Protocol for the TMaC Study: A Patient-Blinded, Randomised, Sham-Controlled, Parallel-Group Study Evaluating Effects of Repetitive Transcranial Magnetic Stimulation on Chronic Chemotherapy-Induced Pain in Bowel Cancer Patients

PurposeThis study aims to (1) examine the prevalence of painful versus non-painful chemotherapy-induced peripheral neuropathy (CIPN) among long-term colorectal cancer (CRC) survivors, (2) identify sociodemographic, clinical, and psychological factors associated with painful and non-painful CIPN, and (3) examine the associations of painful CIPN with health-related quality of life (HRQoL) in comparison with non-painful CIPN, i.e., numbness/tingling.MethodsAll CRC survivors diagnosed between 2000 and 2009 as registered by the population-based Netherlands Cancer Registry (Eindhoven region) were eligible for participation. Chemotherapy-treated survivors (n = 477) completed questions on CIPN (EORTC QLQ-CIPN20) and HRQoL (EORTC QLQ-C30).ResultsPainful CIPN was reported by 9% (n = 45) of survivors and non-painful CIPN was reported by 22% (n = 103). Time since diagnosis was related to painful CIPN, and time since diagnosis, a higher disease stage, osteoarthritis, and more anxiety symptoms were related to non-painful CIPN. Finally, survivors with painful CIPN reported a worse global quality of life and worse physical, role, cognitive, and social functioning compared to survivors with non-painful CIPN and those without any sensory CIPN. No differences were found between survivors with non-painful CIPN and those without sensory CIPN.ConclusionsIt seems that painful CIPN must be distinguished from non-painful CIPN, as only painful CIPN was related to a worse HRQoL. Future research is needed to examine whether painful CIPN must be distinguished from non-painful CIPN regarding predictors, mechanisms, and treatment.

Chronic chemotherapy-induced peripheral neuropathy and pain following paclitaxel versus docetaxel in breast cancer survivors: A cross-sectional study.

Discovering cytokines as targets for chemotherapy-induced painful peripheral neuropathy

BackgroundThe previous effects of acupuncture-related interventions in improving chemotherapy-induced peripheral neuropathy (CIPN) symptoms and quality of life (QoL) remain unclear in terms of pairwise comparisons.AimsThis systematic review and network meta-analysis aimed to determine the hierarchical effects of acupuncture-related interventions on symptoms, pain, and QoL associated with CIPN in cancer patients undergoing chemotherapy.MethodsNine electronic databases were searched, including PubMed, Embase, Cochrane Library, EBSCO, Medline Ovid, Airiti Library, China National Knowledge Infrastructure (CNKI), China Journal full-text database (CJFD), and Wanfang. Medical subject heading terms and text words were used to search for eligible randomized controlled trials published from database inception to May 2023.ResultsA total of 33 studies involving 2,027 participants were included. Pairwise meta-analysis revealed that acupuncture-related interventions were superior to usual care, medication, or dietary supplements in improving CIPN symptoms, CIPN pain, and QoL. Furthermore, network meta-analysis indicated that acupuncture plus electrical stimulation (acupuncture-E) had the greatest overall effect among the various interventions. The surface under the cumulative ranking curve (SUCRA) revealed that acupuncture-E ranked the highest in improving CINP symptoms. Acupuncture alone was most effective in reducing CIPN pain, and acupuncture plus moxibustion (acupuncture-M) ranked highest in enhancing QoL.ConclusionThis finding suggests that acupuncture-related interventions can provide patients with benefits in improving CIPN symptoms, pain, and QoL. In particular, acupuncture-E could be the most effective approach in which the provided evidence offers diverse options for cancer patients and healthcare professionals.Implication for the profession and/or patient careThese findings provide valuable insights into the potential benefits of acupuncture-related interventions for managing symptoms, pain, and QoL associated with CIPN in patients undergoing chemotherapy. Among the various interventions studied, overall, acupuncture-E had the most significant impact and was effective for a minimum duration of 3 weeks. On the other hand, transcutaneous electrical acupoint/nerve stimulation (TEAS) was identified as a noninvasive and feasible alternative for patients who had concerns about needles or the risk of bleeding. It is recommended that TEAS interventions should be carried out for a longer period, preferably lasting 4 weeks, to achieve optimal outcomes.Trial registrationThe study protocol was registered in the International Prospective Register of Systematic Reviews. Registration Number: CRD42022319871.

