[Paraneoplastic Disorders of Peripheral Nervous System].

Paraneoplastic disorders of the peripheral nervous system are immune-mediated neurological syndromes associated with tumors. Several clinical phenotypes have been associated with these disorders. Sensory neuronopathy is the most well-known clinical phenotype, and is caused by neuronal cell injury to the dorsal root ganglia. Symptoms of the peripheral nervous system usually lead to the discovery of tumors. Antineuronal antibodies are occasionally identified in the serum and/or cerebrospinal fluid of these patients. The prevalence of small-cell lung cancer is notable in these patients. Early tumor resection, coupled with the initiation of immunotherapy, may prove effective in improving and stabilizing clinical symptoms.

[Sarcoid Peripheral Neuropathy and Myopathy: A Diagnostic and Therapeutic Challenge].

Sarcoidosis is an idiopathic granulomatous multi-organ disease, primarily affecting the respiratory system, eyes, and skin, with less involvement in peripheral neurons and muscles. Sarcoid peripheral neuropathy encompasses cranial and spinal nerve impairment. Muscle involvement is often asymptomatic and revealed through imaging. Symptomatic muscle involvement is categorized into three clinical types: nodular myopathy, acute myopathy, and chronic myopathy. The identification of noncaseating granulomas in peripheral nerves or muscles, coupled with the exclusion of other diseases, is essential for establishing a definitive diagnosis of sarcoid peripheral neuropathy and myopathy. Sarcoid neuropathy and myopathy are typically managed with high-dose corticosteroids, immunosuppressants, or a combination of both. In recent times, the use of TNF-alpha inhibitors has notably increased. However, these conditions often exhibit resistance to treatment and may necessitate prolonged therapeutic interventions. Therefore, comprehensive examinations should be conducted before considering immunotherapy. Due to the rarity of these conditions, research on manifestation-specific treatments is lacking, and standard treatments for sarcoid neuropathy and myopathy have not been established. Additional treatment options for sarcoid neuropathy and myopathy are expected to become available in the future.

Bortezomib-induced peripheral neuropathy: Clinical features, molecular basis, and therapeutic approach.

Bortezomib is the first-line standard and most effective chemotherapeutic for multiple myeloma; however, bortezomib-induced peripheral neuropathy (BIPN) severely affects the chemotherapy regimen and has long-term impact on patients under maintenance therapy. The pathogenesis of BIPN is poorly understood, and basic research and development of BIPN management drugs are in early stages. Besides chemotherapy dose reduction and regimen modification, no recommended prevention and treatment approaches are available for BIPN apart from the International Myeloma Working Group guidelines for peripheral neuropathy in myeloma. An in-depth exploration of the pathogenesis of BIPN, development of additional therapeutic approaches, and identification of risk factors are needed. Optimizing effective and standardized BIPN treatment plans and providing more decision-making evidence for clinical diagnosis and treatment of BIPN are necessary. This article reviews the recent advances in BIPN research; provides an overview of clinical features, underlying molecular mechanisms, and therapeutic approaches; and highlights areas for future studies.

Summary of evidence on comprehensive healthcare for chemotherapy-induced peripheral neuropathy in cancer patients.

OBJECTIVE: This paper aims to provide an evidence-based summary of the most effective strategies for comprehensive healthcare of chemotherapy-induced peripheral neuropathy (CIPN) in cancer patients. METHOD: Following the "6S" model, relevant evidence on CIPN management was collected from reputable evidence-based resource websites and databases nationally and internationally. The included articles were evaluated for methodological quality, and evidence was extracted using the Australian JBI Evidence-based Health Care Center's literature evaluation standard (2016 edition). RESULTS: A total of 60 articles were included in this study, comprising 2 guidelines, 5 expert consensus statements, and 53 systematic reviews. The findings of these articles were summarized across 7 dimensions, including risk factor screening, assessment, diagnosis, prevention, treatment, management, and health education, resulting in the identification of 42 relevant pieces of evidence. CONCLUSIONS: This study provides a comprehensive synthesis of evidence-based recommendations for managing CIPN in cancer patients, offering guidance for healthcare professionals engaged in clinical practice. However, when implementing these recommendations, it is crucial to consider the individual patient's clinical circumstances, preferences, and expert judgment, ensuring feasibility and applicability in real-world clinical settings.

