Patient-reported (EORTC QLQ-CIPN20) versus physician-reported (CTCAE) quantification of oxaliplatin- and paclitaxel/carboplatin-induced peripheral neuropathy in NCCTG/Alliance clinical trials

Jennifer Le-Rademacher, Rahul Kanwar, Drew Seisler, Deirdre R Pachman, Rui Qin, Alexej Abyzov, Kathryn J Ruddy, Michaela S Banck, Ellen M Lavoie Smith, Susan G Dorsey, Neil K Aaronson, Jeff Sloan, Charles L Loprinzi, Andreas S Beutler, Jennifer Le-Rademacher, Rahul Kanwar, Drew Seisler, Deirdre R Pachman, Rui Qin, Alexej Abyzov, Kathryn J Ruddy, Michaela S Banck, Ellen M Lavoie Smith, Susan G Dorsey, Neil K Aaronson, Jeff Sloan, Charles L Loprinzi, Andreas S Beutler

Abstract

Purpose: 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.

Methods: 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).

Results: 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.

Conclusions: 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.

Keywords: CTCAE; EORTC QLQ-CIPN20; Patient-reported outcome; Peripheral neuropathy; Physician-reported outcome.

Conflict of interest statement

Conflicts of Interest: The authors report no conflicts of interest.

Figures

Figure 1
Figure 1
Box and whisker plot of CIPN20 scores by CTCAE grade for all occurrences and first occurrence in patients treated with oxaliplatin (N08CB). Whiskers show the 5th and 95th percentile of scores. (A) Sum1 – 19 score. (B) Sensory subscale.
Figure 1
Figure 1
Box and whisker plot of CIPN20 scores by CTCAE grade for all occurrences and first occurrence in patients treated with oxaliplatin (N08CB). Whiskers show the 5th and 95th percentile of scores. (A) Sum1 – 19 score. (B) Sensory subscale.
Figure 2
Figure 2
Mean and mean ± SEM of CIPN20 scores by CTCAE grade in patients treated with oxaliplatin (N08CB). (A) The CIPN20 sum1-19 for all occurrences. (B) The CIPN20 sum1-19 at the first occurrence. (C) The CIPN20 sum1-19 for each CTCAE grade at the first and subsequent occurrences (mean)showing a time dependent trend for grade 1. The time dependent trend observed within grade 1 was significant as discussed in the main text.
Figure 3
Figure 3
Box and whisker plot of CIPN20 scores for all occurrences and first occurrence in patients treated with paclitaxel/carboplatin (N08CA). Whiskers show the 5th and 95th percentile of scores. (A) Sum1 – 19 score. (B) Sensory subscale.
Figure 3
Figure 3
Box and whisker plot of CIPN20 scores for all occurrences and first occurrence in patients treated with paclitaxel/carboplatin (N08CA). Whiskers show the 5th and 95th percentile of scores. (A) Sum1 – 19 score. (B) Sensory subscale.
Figure 4
Figure 4
Mean and mean ± SEM of CIPN20 scores by CTCAE grade in patients treated with oxaliplatin (N08CA). (A) The CIPN20 sum1-19 for all occurrences. (B) The CIPN20 sum1-19 at the first occurrence. (C) The CIPN20 sum1-19 for each CTCAE grade at the first and subsequent occurrences (mean)showing a time dependent trend for grade 1.
Figure 5
Figure 5
CIPN20 sub-scales. The mean subscale scores were computed for each first occurrence of a CTCAE grade per patient. (A) N08CB (oxaliplatin). (B) N08CA (paclitaxel/carboplatin).
Figure 5
Figure 5
CIPN20 sub-scales. The mean subscale scores were computed for each first occurrence of a CTCAE grade per patient. (A) N08CB (oxaliplatin). (B) N08CA (paclitaxel/carboplatin).

Source: PubMed

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