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dc.contributor.authorBrüningk, SCen_US
dc.contributor.authorZiegenhein, Pen_US
dc.contributor.authorRivens, Ien_US
dc.contributor.authorOelfke, Uen_US
dc.contributor.authorHaar, GTen_US
dc.date.accessioned2020-01-08T13:53:34Z
dc.date.issued2019-11-27en_US
dc.identifier.citationScientific reports, 2019, 9 (1), pp. 17674 - ?en_US
dc.identifier.issn2045-2322en_US
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/3486
dc.identifier.eissn2045-2322en_US
dc.identifier.doi10.1038/s41598-019-54117-xen_US
dc.description.abstractThermo-radiosensitisation is a promising approach for treatment of radio-resistant tumours such as those containing hypoxic subregions. Response prediction and treatment planning should account for tumour response heterogeneity, e.g. due to microenvironmental factors, and quantification of the biological effects induced. 3D tumour spheroids provide a physiological in vitro model of tumour response and a systems oncology framework for simulating spheroid response to radiation and hyperthermia is presented. Using a cellular automaton model, 3D oxygen diffusion, delivery of radiation and/or hyperthermia were simulated for many ([Formula: see text]) individual cells forming a spheroid. The iterative oxygen diffusion model was compared to an analytical oxygenation model and simulations were calibrated and validated against experimental data for irradiated (0-10 Gy) and/or heated (0-240 CEM43) HCT116 spheroids. Despite comparable clonogenic survival, spheroid growth differed significantly following radiation or hyperthermia. This dynamic response was described well by the simulation ([Formula: see text] > 0.85). Heat-induced cell death was implemented as a fast, proliferation-independent process, allowing reoxygenation and repopulation, whereas radiation was modelled as proliferation-dependent mitotic catastrophe. This framework stands out both through its experimental validation and its novel ability to predict spheroid response to multimodality treatment. It provides a good description of response where biological dose-weighting based on clonogenic survival alone was insufficient.en_US
dc.formatElectronicen_US
dc.format.extent17674 - ?en_US
dc.languageengen_US
dc.language.isoengen_US
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en_US
dc.titleA cellular automaton model for spheroid response to radiation and hyperthermia treatments.en_US
dc.typeJournal Article
dcterms.dateAccepted2019-11-03en_US
rioxxterms.versionofrecord10.1038/s41598-019-54117-xen_US
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0en_US
rioxxterms.licenseref.startdate2019-11-27en_US
rioxxterms.typeJournal Article/Reviewen_US
dc.relation.isPartOfScientific reportsen_US
pubs.issue1en_US
pubs.notesNot knownen_US
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Radiotherapy Physics Modelling
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Therapeutic Ultrasound
pubs.publication-statusPublisheden_US
pubs.volume9en_US
pubs.embargo.termsNot knownen_US
icr.researchteamRadiotherapy Physics Modellingen_US
icr.researchteamTherapeutic Ultrasounden_US
dc.contributor.icrauthorTer Haar, Gailen_US
dc.contributor.icrauthorBrueningk, Sarahen_US


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