A qualitative evaluation of the oncologists', neurologists', and pain specialists' views on the management and care of chemotherapy-induced peripheral neuropathy in The Netherlands.

PURPOSE: In treating cancer, different chemotherapy regimens cause chemotherapy-induced peripheral neuropathy (CIPN). Despite recent international guidelines, a gold standard for diagnosis, treatment, and care is lacking. To identify the current clinical practice and the physicians' point of view and ideas for improvement, we evaluated CIPN care by interviewing different specialists involved. METHODS: We performed semi-structured, audio-recorded, transcribed, and coded interviews with a purposive sample of oncologists, pain specialists, and neurologists involved in CIPN patients' care. Data is analyzed by a constant comparative method for content analysis, using ATLAS.ti software. Codes, categories, and themes are extracted, generating common denominators and conclusions. RESULTS: With oncologists, pain specialists, and neurologists, nine, nine, and eight interviews were taken respectively (including three, two, and two interviews after thematic saturation occurred). While useful preventive measures and predictors are lacking, patient education (e.g., on symptoms and timely reporting) is deemed pivotal, as is low-threshold screening (e.g., anamnesis and questionnaires). Diagnosis focusses on a temporal relationship to chemotherapy, with adjuvant testing (e.g., EMG) used in severe or atypical cases. Symptomatic antineuropathic and topical medication are often prescribed, but personalized and multidimensional care based on individual symptoms and preferences is highly valued. The limited efficacy of existing treatments, and the lack of standardized protocols, interdisciplinary coordination, and awareness among healthcare providers pose significant challenges. CONCLUSION: Besides the obvious need for better therapeutic options, and multidisciplinary exploration of patients' perspectives, a structured and collaborative approach towards diagnosis, treatment, referral, and follow-up, nurtured by improving knowledge and use of existing CIPN guidelines, could enhance care.

Gene therapy approaches for obesity-induced adipose neuropathy: Device-targeted AAV-mediated neurotrophic factor delivery to adipocytes in subcutaneous adipose.

Maintaining functional adipose innervation is critical for metabolic health. We found that subcutaneous white adipose tissue (scWAT) undergoes peripheral neuropathy (PN) with obesity, diabetes, and aging (reduced small-fiber innervation and nerve/synaptic/growth-cone/vesicle markers, altered nerve activity). Unlike with nerve injuries, peripheral nerves do not regenerate with PN, and therefore new therapies are needed for treatment of this condition affecting 20-30 million Americans. Here, we validated a gene therapy approach using an adipocyte-tropic adeno-associated virus (AAV; serotype Rec2) to deliver neurotrophic factors (brain-derived neurotrophic factor [BDNF] and nerve growth factor [NGF]) directly to scWAT to improve tissue-specific PN as a proof-of-concept approach. AAVRec2-BDNF intra-adipose delivery improved tissue innervation in obese/diabetic mice with PN, but after longer periods of dietary obesity there was reduced efficacy, revealing a key time window for therapies. AAVRec2-NGF also increased scWAT innervation in obese mice and was more effective than BDNF, likely because Rec2 targeted adipocytes, the tissue's endogenous NGF source. AAVRec2-NGF also worked well even after 25 weeks of dietary obesity, unlike BDNF, which likely needs a vector that targets its physiological cellular source (stromal vascular fraction cells). Given the differing effects of AAVs carrying NGF versus BDNF, a combined therapy may be ideal for PN.

Paraneoplastic neuropathies and peripheral nerve hyperexcitability disorders.

