Translational health data science for improving population-level survival of people with glioblastoma
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Date
23/11/2022Item status
Restricted AccessEmbargo end date
23/11/2023Author
Poon, Michael Tin Chung
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Abstract
Glioblastoma is the most common malignant primary brain tumour with poor survival of
under one year. The current standard of care treatment offers modest survival benefits, and
treatment options for patients with glioblastoma have not changed since 2005. Incomplete
understanding of glioblastoma tumour biology presents challenges in drug development for
glioblastoma, but inefficiencies resulting from suboptimal methodology may also contribute
to the lack of effective treatment. Systematic evaluation of translational studies and
analyses of population-based data can optimise research strategy to improve survival for
all patients with glioblastoma. This thesis aims to apply epidemiological and health data
science approaches to glioblastoma research data for improving translational research and
population-level survival.
The first chapter of the thesis discusses epidemiological and clinical aspects of
glioblastoma in the context of all brain tumours and outlines the challenges and opportunities
for research. Chapter 2 defines the problem by summarising the longer-term (≥2 years)
survival of people diagnosed with glioblastoma in a systematic review and meta-analysis
of 63 population-based cohort studies. The next chapter (Chapter 3) examines how
changes in diagnostic practice can affect brain tumour incidences and how this may explain
population-level survival described in the previous chapter. The following two chapters
(Chapters 4 and 5) are systematic reviews that evaluated reporting standards, consistencies
and analytic approaches of preclinical glioblastoma studies to identify methodological
limitations precluding clinical translation. Chapter 6 is a cohort study of 414 consecutive patients with glioblastoma in Southeast Scotland that investigated how well clinical trial
findings apply to real-world clinical cohorts concerning the modification of treatment effect of
chemotherapy by a molecular marker. Chapter 7 presents a matched cohort study comparing
the risks of cardiovascular events between brain tumour patients and the general population
in Wales. The final chapter summarises the findings presented in this thesis and discusses
their implications for future research.
The programme of work in this thesis emphasises the need for transparency and
consistency in translational glioblastoma research, and it demonstrates the value of routine
healthcare data to understand population-level survival for people with glioblastoma.