<h3>Objective:</h3> The objective of this study is to identify endogenous mediators controlling CIPN pain resolution. <h3>Background:</h3> Chemotherapies contribute to decreased cancer mortality but are associated with severe side effects including Chemotherapy-Induced Peripheral Neuropathy (CIPN). CIPN presents as a distal symmetric polyneuropathy causing numbness, tingling, and in a subset of patients, pain. Painful CIPN is a main cause for chemotherapy dose reduction, treatment cessation and reduced quality of life. A subset of painful CIPN patients will have pain resolution while others maintain pain persistency, however the mechanisms that mediate pain resolution are unknown and constitute a large gap of knowledge. <h3>Design/Methods:</h3> We developed painful CIPN models in mice using the chemotherapeutic paclitaxel, where mice treated with specific injection protocols develop resolving or persistent mechanical hypersensitivity measured via von Frey. Using these models, we performed bulk RNA sequencing on hind paw, whole dorsal root ganglion (DRG), DRG sensory neurons and spinal cord at initiation, pre-resolution, post-resolution, and persistency time points. DEGs were selected (P-adj &lt;0.05, FC &gt; 2, RPKM &gt; 1) and PANTHER analysis was performed to identify biological processes. To investigate the contribution of particular cell types in these tissues, we used the inducible diphtheria toxin receptor ablation model. <h3>Results:</h3> PANTHER analysis identified upregulation of immune system related genes in the hind paw during resolution of Model-1 not seen in Model-2. As myeloid cells are known to contribute to immune system related genes in the periphery, we ablated myeloid cells. We identified that CD11b+ peripheral, but not IBA1+ central, myeloid cells are critical for painful CIPN resolution. Further RNA sequencing analysis identified pro-inflammatory pathways correlated with painful CIPN resolution. <h3>Conclusions:</h3> These studies provide mechanistic insights for CIPN pain resolution and identify a unique therapeutic strategy for permanent treatment of painful CIPN. Future studies will delineate the myeloid cell sub-type and factors required for CIPN pain resolution. <b>Disclosure:</b> Mr. Naratadam has nothing to disclose. Prof. Akopian has nothing to disclose.

9029 Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a major dose-limiting and persistent consequence of numerous classes of antineoplastic agents affecting up to 30-40% of patients (pts). To date, there is no highly effective prevention or therapy. An evolving hypothesis for reducing CIPN pain involves direct nerve stimulation to reduce the pain impulse. Methods: We evaluated the effect of the MC5-A Calmare therapy device on CIPN. The device is designed to generate a patient-specific cutaneous electrostimulation to reduce the abnormal pain intensity. Gel electrodes like EKG pads are applied below and above the dermatomes of pain. Pts with stable CIPN of > 5 pain, off chemotherapy, from one center received 1-hour interventions daily over 10 working days. NCT00952848. Results: The 16 pts had a mean age of 58.6 years; 4 men, 14 women; duration of CIPN all > 3 months up to 8 years. The most common drugs related to their neuropathy were taxanes, platinums, and bortezimib. The primary goal of a 20% in numeric pain scores after day 10 was achieved in 15 of 16. The primary endpoint of CIPN pain score fell by 59% from day 1 to day 10. Adjusting for the correlations and the variability between patients and daily scores with a repeated measures analysis, there was an overall 64% reduction in pain. A daily treatment benefit was seen with a significant difference between the pre and post daily scores. Four patients had their CIPN reduced to 0. No toxicity was seen. Some responses have been durable without maintenance, and some patients had return of normal sensation and motor function. Conclusions: Patient-specific cutaneous electrostimulationwith theMC5-A Calmare device appears to dramatically reduce pain in refractory CIPN patients with no toxicity. Further studies are underway to define the mechanisms of action, duration of benefit, and optimal schedule. Before After P value Reduction in pain by 20% 0 15 of 16 (94%) <0.0001, Fischer's exact test CIPN pain score 5.81 ± 1.11 2.38 ± 1.82-59% <0.0001, paired t test Adjusted pain scores 4.9 ± 0.4 1.8 ± 0.4-64% < 0.0001, repeated measures analysis Daily reduction in pain scores 3.74 ± 0.38 2.72 ± 0.38-1.02, -27% < 0.001, repeated measures analysis No significant financial relationships to disclose.

