Natural History of Chemotherapy-Induced Peripheral Neuropathy in Paclitaxel-Treated Patients: A Prospective Analysis Using Nerve Conduction Studies and S-LANSS Questionnaires

Natural History of Chemotherapy-Induced Peripheral Neuropathy in Paclitaxel-Treated Patients: A Prospective Analysis Using Nerve Conduction Studies and S-LANSS Questionnaires | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Natural History of Chemotherapy-Induced Peripheral Neuropathy in Paclitaxel-Treated Patients: A Prospective Analysis Using Nerve Conduction Studies and S-LANSS Questionnaires Ikhyun Lim, Yong Wha Moon, MiRi Suh, Seul-Gi Kim This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7523495/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Purpose Chemotherapy-induced peripheral neuropathy (CIPN) is a common and debilitating toxicity of paclitaxel that can compromise treatment adherence and survivorship. We aimed to prospectively characterize the natural history of paclitaxel-induced peripheral neuropathy by integrating objective neurophysiological assessments with patient-reported outcomes. Methods In this prospective study, 26 patients scheduled to receive paclitaxel-based chemotherapy for breast, ovarian, or endometrial cancer were enrolled. Serial evaluations were performed at baseline (T0), immediately post-chemotherapy (T1), three months after completion (T2), and one-year post-treatment (T3). Nerve conduction studies (NCS) of sensory and motor nerves, the self-reported Leeds Assessment of Neuropathic Symptoms and Signs (S-LANSS) questionnaire, and Common Terminology Criteria for Adverse Events (CTCAE) grading were conducted at each time point. Correlations between subjective and objective measures were analyzed. Results Fourteen patients who completed serial assessments up to T2 were included in the final analysis. At T1, S-LANSS scores increased significantly from baseline (1.29 ± 4.81 to 14.29 ± 4.23, p < 0.0001), with partial improvement at T2 and T3, though not fully returning to baseline. While distal latencies showed no significant changes, amplitudes of all studied nerves decreased immediately after chemotherapy. Partial recovery was observed in sural, median, and superficial radial sensory nerve action potentials (SNAPs), whereas tibial compound motor action potential (CMAP) and ulnar SNAP showed minimal recovery and remained significantly impaired at one year. Correlation analyses showed significant associations between patient-reported symptoms and NCS parameters, particularly for ulnar SNAP (r = –0.523, p < 0.0001) and tibial CMAP (r = –0.467, p = 0.0005). Analysis of ≥30% SNAP reductions revealed heterogeneity in recovery trajectories, with early sural involvement showing partial recovery, while median and ulnar nerve impairments persisted. Conclusion Paclitaxel-induced peripheral neuropathy persists long after treatment and demonstrates heterogeneous recovery patterns across nerves. Reliance solely on CTCAE grading may underestimate neuropathy burden; integration of patient-reported outcomes and NCS provides a more comprehensive evaluation. Early identification of high-risk patients through longitudinal monitoring may guide proactive management strategies and mitigate the long-term impact of CIPN. Chemotherapy-induced peripheral neuropathy Paclitaxel Nerve conduction studies S-LANSS questionnaire Neurotoxicity Figures Figure 1 Introduction Chemotherapy-induced peripheral neuropathy (CIPN) is one of the most frequent and clinically significant toxicities encountered in modern oncology [ 1 , 2 ]. It is widely recognized as a dose‑limiting adverse effect of various cytotoxic agents, including taxanes, platinum compounds, vinca alkaloids, and proteasome inhibitors. Among these, paclitaxel has emerged as a cornerstone of treatment for a broad range of solid tumors, particularly breast, ovarian, and uterine cancers [ 3 ]. Its antineoplastic activity is mediated through the stabilization of microtubules, which prevents depolymerization and arrests cells in the mitotic phase, ultimately leading to apoptosis of rapidly dividing cancer cells. However, the same mechanism that disrupts microtubule dynamics in malignant cells also affects non‑dividing cells such as neurons, contributing to significant neurotoxicity [ 4 , 5 ]. Reported incidences of paclitaxel‑related neuropathy vary widely depending on dose intensity and treatment schedule, but sensory neuropathic symptoms have been documented in as many as 60–97% of patients receiving this agent [ 6 ]. Clinically, CIPN most often manifests as symmetric sensory disturbances in a stocking‑and‑glove distribution, characterized by numbness, tingling, burning sensations, or sharp shooting pain in the distal extremities [ 2 ]. In more advanced cases, motor involvement and proprioceptive deficits can occur, leading to gait instability and functional impairment [ 7 ]. These symptoms not only reduce health‑related quality of life but can also force clinicians to implement dose reductions, delays, or even early discontinuation of otherwise effective chemotherapy regimens [ 2 , 4 , 8 ]. Consequently, CIPN poses a significant challenge in balancing treatment efficacy with tolerability, particularly in curative settings where maintaining full‑dose intensity is paramount. The biological mechanisms underlying paclitaxel‑induced neuropathy are multifactorial and incompletely understood [ 3 , 9 ]. Experimental models and clinical data suggest that axonal degeneration, mitochondrial dysfunction, and oxidative stress collectively contribute to sensory nerve damage [ 10 , 11 ]. Additional mechanisms, including microtubule aggregation within axons, impaired axonal transport, and neuroinflammatory pathways, have also been proposed [ 12 ]. These complex processes result in both functional impairment and structural changes in peripheral nerves. Although numerous studies have sought to characterize CIPN, the majority have relied on cross‑sectional assessments or retrospective analyses, which provide only a limited snapshot of the neuropathy’s trajectory [ 13 ]. Objective measurements such as nerve conduction studies (NCS) have been used to quantify large‑fiber dysfunction and have demonstrated correlations with patient‑reported symptoms. However, a single‑time‑point evaluation often fails to reflect the evolving nature of nerve injury, recovery, or progression that occurs over the course of chemotherapy and survivorship. Moreover, subjective tools alone, while important for capturing patient experience, may be influenced by recall bias or comorbid conditions [ 1 , 2 ]. Given these gaps in knowledge, there is a clear need for longitudinal studies that integrate both objective and subjective measures to better understand the natural history of CIPN . Such data could guide clinicians in early identification of patients at risk for persistent neuropathy and inform decisions regarding treatment modifications or supportive interventions. Therefore, the present prospective study was designed to track paclitaxel‑induced peripheral neuropathy over multiple clinically relevant time points, combining serial NCS assessments with validated symptom questionnaires. By doing so, we aimed to provide a more comprehensive characterization of the onset, progression, and potential persistence of CIPN in patients receiving paclitaxel-based chemotherapy. Patients and methods Patients Eligible participants were ≥ 20 years of age with histologically confirmed breast cancer scheduled to receive paclitaxel as neoadjuvant or adjuvant therapy, or with peritoneal, ovarian, or uterine cancer receiving paclitaxel in combination with carboplatin, with or without bevacizumab. Patients were prospectively enrolled at CHA Bundang Medical Center between August 2022 and September 2023 before undergoing paclitaxel‑based chemotherapy for breast or ovarian cancer. Key exclusion criteria included pre‑existing peripheral neuropathy, diabetes mellitus, chronic liver or kidney disease, central nervous system disorders (e.g., dementia), concurrent use of neurotoxic or neuroleptic agents, a history of metastatic disease, and contraindications to NCS (e.g., severe coagulopathy). Chemotherapy Regimen Patients with breast cancer received paclitaxel at a dose of 80 mg/m² administered weekly for a total of 12 cycles as part of their neoadjuvant or adjuvant treatment. Patients with peritoneal, ovarian, or uterine cancer received paclitaxel at a dose of 175 mg/m² combined with carboplatin (target area under the curve [AUC] of 5), with or without bevacizumab, typically administered every three weeks. All chemotherapy regimens were prescribed and administered by board-certified medical oncologists. Dose modifications, including delays or reductions, were made at the discretion of the treating physician based on individual patient tolerance and clinical factors. Outcome Assessment All clinical and neurophysiological evaluations were scheduled at four predefined time points to capture both early and late changes in peripheral nerve function: prior to the initiation of chemotherapy (T0), at the completion of the planned chemotherapy regimen (T1), three months after completing treatment (T2), and one year after treatment completion (T3). Neurophysiological evaluation Nerve conduction studies (NCS) were used to assess both compound motor action potentials (CMAPs) and sensory nerve action potentials (SNAPs) in the upper and lower extremities. Sensory nerves assessed included the median, ulnar, superficial radial, and sural nerves, using an antidromic technique. Each parameter was measured three times, and the average was used for analysis. All examinations were conducted by the same specialist throughout the study. F-waves were recorded with a minimum amplitude threshold of 20 µV to distinguish them from pseudo-responses due to voluntary contraction. The F-wave onset latency was defined as the first deflection