Peripheral neuropathy is a common referral for patients to the neurologic clinics. Paraneoplastic neuropathies account for a small but high morbidity and mortality subgroup. Symptoms include weakness, sensory loss, sweating irregularity, blood pressure instability, severe constipation, and neuropathic pain. Neuropathy is the first presenting symptom of malignancy among many patients. The molecular and cellular oncogenic immune targets reside within cell bodies, axons, cytoplasms, or surface membranes of neural tissues. A more favorable immune treatment outcome occurs in those where the targets reside on the cell surface. Patients with antibodies binding cell surface antigens commonly have neural hyperexcitability with pain, cramps, fasciculations, and hyperhidrotic attacks (CASPR2, LGI1, and others). The antigenic targets are also commonly expressed in the central nervous system, with presenting symptoms being myelopathy, encephalopathy, and seizures with neuropathy, often masked. Pain and autonomic components typically relate to small nerve fiber involvement (nociceptive, adrenergic, enteric, and sudomotor), sometimes without nerve fiber loss but rather hyperexcitability. The specific antibodies discovered help direct cancer investigations. Among the primary axonal paraneoplastic neuropathies, pathognomonic clinical features do not exist, and testing for multiple antibodies simultaneously provides the best sensitivity in testing (AGNA1-SOX1; amphiphysin; ANNA-1-HU; ANNA-3-DACH1; CASPR2; CRMP5; LGI1; PCA2-MAP1B, and others). Performing confirmatory antibody testing using adjunct methods improves specificity. Antibody-mediated demyelinating paraneoplastic neuropathies are limited to MAG-IgM (IgM-MGUS, Waldenström's, and myeloma), with the others associated with cytokine elevations (VEGF, IL6) caused by osteosclerotic myeloma, plasmacytoma (POEMS), and rarely angiofollicular lymphoma (Castleman's). Paraneoplastic disorders have clinical overlap with other idiopathic antibody disorders, including IgG4 demyelinating nodopathies (NF155 and Contactin-1). This review summarizes the paraneoplastic neuropathies, including those with peripheral nerve hyperexcitability.

Home-based high tone therapy may alleviate chemotherapy-induced neuropathic symptoms in patients with colorectal cancer: A randomized double-blind placebo-controlled pilot evaluation.

BACKGROUND: Most oncologic patients receiving chemotherapy suffer from neuropathy, which not only severely affects quality of life but also may lead to chemotherapy dose reductions or even discontinuation of cancer therapy. Still, it is difficult to sufficiently control these symptoms with the currently available pharmacological treatments. High tone therapy was reported to be an effective option for neuropathies due to different etiologies. However, to date, there are no studies on high tone therapy in patients with chemotherapy-induced peripheral neuropathy. METHODS: This randomized, double-blind, and placebo-controlled two-center study was conducted at the Departments of Physical and Rehabilitation Medicine at the Clinics Donaustadt and Ottakring, Vienna, Austria. Patients with histologically verified colorectal carcinoma treated with a platin derivate and neuropathic symptoms were invited to participate. High tone therapy took place in a home-based setting using the HiToP 191 PNP ® or placebo device for three weeks. Neuropathic symptoms and quality of life were assessed via questionnaires. After the follow-up examination, an opt-in was offered to the patients in the placebo group in terms of an open-label treatment with a verum HiToP PNP ® device. In addition, patients with chemotherapy-induced peripheral neuropathy due to various malignant diseases were treated in an open-label setting reflecting a clinical application observation. These patients are reported as a separate group. RESULTS: In the verum group, there was a significant reduction of paresthesias and mental stress due to paresthesias from baseline until end of therapy, compared to placebo. These findings were observed in the opt-in subgroup, as well. In the open-label clinical application observation group, intensity and mental stress due to paresthesia, pain, cramps, and intensity of tightness/pressure were significantly lower at the end of therapy, compared to baseline. CONCLUSIONS: Home-based high tone therapy brought about a significant alleviation in paresthesias and mental stress due to paresthesias in the verum but not the placebo group. In the clinical application observation, a significant alleviation in several further neuropathic symptoms was seen. TRIAL REGISTRATION: This study was registered at clinicaltrials.gov (NCT06048471, 03/02/2020).

Electroacupuncture use for treatment of taxane-induced peripheral neuropathy in patients with breast cancer: protocol for a pilot, randomised, blinded, sham-controlled trial (EA for CIPN).

