Abstract
Background/Aim: Chemotherapy-induced peripheral neuropathy (CIPN) is a common and disabling side-effect of various chemotherapeutic agents. This scoping review aimed to systematically map the existing literature on diagnostic methods used to identify, assess, and monitor CIPN. The review was guided by the research question: “What diagnostic methods have been used in the literature to identify, assess, or monitor chemotherapy-induced peripheral neuropathy in adult cancer patients?”
Materials and Methods: We searched PubMed, Web of Science, Scopus, and the Cochrane Library from 2000 to 2024. Studies were included if they evaluated diagnostic methods for CIPN such as clinical assessments, patient-reported outcomes, biomarkers, neurophysiological tests, or digital tools. Data were extracted and narratively synthesized by diagnostic method type. The methodological quality of each included study was assessed using the Joanna Briggs Institute Critical Appraisal Tools.
Results: Twenty-nine studies met the inclusion criteria. The most frequently used tools were patient-reported questionnaires, notably the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire – Chemotherapy-Induced Peripheral Neuropathy 20 (EORTC QLQ-CIPN20) and the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE). Biomarkers such as neurofilament light chain and microRNAs, neurophysiological tests including nerve conduction studies, diffusion tensor imaging, functional magnetic resonance imaging, as well as digital technologies, such as mobile applications and wearable sensors, were also employed. Studies showed considerable heterogeneity in design, population, timing of assessments, and tool validation.
Conclusion: Despite growing interest in multimodal approaches that integrate subjective and objective tools, a lack of standardization and validation limits the clinical applicability of many diagnostic methods. There is an urgent need to develop and validate reliable, reproducible, and feasible tools for the diagnosis and monitoring of CIPN in routine practice.
Introduction
Chemotherapy-induced peripheral neuropathy (CIPN) is a common side-effect associated with various classes of antineoplastic agents, including platinum compounds, taxanes, vinca alkaloids, and proteasome inhibitors. Significantly, a systematic review of 31 studies (N=4,179) reported a CIPN prevalence of 68.1% at 1 month post-chemotherapy, 60% at 3 months, and 30% at 6 months or later (1). These findings are corroborated by recent 2025 data. For instance, in their study on chronic CIPN, Rahman et al. reported comparable prevalence rates of 68%, 60%, and 30% at 3 months, 6 months, and beyond, respectively (2). Similarly, a global overview found the prevalence to be 70% in the first month and 60% at 3 months (3).
Clinically, CIPN manifests predominantly as sensory, motor, and autonomic disturbances, potentially associated with painful dysesthesia. These symptoms interfere with patients’ quality of life and can lead to dose reduction or therapy discontinuation (4).
Different chemotherapeutic agents can induce neuropathy through distinct mechanisms. The neurotoxic mechanism of platinum compounds involves DNA damage within the dorsal root ganglia. Taxanes and vinca alkaloids interfere with microtubule organization, affecting axonal transport. The proteasome inhibitor bortezomib induces damage at both mitochondrial and microtubule levels and thalidomide can cause CIPN through angiogenic mechanisms (5-7).
Given this complex and heterogeneous pathophysiology and clinical expression, CIPN management remains particularly challenging due to the lack of standardized diagnostic and prognostic methods, applicable across all forms of the disease. In this scenario, clinical evaluation and the use of questionnaires for addressing the patient’s subjective experience and the impact of symptoms on quality of life are recommended (8). Nevertheless, although the 4-grade neuropathy subscale of the National Cancer Institute’s Common Terminology Criteria for Adverse Events (NCI-CTCAE) is a widely used method, it has been criticized for its low inter-rater reliability and limited sensitivity to detect changes over time (9). Different alternatives have been suggested. These methods address functional impairment, neurological and clinical examinations – Total Neuropathy Score – and patient-reported outcome measures, such as the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire – Chemotherapy-Induced Peripheral Neuropathy 20 (EORTC QLQ-CIPN20). Moreover, biomarkers and neuroimaging techniques have been also investigated (10).
This scoping review was conducted to systematically map the existing literature on the diagnostic methods used to assess CIPN, to identify the types of diagnostic tools employed, and to highlight gaps in current knowledge.
The review was guided by the following research question: “What diagnostic methods have been used in the literature to identify, assess, or monitor chemotherapy-induced peripheral neuropathy in adult cancer patients?”