from baseline and averaged over five and ten stimulations. Two diagnostic criteria were used to interpret the NCS data: Criterion A: Absolute sural SNAP amplitude < 10 µV (with adjusted lower thresholds of 3 µV for individuals in their 60s and 1 µV for those in their 70s) [ 14 ]. Criterion B: A ≥ 30% reduction in sural amplitude from baseline, based on previously published studies. These criteria were selected to complement each other and to enhance diagnostic accuracy. The absolute threshold (Criterion A) has been widely used in prior neurophysiological research as a clinically practical cut-off for CIPN, but it may be affected by physiological age-related decline. In contrast, the relative decline criterion (Criterion B) enables individualized longitudinal assessment by capturing progressive changes relative to each patient’s baseline, which has been emphasized in previous prospective studies of oxaliplatin- and taxane-induced neuropathy [ 15 ]. By combining these two complementary approaches, we aimed to achieve both cross-sectional diagnostic interpretation and sensitive longitudinal monitoring of cumulative neurotoxic changes. Clinical Evaluation Subjective neuropathic symptoms were evaluated using the Korean version of the self‑reported Leeds Assessment of Neuropathic Symptoms and Signs (S-LANSS) questionnaire, a validated screening tool for neuropathic pain. A total score of 12 or higher (out of 24) was considered indicative of neuropathic pain. Patients completed the S-LANSS at each of the four assessment time points. In addition, peripheral neuropathy was graded according to the Common Terminology Criteria for Adverse Events (CTCAE), version 5.0, which classifies symptom severity into five levels, ranging from Grade 1 (mild) to Grade 5 (death). The full item lists and scoring criteria for the S-LANSS questionnaire and the CTCAE grading system are provided in Supplementary Table 1 and Supplementary Table 2 , respectively. Statistical Analysis The primary endpoints were the incidence and severity of CIPN and the longitudinal changes in NCS parameters and S‑LANSS scores. Baseline patient characteristics are presented as median (range) for continuous variables and as numbers (percentages) for categorical variables. For longitudinal analyses, within‑subject differences between baseline and each follow‑up time point were evaluated using the Wilcoxon signed‑rank test for non‑normally distributed continuous variables, or paired t‑tests when normality was met. Trends over time were assessed using repeated‑measures ANOVA or the Friedman test, as appropriate. Categorical variables, including CTCAE grades, were compared using the Chi‑square test or Fisher’s exact test when expected frequencies were small. Correlations between objective (NCS) and subjective (S‑LANSS) measures were analyzed using Pearson’s or Spearman’s correlation coefficients based on data distribution. A two‑sided p‑value of < 0.05 was considered statistically significant. All statistical analyses were performed using SPSS software version 20.0 (SPSS Inc., Chicago, IL, USA). Results Patient Demographics and Clinical Characteristics A total of 26 patients provided written informed consent for study participation. Among them, one patient withdrew consent before undergoing the baseline assessment (T0), leaving 25 patients who completed the T0 evaluation. Of these, 18 patients completed the immediate post-chemotherapy assessment (T1), 15 patients underwent the 3-month follow-up assessment (T2), and 12 patients completed all scheduled assessments through the 1-year follow-up (T3). One patient who had completed all assessments subsequently withdrew consent for the use of her data in this study. Given the primary objective of evaluating serial changes, the final analysis was conducted in 14 patients who completed assessments at T0, T1, and T2. Baseline characteristics were analyzed in 14 patients who were included in the final analysis. The median age was 55 years (range, 38–81), the median height was 158.8 cm (range, 148.6–169.0), the median weight was 57.4 kg (range, 47.0–81.5), and the median BMI was 21.9 kg/m² (range, 20.1–36.9). Regarding primary cancer diagnoses, breast cancer accounted for 10 patients (71.4%), ovarian cancer for 3 patients (21.4%), and endometrial cancer for 1 patient (7.1%). All patients received paclitaxel-based chemotherapy; among them, 10 patients (71.4%) were also treated sequentially with anthracyclines, and 4 patients (28.6%) received carboplatin with or without bevacizumab concurrently. The median chemotherapy duration was 133 days (range, 104–223). These baseline demographics and clinical characteristics are summarized in Table 1 . Table 1 Baseline patient demographics and chemotherapy treatment characteristics Characteristics N = 14 (%)* Age (years) 55 (38­81) Height (cm) 158.8 (148.6­169.0) Weight (kg) 57.4 (47.0­81.5) Body Mass Index (BMI, kg/m 2 ) 21.9 (20.1­36.9) Diagnosis Breast cancer 10 (71.4%) Ovarian cancer 3 (21.5%) Endometrial cancer 1 (7.1%) Chemotherapy regimen Paclitaxel 14 (100%) Anthracycline (sequential) 10 (71.4%) Carboplatin \(\:\pm\:\) Bevacizumab (concurrent) 4 (28.6%) Chemotherapy duration (days) 133 (104–223) Paclitaxel dose intensity (%) ✝ Breast cancer 100 (78.3–100) Ovarian cancer 100% (66.7–100) Endometrial cancer 100% *Values are expressed as median (range) or number of patients, as appropriate. ✝ Chemotherapy dose intensity was calculated as the actual delivered dose (mg/m² per week) divided by the standard planned dose (mg/m² per week), and presented as relative dose intensity (%) As all patients were receiving curative-intent chemotherapy, dose modifications were made at the discretion of the medical oncologist. Among the four patients who required dose reduction, one patient with breast cancer underwent reduction due to grade 2 CIPN, and her relative dose intensity was 78.3%. The reasons for dose reduction in the other three patients were neutropenia, recent herpes zoster infection, and advanced age (81 years), respectively. Longitudinal Changes in S-LANSS Scores and Nerve Conduction Study Findings Before starting chemotherapy (T0), only 1 patient had S-LANSS over 12 points while the others all scored 0 points. However, all patients showed symptoms of neuropathy at T1, where all except 2 patients had S-LANSS over 12 points (from 1.29 ± 4.81 at T0 to 14.29 ± 4.23 at T1, p < 0.0001). This significantly improved as time went by throughout T2 (from 14.29 ± 4.23 at T1 to 9.64 ± 5.05 at T2, p = 0.003) and T3 (from 9.64 ± 5.05 at T2 to 4.86 ± 5.88 at T3, p = 0.013). However, S-LANSS score did not restored the initial level even at 1 year after the completion of chemotherapy (1.29 ± 4.81 at T0 vs. 4.86 ± 5.88 at T3, p = 0.023). While distal latencies in the studied nerves did not show significant changes during the four timepoints, amplitudes of all studied nerves dropped immediately after chemotherapy. Amplitudes of sural, median and superficial radial SNAP recovered significantly at T3 compared with T1 ( p = 0.001, 0.002, and 0.006 for sural, median, and superficial radial SNAP, respectively), where largest improvement was shown between T1-T2 period for sural SNAP ( p = 0.002) and T2-T3 period for median ( p = 0.034) and superficial radial ( p = 0.033) SNAP. Meanwhile, amplitudes of tibial CMAP and ulnar SNAP at T2 and T3 did not recover much and showed significant differences compared to the initial level (T3-T0, p = 0.048 and 0.0005 for tibial CMAP and ulnar SNAP, respectively). The detailed results of longitudinal changes in S-LANSS scores and NCS parameters are summarized in Fig. 1 and Table 2 . Table 2 Longitudinal changes in nerve conduction study parameters and clinical symptom scales (S-LANSS, CTCAE) T0 (n = 14) T1 (n = 14) T2 (n = 14) T3 (n = 11) NCS Amplitude of tibial CMAP (µV) 14.13 ± 4.01 11.15 ± 3.59 11.33 ± 3.22 12.14 ± 3.70 Amplitude of sural SNAP (µV) 14.36 ± 6.50 7.50 ± 6.92 13.17 ± 8.13 15.53 ± 8.91 Amplitude of median SNAP (µV) 32.90 ± 15.18 21.02 ± 15.38 23.40 ± 17.61 27.37 ± 18.41 Amplitude of ulnar SNAP (µV) 39.24 ± 16.68 21.30 ± 11.00 24.25 ± 14.37 24.10 ± 12.85 Amplitude of superficial radial SNAP (µV) 37.77 ± 15.25 27.87 ± 12.10 29.98 ± 14.63 34.31 ± 15.71 S-LANSS Score 1.29 ± 4.81 14.29 ± 4.23 9.64 ± 5.05 4.86 ± 5.88 CTCAE grade NE 2 (100%) 2 (100%) Grade 1: 4 (29%) Grade 2: 10 (71%) Notes: Changes of S-LANSS, amplitudes of tibial CMAP, sural, median, ulnar, and superficial radial SNAPs are shown as their mean ± standard deviation at four time points: prior to the initiation of chemotherapy (T0), at the completion (T1), three months after completion (T2) and one year after completion (T3) of scheduled chemotherapy. Peripheral neuropathy was also classified by CTCAE grade, version 5.0 (ranging from grade 1 (mild) to grade 5(death)). Correlations Between Subjective and Objective Measures Some of the objective measures showed significant correlation with subjective measures. Distal latency of sural SNAP showed positive correlation with S-LANSS and CTCAE, while amplitudes of sural, median, ulnar, and superficial radial SNAP, and amplitude of tibial CMAP showed negative correlation with them. Correlation with S-LANSS was stronger in amplitudes of ulnar SNAP (r = -0.523, p < 0.0001) and tibial CMAP (r = -0.467, p = 0.0005), which were two nerves that did not show much improvements in amplitudes until T3. Correlation with CTCAE was also stronger in amplitudes of ulnar SNAP (r = -0.470, p = 0.0003). Detailed correlation analyses between subjective and objective measures are presented in Table 3 . Table 3 Correlations between nerve conduction study parameters and clinical symptom scales (S-LANSS, CTCAE) Parameter S-LANSS ( r , p -value) CTCAE ( r , p -value) Tibial CMAP amplitude -0.467, p = 0.0005 -0.359, p = 0.007 Sural SNAP latency 0.328, p = 0.028 0.317, p = 0.036 Sural SNAP amplitude -0.275, p = 0.049 -0.308, p = 0.0422 Median SNAP