Dosimetric and computational studies for the development of innovative radiotherapy techniques
supervised by Yolanda PREZADO and Sandrine LACOMBE
Radiotherapy is one of the most effective treatments for cancer, yet its therapeutic efficacy is often limited by normal tissue toxicity and by the technological challenges associated with delivering highly conformal radiation beams. This doctoral thesis was carried out within the collaboration between the Centre National de la Recherche Scientifique (CNRS) and the Centre for the Clinical Application of Particles (CCAP) from the Imperial College of London, dedicated to the development of the Laser-hybrid Accelerator for Radiobiological Applications (LhARA). It addresses these challenges through two complementary research lines: spatially fractionated radiation therapy (SFRT) and laser-driven particle acceleration, combining advanced dosimetry, Monte Carlo simulations, machine learning, and preclinical studies.
The first research line focuses on the optimization and characterization of SFRT techniques. Dosimetric studies were carried out for photon mini-GRID radiotherapy and for carbon and helium minibeam radiotherapy (C-MBRT and He-MBRT), including beam characterization and support for the first preclinical in vivo experiments with C-MBRT. An in silico comparison of proton and photon minibeam radiotherapy using a canine brain model identified the clinical scenarios in which each modality provides the greatest dosimetric benefit. In addition, retrospective analyses of microbeam radiotherapy (MRT), minibeam radiotherapy (MBRT), and FLASH radiotherapy using machine learning investigated the relationships between irradiation parameters and biological outcomes, contributing to the development of improved treatment prescription metrics.
The second research line explores the application of laser-driven particle acceleration to radiotherapy and radiobiology. Computational studies were performed to optimize laser wakefield acceleration electron sources for radiobiological applications, while beamline optimization and dosimetric characterization supported the first in vitro radiobiology experiments using laser-driven proton beams within the LhARA collaboration.
Together, these studies provide new dosimetric methodologies, computational tools, and experimental developments that contribute to the optimization of innovative radiotherapy techniques and laser-driven irradiation platforms.