Title:
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Investigation of the radiobiological and dosimetric implications of respiratory motion in advanced radiotherapy
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The primary aim of radiotherapy is to deliver sufficient dose to eradicate a tumour whilst
sparing normal tissue. This balance in tumour control probability (TCP) and normal tissue
complication probability (NTCP) can be influenced by a number of factors, one of which is
respiratory motion. This thesis investigates the potential dosimetric and radiobiological
differences as a result of respiratory motion in lung cancer radiotherapy. It demonstrates
significant dosimetric improvements by using advanced motion management techniques
(4DCT and respiratory gating) and modulated radiotherapy (VMAT), in regi~ns of lung
tumour motion. These techniques confer improvements in NTCP and can allow for dose
escalation. However, when patient characteristics and tumour characteristics are included
in clinical modelling algorithms, the potential gain may not be as clinically relevant as
anticipated. Many advanced techniques currently used in radiotherapy departments, have
been implemented without a clear understanding of potential differences in radiobiological
response compared with previous techniques. This thesis demonstrates significant
differences in the radiation induced bystander effect (RISE), in the presence of respiratory
motion and modulated radiotherapy. In vitro studies of respiratory gating indicate a trend
towards increased survival as treatment delivery time increases. There is an increased
dependence on the use of these radiotherapy techniques which introduce complex spatiotemporal
dose modulation. The data presented in this thesis indicates that radiobiological
consequences may not be fully explained by existing theories. These findings may be of
particular relevance for modulated radiotherapy in NSCLC radiotherapy.
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