amplitude -0.423, p = 0.002 -0.335, p = 0.013 Ulnar SNAP amplitude -0.523, p < 0.0001 -0.470, p = 0.0003 Superficial radial SNAP amplitude -0.341, p = 0.013 -0.344, p = 0.010 Notes: Correlation of S-LANSS and CTCAE between NCS parameters were described by their correlation coefficient( r ) and p-value. *P < 0.05 by Pearson correlation test. Abbreviation: NCS; nerve conduction study, SNAP; sensory nerve action potentials, CMAP; compound motor action potentials, S-LANSS; self‑reported Leeds Assessment of Neuropathic Symptoms, and CTCAE; Common Terminology Criteria for Adverse Events. Recovery Patterns and Persistence at 1-Year Follow-Up Our longitudinal analysis revealed distinct recovery patterns among sensory nerves following chemotherapy. The sural nerve demonstrated the highest vulnerability immediately after treatment, with 64% of patients experiencing a ≥ 30% reduction in amplitude; however, this proportion decreased to 21% at one year, suggesting partial recovery. In contrast, the median and ulnar nerves exhibited more persistent reductions, with over half of patients still meeting the ≥ 30% decline criterion at one year, indicating limited reversibility of neurotoxic injury. The superficial radial nerve displayed a delayed worsening at three months, followed by partial improvement at one year (Table 4 ). Table 4 Proportion of patients with ≥ 30% reduction in sensory nerve action potential (SNAP) amplitudes at each time point Nerve Amplitude > 30% drop at T1 Amplitude > 30% drop at T2 Amplitude > 30% drop at T3 Tibial 36% (N = 5) 36% (N = 5) 29% (N = 4) Sural 64% (N = 9) 29% (N = 4) 21% (N = 3) Median 57% (N = 8) 57% (N = 8) 57% (N = 8) Ulnar 64% (N = 9) 64% (N = 9) 57% (N = 7) Superficial Radial 29% (N = 4) 57% (N = 5) 29% (N = 4) Notes: The proportion of patients with a ≥ 30% reduction in nerve amplitude at each time point (T1: post-chemotherapy, T2: 3 months post-chemotherapy, T3: 12 months post-chemotherapy) compared to baseline (T0) Discussion This prospective study provides valuable insights into the natural history of paclitaxel-induced peripheral neuropathy, integrating both objective neurophysiological evaluations and subjective patient-reported outcomes. As medical oncologists, one of the primary challenges in clinical practice is the early detection and management of CIPN, which not only affects patients’ quality of life but also directly impacts treatment adherence and efficacy [ 16 , 17 ]. Our findings align with prior research demonstrating that serial nerve conduction studies offer a feasible and clinically informative approach when combined with validated symptom assessment tools like the S-LANSS questionnaire, as evidenced by studies showing modest correlations between NCS parameters and patient-reported neuropathic symptoms [ 13 , 18 , 19 ]. The combination of these methods allows for a more comprehensive evaluation of neurotoxicity progression and potential recovery. [ 13 , 19 ] Importantly, our longitudinal data reveal that although partial recovery of both S-LANSS scores and SNAP amplitudes occurred after chemotherapy cessation, these measures did not return to baseline values even after one year, providing electrophysiological evidence of sustained subclinical axonal injury. This pattern is consistent with previous reports that paclitaxel-induced neuropathy is often long-lasting and incompletely reversible, with some patients experiencing symptoms for years after treatment completion [ 20 , 21 ]. Taken together, these results highlight that CIPN after taxane chemotherapy is not easily reversible and may represent a chronic toxicity rather than a transient adverse effect. Furthermore, our analysis of ≥ 30% reductions in SNAP amplitude across multiple sensory nerves underscores heterogeneity in recovery patterns. For example, consistent with previous prospective study reporting preferential vulnerability of certain nerves to platinum- and taxane-based chemotherapy [ 22 ], our data revealed early sural involvement but partial recovery within one year, whereas median nerve injury remained largely persistent across all time points. Similar findings have also been documented in study of vincristine-induced neuropathy, where both sural and non-sural nerves demonstrated sustained SNAP reductions, reinforcing that each nerve follows a distinct pattern of damage and recovery [ 23 ]. Our extended monitoring further reveals unique recovery dynamics, such as modest ulnar improvement (from 64–57%) and fluctuating superficial radial changes, potentially explaining varied patient symptom profiles despite uniform treatment exposures. These findings indicate that CIPN reflects heterogeneous nerve susceptibilities, underscoring the need for tailored monitoring and survivorship strategies. From an oncologist’s perspective, the timing and severity of CIPN should inform therapeutic decisions, especially in curative settings where dose intensity must be balanced with long-term survivorship. The utility of serial NCS in identifying high-risk patients for persistent neuropathy, as seen in our data with early sural and ulnar reductions, supports timely dose modifications or neuroprotective interventions, aligning with ASCO guidelines emphasizing proactive management [ 2 ]. Moreover, while CTCAE grading remains the standard in clinical trials, our findings emphasize the added value of patient-reported outcomes and physiologic measurements in real-world clinical settings. CTCAE grading alone often underestimates the burden of neuropathy [ 24 , 25 ]. For instance, several patients with significant SNAP amplitude reductions did not show corresponding increases in CTCAE grade. In our study, all patients were assigned CTCAE grade 2 at T1 and T2, even though S-LANSS and NCS parameters showed variable changes after chemotherapy. This suggests that a multidimensional approach—integrating CTCAE grading, NCS, and patient-reported outcomes—may provide a more accurate and clinically meaningful assessment of CIPN, in line with prior reports that CTCAE alone often underestimates CIPN severity compared with patient-reported and physiologic assessments. Nevertheless, this study has several limitations. The sample size was modest, and follow-up attrition may have introduced selection bias. Additionally, we did not evaluate genetic or biochemical predictors of neuropathy, which could enhance risk stratification. In addition, distal latency data from severely affected patients were excluded from the analysis, as eight NCS parameters from four patients showed absent responses. While absent amplitudes could be imputed as zero, it was not feasible to assign arbitrary values for absent latencies. Consequently, the potential significance of distal latency changes may have been underestimated, although it is well established that paclitaxel-induced peripheral neuropathy predominantly causes axonal loss, primarily reflected in reduced SNAP amplitudes. Future studies incorporating biomarkers and interventions (e.g., duloxetine, exercise, cryotherapy) are needed to move toward personalized prevention and management of CIPN. In conclusion, this study demonstrates that paclitaxel-induced peripheral neuropathy can persist long after treatment and shows variable recovery trajectories among patients. We should recognize the limitations of relying solely on CTCAE grading and integrate both subjective and objective tools, such as NCS and S-LANSS, into routine clinical assessments where feasible. Early identification of high-risk patients through longitudinal monitoring may enable more proactive management and mitigate the long-term burden of CIPN. Our findings underscore the need for further research into effective prevention strategies and reinforce the importance of patient-centered survivorship care in oncology. Declarations Author contributions Conceptualization: MiRi Suh, Seul-Gi Kim, Yong Wha Moon; Methodology: MiRi Suh, Seul-Gi Kim, Yong Wha Moon; Formal analysis and investigation: Ikhyun Lim, MiRi Suh, Seul-Gi Kim; Writing - original draft preparation: Ikhyun Lim, MiRi Suh, Seul-Gi Kim; Writing review and editing: Ikhyun Lim, MiRi Suh, Seul-Gi Kim; Funding acquisition: Seul-Gi Kim, Yong Wha Moon; Supervision: MiRi Suh, Seul-Gi Kim Funding This study was supported by Samyang Holdings Corp. Data availability The de-identified individual-level participant data of this study can be provided to researchers upon request by e-mail. Please send inquiries to the corresponding. A detailed proposal for how the data will be used is required, and we will review on a case-by-case basis. A data access agreement must also be signed for these data to be transferred. Ethical approval This study was approved by the Institutional Review Board of Bundang CHA Medical Center (IRB No.2022-03-081), and the study was conducted in accordance with the Declaration of Helsinki. Consent to participate Written informed consent was obtained from all participants prior to enrollment. Consent for publication This study did not include any personal data. Competing interests The authors declare no competing interests. Role of the funder/sponsor The funder had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. 