Presenter of 1 Presentation
A MULTISCALE EXTENSION OF THE GENERALIZED STOCHASTIC MICRODOSIMETRIC MODEL (GSM2) TO DESCRIBE DYNAMICAL OXYGENATION AND FAST REACTION KINETICS FOR UNRAVELING THE FLASH EFFECT
Abstract
Background and Aims
FLASH radiotherapy [1], has emerged in the latest years as a promising new avenue for therapeutic use of radiation. It has been collected experimental evidence that FLASH irradiations are able to spare normal tissue being equally efficient for tumour control. Besides this evidence, the mechanism at the basis of FLASH effect remain to date largely unknown.
[1]Favaudon,V.ScienceTranslationalMedicine(2014)
Methods
The Generalized Stochastic Microdosimetric Model (GSM2),[2], is a probabilistic model that describes the time-evolution of the DNA damages in a cell nucleus from microdosimetric principles. Among the most relevant strengths there is the capability of efficiently treat the several levels of spatio-temporal stochasticity happening during a protracted irradiation. We derive a multiscale GSM2 coupling the DNA damage evolution with fast reaction kinetics accounting for radical formations, oxygen consumption and re-oxygenation happening during a given dose delivery time structure.The resulting multiscale GSM2 describes the coupled evolution of the multiscale system composed by DNA damage and fast Reactive Oxygen Species (ROS).
[2]Cordoni,F.Phys.Rev.E(2021).
Results
Via simulations of proton energy deposition in a microscopic volume using TOPAS-nBIO, we study the combined effects of ROS and the time evolution of DNA damages, assessing the resulting cell-survival curve at different beam structures and oxygenation conditions. We show how the multiscale GSM2 is able to justify the empirical patterns of Double Stand Breaks (DSB) yields and normal tissue sparring typical of FLASH radiotherapy, [3].
[3]Buonanno,M,et.al.RadiotherapyAndOncology(2019).
Conclusions
We extended GSM2 coupling DNA damage to fast ROS kinetics to reproduce the suppression of DSB yields and normal tissue sparing typical of FLASH radiotherapy.
Author Of 1 Presentation
A MULTISCALE EXTENSION OF THE GENERALIZED STOCHASTIC MICRODOSIMETRIC MODEL (GSM2) TO DESCRIBE DYNAMICAL OXYGENATION AND FAST REACTION KINETICS FOR UNRAVELING THE FLASH EFFECT
Abstract
Background and Aims
FLASH radiotherapy [1], has emerged in the latest years as a promising new avenue for therapeutic use of radiation. It has been collected experimental evidence that FLASH irradiations are able to spare normal tissue being equally efficient for tumour control. Besides this evidence, the mechanism at the basis of FLASH effect remain to date largely unknown.
[1]Favaudon,V.ScienceTranslationalMedicine(2014)
Methods
The Generalized Stochastic Microdosimetric Model (GSM2),[2], is a probabilistic model that describes the time-evolution of the DNA damages in a cell nucleus from microdosimetric principles. Among the most relevant strengths there is the capability of efficiently treat the several levels of spatio-temporal stochasticity happening during a protracted irradiation. We derive a multiscale GSM2 coupling the DNA damage evolution with fast reaction kinetics accounting for radical formations, oxygen consumption and re-oxygenation happening during a given dose delivery time structure.The resulting multiscale GSM2 describes the coupled evolution of the multiscale system composed by DNA damage and fast Reactive Oxygen Species (ROS).
[2]Cordoni,F.Phys.Rev.E(2021).
Results
Via simulations of proton energy deposition in a microscopic volume using TOPAS-nBIO, we study the combined effects of ROS and the time evolution of DNA damages, assessing the resulting cell-survival curve at different beam structures and oxygenation conditions. We show how the multiscale GSM2 is able to justify the empirical patterns of Double Stand Breaks (DSB) yields and normal tissue sparring typical of FLASH radiotherapy, [3].
[3]Buonanno,M,et.al.RadiotherapyAndOncology(2019).
Conclusions
We extended GSM2 coupling DNA damage to fast ROS kinetics to reproduce the suppression of DSB yields and normal tissue sparing typical of FLASH radiotherapy.