Abstract
Background: Glioblastoma (GBM) is the commonest primary malignant brain tumour in adults. Incidence increases with age and prognosis is poor. Clinical trials have established modest survival benefits in older patients from single and combined chemo-radiotherapy treatment regimes however those recruited into the clinical trials do not well represent this heterogeneous population. A comprehensive evaluation of the clinical and radiological basis by which treatment decisions are made is lacking in the UK population.Aims: To explore pre-treatment characteristics in older GBM patients that could predict for overall survival. To test the feasibility of implementing a geriatric assessment (GA) for older GBM patients. To investigate pre-treatment imaging parameters that predict radiation induced toxicity in older patients with GBM.
Methods: The chapters of this thesis cover: (1) a comprehensive literature review, (2) a multicentre retrospective cohort study, (3) a population based cross-sectional survey of neuro oncology consultants in the UK, (4) a multicentre prospective feasibility trial implementing a GA within outpatient neuro-oncology clinics; and (5) a prospective pilot study exploring the predictive value of MRI imaging parameters in this population, leading to a multicentre, prospective cohort imaging study.
Results: There is a paucity of evidence surrounding the use of GA tools within the neuro oncology population and most currently practicing UK neuro oncology consultants do not routinely use any cognitive or geriatric assessment tools. Pre-treatment clinical and radiological features exist which independently predict for overall survival. The use of a neurologically focussed GA tool was feasible and acceptable to both staff and patients within busy NHS outpatient clinics and the results of this GA were associated with overall survival. Pilot data suggests that Global Cortical Atrophy and Medial Temporal Lobe atrophy scores from pre-treatment MRI scans can predict the likelihood of experiencing CTCAE Grade 3 or 4 acute side effects from cranial radiotherapy.
Conclusion: Older patients with GBM represent a vulnerable and under-researched cohort. A neurologically focussed GA could be used to help predict which patients are more likely to benefit from active treatment, enabling clinicians to have more informed and individualised treatment discussions with patients. Further work is needed to validate which sections of the neurologically focussed GA are predictive amongst a larger group and whether GBM patient specific interventions can be implemented to improve outcomes. Imaging biomarkers from pre-treatment MRI scans may help predict which patients are more likely to suffer from radiotherapy induced side effects.
| Date of Award | May 2019 |
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| Original language | English |
| Awarding Institution |
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| Supervisor | Dr Juliet Brock (Supervisor), Frank Saran (Supervisor), Tim Chevassut (Supervisor) & Anthony Chalmers (Supervisor) |