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Oncol Ther 9:385–450. https://doi.org/10.1007/s40487-021-00168-y Kleinveld VEA, Emmelheinz M, Egle D, Ritter M, Loscher WN, Marth C, Horlings CGC, Wanschitz J, Brunner C (2024) A Prospective Comparison of Subjective Symptoms and Neurophysiological Findings in the Assessment of Neuropathy in Cancer Patients. Diagnostics (Basel) 14. https://doi.org/10.3390/diagnostics14242861 Wang M, Bandla A, Sundar R, Molassiotis A (2022) The phenotype and value of nerve conduction studies in measuring chemotherapy-induced peripheral neuropathy: A secondary analysis of pooled data. Eur J Oncol Nurs 60:102196. https://doi.org/10.1016/j.ejon.2022.102196 Kerckhove N, Collin A, Conde S, Chaleteix C, Pezet D, Balayssac D (2017) Long-Term Effects, Pathophysiological Mechanisms, and Risk Factors of Chemotherapy-Induced Peripheral Neuropathies: A Comprehensive Literature Review. Front Pharmacol 8:86. https://doi.org/10.3389/fphar.2017.00086 Soriano D, Amantani M, Cordoba G, Vanni Y, Varela M, Paletta C, Coronel M (2024) Prevalence, Severity, and Persistence of Chemotherapy-Induced Peripheral Neuropathy in Early-Stage Breast Cancer Patients Treated with Paclitaxel: an Observational Study in a Referral Hospital in Latin America. Journal of Critical Care & Emergency Medicine. https://doi.org/10.47363/JCCEM/2024(3)166 Myftiu B, Hundozi Z, Sermaxhaj F, Blyta A, Shala N, Jashari F, Qorraj Bytyqi H, Hyseni E, Kurtishi I (2022) Chemotherapy-Induced Peripheral Neuropathy (CIPN) in Patients Receiving 4–6 Cycles of Platinum-Based and Taxane-Based Chemotherapy: A Prospective, Single-Center Study from Kosovo. Med Sci Monit 28:e937856. https://doi.org/10.12659/MSM.937856 Philipps J, Knaup M, Katz M et al (2025) Nerve cross-sectional area in vincristine-induced polyneuropathy: A nerve ultrasound pilot study. J Neuroimaging 35:e13255. https://doi.org/10.1111/jon.13255 Matsuoka A, Mitsuma A, Maeda O, Kajiyama H, Kiyoi H, Kodera Y, Nagino M, Goto H, Ando Y (2016) Quantitative assessment of chemotherapy-induced peripheral neurotoxicity using a point-of-care nerve conduction device. Cancer Sci 107:1453–1457. https://doi.org/10.1111/cas.13010 Tan AC, McCrary JM, Park SB, Trinh T, Goldstein D (2019) Chemotherapy-induced peripheral neuropathy-patient-reported outcomes compared with NCI-CTCAE grade. Support Care Cancer 27:4771–4777. https://doi.org/10.1007/s00520-019-04781-6 Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7523495","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":538430281,"identity":"60572800-f637-46b8-ab5f-f2eec86e9bb8","order_by":0,"name":"Ikhyun Lim","email":"","orcid":"","institution":"CHA Bundang Medical Center, CHA University","correspondingAuthor":false,"prefix":"","firstName":"Ikhyun","middleName":"","lastName":"Lim","suffix":""},{"id":538430283,"identity":"f394e5ef-362f-425e-925b-a2c75834c5da","order_by":1,"name":"Yong Wha Moon","email":"","orcid":"","institution":"CHA Bundang Medical Center, CHA University","correspondingAuthor":false,"prefix":"","firstName":"Yong","middleName":"Wha","lastName":"Moon","suffix":""},{"id":538430284,"identity":"06f54033-d624-4ec3-b808-25968c4112c9","order_by":2,"name":"MiRi Suh","email":"","orcid":"","institution":"CHA Bundang Medical Center, CHA University","correspondingAuthor":false,"prefix":"","firstName":"MiRi","middleName":"","lastName":"Suh","suffix":""},{"id":538430289,"identity":"d6718206-ddd0-4f3f-ba55-c0533bc5c837","order_by":3,"name":"Seul-Gi Kim","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA4ElEQVRIiWNgGAWjYHACNoYEhhoeNvYGNpgIMzFajsnw8RwgRQtQkY2cRAKRWuTbe489eFDDxsMm+fjZg585dgz87Q3MxhV4tBicOZdukHBMhodNOs3csHdbMoPEmQPMiWfwaZHIMQM6CWiLdA6bBO+2A0CRBOaDDfgcNgOk5R8z0GFn2CT/EqOF4QZQS2IbUIsE0CKYLYn4tAD9kiaR2HeMh40nzUxadlsyj8SZg82GeB0GDDHJH99q7OXbDz+TfLvNTo6/vfmwJF6HMfBgcBnxa8DQMgpGwSgYBaMAAwAA0xZBCKFOg54AAAAASUVORK5CYII=","orcid":"","institution":"CHA 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16:32:11","extension":"html","order_by":6,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":112225,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-7523495/v1/645645974c72e8494664302d.html"},{"id":95170401,"identity":"7eceb4e6-ae5c-40b6-b672-8b3fc4bf0f55","added_by":"auto","created_at":"2025-11-05 06:27:53","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":70605,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eLongitudinal changes in S-LANSS scores, CTCAE grades, and NCS parameters during the study period \u003c/strong\u003eChanges of S-LANSS, CTCAE, amplitudes of tibial CMAP, sural, median, ulnar, and superficial radial SNAPs are shown as their mean ± standard deviation at four time points: prior to the initiation of chemotherapy (T0), at the completion (T1), three months after completion (T2) and one year after completion (T3) of scheduled chemotherapy.\u003c/p\u003e\n\u003cp\u003e*p\u0026lt;0.05, and **p\u0026lt;0.01 by paired t-test.\u003c/p\u003e\n\u003cp\u003eAbbreviation: S-LANSS; self‑reported Leeds Assessment of Neuropathic Symptoms, CTCAE; Common Terminology Criteria for Adverse Events, NCS; nerve conduction study, CMAP; compound motor action potentials, SNAP; sensory nerve action potentials, Sup.; superficial.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-7523495/v1/11a3cd4a5d0163fe91c392bc.png"},{"id":98622029,"identity":"9c5a4d39-ec87-4377-b7d0-0c79521378ad","added_by":"auto","created_at":"2025-12-19 16:42:13","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1285921,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7523495/v1/12e9a7ad-94bf-4eb9-87ab-2d7a2f6dde39.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Natural History of Chemotherapy-Induced Peripheral Neuropathy in Paclitaxel-Treated Patients: A Prospective Analysis Using Nerve Conduction Studies and S-LANSS Questionnaires","fulltext":[{"header":"Introduction","content":"\u003cp\u003eChemotherapy-induced peripheral neuropathy (CIPN) is one of the most frequent and clinically significant toxicities encountered in modern oncology [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. It is widely recognized as a dose‑limiting adverse effect of various cytotoxic agents, including taxanes, platinum compounds, vinca alkaloids, and proteasome inhibitors. Among these, paclitaxel has emerged as a cornerstone of treatment for a broad range of solid tumors, particularly breast, ovarian, and uterine cancers [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Its antineoplastic activity is mediated through the stabilization of microtubules, which prevents depolymerization and arrests cells in the mitotic phase, ultimately leading to apoptosis of rapidly dividing cancer cells. However, the same mechanism that disrupts microtubule dynamics in malignant cells also affects non‑dividing cells such as neurons, contributing to significant neurotoxicity [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Reported incidences of paclitaxel‑related neuropathy vary widely depending on dose intensity and treatment schedule, but sensory neuropathic symptoms have been documented in as many as 60\u0026ndash;97% of patients receiving this agent [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eClinically, CIPN most often manifests as symmetric sensory disturbances in a stocking‑and‑glove distribution, characterized by numbness, tingling, burning sensations, or sharp shooting pain in the distal extremities [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. In more advanced cases, motor involvement and proprioceptive deficits can occur, leading to gait instability and functional impairment [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. These symptoms not only reduce health‑related quality of life but can also force clinicians to implement dose reductions, delays, or even early discontinuation of otherwise effective chemotherapy regimens [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Consequently, CIPN poses a significant challenge in balancing treatment efficacy with tolerability, particularly in curative settings where maintaining full‑dose intensity is paramount.\u003c/p\u003e\u003cp\u003eThe biological mechanisms underlying paclitaxel‑induced neuropathy are multifactorial and incompletely understood [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Experimental models and clinical data suggest that axonal degeneration, mitochondrial dysfunction, and oxidative stress collectively contribute to sensory nerve damage [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Additional mechanisms, including microtubule aggregation within axons, impaired axonal transport, and neuroinflammatory pathways, have also been proposed [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. These complex processes result in both functional impairment and structural changes in peripheral nerves.\u003c/p\u003e\u003cp\u003eAlthough numerous studies have sought to characterize CIPN, the majority have relied on cross‑sectional assessments or retrospective analyses, which provide only a limited snapshot of the neuropathy\u0026rsquo;s trajectory [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Objective measurements such as nerve conduction studies (NCS) have been used to quantify large‑fiber dysfunction and have demonstrated correlations with patient‑reported symptoms. However, a single‑time‑point evaluation often fails to reflect the evolving nature of nerve injury, recovery, or progression that occurs over the course of chemotherapy and survivorship. Moreover, subjective tools alone, while important for capturing patient experience, may be influenced by recall bias or comorbid conditions [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e].\u003c/p\u003e\u003cp\u003e\u003cb\u003eGiven these gaps in knowledge, there is a clear need for longitudinal studies that integrate both objective and subjective measures to better understand the natural history of CIPN\u003c/b\u003e. Such data could guide clinicians in early identification of patients at risk for persistent neuropathy and inform decisions regarding treatment modifications or supportive interventions. Therefore, the present prospective study was designed to track paclitaxel‑induced peripheral neuropathy over multiple clinically relevant time points, combining serial NCS assessments with validated symptom questionnaires. By doing so, we aimed to provide a more comprehensive characterization of the onset, progression, and potential persistence of CIPN in patients receiving paclitaxel-based chemotherapy.