Development of three-dimensional radiotherapy techniques in breast cancer

Radiotherapy following conservation surgery decreases local relapse and death from breast cancer. Currently, the challenge is to minimise the morbidity caused by this treatment without losing efficacy. Despite many advances in radiation techniques in other sites of the body, the majority of breast cancer patients are still planned and treated using 2-dimensional simple radiotherapy techniques. In addition, breast irradiation currently consumes 30% of the UK's radiotherapy workload. Therefore, any change to more complex treatment should be of proven benefit. The primary objective of this research is to develop and evaluate novel radiotherapy techniques to decrease irradiation of normal structures and improve localisation of the tumour bed. I have developed a forward-planned intensity modulated (IMRT) breast radiotherapy technique, which has shown improved dosimetry results compared to standard breast radiotherapy. Subsequently, I have developed and implemented a phase III randomised controlled breast IMRT trial. This National Cancer Research Network adopted trial will answer an important question regarding the clinical benefit of breast IMRT. It will provide DNA samples linked with high quality clinical outcome data, for a national translational radiogenomics study investigating variation in normal tissue toxicity. Thus, patients with significant late normal tissue side effects despite good dose homogeneity will provide the best model for finding differences due to underlying genetics. I evaluated a novel technique using high definition free-hand 3-dimensional (3D) ultrasound in a phantom study, and the results suggested that this is an accurate and reproducible method for tumour bed localisation. I then compared recognised methods of tumour bed localisation with the 3D ultrasound method in a clinical study. The 3D ultrasound technique appeared to accurately represent the shape and spatial position of the tumour cavity. This tumour bed localisation research facilitated protocol development of a proposed national breast radiotherapy trial investigating IMRT and partial breast irradiation.