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Application of laser-plasma accelerated beams to high dose-rate radiation biology

Abstract : Cancer is the second leading cause of death globally, accounting for an estimated 9.6 million deaths, or one in six deaths, in 2018. Besides surgery and chemotherapy, radiotherapy is one of the major treatment modality. It consists in the use of ionising radiation to kill cancerous cells by depositing energy into the tumour and destroying the genetic material that controls how cells grow and divide. While both cancerous and healthy cells are damaged by radiation, the goal of radiotherapy is to increase the treatment selectivity by sparing as much as possible the healthy tissues. Optimisation of the selectivity reposes on several aspects, including spatial optimisation of the dose, precision of imaging techniques and dosimetry instruments, use of different radiations and temporal structures of dose delivery. In particular, the role of the dose-rate and the total irradiation time has not been extensively explored yet.Clinical accelerators typically deliver the dose with a dose rate around few Gy/min, leading to exposure times in the order of few minutes to deliver a therapeutic dose. While the effect of a reduction of the dose rate in the order of cGy/min is well known, the effect of high-dose rate, fast irradiation on living cells still need to be elucidated. Evidences of an effect of the high dose-rate on the biological response have been recently observed in many studies. In particular, in-vivo studies performed with electrons and photons produced by accelerator prototypes have shown that delivering the prescribed dose in a short exposure time (<500ms) and at a high dose-rate (>40Gy/s) increases the treatment selectivity by reducing the occurrence of secondary effects on healthy tissues compared to conventional treatments with the same total dose. Although theoretical explanations underpinning such phenomenon are still under discussion, the so-called FLASH protocol has been successfully tested with the first human patient in 2019, paving the way for further research in this domain. These important results point out the importance of the dose delivery modality on the treatment selectivity and the potential benefit that high dose-rate protocols may bring to clinics, asking for a deeper understanding of the physico-chemical and biological processes following fast dose deposition.In this scenario, Laser-Driven Particle (LDP) beams represent a unique tool to shed some light on the radiobiological response following high-dose rate irradiation. LDP sources are produced by focusing an ultra-short (~fs) and ultra-intense (1019 W/cm2) laser pulse on a solid or gaseous thin target (~μm), producing proton and electron bunches with duration of respectively a few picoseconds and a few femtoseconds. These characteristics allow the reach of extremely high peak dose-rate in the pulse of the order of ~109 Gy/s in comparison with conventional and FLASH treatment protocols. For this reason, LDP sources have been receiving great attention in the last decade, but their radiobiological effect is still debated and further systematic studies are required.This thesis discusses the potential of both Laser-Accelerated Protons (LAP) and Laser-Accelerated Electrons (LAE) produced by different types of commercially available high-power lasers systems. In particular, it presents experimental and theoretical studies carried out with three different types of LDP beams, i.e. Hz LAPs, single-shot LAPs and kHz LAEs, enabling different temporal modalities of dose delivery. The goal is to address some of the main issues related to the application of such sources to radiation biology and show viable solutions and irradiation protocols to perform systematic radiobiology studies. Such issues include accurate characterisation of the source, optimisation of the dose distribution at the biological target through the design of adapted transport beamlines and investigation of the behaviour of dosimetric instruments for high dose-rate dosimetry.
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Submitted on : Monday, December 21, 2020 - 3:01:18 PM
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Marco Cavallone. Application of laser-plasma accelerated beams to high dose-rate radiation biology. Accelerator Physics [physics.acc-ph]. Institut Polytechnique de Paris, 2020. English. ⟨NNT : 2020IPPAX063⟩. ⟨tel-03085030⟩

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