\u003c/p\u003e"},{"header":"Patients and methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003ePatients\u003c/h2\u003e\u003cp\u003eEligible participants were \u0026ge;\u0026thinsp;20 years of age with histologically confirmed breast cancer scheduled to receive paclitaxel as neoadjuvant or adjuvant therapy, or with peritoneal, ovarian, or uterine cancer receiving paclitaxel in combination with carboplatin, with or without bevacizumab. Patients were prospectively enrolled at CHA Bundang Medical Center between August 2022 and September 2023 before undergoing paclitaxel‑based chemotherapy for breast or ovarian cancer.\u003c/p\u003e\u003cp\u003eKey exclusion criteria included pre‑existing peripheral neuropathy, diabetes mellitus, chronic liver or kidney disease, central nervous system disorders (e.g., dementia), concurrent use of neurotoxic or neuroleptic agents, a history of metastatic disease, and contraindications to NCS (e.g., severe coagulopathy).\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eChemotherapy Regimen\u003c/h3\u003e\n\u003cp\u003ePatients with breast cancer received paclitaxel at a dose of 80 mg/m\u0026sup2; administered weekly for a total of 12 cycles as part of their neoadjuvant or adjuvant treatment. Patients with peritoneal, ovarian, or uterine cancer received paclitaxel at a dose of 175 mg/m\u0026sup2; combined with carboplatin (target area under the curve [AUC] of 5), with or without bevacizumab, typically administered every three weeks. All chemotherapy regimens were prescribed and administered by board-certified medical oncologists. Dose modifications, including delays or reductions, were made at the discretion of the treating physician based on individual patient tolerance and clinical factors.\u003c/p\u003e\n\u003ch3\u003eOutcome Assessment\u003c/h3\u003e\n\u003cp\u003eAll clinical and neurophysiological evaluations were scheduled at four predefined time points to capture both early and late changes in peripheral nerve function: prior to the initiation of chemotherapy (T0), at the completion of the planned chemotherapy regimen (T1), three months after completing treatment (T2), and one year after treatment completion (T3).\u003c/p\u003e\n\u003ch3\u003eNeurophysiological evaluation\u003c/h3\u003e\n\u003cp\u003eNerve conduction studies (NCS) were used to assess both compound motor action potentials (CMAPs) and sensory nerve action potentials (SNAPs) in the upper and lower extremities. Sensory nerves assessed included the median, ulnar, superficial radial, and sural nerves, using an antidromic technique. Each parameter was measured three times, and the average was used for analysis. All examinations were conducted by the same specialist throughout the study.\u003c/p\u003e\u003cp\u003eF-waves were recorded with a minimum amplitude threshold of 20 \u0026micro;V to distinguish them from pseudo-responses due to voluntary contraction. The F-wave onset latency was defined as the first deflection from baseline and averaged over five and ten stimulations.\u003c/p\u003e\u003cp\u003eTwo diagnostic criteria were used to interpret the NCS data: Criterion A: Absolute sural SNAP amplitude\u0026thinsp;\u0026lt;\u0026thinsp;10 \u0026micro;V (with adjusted lower thresholds of 3 \u0026micro;V for individuals in their 60s and 1 \u0026micro;V for those in their 70s) [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Criterion B: A\u0026thinsp;\u0026ge;\u0026thinsp;30% reduction in sural amplitude from baseline, based on previously published studies.\u003c/p\u003e\u003cp\u003eThese criteria were selected to complement each other and to enhance diagnostic accuracy. The absolute threshold (Criterion A) has been widely used in prior neurophysiological research as a clinically practical cut-off for CIPN, but it may be affected by physiological age-related decline. In contrast, the relative decline criterion (Criterion B) enables individualized longitudinal assessment by capturing progressive changes relative to each patient\u0026rsquo;s baseline, which has been emphasized in previous prospective studies of oxaliplatin- and taxane-induced neuropathy [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. By combining these two complementary approaches, we aimed to achieve both cross-sectional diagnostic interpretation and sensitive longitudinal monitoring of cumulative neurotoxic changes.\u003c/p\u003e\n\u003ch3\u003eClinical Evaluation\u003c/h3\u003e\n\u003cp\u003eSubjective neuropathic symptoms were evaluated using the Korean version of the self‑reported Leeds Assessment of Neuropathic Symptoms and Signs (S-LANSS) questionnaire, a validated screening tool for neuropathic pain. A total score of 12 or higher (out of 24) was considered indicative of neuropathic pain. Patients completed the S-LANSS at each of the four assessment time points.\u003c/p\u003e\u003cp\u003eIn addition, peripheral neuropathy was graded according to the Common Terminology Criteria for Adverse Events (CTCAE), version 5.0, which classifies symptom severity into five levels, ranging from Grade 1 (mild) to Grade 5 (death).\u003c/p\u003e\u003cp\u003eThe full item lists and scoring criteria for the S-LANSS questionnaire and the CTCAE grading system are provided in \u003cb\u003eSupplementary Table\u0026nbsp;1 and Supplementary Table\u0026nbsp;2\u003c/b\u003e, respectively.\u003c/p\u003e\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e\u003ch2\u003eStatistical Analysis\u003c/h2\u003e\u003cp\u003e\u003cb\u003eThe primary endpoints were the incidence and severity of CIPN and the longitudinal changes in NCS parameters and S‑LANSS scores.\u003c/b\u003e Baseline patient characteristics are presented as median (range) for continuous variables and as numbers (percentages) for categorical variables.\u003c/p\u003e\u003cp\u003eFor longitudinal analyses, within‑subject differences between baseline and each follow‑up time point were evaluated using the Wilcoxon signed‑rank test for non‑normally distributed continuous variables, or paired t‑tests when normality was met. Trends over time were assessed using repeated‑measures ANOVA or the Friedman test, as appropriate. Categorical variables, including CTCAE grades, were compared using the Chi‑square test or Fisher\u0026rsquo;s exact test when expected frequencies were small. Correlations between objective (NCS) and subjective (S‑LANSS) measures were analyzed using Pearson\u0026rsquo;s or Spearman\u0026rsquo;s correlation coefficients based on data distribution.\u003c/p\u003e\u003cp\u003eA two‑sided p‑value of \u0026lt;\u0026thinsp;0.05 was considered statistically significant. All statistical analyses were performed using SPSS software version 20.0 (SPSS Inc., Chicago, IL, USA).\u003c/p\u003e\u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec10\" class=\"Section2\"\u003e\u003ch2\u003ePatient Demographics and Clinical Characteristics\u003c/h2\u003e\u003cp\u003e A total of 26 patients provided written informed consent for study participation. Among them, one patient withdrew consent before undergoing the baseline assessment (T0), leaving 25 patients who completed the T0 evaluation. Of these, 18 patients completed the immediate post-chemotherapy assessment (T1), 15 patients underwent the 3-month follow-up assessment (T2), and 12 patients completed all scheduled assessments through the 1-year follow-up (T3). One patient who had completed all assessments subsequently withdrew consent for the use of her data in this study. \u003cb\u003eGiven the primary objective of evaluating serial changes, the final analysis was conducted in 14 patients who completed assessments at T0, T1, and T2.\u003c/b\u003e\u003c/p\u003e\u003cp\u003eBaseline characteristics were analyzed in 14 patients who were included in the final analysis. The median age was 55 years (range, 38\u0026ndash;81), the median height was 158.8 cm (range, 148.6\u0026ndash;169.0), the median weight was 57.4 kg (range, 47.0\u0026ndash;81.5), and the median BMI was 21.9 kg/m\u0026sup2; (range, 20.1\u0026ndash;36.9). Regarding primary cancer diagnoses, breast cancer accounted for 10 patients (71.4%), ovarian cancer for 3 patients (21.4%), and endometrial cancer for 1 patient (7.1%). All patients received paclitaxel-based chemotherapy; among them, 10 patients (71.4%) were also treated sequentially with anthracyclines, and 4 patients (28.6%) received carboplatin with or without bevacizumab concurrently. The median chemotherapy duration was 133 days (range, 104\u0026ndash;223). These baseline demographics and clinical characteristics are summarized in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eBaseline patient demographics and chemotherapy treatment characteristics\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"3\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCharacteristics\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eN\u0026thinsp;=\u0026thinsp;14 (%)*\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAge (years)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e55 (38\u0026shy;81)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHeight (cm)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e158.8 (148.6\u0026shy;169.0)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eWeight (kg)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e57.4 (47.0\u0026shy;81.5)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBody Mass Index (BMI, kg/m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e21.9 (20.1\u0026shy;36.9)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDiagnosis\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eBreast cancer\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e10 (71.4%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eOvarian cancer\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3 (21.5%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eEndometrial cancer\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1 (7.1%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eChemotherapy regimen\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003ePaclitaxel\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e14 (100%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eAnthracycline (sequential)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e10 (71.4%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eCarboplatin \u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:\\pm\\:\\)\u003c/span\u003e\u003c/span\u003e Bevacizumab (concurrent)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e4 (28.6%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eChemotherapy duration (days)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e133 (104\u0026ndash;223)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePaclitaxel dose intensity (%)\u003csup\u003e✝\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eBreast cancer\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e100 (78.3\u0026ndash;100)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eOvarian cancer\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e100% (66.7\u0026ndash;100)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eEndometrial cancer\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e100%\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"3\"\u003e*Values are expressed as median (range) or number of patients, as appropriate.