Mathematical model for the thermal enhancement of radiation response: thermodynamic approach

Abstract Radiotherapy can effectively kill malignant cells, but the doses required to cure cancer patients may inflict severe collateral damage to adjacent healthy tissues. Recent technological advances in the clinical application has revitalized hyperthermia treatment (HT) as an option to improve r...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Adriana M. De Mendoza, Soňa Michlíková, Johann Berger, Jens Karschau, Leoni A. Kunz-Schughart, Damian D. McLeod
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/70a7d2ae9c554e15b32ca8a80289d218
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:70a7d2ae9c554e15b32ca8a80289d218
record_format	dspace
spelling	oai:doaj.org-article:70a7d2ae9c554e15b32ca8a80289d2182021-12-02T13:30:10ZMathematical model for the thermal enhancement of radiation response: thermodynamic approach10.1038/s41598-021-84620-z2045-2322https://doaj.org/article/70a7d2ae9c554e15b32ca8a80289d2182021-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-84620-zhttps://doaj.org/toc/2045-2322Abstract Radiotherapy can effectively kill malignant cells, but the doses required to cure cancer patients may inflict severe collateral damage to adjacent healthy tissues. Recent technological advances in the clinical application has revitalized hyperthermia treatment (HT) as an option to improve radiotherapy (RT) outcomes. Understanding the synergistic effect of simultaneous thermoradiotherapy via mathematical modelling is essential for treatment planning. We here propose a theoretical model in which the thermal enhancement ratio (TER) relates to the cell fraction being radiosensitised by the infliction of sublethal damage through HT. Further damage finally kills the cell or abrogates its proliferative capacity in a non-reversible process. We suggest the TER to be proportional to the energy invested in the sensitisation, which is modelled as a simple rate process. Assuming protein denaturation as the main driver of HT-induced sublethal damage and considering the temperature dependence of the heat capacity of cellular proteins, the sensitisation rates were found to depend exponentially on temperature; in agreement with previous empirical observations. Our findings point towards an improved definition of thermal dose in concordance with the thermodynamics of protein denaturation. Our predictions well reproduce experimental in vitro and in vivo data, explaining the thermal modulation of cellular radioresponse for simultaneous thermoradiotherapy.Adriana M. De MendozaSoňa MichlíkováJohann BergerJens KarschauLeoni A. Kunz-SchughartDamian D. McLeodNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Adriana M. De Mendoza Soňa Michlíková Johann Berger Jens Karschau Leoni A. Kunz-Schughart Damian D. McLeod Mathematical model for the thermal enhancement of radiation response: thermodynamic approach
description	Abstract Radiotherapy can effectively kill malignant cells, but the doses required to cure cancer patients may inflict severe collateral damage to adjacent healthy tissues. Recent technological advances in the clinical application has revitalized hyperthermia treatment (HT) as an option to improve radiotherapy (RT) outcomes. Understanding the synergistic effect of simultaneous thermoradiotherapy via mathematical modelling is essential for treatment planning. We here propose a theoretical model in which the thermal enhancement ratio (TER) relates to the cell fraction being radiosensitised by the infliction of sublethal damage through HT. Further damage finally kills the cell or abrogates its proliferative capacity in a non-reversible process. We suggest the TER to be proportional to the energy invested in the sensitisation, which is modelled as a simple rate process. Assuming protein denaturation as the main driver of HT-induced sublethal damage and considering the temperature dependence of the heat capacity of cellular proteins, the sensitisation rates were found to depend exponentially on temperature; in agreement with previous empirical observations. Our findings point towards an improved definition of thermal dose in concordance with the thermodynamics of protein denaturation. Our predictions well reproduce experimental in vitro and in vivo data, explaining the thermal modulation of cellular radioresponse for simultaneous thermoradiotherapy.
format	article
author	Adriana M. De Mendoza Soňa Michlíková Johann Berger Jens Karschau Leoni A. Kunz-Schughart Damian D. McLeod
author_facet	Adriana M. De Mendoza Soňa Michlíková Johann Berger Jens Karschau Leoni A. Kunz-Schughart Damian D. McLeod
author_sort	Adriana M. De Mendoza
title	Mathematical model for the thermal enhancement of radiation response: thermodynamic approach
title_short	Mathematical model for the thermal enhancement of radiation response: thermodynamic approach
title_full	Mathematical model for the thermal enhancement of radiation response: thermodynamic approach
title_fullStr	Mathematical model for the thermal enhancement of radiation response: thermodynamic approach
title_full_unstemmed	Mathematical model for the thermal enhancement of radiation response: thermodynamic approach
title_sort	mathematical model for the thermal enhancement of radiation response: thermodynamic approach
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/70a7d2ae9c554e15b32ca8a80289d218
work_keys_str_mv	AT adrianamdemendoza mathematicalmodelforthethermalenhancementofradiationresponsethermodynamicapproach AT sonamichlikova mathematicalmodelforthethermalenhancementofradiationresponsethermodynamicapproach AT johannberger mathematicalmodelforthethermalenhancementofradiationresponsethermodynamicapproach AT jenskarschau mathematicalmodelforthethermalenhancementofradiationresponsethermodynamicapproach AT leoniakunzschughart mathematicalmodelforthethermalenhancementofradiationresponsethermodynamicapproach AT damiandmcleod mathematicalmodelforthethermalenhancementofradiationresponsethermodynamicapproach
_version_	1718392980571684864

Mathematical model for the thermal enhancement of radiation response: thermodynamic approach

Ejemplares similares