The review was conceptualized using the Population–Concept–Context framework:
Population: Adult patients undergoing chemotherapy.
Concept: Diagnostic methods and tools used for CIPN (e.g. clinical assessments, patient-reported outcomes, biomarkers, neurophysiological tests, digital tools)
Context: All clinical or research settings, regardless of cancer type or treatment phase
Materials and Methods
Protocol and registration. The protocol was drafted using the Preferred Reporting Items for Systematic Reviews and Meta-analysis Protocols (11). It was prospectively registered with the Open Science Framework on April 4, 2025 (12).
Eligibility criteria. To be included in the review, articles needed to address diagnostic methods used in CIPN. Specifically, studies had to include instruments or methods for diagnosing, assessing, or measuring CIPN such as clinical scales, self-report questionnaires, biomarkers, and neurophysiological tests.
Eligible articles were those published in peer-reviewed journals, written in English, and addressing clinical investigations.
Studies were excluded if they did not explicitly focus on CIPN, solely discussed chemotherapy side-effects unrelated to peripheral neuropathy, or did not provide detailed information on diagnostic methods. Pediatric population studies and those exclusively addressing neuropathies caused by factors other than chemotherapy were also excluded.
Information sources and search strategy. To identify potentially relevant documents, the following bibliographic databases were searched from 2000 to March 2024: PubMed, Web of Science, Scopus, and Cochrane Library. The search strategies were drafted by an experienced researcher (M.C.) and further refined through team discussion. The search was conducted in March 2024 and tailored to the syntax and structure of each database. The objective was to retrieve studies focusing on the diagnostic methods used in CIPN, including various approaches such as clinical assessment tools, patient-reported outcomes, biomarkers, neurophysio-logical tests, and digital innovations. The search terms combined both Medical Subject Headings and free-text key words (e.g., “diagnosis”, “diagnos*”, “chemotherapy-induced peripheral neuropathy”, “CIPN”) to ensure sensitivity and comprehensiveness. Boolean operators and truncation symbols were applied as appropriate in each platform (Table I). No filters for language, study design, or publication type were applied at this stage to maintain broad inclusivity. The final search results were exported into Zotero (Corporation for Digital Scholarship, Vienna, VA, USA), and duplicates were removed by a library assistant using Zotero’s built-in duplicate detection tool.
Search string strategies used for PubMed, Web of Science, Scopus and Cochrane Library databases.
The electronic database search was supplemented by scanning the reference lists of relevant reviews and included articles.
Selection of sources of evidence. To increase consistency among reviewers, two reviewers (V.C. and D.E.) screened the same initial sample of 30 publications, discussed the results, and amended the screening and data extraction form before beginning full screening for this review. The form included specific criteria regarding the population (adult patients receiving chemotherapy), the focus on diagnostic methods for CIPN, and publication characteristics (language, date range, study type).
Data charting process. A data charting form was jointly developed by two reviewers (D.E. and M.M.) to determine which variables to extract from the included sources of evidence. Items selected for charting included: Author(s), year of publication, country, study design, population characteristics, diagnostic methods used for CIPN, tools or instruments adopted, and key findings related to diagnosis.
The form was created and managed using Microsoft Excel (Microsoft Corporation, Redmond, WA, USA). Before full data extraction, both reviewers independently tested the charting form on a sample of five included articles to ensure clarity and consistency. Based on this calibration exercise, minor revisions were made, such as refining the definitions of diagnostic tools and specifying how to document combined methods, to enhance reliability and completeness. This process was iterative, and updates to the charting form were applied consistently throughout the review.
Any inconsistencies in the extracted data were discussed and resolved by consensus. When consensus was not reached, a third reviewer was consulted (M.C.). If clarification was needed on study data, attempts were made to contact the original study authors to confirm or obtain missing information.
Data items. We charted data on general study characteristics (e.g., author, year of publication, country, study design), population characteristics (e.g., sample size, patient demographics, cancer type, treatment regimen), and details related to diagnostic methods for CIPN. Specifically, we extracted information on:
i) Type of diagnostic method (e.g., clinical assessment, patient-reported outcomes, biomarkers, neurophysiological tests).
ii) Name and description of the diagnostic tool or instrument.
iii) Timing of the assessment (e.g., during, post-treatment).
iv) Mode of administration (e.g., clinician-administered, self-reported).
v) Outcomes measured and main diagnostic findings.
vi) Any reported strengths, limitations, or validation of the method.
vii) Some items required interpretation, such as categorizing diagnostic tools by type (e.g., objective vs. subjective measures) and identifying the diagnostic aim (e.g., screening, monitoring, confirmation). These were discussed and resolved between reviewers to ensure consistency.
