, 2000, v. 47 n. 4, p. 1073-1083 How to Cite?
AbstractPurpose: The linear-quadratic model typically assumes that tumor sensitivity and repopulation are constant over the time course of radiotherapy. However, evidence suggests that the growth fraction increases and the cell-loss factor decreases as the tumor shrinks. We investigate whether this evolution in tumor geometry, as well as the irregular time intervals between fractions in conventional hyperfractionation schemes, can be exploited by fractionation schedules that employ time-varying fraction sizes.Methods: We construct a mathematical model of a spherical tumor with a hypoxic core and a viable rim, which is most appropriate for a prevascular tumor, and is only a caricature of a vascularized tumor. This model is embedded into the traditional linear-quadratic model by assuming instantaneous reoxygenation. Dynamic programming is used to numerically compute the fractionation regimen that maximizes the tumor-control probability (TCP) subject to constraints on the biologically effective dose of the early and late tissues.Results: In several numerical examples that employ five or 10 fractions per week on a 1-cm or 5-cm diameter tumor, optimally varying the fraction sizes increases the TCP significantly. The optimal regimen incorporates large Friday (afternoon, if 10 fractions per week) fractions that are escalated throughout the course of treatment, and larger afternoon fractions than morning fractions.Conclusion: Numerical results suggest that a significant increase in tumor cure can be achieved by allowing the fraction sizes to vary throughout the course of treatment. Several strategies deserve further investigation: using larger fractions before overnight and weekend breaks, and escalating the dose (particularly on Friday afternoons) throughout the course of treatment. Copyright (C) 2000 Elsevier Science Inc.
Persistent Identifierhttp://hdl.handle.net/10722/151547
ISSN
2015 Impact Factor: 4.495
2015 SCImago Journal Rankings: 2.274
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorWein, LMen_US
dc.contributor.authorCohen, JEen_US
dc.contributor.authorWu, JTen_US
dc.date.accessioned2012-06-26T06:24:27Z-
dc.date.available2012-06-26T06:24:27Z-
dc.date.issued2000en_US
dc.identifier.citationInternational Journal of Radiation Oncology - Biology - Physics, 2000, v. 47 n. 4, p. 1073-1083en_US
dc.identifier.issn0360-3016en_US
dc.identifier.urihttp://hdl.handle.net/10722/151547-
dc.description.abstractPurpose: The linear-quadratic model typically assumes that tumor sensitivity and repopulation are constant over the time course of radiotherapy. However, evidence suggests that the growth fraction increases and the cell-loss factor decreases as the tumor shrinks. We investigate whether this evolution in tumor geometry, as well as the irregular time intervals between fractions in conventional hyperfractionation schemes, can be exploited by fractionation schedules that employ time-varying fraction sizes.Methods: We construct a mathematical model of a spherical tumor with a hypoxic core and a viable rim, which is most appropriate for a prevascular tumor, and is only a caricature of a vascularized tumor. This model is embedded into the traditional linear-quadratic model by assuming instantaneous reoxygenation. Dynamic programming is used to numerically compute the fractionation regimen that maximizes the tumor-control probability (TCP) subject to constraints on the biologically effective dose of the early and late tissues.Results: In several numerical examples that employ five or 10 fractions per week on a 1-cm or 5-cm diameter tumor, optimally varying the fraction sizes increases the TCP significantly. The optimal regimen incorporates large Friday (afternoon, if 10 fractions per week) fractions that are escalated throughout the course of treatment, and larger afternoon fractions than morning fractions.Conclusion: Numerical results suggest that a significant increase in tumor cure can be achieved by allowing the fraction sizes to vary throughout the course of treatment. Several strategies deserve further investigation: using larger fractions before overnight and weekend breaks, and escalating the dose (particularly on Friday afternoons) throughout the course of treatment. Copyright (C) 2000 Elsevier Science Inc.en_US
dc.languageengen_US
dc.publisherElsevier Inc. The Journal's web site is located at http://www.elsevier.com/locate/ijrobpen_US
dc.relation.ispartofInternational Journal of Radiation Oncology - Biology - Physicsen_US
dc.subject.meshAlgorithmsen_US
dc.subject.meshCell Division - Physiology - Radiation Effectsen_US
dc.subject.meshCell Hypoxia - Physiology - Radiation Effectsen_US
dc.subject.meshDna Repairen_US
dc.subject.meshDose Fractionationen_US
dc.subject.meshDose-Response Relationship, Radiationen_US
dc.subject.meshLinear Modelsen_US
dc.subject.meshModels, Biologicalen_US
dc.subject.meshOxygen Consumption - Physiology - Radiation Effectsen_US
dc.subject.meshRadiation Toleranceen_US
dc.subject.meshRadiobiologyen_US
dc.subject.meshRadiotherapy, Computer-Assisteden_US
dc.subject.meshRelative Biological Effectivenessen_US
dc.subject.meshSpheroids, Cellular - Pathology - Physiology - Radiation Effectsen_US
dc.titleDynamic optimization of a linear-quadratic model with incomplete repair and volume-dependent sensitivity and repopulationen_US
dc.typeArticleen_US
dc.identifier.emailWu, JT:joewu@hkucc.hku.hken_US
dc.identifier.authorityWu, JT=rp00517en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1016/S0360-3016(00)00534-4en_US
dc.identifier.pmid10863081-
dc.identifier.scopuseid_2-s2.0-0034237241en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0034237241&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume47en_US
dc.identifier.issue4en_US
dc.identifier.spage1073en_US
dc.identifier.epage1083en_US
dc.identifier.isiWOS:000087845500030-
dc.publisher.placeUnited Statesen_US
dc.identifier.scopusauthoridWein, LM=35560766400en_US
dc.identifier.scopusauthoridCohen, JE=7410009618en_US
dc.identifier.scopusauthoridWu, JT=7409256423en_US

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