INTRODUCTION: Chemotherapy-induced peripheral neuropathy (CIPN) is a common dose-limiting side effect of neurotoxic chemotherapy. Acute symptoms of CIPN during treatment can lead to dose reduction and cessation. Trials using electroacupuncture (EA) to treat established CIPN postchemotherapy have shown some efficacy. The current trial aims to assess the feasibility and preliminary efficacy of using EA to treat CIPN during chemotherapy. METHODS AND ANALYSIS: The current study is a single-centre, 1:1 randomised, sham-controlled pilot study set in a tertiary cancer hospital in Sydney, Australia, and will recruit 40 adult patients with early breast cancer undergoing adjuvant or neoadjuvant paclitaxel chemotherapy. Patients who develop CIPN within the first 6 weeks of chemotherapy will receive either true EA or sham-EA once a week for 10 weeks. The coprimary endpoints are recruitment and adherence rate, successful blinding of patients and compliance with the follow-up period. Secondary endpoints are mean change of CIPN symptoms from randomisation to end of treatment, sustained change in CIPN symptoms at 8-week and 24-week follow-up postchemotherapy, proportion of subjects attaining completion of 12 weeks of chemotherapy without dose reduction or cessation, change in acupuncture expectancy response pretreatment, during treatment and posttreatment. The primary assessment tool for the secondary endpoints will be a validated patient-reported outcome measure (European Organisation for Research and Treatment of Cancer Quality of Life Chemotherapy-Induced Peripheral Neuropathy) captured weekly from randomisation to week 12 of chemotherapy. ETHICS AND DISSEMINATION: The study protocol (2021/ETH12123) has been approved by the institutional Human Research Ethics Committee at St Vincent's Hospital Sydney and Chris O'Brien Lifehouse. Informed consent will be obtained prior to starting study-related procedures. The results will be disseminated in peer-reviewed journals and at scientific conferences. TRIAL REGISTRATION NUMBER: ACTRN12622000081718.

Complementary and alternative medicine in relation to chemotherapy-induced peripheral neuropathy: A narrative review.

PURPOSE: To summarizes the available evidence on the effectiveness, safety, and feasibility of complementary and alternative medicine (CAM) in the management of chemotherapy-induced peripheral neuropathy (CIPN). METHODS: We searched for systematic reviews, and meta-analyzes published up to April 2023 in the Pubmed and Web of Science databases. The latest original research on related topics was also reviewed. The search was restricted to English-language papers. Two independent reviewers performed a quality assessment of the identified literature. RESULTS: The results of 35 systematic reviews and meta-analyzes were included in this study. Preliminary evidence suggests that CAM, including acupuncture, physical activity (PA), herbal and nutritional supplements, mind-body therapies, touch therapy, and non-invasive neuromodulation techniques, have shown tremendous potential for the prevention and treatment of CIPN. Of these, there is strong evidence supporting acupuncture, PA, and herbal medicine. However, existing clinical studies are also limited by the heterogeneity of study methods, insufficient sample size, and poor study design. Further studies are needed to validate the efficacy of CAM in patients with CIPN and to elucidate potential therapeutic mechanisms. CONCLUSIONS: Current research has reached a preliminary conclusion suggesting the potential efficacy of certain CAMs in the management of CIPN. Future clinical trials should incorporate more robust study design protocols and larger sample sizes to enhance the validity of findings.

Efficacy and safety of mirogabalin for chemotherapy-induced peripheral neuropathy: a prospective single-arm trial (MiroCIP study).

BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) is a painful, dose-limiting adverse effect of commonly used chemotherapeutic agents. The purpose of this exploratory study was to evaluate the efficacy and safety of mirogabalin in patients with moderate to severe CIPN during chemotherapy and the effects of 12 weeks' intervention on chemotherapy completion and CIPN severity. METHODS: Patients experiencing moderate to severe CIPN while undergoing oxaliplatin- or taxane-containing chemotherapy for colorectal, gastric, non-small-cell lung, or breast cancer received mirogabalin at between 5 and 15 mg twice daily. The primary endpoint was change in numeric rating scale (NRS) score for pain from baseline to week 12. Secondary endpoints included NRS scores for tingling and sleep, completion of chemotherapy, severity of CIPN, and quality of life (QOL) scores. The safety endpoint was incidence of adverse events. RESULTS: Of 58 patients who consented to participation, 52 were eligible and constituted the full analysis set and safety analysis set. From baseline to week 12 (last observation carried forward [LOCF]), NRS score decreased by 30.9%: mean change (95% confidence interval [CI]), - 1.7 (- 2.4 to - 1.0) (p < 0.001). Patients with baseline NRS of ≥ 6 experienced a 44.0% reduction in score from baseline to week 12 (LOCF): mean change (95% CI), - 3.3 (- 5.0 to - 1.5) (p = 0.002). Chemotherapy was discontinued in 18 (34.6%) patients; CIPN led to discontinuation in only 2 (3.8%). There was no notable worsening of CIPN severity in terms of Common Terminology Criteria for Adverse Events grade or Modified Total Neuropathy Score-reduced, although use of pain medications during chemotherapy might cause worsening of CIPN due to underestimation of subjective symptoms. QOL score based on the EuroQol five-dimensional descriptive system did not worsen during the 12 weeks. Thirty-one percent of patients experienced adverse drug reactions, and the most common event was somnolence (13.5%). Serious adverse events and death occurred in 3 patients and 1 patient, respectively; however, they were unrelated to mirogabalin treatment. CONCLUSIONS: Intervention with mirogabalin during chemotherapy may be effective and safe for cancer patients with moderate to severe CIPN. It can contribute to completion of chemotherapy without worsening of CIPN. TRIAL REGISTRATION: Japan Registry of Clinical Trials (jRCTs031210101, registered 20/5/2021).

