Patient-reported (EORTC QLQ-CIPN20) versus physician-reported (CTCAE) quantification of oxaliplatin- and paclitaxel/carboplatin-induced peripheral neuropathy in NCCTG/Alliance clinical trials
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Clinical practice guidelines on chemotherapy-induced peripheral neuropathy (CIPN) use the NCI Common Terminology Criteria for Adverse Events (CTCAE), while recent clinical trials employ a potentially superior measure, the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-CIPN twenty-item scale (QLQ-CIPN20), a patient-reported outcome (PRO). Practitioners and researchers lack guidance, regarding how QLQ-CIPN20 results relate to the traditional CTCAE during the serial assessment of patients undergoing chemotherapy.
Two large CIPN clinical trial datasets (538 patients) pairing QLQ-CIPN20 and CTCAE outcomes were analyzed using a multivariable linear mixed model with QLQ-CIPN20 score as the outcome variable, CTCAE grade as the main effect, and patient as random effect (accounting for internal correlation of serial measures).
The association between QLQ-CIPN20 scores and CTCAE grades was strong (p < 0.0001), whereby patients with higher CTCAE grade had worse QLQ-CIPN20 scores. Some variation of QLQ-CIPN20 scores was observed based on drug, treatment, and cycle. While there was a marked difference in the mean QLQ-CIPN20 scores between CTCAE grades, the ranges of QLQ-CIPN20 scores within each CTCAE grade were large, leading to large overlap in CIPN20 scores across CTCAE grades.
A strong positive association of QLQ-CIPN20 scores and CTCAE grade provides evidence of convergent validity as well as practical guidance, as to how to quantitatively interpret QLQ-CIPN20 scores at the study level in terms of the traditional CTCAE. The present results also highlight an important clinical caveat, specifically, that conversion of a specific QLQ-CIPN20 score to a specific CTCAE score may not be reliable at the level of an individual patient.
KeywordsPeripheral neuropathy CTCAE EORTC QLQ-CIPN20 Patient-reported outcome Physician-reported outcome
The authors wish to thank Dr. Cynthia Lynch from the Mayo Clinic for the accrual contribution to NCCTG N08CA and Dr. Nassim Nabbout from the Wichita NCI Community Oncology Research Program for the accrual contribution to NCCTG N08CB.
Compliance with ethical standards
Research reported in this publication was supported by the National Cancer Institute of the National Institutes of Health under the Award Number UG1CA189823 (to the Alliance for Clinical Trials in Oncology NCORP Grant) and U10CA180790 and by the National Institute of Nursing Research (NINR) of the National Institutes of Health (NIH) under Award Number R01NR015259 (to A.S.B.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
Conflict of interest
The authors declare that they have no conflicts of interest.
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