\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd colspan=\"3\"\u003e\u003csup\u003e✝\u003c/sup\u003eChemotherapy dose intensity was calculated as the actual delivered dose (mg/m\u0026sup2; per week) divided by the standard planned dose (mg/m\u0026sup2; per week), and presented as relative dose intensity (%)\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003eAs all patients were receiving curative-intent chemotherapy, dose modifications were made at the discretion of the medical oncologist. Among the four patients who required dose reduction, one patient with breast cancer underwent reduction due to grade 2 CIPN, and her relative dose intensity was 78.3%. The reasons for dose reduction in the other three patients were neutropenia, recent herpes zoster infection, and advanced age (81 years), respectively.\u003c/b\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e\u003ch2\u003eLongitudinal Changes in S-LANSS Scores and Nerve Conduction Study Findings\u003c/h2\u003e\u003cp\u003eBefore starting chemotherapy (T0), only 1 patient had S-LANSS over 12 points while the others all scored 0 points. However, all patients showed symptoms of neuropathy at T1, where all except 2 patients had S-LANSS over 12 points (from 1.29\u0026thinsp;\u0026plusmn;\u0026thinsp;4.81 at T0 to 14.29\u0026thinsp;\u0026plusmn;\u0026thinsp;4.23 at T1, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.0001). This significantly improved as time went by throughout T2 (from 14.29\u0026thinsp;\u0026plusmn;\u0026thinsp;4.23 at T1 to 9.64\u0026thinsp;\u0026plusmn;\u0026thinsp;5.05 at T2, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.003) and T3 (from 9.64\u0026thinsp;\u0026plusmn;\u0026thinsp;5.05 at T2 to 4.86\u0026thinsp;\u0026plusmn;\u0026thinsp;5.88 at T3, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.013). However, S-LANSS score did not restored the initial level even at 1 year after the completion of chemotherapy (1.29\u0026thinsp;\u0026plusmn;\u0026thinsp;4.81 at T0 vs. 4.86\u0026thinsp;\u0026plusmn;\u0026thinsp;5.88 at T3, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.023).\u003c/p\u003e\u003cp\u003eWhile distal latencies in the studied nerves did not show significant changes during the four timepoints, amplitudes of all studied nerves dropped immediately after chemotherapy. Amplitudes of sural, median and superficial radial SNAP recovered significantly at T3 compared with T1 (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.001, 0.002, and 0.006 for sural, median, and superficial radial SNAP, respectively), where largest improvement was shown between T1-T2 period for sural SNAP (\u003cem\u003ep\u0026thinsp;=\u003c/em\u003e\u0026thinsp;0.002) and T2-T3 period for median (\u003cem\u003ep\u0026thinsp;=\u003c/em\u003e\u0026thinsp;0.034) and superficial radial (\u003cem\u003ep\u0026thinsp;=\u003c/em\u003e\u0026thinsp;0.033) SNAP. Meanwhile, amplitudes of tibial CMAP and ulnar SNAP at T2 and T3 did not recover much and showed significant differences compared to the initial level (T3-T0, \u003cem\u003ep\u0026thinsp;=\u003c/em\u003e\u0026thinsp;0.048 and 0.0005 for tibial CMAP and ulnar SNAP, respectively). The detailed results of longitudinal changes in S-LANSS scores and NCS parameters are summarized in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e and Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eLongitudinal changes in nerve conduction study parameters and clinical symptom scales (S-LANSS, CTCAE)\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"6\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eT0\u003c/p\u003e\u003cp\u003e(n\u0026thinsp;=\u0026thinsp;14)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eT1\u003c/p\u003e\u003cp\u003e(n\u0026thinsp;=\u0026thinsp;14)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eT2\u003c/p\u003e\u003cp\u003e(n\u0026thinsp;=\u0026thinsp;14)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003eT3\u003c/p\u003e\u003cp\u003e(n\u0026thinsp;=\u0026thinsp;11)\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eNCS\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eAmplitude of tibial CMAP (\u0026micro;V)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e14.13\u0026thinsp;\u0026plusmn;\u0026thinsp;4.01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e11.15\u0026thinsp;\u0026plusmn;\u0026thinsp;3.59\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e11.33\u0026thinsp;\u0026plusmn;\u0026thinsp;3.22\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e12.14\u0026thinsp;\u0026plusmn;\u0026thinsp;3.70\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eAmplitude of sural SNAP (\u0026micro;V)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e14.36\u0026thinsp;\u0026plusmn;\u0026thinsp;6.50\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e7.50\u0026thinsp;\u0026plusmn;\u0026thinsp;6.92\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e13.17\u0026thinsp;\u0026plusmn;\u0026thinsp;8.13\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e15.53\u0026thinsp;\u0026plusmn;\u0026thinsp;8.91\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eAmplitude of median SNAP (\u0026micro;V)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e32.90\u0026thinsp;\u0026plusmn;\u0026thinsp;15.18\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e21.02\u0026thinsp;\u0026plusmn;\u0026thinsp;15.38\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e23.40\u0026thinsp;\u0026plusmn;\u0026thinsp;17.61\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e27.37\u0026thinsp;\u0026plusmn;\u0026thinsp;18.41\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eAmplitude of ulnar SNAP (\u0026micro;V)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e39.24\u0026thinsp;\u0026plusmn;\u0026thinsp;16.68\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e21.30\u0026thinsp;\u0026plusmn;\u0026thinsp;11.00\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e24.25\u0026thinsp;\u0026plusmn;\u0026thinsp;14.37\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e24.10\u0026thinsp;\u0026plusmn;\u0026thinsp;12.85\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eAmplitude of superficial radial SNAP (\u0026micro;V)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e37.77\u0026thinsp;\u0026plusmn;\u0026thinsp;15.25\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e27.87\u0026thinsp;\u0026plusmn;\u0026thinsp;12.10\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e29.98\u0026thinsp;\u0026plusmn;\u0026thinsp;14.63\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e34.31\u0026thinsp;\u0026plusmn;\u0026thinsp;15.71\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u003cp\u003e\u003cb\u003eS-LANSS Score\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.29\u0026thinsp;\u0026plusmn;\u0026thinsp;4.81\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e14.29\u0026thinsp;\u0026plusmn;\u0026thinsp;4.23\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e9.64\u0026thinsp;\u0026plusmn;\u0026thinsp;5.05\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e4.86\u0026thinsp;\u0026plusmn;\u0026thinsp;5.88\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u003cp\u003e\u003cb\u003eCTCAE grade\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eNE\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e2 (100%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e2 (100%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eGrade 1: 4 (29%)\u003c/p\u003e\u003cp\u003eGrade 2: 10 (71%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"6\"\u003eNotes: Changes of S-LANSS, amplitudes of tibial CMAP, sural, median, ulnar, and superficial radial SNAPs are shown as their mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation at four time points: prior to the initiation of chemotherapy (T0), at the completion (T1), three months after completion (T2) and one year after completion (T3) of scheduled chemotherapy. Peripheral neuropathy was also classified by CTCAE grade, version 5.0 (ranging from grade 1 (mild) to grade 5(death)).