Living with chemotherapy-induced peripheral neuropathy: a nested qualitative study.

BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) is a dose-limiting side-effect for patients undergoing a variety of chemotherapy regimens. These effects can have a detrimental impact on patients' quality of life and ability to perform everyday tasks. OBJECTIVE: This study aimed to explore the experience of living with CIPN prior to and while participating in a randomised study of acupuncture versus a control wait group. DESIGN: The study was nested within a randomised trial (n=120) with participants randomised to acupuncture or to control (wait list for acupuncture). METHOD: Participants (n=23) volunteered to be interviewed either by telephone (n=20) or face to face (n=3). The audiotapes produced were transcribed verbatim and analysed using a thematic approach. RESULTS: Four themes developed; these included daily life with CIPN, signs and symptoms, interacting with others and management of CIPN. Patients reported compromised dexterity and ability to safely carry out activities. They were often reliant on help and sought out information from others living with the condition. There were also concerns about the lack of effectiveness and the side-effects of medication prescribed. CONCLUSION: Participants were self-selecting volunteers across different cancer groups, but the information gathered could influence future study designs and increase understanding of the impact of CIPN on patients' lives.

Autoimmune Axonal Neuropathies.

OBJECTIVE: This article reviews autoimmune axonal neuropathies, their characteristic clinical features, disease and antibody associations, appropriate ancillary testing, treatment, and prognosis. LATEST DEVELOPMENTS: In 2021, the American College of Rheumatology and the Vasculitis Foundation released new summary guidelines for the treatment of antineutrophil cytoplasmic autoantibody-associated vasculitides. In addition, novel autoantibodies have been recently identified; they are often paraneoplastic and associated with axonal neuropathies. ESSENTIAL POINTS: Recognition of autoimmune axonal neuropathies is important because of the potential for effective treatment to either reverse deficits or slow the progression of disease. It is necessary to properly assess for associations with other systemic disorders (eg, systemic vasculitis, connective tissue disease, neoplasm) so that adequate treatment for both neurologic and non-neurologic aspects of the disease can be initiated.

Toxic Neuropathies.

OBJECTIVE: The purpose of this article is to provide an overview and update on the most clinically relevant toxic neuropathies. LATEST DEVELOPMENTS: Broadly, toxic neuropathies were previously quite rare with the notable exception of neuropathy from alcohol or older chemotherapeutics. The development of newer therapies, particularly immunotherapy to treat malignancy, has resulted in a substantial increase in the occurrence of toxic neuropathies that require timely recognition and treatment. The understanding of other toxic neuropathies continues to evolve, such as statin-induced neuropathy, which new evidence suggests is much less common than previously suspected. ESSENTIAL POINTS: Toxic neuropathies can be caused by medications, supplements, and recreational substances that injure peripheral nerves. Medications have evolved in the past 2 decades, as have the types of neuropathies that can be seen as related toxicities. In some areas of medicine, new classes and generations of drugs are associated with a lower incidence of toxic neuropathy.

Nutritional Neuropathies.

