Surgery (RMH) - Theses
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ItemBiomarkers of tumour vascularity in high grade glioma( 2016)Australia has one of the highest cancer incidences in the world, and while brain cancer is a relatively rare diagnosis, its impact on the Australian healthcare system is significant. Despite being responsible for only 1.4% of all cancer diagnoses, brain cancer has an overall impact of disease as measured by DALYs similar to much more prevalent malignancies such as melanoma and leukaemia. A young median age of diagnosis and poor 5-year survival both contribute to this. No other cancer group is responsible for a greater premature loss of life, with an average of 12 years lost per person. High grade gliomas, particularly glioblastoma multiforme, are by far the most common brain cancers, and remains incurable and highly malignant. Glioblastoma multiforme is one of the most vascular cancers found in humans, and the degree of this vascularity (as seen histologically) is known to correlate with brain tumour prognosis. More recently there has been renewed interest in tumour vascularity, with the emergence of the anti-angiogenic therapy as the newest modality of cancer treatment. Some of these agents are currently under trial in brain cancer patients in Australia. Despite its prognostic value and its potential utility perhaps as a surrogate endpoint in anti-angiogenic therapy, histopathological assessment of tumour vascularity has never been routinely used in clinical practice. This is due to its invasive nature of procurement, as well as documented concerns regarding sampling errors and inter-observer variability. These concerns would be potentially negated by the identification of appropriate biomarker of tumour vascularity. This thesis investigated candidate biomarkers of tumour vascularity in an effort to identify clinically useful tools to help in the management of high grade glioma patients. Biomarkers from each marker category were represented – molecular (serum vascular endothelial growth factor), cellular (circulating endothelial cells and their progenitors), and functional (perfusion magnetic resonance imaging).