\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec12\" class=\"Section2\"\u003e\u003ch2\u003eCorrelations Between Subjective and Objective Measures\u003c/h2\u003e\u003cp\u003eSome of the objective measures showed significant correlation with subjective measures. Distal latency of sural SNAP showed positive correlation with S-LANSS and CTCAE, while amplitudes of sural, median, ulnar, and superficial radial SNAP, and amplitude of tibial CMAP showed negative correlation with them. Correlation with S-LANSS was stronger in amplitudes of ulnar SNAP (r = -0.523, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.0001) and tibial CMAP (r = -0.467, \u003cem\u003ep\u0026thinsp;=\u003c/em\u003e\u0026thinsp;0.0005), which were two nerves that did not show much improvements in amplitudes until T3. Correlation with CTCAE was also stronger in amplitudes of ulnar SNAP (r = -0.470, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.0003). Detailed correlation analyses between subjective and objective measures are presented in Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eCorrelations between nerve conduction study parameters and clinical symptom scales (S-LANSS, CTCAE)\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"3\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eParameter\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eS-LANSS (\u003cem\u003er\u003c/em\u003e, \u003cem\u003ep\u003c/em\u003e-value)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eCTCAE (\u003cem\u003er\u003c/em\u003e, \u003cem\u003ep\u003c/em\u003e-value)\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTibial CMAP amplitude\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e-0.467, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.0005\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e-0.359, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.007\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSural SNAP latency\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.328, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.028\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.317, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.036\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSural SNAP amplitude\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e-0.275, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.049\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e-0.308, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.0422\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMedian SNAP amplitude\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e-0.423, \u003cem\u003ep\u0026thinsp;=\u003c/em\u003e\u0026thinsp;0.002\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e-0.335, \u003cem\u003ep\u0026thinsp;=\u003c/em\u003e\u0026thinsp;0.013\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eUlnar SNAP amplitude\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e-0.523, \u003cem\u003ep\u0026thinsp;\u0026lt;\u003c/em\u003e\u0026thinsp;0.0001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e-0.470, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.0003\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSuperficial radial SNAP amplitude\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e-0.341, \u003cem\u003ep\u0026thinsp;=\u003c/em\u003e\u0026thinsp;0.013\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e-0.344, \u003cem\u003ep\u0026thinsp;=\u003c/em\u003e\u0026thinsp;0.010\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"3\"\u003eNotes: Correlation of S-LANSS and CTCAE between NCS parameters were described by their correlation coefficient(\u003cem\u003er\u003c/em\u003e) and p-value.\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd colspan=\"3\"\u003e*P\u0026thinsp;\u0026lt;\u0026thinsp;0.05 by Pearson correlation test.\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd colspan=\"3\"\u003eAbbreviation: NCS; nerve conduction study, SNAP; sensory nerve action potentials, CMAP; compound motor action potentials, S-LANSS; self‑reported Leeds Assessment of Neuropathic Symptoms, and CTCAE; Common Terminology Criteria for Adverse Events.\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec13\" class=\"Section2\"\u003e\u003ch2\u003eRecovery Patterns and Persistence at 1-Year Follow-Up\u003c/h2\u003e\u003cp\u003eOur longitudinal analysis revealed distinct recovery patterns among sensory nerves following chemotherapy. The sural nerve demonstrated the highest vulnerability immediately after treatment, with 64% of patients experiencing a\u0026thinsp;\u0026ge;\u0026thinsp;30% reduction in amplitude; however, this proportion decreased to 21% at one year, suggesting partial recovery. In contrast, the median and ulnar nerves exhibited more persistent reductions, with over half of patients still meeting the \u0026ge;\u0026thinsp;30% decline criterion at one year, indicating limited reversibility of neurotoxic injury. The superficial radial nerve displayed a delayed worsening at three months, followed by partial improvement at one year (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eProportion of patients with \u0026ge;\u0026thinsp;30% reduction in sensory nerve action potential (SNAP) amplitudes at each time point\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"4\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNerve\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eAmplitude\u0026thinsp;\u0026gt;\u0026thinsp;30% drop at T1\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eAmplitude\u0026thinsp;\u0026gt;\u0026thinsp;30% drop at T2\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eAmplitude\u0026thinsp;\u0026gt;\u0026thinsp;30% drop at T3\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTibial\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e36% (N\u0026thinsp;=\u0026thinsp;5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e36% (N\u0026thinsp;=\u0026thinsp;5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e29% (N\u0026thinsp;=\u0026thinsp;4)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSural\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e64% (N\u0026thinsp;=\u0026thinsp;9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e29% (N\u0026thinsp;=\u0026thinsp;4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e21% (N\u0026thinsp;=\u0026thinsp;3)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMedian\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e57% (N\u0026thinsp;=\u0026thinsp;8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e57% (N\u0026thinsp;=\u0026thinsp;8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e57% (N\u0026thinsp;=\u0026thinsp;8)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eUlnar\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e64% (N\u0026thinsp;=\u0026thinsp;9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e64% (N\u0026thinsp;=\u0026thinsp;9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e57% (N\u0026thinsp;=\u0026thinsp;7)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSuperficial Radial\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e29% (N\u0026thinsp;=\u0026thinsp;4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e57% (N\u0026thinsp;=\u0026thinsp;5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e29% (N\u0026thinsp;=\u0026thinsp;4)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"4\"\u003eNotes: The proportion of patients with a\u0026thinsp;\u0026ge;\u0026thinsp;30% reduction in nerve amplitude at each time point (T1: post-chemotherapy, T2: 3 months post-chemotherapy, T3: 12 months post-chemotherapy) compared to baseline (T0)\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis prospective study provides valuable insights into the natural history of paclitaxel-induced peripheral neuropathy, integrating both objective neurophysiological evaluations and subjective patient-reported outcomes. As medical oncologists, one of the primary challenges in clinical practice is the early detection and management of CIPN, which not only affects patients\u0026rsquo; quality of life but also directly impacts treatment adherence and efficacy [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eOur findings align with prior research demonstrating that serial nerve conduction studies offer a feasible and clinically informative approach when combined with validated symptom assessment tools like the S-LANSS questionnaire, as evidenced by studies showing modest correlations between NCS parameters and patient-reported neuropathic symptoms [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. The combination of these methods allows for a more comprehensive evaluation of neurotoxicity progression and potential recovery. [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e] Importantly, our longitudinal data reveal that although partial recovery of both S-LANSS scores and SNAP amplitudes occurred after chemotherapy cessation, these measures did not return to baseline values even after one year, providing electrophysiological evidence of sustained subclinical axonal injury. This pattern is consistent with previous reports that paclitaxel-induced neuropathy is often long-lasting and incompletely reversible, with some patients experiencing symptoms for years after treatment completion [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. Taken together, these results highlight that CIPN after taxane chemotherapy is not easily reversible and may represent a chronic toxicity rather than a transient adverse effect.\u003c/p\u003e\u003cp\u003eFurthermore, our analysis of \u0026ge;\u0026thinsp;30% reductions in SNAP amplitude across multiple sensory nerves underscores heterogeneity in recovery patterns. For example, consistent with previous prospective study reporting preferential vulnerability of certain nerves to platinum- and taxane-based chemotherapy [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e], our data revealed early sural involvement but partial recovery within one year, whereas median nerve injury remained largely persistent across all time points. Similar findings have also been documented in study of vincristine-induced neuropathy, where both sural and non-sural nerves demonstrated sustained SNAP reductions, reinforcing that each nerve follows a distinct pattern of damage and recovery [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. Our extended monitoring further reveals unique recovery dynamics, such as modest ulnar improvement (from 64\u0026ndash;57%) and fluctuating superficial radial changes, potentially explaining varied patient symptom profiles despite uniform treatment exposures. These findings indicate that CIPN reflects heterogeneous nerve susceptibilities, underscoring the need for tailored monitoring and survivorship strategies.