Self-Reported Severity, Characteristics, and Functional Limitations of Chemotherapy-Induced Peripheral Neuropathy

To compare the efficacy of serotonin-norepinephrine reuptake inhibitors (SNRIs) treatment for chemotherapy-induced peripheral neuropathy (CIPN) METHODS:: Two authors independently searched MEDLINE, Embase, Cochran Library, and Web of Science to identify and review articles published from January 1998 until December 2018 according to selection criteria. Outcomes were expressed as mean difference, the pooled odds ratio, or relative risk in a meta-analysis model. A total of 10 studies were included in this meta-analysis: 6 randomized-controlled studies and 4 observational studies. Meta-analysis showed that CIPN was improved after treatment with SNRI (standardized mean difference = 2.20; 95% confidence interval, 0.90-3.49; I = 93% in 3 randomized controlled studies). Somnolence and insomnia occurred in <15% of patients. Incidence of somnolence was lower than with pregabalin treatment, and insomnia was comparable to that in expectant management or pregabalin treatment. Incidence of nausea and vomiting was higher than in expectant management, but no significant difference was found when compared to expectant management. From the several available studies suitable for indirect comparison, SNRI shows excellent efficacy and tolerability to CIPN. SNRI could provide an important treatment option for CIPN.

Background: Yoga is a meditative movement therapy that improves body conditioning, flexibility, and balance through mind-body awareness. We conducted a two-armed pilot randomized wait-list controlled trial in breast and gynecological (GYN) cancer survivors with persistent moderate to severe chemotherapy-induced peripheral neuropathy (CIPN) and found that yoga significantly reduced CIPN pain. Here we report on the HRQOL results. Patients and Methods: We randomized breast and GYN cancer survivors with persistent moderate to severe CIPN to eight weeks of yoga or usual care (UC). The HRQOL endpoints were Hospital Anxiety and Depression Score (HADS), Treatment Expectancy Scale (TES), Brief Fatigue Inventory (BFI), and Insomnia Severity Index (ISI). We estimated and compared the mean changes from baseline to weeks 8 and 12 along with 95% confidence intervals (CIs) between arms using linear mixed models. Results: From February 2018 to May 2019, we enrolled and randomized 41 female cancer survivors (93% breast, 7% GYN; mean (SD) age 61.7 (10.2) years; 56% white/non-Hispanic, 20% African American, 12% Asian, 12% other) to yoga (N=21) and UC (N=20) arms. The HADS anxiety score significantly reduced in the yoga arm compared to usual care at weeks 8 and 12. At baseline, the mean (95% CI) HADS anxiety score was 9.23 (7.42, 11.04) in the yoga arm, and 5.05 (3.19, 6.91) in the UC arm (p=0.002). At week 8, the mean (95% CI) HADS anxiety score decreased by -1.91 (-3.07, -0.76) points in the yoga arm, and by -0.02 (-1.10, 1.06) points in the UC arm (p=0.019). At week 12, in the yoga arm, the mean HADS anxiety score was 7.50 (5.62, 9.39), and a decrease of 1.73 (-2.88, -0.57) points; in the UC arm, the mean was 5.81 (3.94, 7.69) with an increase of 0.76 (-0.32, 1.84) points (p=0.002). There was no difference in HADS depression, BFI, and ISI scores between yoga and UC arms at baseline, week 8, and week 12. The TES at baseline was 14.9 (3.27) in the yoga arm, which was significantly higher than in the UC arm 14.9 (SD 3.27) vs. 12.7 (SD: 2.58), p= 0.019. The TES was not associated with HADS anxiety reduction, and HADS anxiety reduction was not associated with CIPN pain reduction. Conclusions: Our trial showed that a yoga intervention may be useful to reduce anxiety in patients with CIPN. We previously found that a yoga intervention reduced CIPN pain. CIPN pain reduction was not associated with anxiety reduction or TES. Future studies are needed to confirm our findings and to explore the mechanism of yoga in CIPN pain reduction. Citation Format: Wanqing Iris Zhi, Raymond Baser, Lillian Zhi, Lauren Piulson, Qing Li, Ting Bao. Health-related quality of life (HRQOL) outcomes in arandomized controlled trial of yoga in breast and gynecological cancer survivors with chemotherapy-induced peripheral neuropathy [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS9-19.

