Dose reductions, toxicities and survival in patients with excess weight undergoing adjuvant chemotherapy for colon and rectal cancers: individual patient data secondary analyses of consortium trials and causal inference modelling

Abstract

Introduction: Elevated body mass index (BMI) may be associated with reduced survival in non-metastatic colorectal cancer (CRC). Whether this occurs directly, or indirectly through treatment-related mechanisms such as capping of adjuvant chemotherapy (ACT) doses and toxicity, is unclear. This thesis aimed to disentangle the effects of BMI, ACT adherence and toxicity on survival using individual participant data (IPD), causal mediation, and meta-analysis. Methods: Data from four randomised clinical ACT trials (MOSAIC, SCOT, CHRONICLE and PROCTOR-SCRIPT [five datasets - SCOT arms analysed individually]), with derivable BMI (at trial enrolment) cycle-level dosing and toxicity data were utilised from the OCTOPUS consortium. Dose capping was defined as

Date of Award	31 Dec 2022
Original language	English
Awarding Institution	The University of Manchester
Supervisor	Andrew Renehan (Supervisor), Jorge Barriuso (Supervisor) & Hui Guo (Supervisor)