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...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2021-03-01
|
| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-021-84620-z |
| _version_ | 1831582732740722688 |
|---|---|
| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-17T20:29:51Z |
| format | Article |
| id | doaj.art-70a7d2ae9c554e15b32ca8a80289d218 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-17T20:29:51Z |
| publishDate | 2021-03-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-70a7d2ae9c554e15b32ca8a80289d2182022-12-21T21:33:38ZengNature PortfolioScientific Reports2045-23222021-03-0111111410.1038/s41598-021-84620-zMathematical model for the thermal enhancement of radiation response: thermodynamic approachAdriana M. De Mendoza0Soňa Michlíková1Johann Berger2Jens Karschau3Leoni A. Kunz-Schughart4Damian D. McLeod5OncoRay - National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, TU Dresden, Helmholtz-Zentrum Dresden-RossendorfOncoRay - National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, TU Dresden, Helmholtz-Zentrum Dresden-RossendorfICCAS - Innovation Center Computer Assisted Surgery, University of LeipzigOncoRay - National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, TU Dresden, Helmholtz-Zentrum Dresden-RossendorfOncoRay - National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, TU Dresden, Helmholtz-Zentrum Dresden-RossendorfOncoRay - National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, TU Dresden, Helmholtz-Zentrum Dresden-RossendorfAbstract 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.https://doi.org/10.1038/s41598-021-84620-z |
| spellingShingle | 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 Scientific Reports |
| title | 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_short | Mathematical model for the thermal enhancement of radiation response: thermodynamic approach |
| title_sort | mathematical model for the thermal enhancement of radiation response thermodynamic approach |
| url | https://doi.org/10.1038/s41598-021-84620-z |
| work_keys_str_mv | AT adrianamdemendoza mathematicalmodelforthethermalenhancementofradiationresponsethermodynamicapproach AT sonamichlikova mathematicalmodelforthethermalenhancementofradiationresponsethermodynamicapproach AT johannberger mathematicalmodelforthethermalenhancementofradiationresponsethermodynamicapproach AT jenskarschau mathematicalmodelforthethermalenhancementofradiationresponsethermodynamicapproach AT leoniakunzschughart mathematicalmodelforthethermalenhancementofradiationresponsethermodynamicapproach AT damiandmcleod mathematicalmodelforthethermalenhancementofradiationresponsethermodynamicapproach |