{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T01:14:21Z","timestamp":1792545261234,"version":"4.5.0"},"reference-count":46,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2023,8,23]],"date-time":"2023-08-23T00:00:00Z","timestamp":1692748800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Eli Lilly and Company"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Chemotherapy-induced peripheral neuropathy (CIPN) is one of the most common and disabling dose-limiting toxicities of chemotherapy. We report here the results of two separate non-interventional studies (49 patients), which evaluated blood neurofilament light chain (NfL) as a biomarker of CIPN in breast cancer patients treated with paclitaxel. All patients underwent a standard treatment protocol that was established independently of the present studies. NfL was measured in serum using an ultrasensitive single-molecule array and compared with the self-administered European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-CIPN twenty-item scale (CIPN20) and Total Neuropathy Score clinical version (TNSc), a clinician-reported measure of neuropathy progression. The TNSc increased with cumulative dose compared with baseline, and the NfL concentrations were also strongly associated with the cumulative dose of chemotherapy. The analysis showed a correlation between TNSc and NfL. Both TNSc and NfL showed weak to moderate associations with CIPN20 subscores, with a better association for the CIPN20 sensory compared with motor and autonomic subscores. Data from the two studies provide evidence that serum NfL has the potential to be used as a biomarker to monitor and mitigate CIPN. However, studies with additional patients planned in the ongoing clinical trial will determine the universal application of NfL as a biomarker in CIPN.<\/jats:p>","DOI":"10.3390\/cancers15174216","type":"journal-article","created":{"date-parts":[[2023,8,23]],"date-time":"2023-08-23T08:01:21Z","timestamp":1692777681000},"page":"4216","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["Studies to Assess the Utility of Serum Neurofilament Light Chain as a Biomarker in Chemotherapy-Induced Peripheral Neuropathy"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4128-2406","authenticated-orcid":false,"given":"Guido","family":"Cavaletti","sequence":"first","affiliation":[{"name":"Experimental Neurology Unit, School of Medicine and Surgery, University of Milano-Bicocca, 20900 Monza, Italy"},{"name":"Fondazione IRCCS San Gerardo dei Tintori, 20900 Monza, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5519-0313","authenticated-orcid":false,"given":"Chiara","family":"Pizzamiglio","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine, University of Piemonte Orientale, 28100 Novara, Italy"},{"name":"Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, The National Hospital for Neurology and Neurosurgery, London WC1N 3BG, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Albert","family":"Man","sequence":"additional","affiliation":[{"name":"Eli Lilly and Company, Indianapolis, IN 46285, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6528-7303","authenticated-orcid":false,"given":"Thomas M.","family":"Engber","sequence":"additional","affiliation":[{"name":"Eli Lilly and Company, Indianapolis, IN 46285, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6862-9468","authenticated-orcid":false,"given":"Cristoforo","family":"Comi","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine, University of Piemonte Orientale, 28100 Novara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darren","family":"Wilbraham","sequence":"additional","affiliation":[{"name":"Eli Lilly and Company, Indianapolis, IN 46285, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,8,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1007\/s10549-016-3939-0","article-title":"Long-term chemotherapy-induced peripheral neuropathy among breast cancer survivors: Prevalence, risk factors, and fall risk","volume":"159","author":"Bao","year":"2016","journal-title":"Breast Cancer Res. Treat."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"86","DOI":"10.3389\/fphar.2017.00086","article-title":"Long-term effects, pathophysiological mechanisms, and risk factors of chemotherapy-induced peripheral neuropathies: A comprehensive literature review","volume":"8","author":"Kerckhove","year":"2017","journal-title":"Front. Pharmacol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1016\/j.ygyno.2015.11.011","article-title":"Chemotherapy-induced peripheral neuropathy: Current status and progress","volume":"140","author":"Brewer","year":"2016","journal-title":"Gynecol. Oncol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1186\/2193-1801-3-366","article-title":"Chemotherapy dose reduction due to chemotherapy induced peripheral neuropathy in breast cancer patients receiving chemotherapy in the neoadjuvant or adjuvant settings: A single-center experience","volume":"3","author":"Bhatnagar","year":"2014","journal-title":"Springerplus"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1016\/j.clbc.2018.02.003","article-title":"Chemotherapy dose intensity and overall survival among patients with advanced breast or ovarian cancer","volume":"18","author":"Denduluri","year":"2018","journal-title":"Clin. Breast Cancer"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1007\/s00277-008-0447-2","article-title":"Association of reduced relative dose intensity and survival in lymphoma patients receiving CHOP-21 chemotherapy","volume":"87","author":"Pettengell","year":"2008","journal-title":"Ann. Hematol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2289","DOI":"10.1002\/cncr.31248","article-title":"Beyond