Critical appraisal of individual sources of evidence. In line with an expanded methodological approach, we included a critical appraisal of the included studies to provide additional context on the rigor and quality of the available evidence regarding diagnostic methods for CIPN. Although not required by the scoping review methodology, this step was conducted to strengthen the interpretation of findings and identify potential limitations in the evidence base.
The methodological quality of each included study was assessed using the Joanna Briggs Institute (JBI) Critical Appraisal Tools, selected according to the study design (e.g., cross-sectional studies, diagnostic test accuracy studies, qualitative research) (13). Each checklist consists of a structured set of questions evaluating aspects such as the appropriateness of the study design, reliability of measurements, clarity in reporting, and risk of bias. Additionally, the appraisal involved evaluating multiple quality criteria, including clarity of population selection, validity and reliability of outcome measurement, control of confounding factors, completeness of follow-up, and appropriateness of statistical analysis. Each item was rated as “Yes”, “No”, “Unclear”, or “Not Applicable”. Each criterion was rated as “Yes”, “No”, “Unclear”, or “Not Applicable (N/A)”. Methodological quality was assessed by calculating the percentage of “Yes” responses, providing an overall score for each study. For cross-sectional studies, we assessed the clarity of sample inclusion criteria, detailed description of study subjects and setting, valid and reliable measurement of exposure and outcomes, appropriate statistical analysis, adequate statistical methods description, and accounting for confounders. In diagnostic accuracy studies, the appraisal included clarity of the target condition definition, representativeness of participants, independent interpretation of both the diagnostic test and reference standard, appropriate interval between tests, consistent application of the reference standard, completeness of participant analysis, and appropriate statistical methods. For cohort studies, we evaluated the similarity of comparison groups, valid and consistent exposure measurement, identification and management of confounders, absence of the outcome at study initiation, valid and reliable outcome measurement, and adequacy of follow-up duration.
Two reviewers (S.B. and A.C.) independently appraised each study. Discrepancies were resolved through discussion and, when necessary, with input from a third reviewer (M.C.). The results of the appraisal were not used as criteria for exclusion but were reported descriptively and considered in the synthesis to contextualize the robustness of the evidence.
To visually summarize the appraisal results, the JBI items were conceptually grouped into five overarching domains: (i) Inclusion criteria and population description, (ii) measurement of exposure and outcome, (iii) identification and management of confounding variables, (iv) follow-up completeness and adequacy, and (v) appropriateness of statistical analysis and study design. Based on these domains, we generated a traffic light plot and weighted bar plot using the robvis web tool (14), to provide a visual representation of methodological quality across studies.
Synthesis of results. We synthesized the included sources of evidence using a descriptive and narrative approach aligned with the objectives of the scoping review.
The results of the included studies were synthesized narratively and structured according to the types of diagnostic methods identified. Studies were grouped into key categories: Clinical assessment tools, patient-reported outcome measures, biomarkers, neurophysiological tests, and digital technologies (e.g., wearable sensors, smartphone-based tools).
Within each category, the methods were compared in terms of clinical use, timing, validity, and sensitivity for detecting CIPN.
Results
Selection of sources of evidence. The selection process followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews guidelines (15) and is illustrated in a flow diagram (see Figure 1). A total of 1,550 papers were retrieved. After removing duplicates (n=350), and record screening, 20 articles were assessed for eligibility. Reasons for exclusion were documented at the full-text screening stage and are detailed in the flow diagram. The most common reasons for exclusion included lack of focus on CIPN, absence of diagnostic method description, or use of non-chemotherapy-related neuropathy as the primary outcome. The literature search identified 11 additional articles, but three were excluded. Finally, we collected a total of 28 articles. These studies were then assessed in full text and included in the final synthesis (16-43).
Preferred Reporting Items for Systematic Reviews and Meta-Analyses (11) flow diagram. CIPN: Chemotherapy-induced peripheral neuropathy. *Records excluded during title and abstract screening.