Simple SummaryChemotherapy-induced peripheral neuropathy (CIPN) is often painful, arising during or after the end of oncological treatments. The high-concentration capsaicin patch (HCCP) is recommended in second line for its treatment but based on low-powered studies. The objective of this retrospective real-world-data study was to evaluate efficacy and tolerability of HCCP applications in CIPN. Our study demonstrated an important or complete pain relief for 33.2% of the applications, corresponding to 43.9% patients. We found a significative difference in efficacy depending on the responsible chemotherapy. The efficacy was significatively different depending on the analgesic treatment line for HCCP. The efficacy of HCCP was significatively higher starting the third application. HCCPs were mainly responsible for local adverse events. HCCP applications in painful CIPN induce important pain relief with a global satisfying tolerability.Introduction: Chemotherapy-induced peripheral neuropathy (CIPN) is often painful and can arise during or after the end of oncological treatments. They are mostly induced by platinum salts, taxanes, and immunotherapies. Their incidence is estimated between 19 and 85%. They can require a chemotherapy dose reduction or early termination. The European Society for Medical Oncology (ESMO) recommends high-concentration capsaicin patch (HCCP) in second line for the treatment of painful CIPN. This treatment induces a significative pain relief but only shown by low-powered studies. The objective of this study was to evaluate efficacy and tolerability of HCCP applications in CIPN. Methods: This monocentric observational retrospective real-world-data study of the CERCAN cohort took place in the Western Cancer Institute’s Anaesthesiology and Pain Department at Angers, France. Independent pain physicians completed the CGIC (Clinician Global Impression of Change) for each patient who benefited from HCCP applications for painful CIPN starting from 1 January 2014 to 22 December 2021, based on the collected data after every patch application. Results: A total of 57 patients (80.7% women) was treated with HCCP for painful CIPN, and 184 applications were realized, consisting of 296 sessions. CGIC found an important or complete pain relief for 61 applications (33.2%, corresponding to 43.9% patients). We found less efficacy for platinum-salts-induced CIPN compared to others (p = 0.0238). The efficacy was significatively higher for repeated applications when HCCP was used in second line compared to third line (p = 0.018). The efficacy of HCCP was significatively higher starting the third application (p = 0.0334). HCCPs were mainly responsible for local adverse events found in 66.6% patients (65.1% burning or painful sensation, 21.1% erythema). Conclusion: HCCP applications in painful CIPN induce an important pain relief with a global satisfying tolerability.

