M Piatti

The chemotherapy-induced peripheral neuropathy outcome measures standardization study: from consensus to the first validity and reliability findings

BACKGROUND Chemotherapy-induced peripheral neuropathy (CIPN) is a debilitating and dose-limiting complication of cancer treatment. Thus far, the impact of CIPN has not been studied in a systematic clinimetric manner. The objective of the study was to select outcome measures for CIPN evaluation and to establish their validity and reproducibility in a cross-sectional multicenter study. PATIENTS AND METHODS After literature review and a consensus meeting among experts, face/content validity were obtained for the following selected scales: the National Cancer Institute-Common Toxicity Criteria (NCI-CTC), the Total Neuropathy Score clinical version (TNSc), the modified Inflammatory Neuropathy Cause and Treatment (INCAT) group sensory sumscore (mISS), the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30, and CIPN20 quality-of-life measures. A total of 281 patients with stable CIPN were examined. Validity (correlation) and reliability studies were carried out. RESULTS Good inter-/intra-observer scores were obtained for the TNSc, mISS, and NCI-CTC sensory/motor subscales. Test-retest values were also good for the EORTC QLQ-C30 and CIPN20. Acceptable validity scores were obtained through the correlation among the measures. CONCLUSION Good validity and reliability scores were demonstrated for the set of selected impairment and quality-of-life outcome measures in CIPN. Future studies are planned to investigate the responsiveness aspects of these measures.BACKGROUND Chemotherapy-induced peripheral neuropathy (CIPN) is a debilitating and dose-limiting complication of cancer treatment. Thus far, the impact of CIPN has not been studied in a systematic clinimetric manner. The objective of the study was to select outcome measures for CIPN evaluation and to establish their validity and reproducibility in a cross-sectional multicenter study. PATIENTS AND METHODS After literature review and a consensus meeting among experts, face/content validity were obtained for the following selected scales: the National Cancer Institute-Common Toxicity Criteria (NCI-CTC), the Total Neuropathy Score clinical version (TNSc), the modified Inflammatory Neuropathy Cause and Treatment (INCAT) group sensory sumscore (mISS), the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30, and CIPN20 quality-of-life measures. A total of 281 patients with stable CIPN were examined. Validity (correlation) and reliability studies were carried out. RESULTS Good inter-/intra-observer scores were obtained for the TNSc, mISS, and NCI-CTC sensory/motor subscales. Test-retest values were also good for the EORTC QLQ-C30 and CIPN20. Acceptable validity scores were obtained through the correlation among the measures. CONCLUSION Good validity and reliability scores were demonstrated for the set of selected impairment and quality-of-life outcome measures in CIPN. Future studies are planned to investigate the responsiveness aspects of these measures.

The Total Neuropathy Score as an assessment tool for grading the course of chemotherapy-induced peripheral neurotoxicity: comparison with the National Cancer Institute-Common Toxicity Scale

Abstract  Chemotherapy‐induced peripheral neurotoxicity (CIPN) is a major side effect of several antineoplastic drugs. However, despite its clinical importance, there is no agreement as to the best way to assess the severity and changes in CIPN. We have previously demonstrated a correlation between the severity of CIPN, assessed using the Total Neuropathy Score (TNS) or its reduced versions, and several common toxicity scales. In this study, we investigated two series of patients (total number = 173) who were evaluated at baseline and during chemotherapy with the TNS (n= 122) or the TNSc (the TNS version based exclusively on the clinical evaluation of the patients, n= 51) and with the National Cancer Institute‐Common Toxicity Criteria (NCI‐CTC) 2.0, with the aim of comparing the sensitivity to the changes in CIPN severity. In both series, the TNS and the TNSc had a significant correlation with the NCI‐CTC in scoring the severity of CIPN, confirming the results of previous studies. Moreover, both the TNS and the TNSc showed a higher sensitivity to CIPN changes. We, therefore, propose the TNSc as a reliable method for assessing not only the severity but also the changes in CIPN.

Grading of chemotherapy-induced peripheral neurotoxicity using the Total Neuropathy Scale

The authors compared clinically based neurotoxicity scales with the Total Neuropathy Scale, with the aim of improving the grading of the severity of chemotherapy-induced peripheral neuropathy (CIPN). The severity of CIPN was evaluated in a series of 60 women treated with cisplatin- and paclitaxel-based chemotherapy. A reduced version of TNS (TNSr) was also compared. The authors concluded that the TNS and TNSr can be used to assess the severity of CIPN effectively, and the results of this evaluation can be reliably correlated with the oncologic grading of sensory peripheral neurotoxicity.