\u003c/p\u003e\u003cp\u003eFrom an oncologist\u0026rsquo;s perspective, the timing and severity of CIPN should inform therapeutic decisions, especially in curative settings where dose intensity must be balanced with long-term survivorship. The utility of serial NCS in identifying high-risk patients for persistent neuropathy, as seen in our data with early sural and ulnar reductions, supports timely dose modifications or neuroprotective interventions, aligning with ASCO guidelines emphasizing proactive management [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eMoreover, while CTCAE grading remains the standard in clinical trials, our findings emphasize the added value of patient-reported outcomes and physiologic measurements in real-world clinical settings. CTCAE grading alone often underestimates the burden of neuropathy [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. For instance, several patients with significant SNAP amplitude reductions did not show corresponding increases in CTCAE grade. In our study, all patients were assigned CTCAE grade 2 at T1 and T2, even though S-LANSS and NCS parameters showed variable changes after chemotherapy. This suggests that a multidimensional approach\u0026mdash;integrating CTCAE grading, NCS, and patient-reported outcomes\u0026mdash;may provide a more accurate and clinically meaningful assessment of CIPN, in line with prior reports that CTCAE alone often underestimates CIPN severity compared with patient-reported and physiologic assessments.\u003c/p\u003e\u003cp\u003eNevertheless, this study has several limitations. The sample size was modest, and follow-up attrition may have introduced selection bias. Additionally, we did not evaluate genetic or biochemical predictors of neuropathy, which could enhance risk stratification. In addition, distal latency data from severely affected patients were excluded from the analysis, as eight NCS parameters from four patients showed absent responses. While absent amplitudes could be imputed as zero, it was not feasible to assign arbitrary values for absent latencies. Consequently, the potential significance of distal latency changes may have been underestimated, although it is well established that paclitaxel-induced peripheral neuropathy predominantly causes axonal loss, primarily reflected in reduced SNAP amplitudes. Future studies incorporating biomarkers and interventions (e.g., duloxetine, exercise, cryotherapy) are needed to move toward personalized prevention and management of CIPN.\u003c/p\u003e\u003cp\u003eIn conclusion, this study demonstrates that paclitaxel-induced peripheral neuropathy can persist long after treatment and shows variable recovery trajectories among patients. We should recognize the limitations of relying solely on CTCAE grading and integrate both subjective and objective tools, such as NCS and S-LANSS, into routine clinical assessments where feasible. Early identification of high-risk patients through longitudinal monitoring may enable more proactive management and mitigate the long-term burden of CIPN. Our findings underscore the need for further research into effective prevention strategies and reinforce the importance of patient-centered survivorship care in oncology.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAuthor contributions\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eConceptualization: MiRi Suh, Seul-Gi Kim, Yong Wha Moon; Methodology: MiRi Suh, Seul-Gi Kim, Yong Wha Moon; Formal analysis and investigation: Ikhyun Lim, MiRi Suh, Seul-Gi Kim; Writing - original draft preparation: Ikhyun Lim, MiRi Suh, Seul-Gi Kim; Writing review and editing: Ikhyun Lim, MiRi Suh, Seul-Gi Kim; Funding acquisition: Seul-Gi Kim, Yong Wha Moon; Supervision: MiRi Suh, Seul-Gi Kim\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was supported by Samyang Holdings Corp.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe de-identified individual-level participant data of this study can be provided to researchers upon request by e-mail. Please send inquiries to the corresponding. A detailed proposal for how the data will be used is required, and we will review on a case-by-case basis. A data access agreement must also be signed for these data to be transferred.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthical approval\u0026nbsp;\u003c/strong\u003eThis study was approved by the Institutional Review Board of Bundang CHA Medical Center (IRB No.2022-03-081), and the study was conducted in accordance with the Declaration of Helsinki.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent to participate\u003c/strong\u003e Written informed consent was obtained from all participants prior to enrollment.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e This study did not include any personal data.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e The authors declare no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eRole of the funder/sponsor\u0026nbsp;\u003c/strong\u003eThe funder had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eWu S, Xiong T, Guo S, Zhu C, He J, Wang S (2023) An up-to-date view of paclitaxel-induced peripheral neuropathy. 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Cancer Sci 107:1453\u0026ndash;1457. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1111/cas.13010\u003c/span\u003e\u003cspan address=\"10.1111/cas.13010\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eTan AC, McCrary JM, Park SB, Trinh T, Goldstein D (2019) Chemotherapy-induced peripheral neuropathy-patient-reported outcomes compared with NCI-CTCAE grade. Support Care Cancer 27:4771\u0026ndash;4777. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1007/s00520-019-04781-6\u003c/span\u003e\u003cspan address=\"10.1007/s00520-019-04781-6\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Chemotherapy-induced peripheral neuropathy, Paclitaxel, Nerve conduction studies, S-LANSS questionnaire, Neurotoxicity","lastPublishedDoi":"10.21203/rs.3.rs-7523495/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7523495/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003ePurpose\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eChemotherapy-induced peripheral neuropathy (CIPN) is a common and debilitating toxicity of paclitaxel that can compromise treatment adherence and survivorship. We aimed to prospectively characterize the natural history of paclitaxel-induced peripheral neuropathy by integrating objective neurophysiological assessments with patient-reported outcomes.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIn this prospective study, 26 patients scheduled to receive paclitaxel-based chemotherapy for breast, ovarian, or endometrial cancer were enrolled. Serial evaluations were performed at baseline (T0), immediately post-chemotherapy (T1), three months after completion (T2), and one-year post-treatment (T3). Nerve conduction studies (NCS) of sensory and motor nerves, the self-reported Leeds Assessment of Neuropathic Symptoms and Signs (S-LANSS) questionnaire, and Common Terminology Criteria for Adverse Events (CTCAE) grading were conducted at each time point. Correlations between subjective and objective measures were analyzed.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eFourteen patients who completed serial assessments up to T2 were included in the final analysis. At T1, S-LANSS scores increased significantly from baseline (1.29 ± 4.81 to 14.29 ± 4.23, \u003cem\u003ep \u0026lt;\u003c/em\u003e 0.0001), with partial improvement at T2 and T3, though not fully returning to baseline. While distal latencies showed no significant changes, amplitudes of all studied nerves decreased immediately after chemotherapy. Partial recovery was observed in sural, median, and superficial radial sensory nerve action potentials (SNAPs), whereas tibial compound motor action potential (CMAP) and ulnar SNAP showed minimal recovery and remained significantly impaired at one year. Correlation analyses showed significant associations between patient-reported symptoms and NCS parameters, particularly for ulnar SNAP (r = –0.523, \u003cem\u003ep \u0026lt;\u003c/em\u003e0.0001) and tibial CMAP (r = –0.467, \u003cem\u003ep\u003c/em\u003e = 0.0005). Analysis of ≥30% SNAP reductions revealed heterogeneity in recovery trajectories, with early sural involvement showing partial recovery, while median and ulnar nerve impairments persisted.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePaclitaxel-induced peripheral neuropathy persists long after treatment and demonstrates heterogeneous recovery patterns across nerves. Reliance solely on CTCAE grading may underestimate neuropathy burden; integration of patient-reported outcomes and NCS provides a more comprehensive evaluation. Early identification of high-risk patients through longitudinal monitoring may guide proactive management strategies and mitigate the long-term impact of CIPN.\u003c/p\u003e","manuscriptTitle":"Natural History of Chemotherapy-Induced Peripheral Neuropathy in Paclitaxel-Treated Patients: A Prospective Analysis Using Nerve Conduction Studies and S-LANSS Questionnaires","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-11-05 06:27:48","doi":"10.21203/rs.3.rs-7523495/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"1b71fdcc-f480-44f9-a338-358339c3a8ad","owner":[],"postedDate":"November 5th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-12-10T18:08:51+00:00","versionOfRecord":[],"versionCreatedAt":"2025-11-05 06:27:48","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7523495","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7523495","identity":"rs-7523495","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}