Chemotherapy-Induced Peripheral Neuropathy: Assessment, Phenotypes and Risk Factors

This thesis examined treatment specific chemotherapy-induced peripheral neuropathy (CIPN) profiles and explored patient characteristics which may contribute to CIPN severity utilising multimodal CIPN assessment in taxane and oxaliplatin treated patients. Initially, bilateral neuropathy assessments including clinical examination, neurophysiology and patient questionnaires revealed discrepancies between the patient experience and objective CIPN following taxane treatment. Further electrophysiological assessments revealed features more typical of entrapment neuropathy present in >50% of taxane-treated patients. These studies provided evidence for the variability in the clinical presentation of CIPN, highlighting discrepancies between the clinical definition, objective assessment, and patient experience and emphasising the need for a multimodal approach. Studies were undertaken in in a homogenously treated cohort of paclitaxel treated patients to elucidate the phenotypic profile and longitudinal development of CIPN and assess the role of dose modification on neuropathy outcomes. Neuropathy was evident early in the treatment course and demonstrated limited recovery, identifying CIPN as a persistent neurological sequela. When evaluating the role of dose modification, patients who received dose reduction had worse patient and clinical neuropathy outcomes compared to those who received the full dose three months post-treatment, suggesting that individual risk factors likely play an important role in addition to cumulative dose. A systematic review of the literature surrounding metabolic risk factors and their association with CIPN was undertaken and identified potential patient characteristics which are prevalent in the general population, including obesity and metabolic dysfunction. Finally, the role of obesity on symptomatic, objective, and functional CIPN outcome measures was investigated, with overweight cancer survivors demonstrating significantly worse CIPN across symptomatic, objective clinical and functional outcomes compared to those with a normal body mass index (BMI). This study also identified older age, larger waist circumference and larger body surface area (BSA) as predictors of CIPN severity. In summary, this thesis has demonstrated variability in clinical presentation of taxane-induced neuropathy, provided a comprehensive understanding of the clinical manifestations and outcomes of weekly paclitaxel-induced neuropathy, highlighted the variation in response to dose modification on neuropathy outcomes and identified potential risk factors which are prevalent in the general population. The findings established in this thesis will assist in the development of appropriate assessment tools allowing for the identification of early CIPN and neuroprotective strategies. Additionally, understanding CIPN risk profiles and treatment specific neuropathy phenotypes will also assist with treatment decisions, and identification of patients who require intervention and supportive care, enabling personalised medicine and subsequently improving clinical outcomes for cancer survivors