OBJECTIVE: This article reviews the etiologies, presentations, and management of neuropathies related to nutritional deficiencies. LATEST DEVELOPMENTS: Peripheral neuropathy can be the predominant or only manifestation of certain nutrient deficiencies. Cognitive difficulties or involvement of other parts of the central nervous system, such as the optic nerve and spinal cord, may accompany nutritional peripheral neuropathies. In most patients, the nutritional deficiency may have a single predominant cause, but in some cases, multiple causes may coexist. Obesity, for unclear reasons, can be associated with nutrient deficiencies. The rising rates of bariatric surgery and the incidence of nutrient deficiencies following bariatric surgery make this a particularly relevant topic for neurologists. ESSENTIAL POINTS: Neuropathies caused by nutrient deficiencies are preventable with appropriate supplementation in high-risk situations. Early recognition and prompt treatment are essential to ensure an optimal outcome and minimize neurologic morbidity.

The Efficacy of Acupuncture in the Treatment of Chemotherapy-Induced Peripheral Neuropathy: A Network Meta-Analysis.

Background: Chemotherapy-induced peripheral neuropathy (CIPN), one of the most common adverse events associated with chemotherapy, may affect efficacy because of the interruption of chemotherapy or change of regimen in severe cases, and may even increase cancer mortality. Relevant data supports the evidence that acupuncture can treat pain and sensory abnormalities. However, choosing the most effective acupuncture therapy is difficult because of the lack of evidence-based medicine and comparisons between different acupuncture therapies for treating CIPN. The aim of this study was to use a network meta-analysis (NMA) to evaluate the efficacy of different acupuncture therapies for CIPN. Methods: We searched Embase, PubMed, Web of Science, The Cochrane Library, The Chinese Journal Full Text Database, Chinese Biomedical Literature Database, and WanFang Database for randomized controlled trials (RCTs) of acupuncture for CIPN. The search period was from the creation of the relevant library to August 10, 2023. A total of 2 investigators independently performed literature screening, data extraction, and risk for bias evaluation. Stata 14.0 software (StataCorp LLC, College Station, Texas USA), was used for the NMA. Results: A total of 13 eligible RCTs involving 746 patients and 6 acupuncture therapies were included in the study. The NMA results showed that electroacupuncture was superior to moxibustion, manual acupuncture, acupoint injection and Western medicine in improving the total effective rate of treatment of CIPN; electroacupuncture + moxibustion was better than manual acupuncture, acupoint injection, and Western medicine. Manual acupuncture's total effective rate was better than Western medicine. However, electroacupuncture was the most effective treatment for CIPN according to the surface under the cumulative ranking curve (SUCRA) ranking. Conclusion: After a comprehensive evaluation of 6 acupuncture therapies for treating CIPN based on NMA, electroacupuncture may be the best option for treating CIPN. However, would be more convincing to get evidence from more RCTs.

An umbrella review of the evidence to guide decision-making in acupuncture therapies for chemotherapy-induced peripheral neuropathy.

BACKGROUND: Acupuncture therapy is believed to have therapeutic potential for patients suffering from chemotherapy-induced peripheral neuropathy (CIPN). This umbrella review aims to summarize and evaluate the evidence from current systematic reviews/meta-analyses (SRs/MAs) on the effectiveness of acupuncture treatment for CIPN. METHODS: We conducted a comprehensive search in eight electronic databases for SRs/MAs that included RCTs on acupuncture treatment for CIPN. Two separate researchers independently evaluated the methodological quality, reporting quality, and evidence quality of the SRs/MAs that were included in the study. Additionally, we examined the extent of overlap among the included RCTs by calculating the corrected covered area (CCA). Furthermore, we assessed the dependability of the effect sizes by conducting excess significance tests. We conducted a quantitative synthesis of all RCTs included in the SRs/MAs to obtain objective and updated conclusions. Furthermore, we also conducted an analysis of the acupuncture points used in RCTs. RESULTS: This umbrella review includes 9 SRs/MAs, and their methodological quality, risk of bias, reporting quality, and evidence quality were all deemed unsatisfactory. Out of the 9 SRs/MAs, 28 RCTs were included, with a total CCA of 25.4%, indicating a high degree of overlap. The test of super-significance did not yield any significant results. Our updated meta-analysis suggests that CIPN patients can benefit from acupuncture therapy, as indicated by effectiveness in measures including BPI-SF, VAS, FACT-NTX, NRS, SCV, and NCI-CTCAE. Egger's test and sensitivity analysis demonstrate the reliability and stability of this conclusion. The commonly used acupuncture points in the current RCTs include ST36, LI11, LI4, LR3, and SP6. CONCLUSION: Based on the existing evidence, acupuncture is effective and safe for patients with CIPN, as it can significantly improve effective rate, pain symptoms, quality of life, and nerve conduction velocity. However, given the low quality of current evidence, we should be cautious in interpreting this conclusion.

