Prospective Evaluation of Health Care Provider and Patient Assessments in Chemotherapy-Induced Peripheral Neurotoxicity

doi:10.1212/WNL.0000000000012300

Observational Study

. 2021 Aug 17;97(7):e660-e672.

doi: 10.1212/WNL.0000000000012300. Epub 2021 Jun 2.

Prospective Evaluation of Health Care Provider and Patient Assessments in Chemotherapy-Induced Peripheral Neurotoxicity

Paola Alberti¹, Davide P Bernasconi¹, David R Cornblath¹, Ingemar S J Merkies¹, Susanna B Park¹, Roser Velasco¹, Jordi Bruna¹, Dimitri Psimaras¹, Susanne Koeppen¹, Andrea Pace¹, Susan G Dorsey¹, Andreas A Argyriou¹, Haralabos P Kalofonos¹, Chiara Briani¹, Angelo Schenone¹, Catharina G Faber¹, Anna Mazzeo¹, Wolfgang Grisold¹, MariaGrazia Valsecchi¹, Guido Cavaletti²; CI-PeriNomS group

Collaborators, Affiliations

Collaborators

CI-PeriNomS group:
Marina Elena Cazzaniga, Raffaella Longarini, Alessandro Guidi, Tjeerd J Postma, David Goldstein, Damien Ricard, Camille Tafani, DuBose Brooks, Cynthia L Renn, Edvina Galiè, Marta Campagnolo, Francesca Castellani, Marina Grandis, Roy I Lalisang, Luca Gentile, Massimo Russo, Antonio Toscano

Affiliations

¹ From Experimental Neurology Unit (P.A., G.C.) and Bicocca Bioinformatics Biostatistics and Bioimaging Centre-B4 (D.P.B., M.G.V.), School of Medicine and Surgery, University of Milano-Bicocca, Monza; NeuroMI (Milan Center for Neuroscience) (P.A., G.C.), Milan, Italy; Johns Hopkins University School of Medicine (D.R.C.), Baltimore, MD; Department of Neurology (I.S.J.M., C.G.F.), Maastricht University Medical Centre, the Netherlands; Department of Neurology (I.S.J.M.), St Elisabeth Hospital, Willemstad, Curaçao; University of New South Wales (S.B.P.), Sydney, Australia; Unit of Neuro-Oncology, Neurology Department (R.V., J.B.), Hospital Universitari de Bellvitge-ICO l'Hospitalet, IDIBELL, L'Hospitalet de Llobregat, Barcelona; Institute of Neurosciences and Department of Cell Biology, Physiology and Immunology (R.V., J.B.), Universitat Autònoma de Barcelona, Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Bellaterra, Spain; Service de Neurologie Mazarin (D.P.), Hôpital de la Pitié-Salpêtrière, Université Paris Sorbonne, Paris, France; Department of Neurology and West German Cancer Center (S.K.), University of Essen, Germany; IRCCS Regina Elena Cancer Institute (A.P.), Neuro-Oncology Unit, Rome, Italy; Department of Pain & Translational Symptom Science (S.G.D.), University of Maryland Baltimore; Neurological Department (A.A.A.), Saint Andrew's General Hospital of Patras; Department of Medicine, Division of Oncology (A.A.A., H.P.K.), Medical School, University of Patras, Greece; Department of Neurosciences (C.B.), University of Padova; Department of Neurosciences, Rehabilitation, Ophthalmology, Genetic and Maternal and Infantile Sciences (DINOGMI) (A.S.), University of Genova; Unit of Neurology and Neuromuscular Diseases (A.M.), Department of Clinical and Experimental Medicine, University of Messina, Italy; and Ludwig Boltzmann Institute for Experimental und Clinical Traumatology (W.G.), Vienna, Austria.
² From Experimental Neurology Unit (P.A., G.C.) and Bicocca Bioinformatics Biostatistics and Bioimaging Centre-B4 (D.P.B., M.G.V.), School of Medicine and Surgery, University of Milano-Bicocca, Monza; NeuroMI (Milan Center for Neuroscience) (P.A., G.C.), Milan, Italy; Johns Hopkins University School of Medicine (D.R.C.), Baltimore, MD; Department of Neurology (I.S.J.M., C.G.F.), Maastricht University Medical Centre, the Netherlands; Department of Neurology (I.S.J.M.), St Elisabeth Hospital, Willemstad, Curaçao; University of New South Wales (S.B.P.), Sydney, Australia; Unit of Neuro-Oncology, Neurology Department (R.V., J.B.), Hospital Universitari de Bellvitge-ICO l'Hospitalet, IDIBELL, L'Hospitalet de Llobregat, Barcelona; Institute of Neurosciences and Department of Cell Biology, Physiology and Immunology (R.V., J.B.), Universitat Autònoma de Barcelona, Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Bellaterra, Spain; Service de Neurologie Mazarin (D.P.), Hôpital de la Pitié-Salpêtrière, Université Paris Sorbonne, Paris, France; Department of Neurology and West German Cancer Center (S.K.), University of Essen, Germany; IRCCS Regina Elena Cancer Institute (A.P.), Neuro-Oncology Unit, Rome, Italy; Department of Pain & Translational Symptom Science (S.G.D.), University of Maryland Baltimore; Neurological Department (A.A.A.), Saint Andrew's General Hospital of Patras; Department of Medicine, Division of Oncology (A.A.A., H.P.K.), Medical School, University of Patras, Greece; Department of Neurosciences (C.B.), University of Padova; Department of Neurosciences, Rehabilitation, Ophthalmology, Genetic and Maternal and Infantile Sciences (DINOGMI) (A.S.), University of Genova; Unit of Neurology and Neuromuscular Diseases (A.M.), Department of Clinical and Experimental Medicine, University of Messina, Italy; and Ludwig Boltzmann Institute for Experimental und Clinical Traumatology (W.G.), Vienna, Austria. [email protected].