symptomatic relief for chemotherapy-induced peripheral neuropathy: Targeting the source","volume":"124","author":"Ma","year":"2018","journal-title":"Cancer"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2461","DOI":"10.1016\/j.pain.2014.09.020","article-title":"Incidence, prevalence, and predictors of chemotherapy-induced peripheral neuropathy: A systematic review and meta-analysis","volume":"155","author":"Seretny","year":"2014","journal-title":"Pain"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1634\/theoncologist.2009-S505","article-title":"Types and epidemiology of cancer-related neuropathic pain: The intersection of cancer pain and neuropathic pain","volume":"15","author":"Lema","year":"2010","journal-title":"Oncologist"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"636","DOI":"10.1136\/jnnp-2017-317215","article-title":"Incidence and disease burden of chemotherapy-induced peripheral neuropathy in a population-based cohort","volume":"89","author":"Shah","year":"2018","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"iv45","DOI":"10.1093\/neuonc\/nos203","article-title":"Peripheral neuropathies from chemotherapeutics and targeted agents: Diagnosis, treatment, and prevention","volume":"14","author":"Grisold","year":"2012","journal-title":"Neuro Oncol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1097\/WCO.0000000000000234","article-title":"Chemotherapy-induced peripheral neurotoxicity","volume":"28","author":"Cavaletti","year":"2015","journal-title":"Curr. Opin. Neurol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1111\/j.1529-8027.2007.00141.x","article-title":"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","volume":"12","author":"Cavaletti","year":"2007","journal-title":"J. Peripher. Nerv. Syst."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1111\/j.1085-9489.2006.00078.x","article-title":"Multi-center assessment of the total neuropathy score for chemotherapy-induced peripheral neurotoxicity","volume":"11","author":"Cavaletti","year":"2006","journal-title":"J. Peripher. Nerv. Syst."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1135","DOI":"10.1016\/j.ejca.2005.02.012","article-title":"The development of an EORTC quality of life questionnaire to assess chemotherapy-induced peripheral neuropathy: The QLQ-CIPN20","volume":"41","author":"Postma","year":"2005","journal-title":"Eur. J. Cancer"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1032","DOI":"10.1016\/j.jpain.2015.07.002","article-title":"Measuring therapy-induced peripheral neuropathy: Preliminary development and validation of the treatment-induced neuropathy assessment scale","volume":"16","author":"Mendoza","year":"2015","journal-title":"J. Pain"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1021","DOI":"10.1007\/s00520-018-4391-y","article-title":"Concept domain validation and item generation for the treatment-induced neuropathy assessment scale (TNAS)","volume":"27","author":"Williams","year":"2019","journal-title":"Support. Care Cancer"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Zaj\u0105czkowska, R., Kocot-K\u0119pska, M., Leppert, W., Wrzosek, A., Mika, J., and Wordliczek, J. (2019). Mechanisms of chemotherapy-induced peripheral neuropathy. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20061451"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"e59","DOI":"10.1212\/WNL.0000000000009559","article-title":"Validation of serum neurofilaments as prognostic and potential pharmacodynamic biomarkers for ALS","volume":"95","author":"Benatar","year":"2020","journal-title":"Neurology"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1002\/ana.24954","article-title":"Serum neurofilament light: A biomarker of neuronal damage in multiple sclerosis","volume":"81","author":"Disanto","year":"2017","journal-title":"Ann. Neurol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.parkreldis.2021.04.016","article-title":"Plasma NfL, clinical subtypes and motor progression in Parkinson\u2019s disease","volume":"87","author":"Pilotto","year":"2021","journal-title":"Park. Relat. Disord."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"e610","DOI":"10.1212\/WNL.0000000000009983","article-title":"Neurofilament light as a biomarker in traumatic brain injury","volume":"95","author":"Shahim","year":"2020","journal-title":"Neurology"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"7995","DOI":"10.1038\/s41598-020-64511-5","article-title":"Serum neurofilament light chain levels as a biomarker of neuroaxonal injury and severity of oxaliplatin-induced peripheral neuropathy","volume":"10","author":"Kim","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"e54395","DOI":"10.1172\/jci.insight.154395","article-title":"Neurofilament proteins as a potential biomarker in chemotherapy-induced polyneuropathy","volume":"7","author":"Huehnchen","year":"2022","journal-title":"JCI Insight"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.neucli.2019.12.001","article-title":"Nerve conduction, circulating osteopontin and taxane-induced neuropathy in breast cancer patients","volume":"50","author":"Pizzamiglio","year":"2020","journal-title":"Neurophysiol. Clin."