Are we mis-estimating chemotherapy-induced peripheral neuropathy? Analysis of assessment methodologies from a prospective, multinational, longitudinal cohort study of patients receiving neurotoxic chemotherapy

Abstract

BackgroundThere are inconsistencies in the literature regarding the prevalence and assessment of chemotherapy-induced peripheral neuropathy (CIPN). This study explored CIPN natural history and its characteristics in patients receiving taxane- and platinum-based chemotherapy.Patients and methodsMulti-country multisite prospective longitudinal observational study. Patients were assessed before commencing and three weekly during chemotherapy for up to six cycles, and at 6,9, and 12 months using clinician-based scales (NCI-CTCAE; WHO-CIPN criterion), objective assessments (cotton wool test;10 g monofilament); patient-reported outcome measures (FACT/GOG-Ntx; EORTC-CIPN20), and Nerve Conduction Studies.ResultsIn total, 343 patients were recruited in the cohort, providing 2399 observations. There was wide variation in CIPN prevalence rates using different assessments (14.2–53.4%). Prevalence of sensory neuropathy (and associated symptom profile) was also different in each type of chemotherapy, with paclitaxel (up to 63%) and oxaliplatin (up to 71.4%) showing the highest CIPN rates in most assessments and a more complex symptom profile. Peak prevalence was around the 6-month assessment (up to 71.4%). Motor neurotoxicity was common, particularly in the docetaxel subgroup (up to 22.1%; detected by NCI-CTCAE). There were relatively moderately-to-low correlations between scales (rs = 0.15,p < 0.05-rs = 0.48 p < 0.001), suggesting that they measure different neurotoxicity aspects from each other. Cumulative chemotherapy dose was not associated with onset and course of CIPN.ConclusionThe historical variation reported in CIPN incidence and prevalence is possibly confounded by disagreement between assessment modalities. Clinical practice should consider assessment of motor neuropathy for neurotoxic chemotherapy. Current scales may not be all appropriate to measure CIPN in a valid way, and a combination of scales are needed.

Safety and tolerability of cryocompression as a method of enhanced limb hypothermia to reduce taxane-induced peripheral neuropathy

“…It is important to note, however, that the NCS findings were exploratory in nature and not intended as a primary objective of the study. Moreover, NCS may not be the most reliable method of measuring CIPN [18]. We postulate that the enhanced cooling is a major factor for the vasoconstriction-driven neuroprotection.…”

Risk factors for chemotherapy‐induced peripheral neuropathy in patients receiving taxane‐ and platinum‐based chemotherapy

“…Also, clinician‐based assessments, such as the NCI‐CTCAE tend to underestimate CIPN incidence (Dorsey et al, ). We have explained these reasons in more detail in the parent larger study (Molassiotis et al, ). However, in a systematic review it was shown that CIPN incidence at 6 months was 30% (Seretny et al, ) and our incidence in the combined tools was 26%.…”

“…This analysis used data from the 6‐month CIPN assessment after starting chemotherapy from a larger prospective observational study on CIPN prevalence and quality of life (Molassiotis et al, ), focusing on one of the primary objectives of the study.…”

Overview and critical revision of clinical assessment tools in chemotherapy‐induced peripheral neurotoxicity

“…The majority of these tools were PROs (41.5% of identified tools), underscoring the increasing importance of patient‐based assessment of symptoms to provide a complete appraisal. Importantly, there is significant evidence that the prevalence of CIPN is greater with PROs than with clinician‐based measures and PRO assessments identify earlier functional impairment than clinician‐based tools . In total, there has been a lack of patient involvement in the development of tools across different types of peripheral neuropathy, a feature which may impact the ability of assessment tools to qualify for inclusion as an outcome measure by the FDA and other regulatory bodies.…”