A multiscale radiation biophysical stochastic model describing the cell survival response at ultra-high dose rate

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Hauptverfasser: Battestini, Marco, Missiaggia, Marta, Bolzoni, Sara, Cordoni, Francesco G., Scifoni, Emanuele
Format: Preprint
Veröffentlicht: 2024
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author Battestini, Marco
Missiaggia, Marta
Bolzoni, Sara
Cordoni, Francesco G.
Scifoni, Emanuele
author_facet Battestini, Marco
Missiaggia, Marta
Bolzoni, Sara
Cordoni, Francesco G.
Scifoni, Emanuele
contents Ultra-high dose-rate (UHDR) radiotherapy, characterized by an extremely high radiation delivery rate, represents one of the most recent and promising frontier in radiotherapy. UHDR radiotherapy, addressed in the field as FLASH radiotherapy, is a disruptive treatment modality with several benefits, including significantly shorter treatment times, unchanged effectiveness in treating tumors, and clear reductions in side effects on normal tissues. While the benefits of UHDR irradiation have been well highlighted experimentally, the biological mechanism underlying the FLASH effect is still unclear and highly debated. Nonetheless, to effectively use UHDR radiotherapy in clinics, understanding the driving biological mechanism is paramount. Since the concurrent involvement of multiple scales of radiation damage has been suggested, we developed the MultiScale Generalized Stochastic Microdosimetric Model (MS-GSM2), a multi-stage extension of the GSM2, which is a probabilistic model describing the time evolution of the DNA damage in an irradiated cell nucleus. The MS-GSM2 can investigate several chemical species combined effects, DNA damage formation, and time evolution. We demonstrate that the MS-GSM2 can predict various in-vitro UHDR experimental results across various oxygenation levels, radiation types, and energies. The MS-GSM2 can accurately describe the empirical trend of dose and dose rate-dependent cell sensitivity over a wide range, consistently describing multiple aspects of the FLASH effect and reproducing the main evidence from the in-vitro experimental data. Our model also proposes a consistent explanation for the differential outcomes observed in normal tissues and tumors, in-vivo and in-vitro.
format Preprint
id arxiv_https___arxiv_org_abs_2412_16322
institution arXiv
publishDate 2024
record_format arxiv
spellingShingle A multiscale radiation biophysical stochastic model describing the cell survival response at ultra-high dose rate
Battestini, Marco
Missiaggia, Marta
Bolzoni, Sara
Cordoni, Francesco G.
Scifoni, Emanuele
Biological Physics
Medical Physics
Ultra-high dose-rate (UHDR) radiotherapy, characterized by an extremely high radiation delivery rate, represents one of the most recent and promising frontier in radiotherapy. UHDR radiotherapy, addressed in the field as FLASH radiotherapy, is a disruptive treatment modality with several benefits, including significantly shorter treatment times, unchanged effectiveness in treating tumors, and clear reductions in side effects on normal tissues. While the benefits of UHDR irradiation have been well highlighted experimentally, the biological mechanism underlying the FLASH effect is still unclear and highly debated. Nonetheless, to effectively use UHDR radiotherapy in clinics, understanding the driving biological mechanism is paramount. Since the concurrent involvement of multiple scales of radiation damage has been suggested, we developed the MultiScale Generalized Stochastic Microdosimetric Model (MS-GSM2), a multi-stage extension of the GSM2, which is a probabilistic model describing the time evolution of the DNA damage in an irradiated cell nucleus. The MS-GSM2 can investigate several chemical species combined effects, DNA damage formation, and time evolution. We demonstrate that the MS-GSM2 can predict various in-vitro UHDR experimental results across various oxygenation levels, radiation types, and energies. The MS-GSM2 can accurately describe the empirical trend of dose and dose rate-dependent cell sensitivity over a wide range, consistently describing multiple aspects of the FLASH effect and reproducing the main evidence from the in-vitro experimental data. Our model also proposes a consistent explanation for the differential outcomes observed in normal tissues and tumors, in-vivo and in-vitro.
title A multiscale radiation biophysical stochastic model describing the cell survival response at ultra-high dose rate
topic Biological Physics
Medical Physics
url https://arxiv.org/abs/2412.16322