Exploring new approaches in radiotherapy to optimise the design of LhARA
File(s)
Author(s)
McGarrigle, Josie May
Type
Thesis
Abstract
Radiotherapy is a key part of cancer treatment, used in around 60–70% of patient cases, but conventional approaches have limitations in dose conformality and normal-tissue sparing. Emerging modalities exploit beam modifications in the temporal domain (ultra-high dose-rate radiotherapy—FLASH) and spatial domain (Spatially Fractionated Radiation Therapy—SFRT), alongside innovative delivery systems, to improve therapeutic outcomes. The Laser-hybrid Accelerator for Radiobiological Applications (LhARA) is conceived as a uniquely flexible international facility dedicated to studying the biological response to ionising radiation, with a design enabling exploration of these new modalities.
FLASH and SFRT have shown potential to reduce normal-tissue toxicities, though the underlying mechanisms remain unclear. A systematic review was conducted to assess the impact of key beam parameters across published FLASH and SFRT experiments, using a semi-quantitative approach to evaluate normal-tissue sparing and tumour control, and to guide the LhARA design. The FLASH review indicated a correlation between dose rates and tissue sparing, while the SFRT review suggested that dosimetric parameters play a critical role in Minibeam Radiation Therapy (MBRT), whereas Microbeam Radiation Therapy (MRT) appears to be more strongly influenced by the beam's geometric properties.
To address gaps in the SFRT review, a tumour and normal-tissue environment was modelled in TOPAS to simulate broader beam configurations. Discrepancies with the literature likely stem from the linear-quadratic model's inability to capture complex processes such as the radiation bystander effect. To explore this and investigate repair kinetics following SFRT, an in vitro experiment tracked radiation-induced damage: irradiated `peaks' exhibited an exponential repair response that slowed toward a plateau, though setup limitations restricted information on the non-irradiated `valleys'.
Additionally, a machine learning–based beamline optimisation framework was developed, parametrising laser-driven beams to identify optimal component positions and maximise transmission efficiency, supporting integration with LhARA and future radiotherapy accelerator facilities.
FLASH and SFRT have shown potential to reduce normal-tissue toxicities, though the underlying mechanisms remain unclear. A systematic review was conducted to assess the impact of key beam parameters across published FLASH and SFRT experiments, using a semi-quantitative approach to evaluate normal-tissue sparing and tumour control, and to guide the LhARA design. The FLASH review indicated a correlation between dose rates and tissue sparing, while the SFRT review suggested that dosimetric parameters play a critical role in Minibeam Radiation Therapy (MBRT), whereas Microbeam Radiation Therapy (MRT) appears to be more strongly influenced by the beam's geometric properties.
To address gaps in the SFRT review, a tumour and normal-tissue environment was modelled in TOPAS to simulate broader beam configurations. Discrepancies with the literature likely stem from the linear-quadratic model's inability to capture complex processes such as the radiation bystander effect. To explore this and investigate repair kinetics following SFRT, an in vitro experiment tracked radiation-induced damage: irradiated `peaks' exhibited an exponential repair response that slowed toward a plateau, though setup limitations restricted information on the non-irradiated `valleys'.
Additionally, a machine learning–based beamline optimisation framework was developed, parametrising laser-driven beams to identify optimal component positions and maximise transmission efficiency, supporting integration with LhARA and future radiotherapy accelerator facilities.
Date Issued
2025-09-12
Date Awarded
2026-06-01
Copyright Statement
Attribution-NonCommercial 4.0 International Licence (CC BY-NC)
License URL
Advisor
Long, Kenneth
Prezado, Yolanda
Publisher Department
Department of Physics
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)