PMID: 34078718
PMCID: PMC10365895
DOI: 10.1212/WNL.0000000000012300

Observational Study

Prospective Evaluation of Health Care Provider and Patient Assessments in Chemotherapy-Induced Peripheral Neurotoxicity

Paola Alberti et al. Neurology. 2021.

. 2021 Aug 17;97(7):e660-e672.

doi: 10.1212/WNL.0000000000012300. Epub 2021 Jun 2.

Authors

Collaborators

CI-PeriNomS group:
Marina Elena Cazzaniga, Raffaella Longarini, Alessandro Guidi, Tjeerd J Postma, David Goldstein, Damien Ricard, Camille Tafani, DuBose Brooks, Cynthia L Renn, Edvina Galiè, Marta Campagnolo, Francesca Castellani, Marina Grandis, Roy I Lalisang, Luca Gentile, Massimo Russo, Antonio Toscano

Affiliations

¹ From Experimental Neurology Unit (P.A., G.C.) and Bicocca Bioinformatics Biostatistics and Bioimaging Centre-B4 (D.P.B., M.G.V.), School of Medicine and Surgery, University of Milano-Bicocca, Monza; NeuroMI (Milan Center for Neuroscience) (P.A., G.C.), Milan, Italy; Johns Hopkins University School of Medicine (D.R.C.), Baltimore, MD; Department of Neurology (I.S.J.M., C.G.F.), Maastricht University Medical Centre, the Netherlands; Department of Neurology (I.S.J.M.), St Elisabeth Hospital, Willemstad, Curaçao; University of New South Wales (S.B.P.), Sydney, Australia; Unit of Neuro-Oncology, Neurology Department (R.V., J.B.), Hospital Universitari de Bellvitge-ICO l'Hospitalet, IDIBELL, L'Hospitalet de Llobregat, Barcelona; Institute of Neurosciences and Department of Cell Biology, Physiology and Immunology (R.V., J.B.), Universitat Autònoma de Barcelona, Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Bellaterra, Spain; Service de Neurologie Mazarin (D.P.), Hôpital de la Pitié-Salpêtrière, Université Paris Sorbonne, Paris, France; Department of Neurology and West German Cancer Center (S.K.), University of Essen, Germany; IRCCS Regina Elena Cancer Institute (A.P.), Neuro-Oncology Unit, Rome, Italy; Department of Pain & Translational Symptom Science (S.G.D.), University of Maryland Baltimore; Neurological Department (A.A.A.), Saint Andrew's General Hospital of Patras; Department of Medicine, Division of Oncology (A.A.A., H.P.K.), Medical School, University of Patras, Greece; Department of Neurosciences (C.B.), University of Padova; Department of Neurosciences, Rehabilitation, Ophthalmology, Genetic and Maternal and Infantile Sciences (DINOGMI) (A.S.), University of Genova; Unit of Neurology and Neuromuscular Diseases (A.M.), Department of Clinical and Experimental Medicine, University of Messina, Italy; and Ludwig Boltzmann Institute for Experimental und Clinical Traumatology (W.G.), Vienna, Austria.
² From Experimental Neurology Unit (P.A., G.C.) and Bicocca Bioinformatics Biostatistics and Bioimaging Centre-B4 (D.P.B., M.G.V.), School of Medicine and Surgery, University of Milano-Bicocca, Monza; NeuroMI (Milan Center for Neuroscience) (P.A., G.C.), Milan, Italy; Johns Hopkins University School of Medicine (D.R.C.), Baltimore, MD; Department of Neurology (I.S.J.M., C.G.F.), Maastricht University Medical Centre, the Netherlands; Department of Neurology (I.S.J.M.), St Elisabeth Hospital, Willemstad, Curaçao; University of New South Wales (S.B.P.), Sydney, Australia; Unit of Neuro-Oncology, Neurology Department (R.V., J.B.), Hospital Universitari de Bellvitge-ICO l'Hospitalet, IDIBELL, L'Hospitalet de Llobregat, Barcelona; Institute of Neurosciences and Department of Cell Biology, Physiology and Immunology (R.V., J.B.), Universitat Autònoma de Barcelona, Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Bellaterra, Spain; Service de Neurologie Mazarin (D.P.), Hôpital de la Pitié-Salpêtrière, Université Paris Sorbonne, Paris, France; Department of Neurology and West German Cancer Center (S.K.), University of Essen, Germany; IRCCS Regina Elena Cancer Institute (A.P.), Neuro-Oncology Unit, Rome, Italy; Department of Pain & Translational Symptom Science (S.G.D.), University of Maryland Baltimore; Neurological Department (A.A.A.), Saint Andrew's General Hospital of Patras; Department of Medicine, Division of Oncology (A.A.A., H.P.K.), Medical School, University of Patras, Greece; Department of Neurosciences (C.B.), University of Padova; Department of Neurosciences, Rehabilitation, Ophthalmology, Genetic and Maternal and Infantile Sciences (DINOGMI) (A.S.), University of Genova; Unit of Neurology and Neuromuscular Diseases (A.M.), Department of Clinical and Experimental Medicine, University of Messina, Italy; and Ludwig Boltzmann Institute for Experimental und Clinical Traumatology (W.G.), Vienna, Austria. [email protected].

