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Antiprotons have been proposed for use in radiotherapy due to their similar energy deposition in water to protons except for an increased dose near the Bragg peak due to antiproton annihilation at rest. There has been skepticism about the use of antiprotons for therapy therefore radiobiological investigations are required to gain a better understanding of the biological effectiveness of antiprotons along the beam path and in the out-of-field regions. Antiproton induced DNA damage in AG01522 fibroblast cells has been investigated using the yH2AX assay. DNA damage and repair have been correlated with cell killing and sub lethal damage. Analogous experiments were conducted with proton and carbon-ion beams that are already used for radiotherapy. DNA damage in cells in the middle of the spread-out Bragg peak persisted longer than that caused by X-rays, plateau anti protons or protons but were repaired quicker than those caused by carbon-ions. Antiproton induced foci appear also larger than those induced by the other radiation modalities investigated. The persistence of foci has been related to LET and is correlated with increased biological effectiveness for cell killing and micronucleus/chromosome aberration formation. The effects outside radiation fields have also been investigated. This study suggests that radiation induced bystander effects in the AG01522 cell line may be LET dependent and appear at late time points after radiation. Investigation into the impact of antiproton annihilation secondary particles outside the primary beam revealed a dose dependent increase in DNA damage at 26 h after exposure in cells that also shared media with cells in the beam at the time of irradiation. This was only significant however for a single dose point. Cells that did not share media with the cells in the beam during the irradiation had low levels of DNA damage that was only significant for 5.56 and 6 Gy doses.

Severaa aspects of the IMRT treatment chain are evaluated with a view to improving the accuracy with which the treatment can be delivered and also the radiobiological outcome for the patient. A safe, non-invasive way of evaluating patient repositioning for multi-fraction treatments is developed and presented, with results highlighting the head-and-neck immobilisation system that provides the best results at Addenbrooke's radiotherapy centre. Previously published dose evaluation metrics sre studied in depth, identifying ways in which they differ. A new method of calculating the popular Gamma index is proposed, along with a new Kappa index which can highlight areas of dose mismatch more readily than the Gamma index. Using a specially developed dose calculation system, systematic errors found with the IMRT treatment machines at Addenbrooke's are simulated to determine the dose differences created by these errors, which are then evaluated using the Kappa index with typical tolerances used by previous authors. The concept of equivalent uniform dose( EUD) is then used to assess whether the tolerances for distance and dose are equivalent to each other. They are found not to be equivalent, and better relative values of the two quantities are suggested for use in composite indices. The use of the EUD is extended further into analysing the equivalent dose differences of the treatment delivery errors previously calculated. It is found that the equivalent dose to the target volume is changed by more than the composite indices indicate. The EUD is then used to calculate normal tissue complication probabilities, the probability of uncomplicated control and therapeutic gain. It is found that the dose errors predicted can actually be beneficial to the patient outcome, although not always. It is concluded that dose evaluation for complex treatments such as IMRT should be more radiobiologically-based in order to assess patient outcomes properly.

The introduction in Radiation Oncology of x-ray beams fluence modulation, the treatment technique known as Intensity Modulated Radiation Therapy (IMRT), is leading to the flourishing of new and increasingly sophisticated treatments. It is within this context that delivery systems have been evolving from static to rotational IMRT techniques through which significant advantages have occurred in terms of treatment plan quality, delivery efficiency and accuracy, although paying the price of longer calculation times for the plan optimization. The point has been reached where the perceived advantages of rotational IMRT techniques, for which some companies have marketed therapy systems with different architecture from that of conventional linear accelerators, have led users to question whether the established and more conventional systems are becoming obsolete. However, the newly available methods of delivering Intensity Modulated Arc Therapies (IMAT) using conventional accelerators, an advanced form of rotational IMRT that combines multiple arcs with variable fluence and gantry speed, seem to have provided a preliminary answer to this concern. Although it is difficult to know which of these treatment modalities will be discontinued in the near future, it is clear that the rotational IMR T is expected to become increasingly important. Therefore, the problem of understanding which are the strengths of these techniques, or the most effective methods (forward or inverse-planning based) of their treatment planning procedures, as well as the most robust and effective systems for verifying dosimetrically such rotational deliveries can be considered current research topics. As a results, different aspects of rotational IMRT techniques have been investigated in this work, starting with the pre-clinical dosimetry of IMAT therapies, passing through the planning procedures also in comparison with static IMR T, and advancing to a special application of 'rotational IMRT': the simulation of radiobiologically optimised, voxel-based dose-painting, guided by the metabolic tumour imaging. In particular we have worked on: two methods for the pre-clinical dosimetry of IMA T treatments using a matrix detector of ionization-chambers and an electronic portal imaging device, a forward and an inverse-planning approach for simulating IMAT treatments, a ranking of plans simulated with static and rotational IMRT modalities on prostate tumour. The high conformality achievable by rotational IMRT, as well as its potential to deliver selectively different doses inside a heterogeneous target volume, together with the image guidance capabilities of the newest therapy units, makes arc modulation the most appropriate and suitable instrument for assessing future "dose painting" treatments. In this regard, two radiobiological objective functions for guiding the dose redistribution inside a group of prostate tumours according to their estimated clonogenic density distribution (based on Position Emission Tomography imaging) were developed, compared and analysed.