OPTIMISING OUTCOMES IN PATIENTS WITH GLIOBLASTOMA RECEIVING RADIOTHERAPY

Abstract

More than 1,400 new cases of malignant brain tumours are diagnosed each year in Australia. Glioblastoma, or GBM, remains the most common primary brain tumour in adults and the most devastating. The median age at diagnosis is 61 years and the median survival from diagnosis is only approximately 14 months. The aim of the work presented in this thesis is to optimise radiotherapy protocols in patients with glioblastoma to improve patient outcomes by targeting particular time points along the patients’ treatment journey. After describing the disease and epidemiology of GBM in Chapter 1, Chapter 2 explores the evolution of RT technique in treating this disease throughout the ages. In this disease patients >65 years are considered “elderly” and have a poorer prognosis compared with their younger cohorts. They also represent the majority of patients with GBM as the incidence for this tumour peaks in the sixth and seventh decades. There is currently no internationally accepted standard of care for treating this group. Chapter 3 analyses different RT protocols in this cohort of patients. The remaining chapters examine different aspects of the patient’s post-RT journey. Chapter 4 analyses the phenomenon of pseudoprogression (PsP), a radiological diagnosis of an increase in abnormality on post-RT magnetic resonance imaging (MRI) scan which subsequently improves over time with no change in treatment. This phenomenon is poorly understood and the pathological characteristics are explored. Directly expanding from the work on pseudoprogression, Chapter 5 introduces novel volumetric techniques to analyse post-RT MRI changes and explores whether these impact patients’ survival. Chapter 6 deals with the survivorship issue of a patient’s ability to return to work following RT. As patients are living longer with this disease, and a greater proportion are remaining functionally well until late in the course of the disease, more patients are being offered re-irradiation as part of their salvage treatment. Chapter 7 analyses the evolving role of re-irradiation. RT in addition to surgery remains the cornerstone of treatment of GBM. With ongoing improvements in the technical delivery of RT we expect there to be clinical benefit for patients with reduced short-and late toxicity, if not an improvement in survival. This thesis explores different aspects of the patients’ treatment journey on topics that have previously been poorly understood or novel areas of research.