Translational health data science for improving population-level survival of people with glioblastoma

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.