Peripheral Neuropathy in Cancer Patients- Multifactorial Contributors to Dose Limiting and Chronic Toxicity

Abstract Background and Objective Chemotherapy-induced peripheral neuropathy (CIPN) is a complex and dose-limiting toxicity of anticancer treatments with chronic symptoms leading to increased disability and reduced quality of life. The present study evaluated clinical risk factors associated with development of chronic, severe and dose-limiting CIPN, utilising a comprehensive multi-modal battery of neuropathy assessment. Methods Baseline clinical risk factors were investigated in patients who had completed neurotoxic chemotherapy (including taxanes, platinums and haematological cancer therapies). CIPN was assessed using neurological evaluation (Total Neuropathy Score, sural nerve conduction studies), patient reported outcome measure (EORTC QLQ-CIPN20), and clinically graded neuropathy (NCI-CTCAE). Multivariate models of risk factors associated with development of chronic, severe and dose-limiting CIPN were evaluated using backwards stepwise regression model building. Results The study recruited 903 patients (age 61 (IQR 50-69) years) who were assessed 12 (IQR 6-24) months post neurotoxic treatment. 73% of patients presented with CIPN at time of assessment, with 37% having moderate to severe symptoms. 32% of patients experienced neurotoxic treatment dose modification due to CIPN. Across the various CIPN assessment approaches, risk factors for chronic CIPN included older age, diabetes diagnosis, higher BMI and prior exposure to neurotoxic treatment (all P<0.05). Risk factors for severe CIPN included older age, higher BMI, prior neurotoxic treatment and female sex (all P<0.05), whereas risk factors for dose-limiting CIPN included older age and female sex (all P<0.05). Discussion This study identified baseline clinical risk factors associated chronic, severe and dose-limiting CIPN. Closer monitoring of these vulnerable cohorts will allow for timely CIPN management, including referral pathways to intervention and rehabilitation therapies which will ultimately lead to improved CIPN morbidity.