Developing the Role of Proton Beam Therapy in Oesophageal Cancer

Abstract

Oesophageal cancer continues to be associated with a poor prognosis. Proton beam therapy’s distinct physical characteristics widen the therapeutic ratio in oesophageal cancer and has the potential to improve outcomes. This thesis aims to examine how proton beam therapy may improve outcomes in oesophageal cancer and documents efforts to expand its role. In Chapter 2, a comprehensive systematic literature review demonstrates the paucity of high-quality evidence in this field. Following this, a series of radiotherapy planning studies investigates potential dosimetric advantages of proton beam therapy for distal oesophageal cases. In chapter 3, proton beam therapy is shown to reduce lung and heart dose compared to photon radiotherapy. Normal tissue complication probability modelling establishes that this may reduce the risk of treatment related pulmonary and cardiac toxicity. Chapter 4 demonstrates that spleen dose constraints may successfully be introduced in oesophageal cancer for proton and photon plans, potentially resulting in lower lymphopenia rates and greater immune sparing. Chapter 5 highlights the impact of different beam arrangements on dose to organs at risk and individual cardiac substructures. The latter half of the thesis highlights work underpinning the development of novel clinical trials of proton beam therapy in oesophageal cancer. Chapter 6 details the work of creating a radiotherapy delineation protocol by comparing two established protocols in a delineation comparison study, showing that geometric expansion of volumes results in more consistent target volumes compared to ‘free-hand’ delineation. In chapter 7, public and patient involvement work is shown to inform and refine the design of a two new trials of proton beam therapy in oesophageal cancer. A final chapter discusses and summarises the current areas of interest in this field, expanding on current trial development work and future directions.