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"456","DOI":"10.3389\/fpsyg.2017.00456","article-title":"Repeated measures correlation","volume":"8","author":"Bakdash","year":"2017","journal-title":"Front. Psychol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1136\/bmj.310.6977.446","article-title":"Calculating correlation coefficients with repeated observations: Part 1\u2013correlation within subjects","volume":"310","author":"Bland","year":"1995","journal-title":"BMJ"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2247","DOI":"10.1212\/WNL.0000000000001642","article-title":"Neurofilament light chain: A prognostic biomarker in amyotrophic lateral sclerosis","volume":"84","author":"Lu","year":"2015","journal-title":"Neurology"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"e1007","DOI":"10.1212\/WNL.0000000000007032","article-title":"Blood neurofilament light chain as a biomarker of MS disease activity and treatment response","volume":"92","author":"Kuhle","year":"2019","journal-title":"Neurology"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1080\/14656566.2017.1415326","article-title":"Pharmacotherapy options for managing chemotherapy-induced peripheral neurotoxicity","volume":"19","author":"Cavaletti","year":"2018","journal-title":"Expert Opin. Pharmacother."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"981","DOI":"10.1080\/03007995.2017.1284051","article-title":"Chemotherapy-induced peripheral neuropathy: Limitations in current prophylactic strategies and directions for future research","volume":"33","author":"Cascella","year":"2017","journal-title":"Curr. Med. Res. Opin."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"806","DOI":"10.1002\/ana.22169","article-title":"Evidence for acute neurotoxicity after chemotherapy","volume":"68","author":"Petzold","year":"2010","journal-title":"Ann. Neurol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1212\/WNL.0000000000004272","article-title":"Chemotherapy-induced peripheral neuropathy clinical trials: Review and recommendations","volume":"89","author":"Gewandter","year":"2017","journal-title":"Neurology"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/j.expneurol.2018.06.005","article-title":"Neurofilament light chain as disease biomarker in a rodent model of chemotherapy induced peripheral neuropathy","volume":"307","author":"Meregalli","year":"2018","journal-title":"Exp. Neurol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1083\/jcb.143.1.171","article-title":"Neurofilament-dependent radial growth of motor axons and axonal organization of neurofilaments does not require the neurofilament heavy subunit (NF-H) or its phosphorylation","volume":"143","author":"Rao","year":"1998","journal-title":"J. Cell Biol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"14114","DOI":"10.1038\/s41598-017-14179-1","article-title":"Neurofilament light protein in CSF and blood is associated with neurodegeneration and disease severity in Huntington\u2019s disease R6\/2 mice","volume":"7","author":"Sandelius","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"870","DOI":"10.1136\/jnnp-2018-320106","article-title":"Neurofilament light chain as a biomarker in neurological disorders","volume":"90","author":"Gaetani","year":"2019","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1002\/ana.22247","article-title":"Axonal damage in relapsing multiple sclerosis is markedly reduced by natalizumab","volume":"69","author":"Gunnarsson","year":"2011","journal-title":"Ann. Neurol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2013","DOI":"10.1046\/j.1471-4159.1996.67052013.x","article-title":"Patients with amyotrophic lateral sclerosis and other neurodegenerative diseases have increased levels of neurofilament protein in CSF","volume":"67","author":"Rosengren","year":"1996","journal-title":"J. Neurochem."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1038\/s41582-018-0058-z","article-title":"Neurofilaments as biomarkers in neurological disorders","volume":"14","author":"Khalil","year":"2018","journal-title":"Nat. Rev. Neurol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1111\/jns.12493","article-title":"Prospectively assessing serum neurofilament light chain levels as a biomarker of paclitaxel-induced peripheral neurotoxicity in breast cancer patients","volume":"27","author":"Karteri","year":"2022","journal-title":"J. Peripher. Nerv. Syst."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1093\/annonc\/mds329","article-title":"The chemotherapy-induced peripheral neuropathy outcome measures standardization study: From consensus to the first validity and reliability findings","volume":"24","author":"Cavaletti","year":"2013","journal-title":"Ann. Oncol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1007\/s00520-011-1141-9","article-title":"The relationship between numbness, tingling, and shooting\/burning pain in patients with chemotherapy-induced peripheral neuropathy (CIPN) as measured by the EORTC QLQ-CIPN20 instrument, N06CA","volume":"20","author":"Wolf","year":"2012","journal-title":"Support. Care Cancer"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2787","DOI":"10.1007\/s11136-013-0379-8","article-title":"Assessing patient-reported peripheral neuropathy: The reliability and validity of the European Organization for Research and Treatment of Cancer QLQ-CIPN20 Questionnaire","volume":"22","author":"Barton","year":"2013","journal-title":"Qual. Life Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"15593","DOI":"10.1038\/s41598-022-18716-5","article-title":"Neurofilament light as a predictive biomarker of unresolved chemotherapy-induced peripheral neuropathy in subjects receiving paclitaxel and carboplatin","volume":"12","author":"Burgess","year":"2022","journal-title":"Sci. Rep."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"e2248593","DOI":"10.1001\/jamanetworkopen.2022.48593","article-title":"Types and concentrations of blood-based biomarkers in adults with peripheral neuropathies: A systematic review and meta-analysis","volume":"5","author":"Fundaun","year":"2022","journal-title":"JAMA Netw. 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