Chemotherapy-Induced Peripheral Neuropathy: Diagnosis, Agents, General Clinical Presentation, and Treatments.

PURPOSE OF REVIEW: This review aims to discuss pathophysiology, diagnosis, clinical presentation, and treatment of chemotherapy-induced peripheral neuropathy. Agent-specific presentation and pathophysiology is also being discussed. RECENT FINDINGS: As new systemic oncological treatments continue to be developed, the number of cancer survivors continues to grow. Survivors are living longer with the long-term side effects of oncological treatments. We reviewed the pathophysiology of agent-specific chemotherapy-induced peripheral neuropathy and the updates in its treatment and preventative tools. Chemotherapy-induced peripheral neuropathy is a debilitating long-term side effect that often impairs cancer survivors' function and quality of life. The increasing life expectancy of cancer survivors has resulted in increased prevalence of this condition. Understanding its intricacies can provide physicians with better treatment tools and research opportunities to develop or identify new therapeutic agents.

Effect of Exercise on Chemotherapy-Induced Peripheral Neuropathy Among Patients Treated for Ovarian Cancer: A Secondary Analysis of a Randomized Clinical Trial.

Importance: Chemotherapy-induced peripheral neuropathy (CIPN), one of the most common and severe adverse effects of chemotherapy, is associated with worse quality of life among survivors of ovarian cancer. Currently, there is no effective treatment for CIPN. Objective: To evaluate the effect of a 6-month aerobic exercise intervention vs attention-control on CIPN among women treated for ovarian cancer in the Women's Activity and Lifestyle Study in Connecticut (WALC) to provide evidence to inform the guidelines and recommendations for prevention or treatment of CIPN. Design, Setting, and Participants: This prespecified secondary analysis evaluated the Women's Activity and Lifestyle Study in Connecticut (WALC), a multicentered, open-label, population-based, phase 3 randomized clinical trial of an aerobic exercise intervention vs attention control for CIPN in patients who were diagnosed with ovarian cancer. Only WALC participants who received chemotherapy were included in this analysis. Participants were randomized 1:1 to either a 6-month aerobic exercise intervention or to attention control. All analyses were conducted between September 2022 and January 2023. Interventions: The exercise intervention consisted of home-based moderate-intensity aerobic exercise facilitated by weekly telephone counseling from an American College of Sports Medicine/American Cancer Society-certified cancer exercise trainer. Attention control involved weekly health education telephone calls from a WALC staff member. Main Outcomes and Measure: Change in CIPN was the primary outcome in this secondary analysis. This outcome was represented by CIPN severity, which was self-measured by participants at baseline and 6 months using the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity scale, with a score range of 0 to 44. A mixed-effects model was used to assess the 6-month change in CIPN between the exercise intervention and attention control arms. Results: Of the 134 participants (all females; mean [SD] age, 57.5 [8.3] years) included in the analysis, 69 were in the exercise intervention arm and 65 were in the attention control arm. The mean (SD) time since diagnosis was 1.7 (1.0) years. The mean (SD) baseline CIPN scores were 8.1 (5.6) in the exercise intervention arm and 8.8 (7.9) in the attention control arm (P = .56). At 6 months, the self-reported CIPN score was reduced by 1.3 (95% CI, -2.3 to -0.2) points in the exercise intervention arm compared with an increase of 0.4 (95% CI, -0.8 to 1.5) points in the attention control arm. The between-group difference was -1.6 (95% CI, -3.1 to -0.2) points. The point estimate was larger among the 127 patients with CIPN symptoms at enrollment (-2.0; 95% CI, -3.6 to -0.5 points). Conclusions and Relevance: Findings of this secondary analysis of the WALC trial indicate that a 6-month aerobic exercise intervention vs attention control significantly improved self-reported CIPN among patients who were treated for ovarian cancer. While replication of the findings in other studies is warranted, incorporating referrals to exercise programs into standard oncology care could reduce CIPN symptoms and increase quality of life in patients with ovarian cancer. Trial Registration: ClinicalTrials.gov Identifier: NCT02107066.