Characteristics of source evidence. The characteristics of the included studies are summarized in Table II. Studies were conducted across various countries and settings, reflecting a broad spectrum of clinical and research environments. The findings varied across studies: Some studies focused on clinical scales (e.g., NCI-CTCAE, EORTC QLQ-CIPN20) (16-20, 24, 28, 29, 32, 35, 37, 39-41); others investigated molecular biomarkers such as neurofilament light chain (NfL), microRNAs (miRNAs), and genetic polymorphisms (16-20, 34, 35, 41); or focused on imaging techniques such as in-vivo corneal confocal microscopy, functional magnetic resonance imaging (fMRI), diffusion tensor imaging (DTI), and nerve conduction studies (NCS) (21-23, 25-27, 20, 33-43). Additionally, several studies assessed both subjective (patient-reported) and objective (clinician- or instrument-based) measures (21, 24, 32, 33, 37, 41). Therefore, the results underscore considerable heterogeneity in terms of diagnostic tools, assessment timing, and reporting practices.
Characteristics of the included studies on chemotherapy-induced peripheral neurotoxicity (CIPN).
Critical appraisal within sources of evidence. The results of the appraisal are summarized in Table III. A graphical summary of the domain-level methodological appraisal is presented in Figure 2.
Results of the critical appraisal of included studies on chemotherapy-induced peripheral neurotoxicity (CIPN) using Joanna Briggs Institute (JBI) tools.
Summary of critical appraisal by domain across the included studies (n=28) using Joanna Briggs Institute (JBI) tools. Risk of bias summary plot generated with robvis tool (12). Each row represents a domain from the JBI checklists, and each horizontal bar shows the proportion of included studies (n=28) judged at each level of risk of bias for that domain. Domains were: 1: inclusion criteria and population description; 2: measurement of exposure and outcome; 3: identification and management of confounding variables; 4: follow-up completeness and adequacy; and 5: appropriateness of statistical analysis and study design. Color codes indicate the risk of bias for each item: green = low, yellow = unclear, red = high, dark red = critical and blue = not reported (no information). The ‘Overall’ row summarizes the cumulative judgment for each study. The heatmap was generated using the robvis tool, based on the JBI checklist ratings for each included study.
Table IV summarizes the main diagnostic categories identified in the included studies, the tools most used within each category, and relevant observations. Among the results, we found that patient-reported measures such as the EORTC QLQ-CIPN20 were widely used and demonstrated strong consistency across studies, while objective tools such as nerve conduction studies and neurofilament light chain levels provided more specific, albeit less commonly adopted, metrics.
Synthesis of results.
The synthesis also revealed heterogeneity in study designs, sample sizes, and diagnostic protocols, which limits direct comparability. However, patterns emerged suggesting that multi-modal approaches combining subjective and objective tools may enhance diagnostic accuracy. Gaps in the literature were noted in validation, especially for novel biomarkers and digital tools.
Discussion
Although different systematic reviews have previously addressed the topic of CIPN (44, 45), considering the clinical relevance of this side-effect, there was a need for an updated review focused on diagnosis. Notably, the results highlight the considerable heterogeneity in the diagnostic methods used to evaluate the disease. Therefore, despite the clinical relevance and high prevalence of CIPN among patients with cancer, there is no universally accepted standard for its diagnosis. Different strategies, including questionnaires, biomarkers, neurophysiological tests, and digital technologies, have been employed with varying degrees of success and validation. Patient-reported instruments, particularly the EORTC QLQ-CIPN20 and the NCI-CTCAE grading scale, emerged as the most frequently used diagnostic tools (16-20, 24, 28, 29, 32, 35, 37, 39-42). These questionnaires are valued for their ease of administration and their ability to incorporate the patient’s subjective experience of symptoms. However, they are not without limitations; for example, these tools may not capture subtle or early manifestations of CIPN, particularly in the context of longitudinal monitoring.