Thalidomide sensory neurotoxicity: A clinical and neurophysiologic study

The clinical and neurophysiologic data from 65 patients taking thalidomide were reviewed. Thalidomide sensory neurotoxicity was found to be cumulative dose dependent but occurs only when the total dose is relatively high (>20 g). The risk of developing sensory neuropathy is around 10% below this threshold but increases with higher doses.

Chemotherapy-Induced Neuropathy

Opinion StatementChemotherapy-induced peripheral neurotoxicity (CIPN) is one of the most severe and unpredictable side effects of modern anticancer treatment. In recent years, a clear understanding of the importance of an integrated approach to CIPN has become evident, and efforts are increasing to better characterize its features and to identify more accurate methods to report and grade its occurrence. The clinically relevant impact of CIPN on cancer patients has been known for a long time, but knowledge of its pathogenetic aspects is still very limited. This incomplete knowledge is one of the major limitations in identifying targets for evidence-based neuroprotective strategies. Nevertheless, several studies have been devoted to the prevention or at least the effective treatment of symptoms secondary to peripheral nerve damage and to the early identification of patients at high risk of developing severe CIPN. Unfortunately, none of these studies has been successful and the optimal management of CIPN patients is still an unmet clinical need. Therefore, the modification of chemotherapy is currently the only available approach to limit the severity of neuropathy in the vast majority of patients. The indications for treatment modification are not universally accepted and they can differ among the various drugs. Generally, treatment modification should be considered as soon as symptoms and signs impair the daily life activities of the patient, but the possibility of a delayed worsening of CIPN after treatment withdrawal (“coasting”) should always be considered, and delay of modification decisions should be avoided.

Total neuropathy scale items as early predictors of chemotherapy-induced peripheral neurotoxicity

We investigated the possible use of individual Total Neuropathy Scale (TNS) items to predict the neurological outcome in patients undergoing cisplatin and paclitaxel combination chemotherapy in a series of thirty‐four women divided, according to the worst TNS score reached during the period of observation, into three groups, i.e. with a score <5 (n = 14), >5 but <10 (n = 5) or >10 (n = 15). At the visit performed before the onset of the worst neuropathy signs, 14 out of the 15 patients with the worst TNS had a change of 2 or more points in the sum of the semiquantitative vibration score (tuning fork) plus the DTR examination. In 12 of them the change was due to both vibration perception and DTR impairment. A change in the combined score was observed also in 7 out of the 14 patients with the better neurological outcome, but none of them had any change in the vibration perception. Early disappearance of DTR in the lower limbs (i.e. both ankle and patellar reflexes bilaterally) was observed in 7 out of the 15 patients with a worst outcome, while only 1 patient in the better outcome group had this clinical sign. The results of the VDT score obtained with a vibrameter did not improve the accuracy of the neurological assessment. Our study indicates that the accurate clinical evaluation of the patients treated with platinum and taxane combination polychemotherapy can be used to predict the final neurological outcome of the treatment.

THalidomide sensory neurotoxicity: results of a collaborative clinical and neurophysiolgical study

Despite long‐lasting use, several features of thalidomide neurotoxicity have yet to be resolved. A more detailed knowledge of thalidomide‐induced sensory neurotoxicity is desirable, particularly in view of the future use of thalidomide derivatives which are currently under investigation. Our study demonstrates that thalidomide sensory neurotoxicity is cumulative dose‐dependent, but this effect is evident only when the dose is relatively high (in our study >20 g). In fact, the risk of developing sensory neuropathy is low (around 10%) below this threshold, while it steadily increases with increasing cumulative doses. In our series, a discrepancy between clinical and neurophysiological results was frequent when a low cumulative dose of thalidomide was administered. Regarding the need for thalidomide withdrawal at the onset of any evidence of peripheral neuropathy, we followed up the course of seven patients who were clinically and neurophysiologically normal at baseline, but had treatment‐induced neurotoxicity and a very severe change in their SAPs. In all these cases the thalidomide dose was reduced and no clinically‐relevant worsening was observed despite a further marked reduction in their SAPs. This finding suggests that thalidomide withdrawal is not mandatory even in the presence of marked abnormalities in sensory neurophysiological parameters, provided that an accurate clinical follow‐up is guaranteed and the dose is adjusted.