Gains, JE; (2015) Improving the outcomes for high-­risk neuroblastoma through the optimisation of radiotherapeutic techniques. Doctoral thesis , UCL (University College London).

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Abstract

Neuroblastoma is a childhood cancer with highly variable clinical behaviour and outcomes. The long-­‐term survival rate for high-­‐risk neuroblastoma remains poor and new therapeutic advances and optimisation of existing therapies is therefore required. Both external beam radiotherapy and molecular radiotherapy have a significant role to play in the multi-­‐modality treatment of high-­‐risk disease. This collection of work examines ways in which the outcome for neuroblastoma may be improved through the introduction of new and enhancement of existing radiotherapeutic techniques. 131I-­‐meta-­‐Iodobenzylguanidine molecular radiotherapy has been used in the treatment of neuroblastoma since the mid 1980’s. Despite this, its role and efficacy remain undefined. A systematic review of 131I-­‐mIBG therapy in neuroblastoma is therefore presented. Radiolabelled somatostatin analogues target a distinct and separate molecular target on neuroblastoma cells to the noradrenaline transporter targeted by 131I-­‐mIBG. This study reports on the use of radiolabelled somatostatin analogues for the imaging and therapy of patients with high-­‐risk neuroblastoma. The expression of the two different molecular targets by immunohistochemistry for the noradrenaline transporter molecule and somatostatin receptor type-­‐2 in archived neuroblastoma tumour samples is also explored. The radiation doses received by comforters and carers providing necessary support to children undergoing molecular radiotherapy over a 10 year period is presented. The gold standard imaging modality for response assessment in neuroblastoma is 123I-­‐mIBG scinitgraphy. The role of other functional imaging techniques such as 18F-­‐ FDG PET/CT remains undefined. This study will look to see if 18F-­‐FDG PET/CT can give additional information with regards to response assessment. External beam radiotherapy is standardly delivered using conventional anterior and posterior parallel opposed beams and this can result in a compromise on target volume coverage to stay within the tolerance of normal tissues. The use of an Intensity Modulated Arc Therapy technique to improve target volume coverage is examined.

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