PMID: 34078718
PMCID: PMC10365895
DOI: 10.1212/WNL.0000000000012300

Abstract

Background and objective: There is no agreement on the gold standard for detection and grading of chemotherapy-induced peripheral neurotoxicity (CIPN) in clinical trials. The objective is to perform an observational prospective study to assess and compare patient-based and physician-based methods for detection and grading of CIPN.

Methods: Consecutive patients, aged 18 years or older, candidates for neurotoxic chemotherapy, were enrolled in the United States, European Union, or Australia. A trained investigator performed physician-based scales (Total Neuropathy Score-clinical [TNSc], used to calculate Total Neuropathy Score-nurse [TNSn]) and supervised the patient-completed questionnaire (Functional Assessment of Cancer Treatment/Gynecologic Oncology Group-Neurotoxicity [FACT/GOG-NTX]). Evaluations were performed before and at the end of chemotherapy. On participants without neuropathy at baseline, we assessed the association between TNSc, TNSn, and FACT/GOG-NTX. Considering a previously established minimal clinically important difference (MCID) for FACT/GOG-NTX, we identified participants with and without a clinically important deterioration according to this scale. Then, we calculated the MCID for TNSc and TNSn as the difference in the mean change score of these scales between the 2 groups.

Results: Data from 254 participants were available: 180 (71%) had normal neurologic status at baseline. At the end of the study, 88% of participants developed any grade of neuropathy. TNSc, TNSn, and FACT/GOG-NTX showed good responsiveness (standardized mean change from baseline to end of chemotherapy >1 for all scales). On the 153 participants without neuropathy at baseline and treated with a known neurotoxic chemotherapy regimen, we verified a moderate correlation in both TNSc and TNSn scores with FACT/GOG-NTX (Spearman correlation index r = 0.6). On the same sample, considering as clinically important a change in the FACT/GOG-NTX score of at least 3.3 points, the MCID was 3.7 for TNSc and 2.8 for the TNSn.

Conclusions: MCID for TNSc and TNSn were calculated and the TNSn can be considered a reliable alternative objective clinical assessment if a more extended neurologic examination is not possible. The FACT/GOG-NTX score can be reduced to 7 items and these items correlate well with the TNSc and TNSn.

Classification of evidence: This study provides Class III evidence that a patient-completed questionnaire and nurse-assessed scale correlate with a physician-assessed scale.

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Conflict of interest statement

The authors report no disclosures relevant to the manuscript. Go to Neurology.org/N for full disclosures.

Figures

**Figure 1. Comparison Between Total Neuropathy Score, Clinical Version (TNSc) and Total Neuropathy Score, Nurse-Assessed Version (TNSn) at T1**
The radius of the bubbles is proportional to the absolute frequency. Spearman correlation index = 88.7%.

