Dynamic changes in cervical cancer.

Locally advanced cervical cancer is treated with chemoradiotherapy. The 5 year survival for stage II and III disease ranges from 40-60% and therefore there is scope for improvement of treatment either using dose escalation or adding in additional therapeutic agents. However, the burden of toxicity following chemoradiotherapy is not insignificant and therefore whilst trying to improve the cure rate, it is also important to reduce the dose to the organs at risk. This thesis looks at methods of increasing the dose delivered to the tumour whilst reducing the dose to the organs at risk. The methods used to achieve this are the use of a bladder scanner to reduce internal organ movement, the use of a plan of the day strategy, the use of interstitial needles for brachytherapy and the use of texture analysis to predict those patients who are not going to achieve a complete response to chemoradiotherapy. The final chapter starts to explore the question of whether immunotherapy in the form of immune checkpoint blockade drugs could potentially be of benefit in cervical cancer. The tumour microenvironment was assessed before and during chemoradiotherapy by looking at tumour infiltrating lymphocyte populations and the expression of PD-1 and PD-L1. These were also studied in the peripheral blood.