Radiotherapy is an important modality in the management of the primary tumour in bone and soft tissue sarcomas. Traditionally radiotherapy for sarcomas has been delivered with a three-dimensional conformal technique (3DCRT). In extremity soft tissue sarcomas this frequently leads to high doses of radiation being given to normal soft tissues outside the target. In Ewing sarcoma arising in specific sites such as the pelvis, it is difficult to avoid significant dose from 3DCRT to sensitive normal tissue structures adjacent to the target (small bowel, rectum, bladder and reproductive organs), potentially limiting the dose that can safely be given to the target. This body of work explores the burden of late effects of 3DCRT in patients with bone and soft tissue sarcoma and how advanced radiotherapy techniques including intensity modulated radiotherapy (IMRT) and proton beam therapy (PBT), that produce more conformal dose distributions around the target, might be used to reduce the risk of late side effects while optimising target coverage. The experimental work comprises three studies examining different aspects of the research topic, culminating in the development of a prospective phase II clinical trial. The first study is a survey of late effects and functional outcomes in patients with extremity bone and soft tissue sarcoma treated with 3DCRT. Risk factors for late toxicity in this cohort are identified. The second study is a comparative planning study of 3DCRT versus volumetric modulated arc therapy (VMAT), a rotational IMRT technique, in upper and lower extremity sarcomas. The third study is a comparative double planning study of VMAT and PBT in patients with pelvic Ewing sarcoma. How this work has directly fed into the development and opening of IMRiS, a currently recruiting prospective national phase II clinical trial of IMRT in bone and soft tissue sarcoma, is discussed
