Specialised Software and Protocols Enabling Patient Specific Treatment Using Microbeam Radiation Therapy

<p dir="ltr">Cancer is the leading cause of premature death in 57 countries, including Australia. Radiotherapy plays an essential role in modern cancer treatment, with more than half of all patients diagnosed with cancer receiving radiotherapy as part of their treatment.</p><p dir="ltr">Continued improvements in radiotherapy over the past 40 years have seen the five year survival rate in Australia increase from 48% to 71%. However, this improvement has not been realised uniformly in all types of cancer. For example, cancers of the brain have proven particularly difficult to treat, with survival rates increasing only marginally from 21% to 22% in the past 30 years. The maximum tolerable dose to healthy tissue limits the ability to deliver a therapeutic dose of radiation to the certain tumours, such as brain tumours.</p><p dir="ltr">Research has demonstrated the potential to preserve healthy tissue in deep-seated tumours, without impacting tumour control probability, by utilising high-dose rates and spatially fractionated radiation fields. Firstly, radiation therapy delivered at very high dose rates (≥ 40 Gy/s) has been shown to increase the radiation tolerance of healthy tissue. This is a phenomenon known as the ‘FLASH’ effect. In addition, spatial fractionation of the treatment field has also been shown to preserve healthy tissue. To preserve spatial fractionation on the micron scale, and mitigate the effect of motion in biological samples, it is necessary to deliver the treatment at a high-dose rate. The combination of high-dose rates and spatial fractionation on the micron scale is known as Microbeam Radiation Therapy (MRT). With its excellent healthy tissue sparing properties, MRT has great potential for application of the treatment of cancers previously thought to be untreatable.</p><p dir="ltr">MRT is in the pre-clinical development phase, only possible at the small number of specialist facilities, called synchrotrons, that are capable of producing radiation fields with the specific beam properties needed for effective delivery of MRT. Limited access to these facilities impedes progress. Additionally, there are many medical physics challenges that need to be addressed to ensure the delivery of safe and accurate MRT treatment. In particular, further work is needed to develop treatment planning capabilities, along with specialised dosimetry and quality assurance protocols. Only then will sufficient solutions be in place to provide confidence in treatment delivery.</p><p dir="ltr">This thesis adopts a holistic, patient-centred approach to these pre-treatment planning processes. A patient specific imaging protocol, applicable for pre-clinical and clinical trials of MRT, is developed. Optimisation of patient imaging is a critical precursor to clinical trials. It is necessary for accurate tumour identification and contouring, to inform dose simulations, and to enable accurate patient alignment prior to treatment.</p><p dir="ltr">In addition, a new software package, DoseMRT has been developed and validated for use in synchrotron generatedMRT. DoseMRT addresses many of the limitations of current treatment planning systems for MRT. The system enables simulation of treatment plans using individualised Computed Tomography (CT) datasets with customised beam geometry, contouring of the target volume and calculating dose volume histograms. DoseMRT utilises an industry gold standard software toolkit (Geant4) and the Monte Carlo Method to simulate synchrotron radiation production and dose deposition in complex heterogeneous phantoms with the ability to perform absolute dose calculations. Finally, DoseMRT is validated against experimental dosimetry, with a high degree of accuracy, and its capability to perform absolute dosimetry without the need for experimental calibration is explored. The system overcomes many of the key limitations of currently available treatment planning systems, and has been instrumental in the continued development of MRT.</p><p dir="ltr">These advancements in the pre-treatment patient planning process supports continued progress toward harnessing the therapeutic potential of MRT.</p>