There is a growing interest in the use of biomarkers such as NfL, glial fibrillary acidic protein, miRNAs, and genetic polymorphisms such as of ATP binding cassette subfamily B member 1 (ABCB1), as objective indicators of CIPN (16-20, 34, 35, 41). Although these markers hold significant potential for use in early diagnosis and risk stratification, their application remains largely confined to research settings, and most have yet to undergo validation in large, diverse patient cohorts. Therefore, this lack of standardization limits their current clinical utility. Similarly, neurophysiological tests, including NCS, DTI, and fMRI, offer objective and sensitive measures of nerve damage (21-23, 25-27, 30, 33-43).
These tools can provide insights into both structural and functional neural alterations associated with chemotherapy-induced toxicity. However, their use is typically restricted to specialized centers due to high costs, complex protocols, and the need for trained personnel, which hampers their broader implementation in routine oncology care. From a healthcare systems perspective, these interesting strategies may not be feasible, especially in low-resource settings.
Additionally, applications, digital sensors, and novel biomarkers offer promising prospects for the assessment of CIPN (24, 32, 33, 37, 40). Nevertheless, most of these tools have been tested only in small patient cohorts, limiting the generalizability and clinical applicability of their findings.
Numerous challenges could potentially be addressed through the application of artificial intelligence (AI) (46). Recent evidence shows that CIPN remains a significant clinical issue. For example, Rades etal. reported a 27.8% incidence of moderate to severe peripheral neuropathy in patients with breast cancer undergoing adjuvant radiotherapy after chemotherapy, highlighting the urgent need for improved diagnostic tools (47). AI technologies can integrate existing knowledge on risk factors, pathophysiology, clinical manifestations, and treatment options for CIPN. AI-based multimodal approaches can allow not only the early identification of the condition but also selection of the most appropriate therapeutic intervention, for example for evaluating innovative treatments (48). Furthermore, the implementation of AI-based software tools might support the monitoring of CIPN progression, helping assess the effectiveness of treatment approaches and guiding decisions on whether to reduce chemotherapy doses or intensify neuropathy management.
This scoping review has several limitations. Firstly, the included studies demonstrated substantial heterogeneity in terms of study design, population characteristics, timing of assessments, and diagnostic tools. This limits their direct comparability and precluded carrying out meta-analysis. Additionally, while an effort was made to appraise methodological quality using the JBI tools, some investigations lacked sufficient detail on key elements such as confounder control and follow-up duration, introducing potential bias. Additionally, the review focused exclusively on English-language publications, which may have led to language bias and the exclusion of relevant data. The scope also did not include unpublished data or grey literature, which may provide further insight, especially for novel biomarkers and digital tools. Finally, many of the innovative diagnostic methods identified, such as particularly biomarkers and digital technologies, remain in early development stages and lack validation in large, diverse clinical populations, limiting their immediate applicability in routine care.
Conclusion
CIPN diagnosis is a serious issue. There is interest in multimodal approaches that integrate subjective and objective tools. Nevertheless, the absence of standardized validation, especially for emerging biomarkers and digital innovations, remains a major limitation. To address this critical gap, there is an urgent need for the development and validation of diagnostic tools that are reliable, reproducible, and applicable in clinical practice.
Acknowledgements
The Authors thank Maria Cristina Romano for assistance with data management and literature retrieval. This work was partially supported by the Italian Ministry of Health 5X Mille funds, YEAR 2022.
Footnotes
Authors’ Contributions
This scoping review was conceived by VC and MC. The literature search strategy, data analysis, and methodological design were primarily developed by MM, with support from VA, SB, AC, MLGL, VC and DE. VA supported the data synthesis, contributed to the organization of tables and supplementary files, and assisted in the editing process. The initial manuscript draft was written by VC and reviewed critically for intellectual content by all Authors. MC provided overall methodological supervision, ensured consistency with the review framework, and approved the final version of the manuscript. All Authors read and approved the final version.
Conflicts of Interest
The Authors have no relevant financial or non-financial interests to disclose.
Data Availability
All data are available here and at the link DOI: 10.5281/zenodo.15656304
Funding
This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.
Artificial Intelligence (AI) Disclosure
No artificial intelligence (AI) tools, including large language models or machine-learning software, were used in the preparation, analysis, or presentation of this manuscript.
- Received June 13, 2025.
- Revision received July 3, 2025.
- Accepted July 21, 2025.
- Copyright © 2025 The Author(s). Published by the International Institute of Anticancer Research.
This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY-NC-ND) 4.0 international license (https://creativecommons.org/licenses/by-nc-nd/4.0).
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