Identifying Risk Factors, Phenotypes and Outcome Measures for Chemotherapy-Induced Peripheral Neuropathy with a Focus on the Treatment of Haematological Malignancies

Abstract

This thesis evaluated the various approaches to assessing chemotherapy-induced peripheral neuropathy (CIPN) to identify the optimal outcome measure and further provided guidelines on how to maximise translation.

A systematic review was conducted in Chapter 3 to identify which CIPN patient reported outcome measures (PROMs) possessed the most optimal measurement properties. This study identified 13 CIPN PROMs that have been evaluated in the literature.

Chapter 4 provided interpretation guidelines for CIPN PROMs by establishing minimally important difference thresholds. A longitudinal study was conducted to evaluate changes in PROM scores which denote development of minimally important CIPN.

Chapter 5 compared the validity and responsiveness of nine CIPN assessment methods to determine which should be considered the ‘standardised’ assessment approach. PROMs were the only measures that demonstrated acceptable criteria of convergent validity, known-groups validity and responsiveness.

Chapter 6 investigated clinical risk factors associated with developing chronic, severe and dose-limiting CIPN. This adopted a comprehensive battery of multi-modal CIPN assessments including PROM, clinical, neurological and neurophysiological CIPN outcome measures.

Chapter 7 provided a natural history analysis of adults treated with vincristine. Longitudinal and cross-sectional studies were undertaken to phenotype the signs and symptoms of vincristine-induced peripheral neuropathy (VIPN).

Chapter 8 undertook a study investigating VIPN in the paediatric haematological malignancy cohort. Threshold nerve excitability studies were serially completed in children treated with vincristine, coupled with clinically graded neuropathy and quality of life assessment.

This thesis presents a body of work evaluating the optimal measures of CIPN, and demonstrates how the adoption of these outcome measures can improve methodology and validity of results in CIPN risk factor and natural history studies.