Figure 2. Distribution of Deteriorated Functional Assessment of Cancer Treatment/Gynecologic Oncology Group–Neurotoxicity (FACT/GOG-NTX) Items by Total Neuropathy Score, Clinical Version (TNSc) Category
(A) Overall. (B) Patients treated with taxanes. (C) Patients treated with platinum drugs. (D) Patients treated with taxanes + platinum drugs. For all groups, the Kruskal-Wallis test p value was <0.001.

Figure 3. Distribution of Deteriorated Functional Assessment of Cancer Treatment/Gynecologic Oncology Group–Neurotoxicity (FACT/GOG-NTX) Items by Total Neuropathy Score, Nurse-Assessed Version (TNSn) Category
(A) Overall. (B) Patients treated with taxanes. (C) Patients treated with platinum drugs. (D) Patients treated with taxanes + platinum drugs. For all groups, the Kruskal-Wallis test p value was ≤0.001.

See this image and copyright information in PMC

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References

1. Staff NP, Grisold A, Grisold W, Windebank AJ. Chemotherapy-induced peripheral neuropathy: a current review. Ann Neurol. 2017;81(6):772-781. - PMC - PubMed
1. Shah A, Hoffman EM, Mauermann ML, et al. . Incidence and disease burden of chemotherapy-induced peripheral neuropathy in a population-based cohort. J Neurol Neurosurg Psychiatry. 2018;89(6):636-641. - PMC - PubMed
1. Cavaletti G, Marmiroli P. Chemotherapy-induced peripheral neurotoxicity. Curr Opin Neurol. 2015;28(5):500-507. - PubMed
1. Cavaletti G, Alberti P, Argyriou AA, et al. . Chemotherapy-induced peripheral neurotoxicity: a multifaceted, still unsolved issue. J Peripher Nerv Syst. 2019;24(suppl 2):S6-S12. - PubMed
1. Briani C, Argyriou AA, Izquierdo C, et al. . Long-term course of oxaliplatin-induced polyneuropathy: a prospective 2-year follow-up study. J Peripher Nerv Syst. 2014;19(4):299-306. - PubMed

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[1] Staff NP, Grisold A, Grisold W, Windebank AJ. Chemotherapy-induced peripheral neuropathy: a current review. Ann Neurol. 2017;81(6):772-781. - PMC - PubMed

[2] Staff NP, Grisold A, Grisold W, Windebank AJ. Chemotherapy-induced peripheral neuropathy: a current review. Ann Neurol. 2017;81(6):772-781. - PMC - PubMed

[3] Shah A, Hoffman EM, Mauermann ML, et al. . Incidence and disease burden of chemotherapy-induced peripheral neuropathy in a population-based cohort. J Neurol Neurosurg Psychiatry. 2018;89(6):636-641. - PMC - PubMed

[4] Shah A, Hoffman EM, Mauermann ML, et al. . Incidence and disease burden of chemotherapy-induced peripheral neuropathy in a population-based cohort. J Neurol Neurosurg Psychiatry. 2018;89(6):636-641. - PMC - PubMed

[5] Cavaletti G, Marmiroli P. Chemotherapy-induced peripheral neurotoxicity. Curr Opin Neurol. 2015;28(5):500-507. - PubMed

[6] Cavaletti G, Marmiroli P. Chemotherapy-induced peripheral neurotoxicity. Curr Opin Neurol. 2015;28(5):500-507. - PubMed

[7] Cavaletti G, Alberti P, Argyriou AA, et al. . Chemotherapy-induced peripheral neurotoxicity: a multifaceted, still unsolved issue. J Peripher Nerv Syst. 2019;24(suppl 2):S6-S12. - PubMed

[8] Cavaletti G, Alberti P, Argyriou AA, et al. . Chemotherapy-induced peripheral neurotoxicity: a multifaceted, still unsolved issue. J Peripher Nerv Syst. 2019;24(suppl 2):S6-S12. - PubMed

[9] Briani C, Argyriou AA, Izquierdo C, et al. . Long-term course of oxaliplatin-induced polyneuropathy: a prospective 2-year follow-up study. J Peripher Nerv Syst. 2014;19(4):299-306. - PubMed

[10] Briani C, Argyriou AA, Izquierdo C, et al. . Long-term course of oxaliplatin-induced polyneuropathy: a prospective 2-year follow-up study. J Peripher Nerv Syst. 2014;19(4):299-306. - PubMed

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Prospective Evaluation of Health Care Provider and Patient Assessments in Chemotherapy-Induced Peripheral Neurotoxicity

Collaborators

Affiliations

Prospective Evaluation of Health Care Provider and Patient Assessments in Chemotherapy-Induced Peripheral Neurotoxicity

Authors

Collaborators

Affiliations

Abstract

Conflict of interest statement

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