Hall, Helen Katherine; (2023) Analysis of screen-detected lung cancers’ genomic traits (ASCENT): Risk stratification and implications for clinical management. Doctoral thesis (Ph.D), UCL (University College London).

Text Helen Hall_PhD thesis_student id 19184695_final_clean.pdf - Submitted Version Access restricted to UCL open access staff until 1 February 2025. Download (16MB)

Abstract

Lung cancer screening using low dose computed tomography scanning has been shown to reduce mortality in individuals at high risk for lung cancer (Aberle et al., 2011; de Koning et al., 2020), by identifying disease at an early stage where treatments can be delivered with curative intent. However, early-stage lung cancers represent a heterogeneous spectrum of disease in terms of aggressiveness and prognostic potential (Grimes et al., 2017). Cancers detected at different timepoints during screening differ in terms of survival despite controlling for stage (Schabath et al., 2016), and may harbour molecular differences to those detected clinically (Verri et al., 2017). At present, a detailed understanding of these differences and a line of sight to clinical utility are lacking. This thesis describes the set up and delivery of the ASCENT study, an observational prospective cohort study of individuals undergoing surgical resection for lung cancer following participation in lung cancer screening. Chapter 3 presents data supporting the hypothesis that the prognostic significance of these lesions may be best identified through their radiological characteristics, with growth rate demonstrated as an independent predictor of histological aggressiveness versus indolence. However, exome sequencing data reported in chapter 4 point towards a more complex picture, with both histologically indolent lesions identified as harbouring a similar degree of genomic alteration to more aggressive lesions, and instances of surprisingly little alteration occurring in cancers with high-risk pathological features. In chapter 5, the above findings are reviewed alongside the real-world clinical management of this cohort, through which risk factors for upstaging are identified, and recommendations made regarding the role of lymph node dissection and testing for therapeutically targetable biomarkers. Finally, the future direction of the study is described, including work in progress towards delivery of a multi-platform approach to molecular characterisation of this cohort.

Download activity - last month

Export as CSVJSONXML

Download activity - last 12 months

Export as XMLJSONCSV

Downloads by country - last 12 months

Export as JSONCSVXML

Archive Staff Only

View Item