CRA9013 Background: CALGB 170601 was a randomized, placebo-controlled phase III trial to determine whether duloxetine reduces painful chemotherapy-induced peripheral neuropathy (CIPN). The secondary study endpoint was treatment-related adverse events. Methods: The study used a double-blinded placebo-controlled crossover design with equally weighted randomization to one of two arms. Arm A participants received duloxetine followed by placebo. Arm B participants received placebo followed by duloxetine. The initial and crossover periods each consisted of six weeks of drug/placebo followed by one week of washout. Randomization was stratified by neurotoxic agent and high risk for developing painful CIPN. Eligible patients were 18 years or older with an average CIPN pain score &gt; 4/10 attributed to prior single agent taxane or platinum treatment. Participants took one capsule daily (30mg) for one week, and then two capsules (60mg) daily for four additional weeks. Participants completed the Brief Pain Inventory-Short Form (BPI-SF) at baseline and then weekly. The primary study endpoint was the change in BPI-SF scores within the initial treatment period. Analysis of covariance with an intent-to-treat approach was used to test the effect of treatment on change in pain score. Results: The target accrual goal (N = 231) was met, of which 185 (80%) completed the initial treatment period. Oxaliplatin was the most commonly received neurotoxic agent (59%). Individuals receiving duloxetine over the initial treatment period had a larger average decrease in pain score (mean change score = -1.09; S.E. = 0.19) than those receiving placebo (mean change score = -0.33; S.E. = 0.18) (p = 0.004). There was no difference in duloxetine efficacy based on the specific neurotoxic agent received. Severe (Grade 3) non-hematologic toxicity was reported by 11%, and 41% reported moderate (Grade 2) toxicities. The incidence of Grade 2+ fatigue, the most commonly reported side effect, was significantly higher in the duloxetine arm as compared to placebo (11% vs. 3%, p = 0.029). Conclusions: Duloxetine 60mg daily is an efficacious and well-tolerated intervention for the treatment of taxane or platinum-related painful CIPN.

TPS12146 Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a common, painful, and debilitating side effect of many standard chemotherapy regimens. Patients with CIPN typically experience pain, paresthesia, and muscle weakness, and may exhibit significant functional decline and worsened quality of life. Our prior study showed more than half of breast cancer survivors experience persistent CIPN up to a mean duration of 5.6 years, which is associated with a doubled fall risk. Identifying nonpharmacological approaches to reduce CIPN symptoms and improve cancer survivors’ outcomes is urgently needed. Yoga is a meditative movement therapy that that includes stretching, and flexibility and balance training. Our pilot study (NCT03292328) demonstrated that yoga reduced CIPN-related symptoms, and improved quality of life and functional reach scores compared to waitlist control. We hypothesize that yoga can reduce CIPN symptoms, improve function, and reduce the risk of falls. Methods: We are conducting a three-arm randomized education and usual care-controlled trial in cancer survivors with chronic CIPN pain at Memorial Sloan Kettering Cancer Center (MSK), New York, NY. Participants in the intervention arm will receive twice-weekly one-hour Hatha yoga classes virtually or in-person taught by MSK instructors, and practice yoga at home daily for eight weeks. Participants in the education control arm will receive one-hour virtual education classes twice per week taught by an MSK mind-body therapist for eight weeks. Participants in the usual care arm will continue their usual care for CIPN for eight weeks. The primary endpoint is the Brief Pain Inventory-Short Form (BPI-SF) average pain item at weeks 8 and 24. Secondary outcomes include the Neuropathic Pain Scale (NPS), Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT/GOG-Ntx), Patient-Reported Outcomes Measurement Information System (PROMIS) Global Health outcome measure, Brief Fatigue Inventory (BFI), Insomnia Severity Index (ISI), Hospital Anxiety and Depression Scale (HADS), QLQ-CIPN-20, Functional Assessments, and quantitative sensory testing (QST) at weeks 0, 4, 8, 12, 18, and 24. Eligibility criteria included: 1) Moderate-to-severe CIPN pain, defined by a score of 4 or greater on a 0-10 numerical rating scale; 2) completion of neurotoxic chemotherapy at least three months prior; 3) no changes in anti-neuropathy medications within three months of enrollment; and 4) changes in balance and functionality. We have accrued five participants as of February 2022 with a total accrual target of 268 participants. We anticipate completing accrual in March 2025. Funding resource: NIH R01CA251470. Clinical trial information: NCT05121558.

Chemotherapy-induced peripheral neuropathy (CIPN) affects ∼68% of patients undergoing chemotherapy, causing debilitating neuropathic pain and reducing quality of life. Cisplatin is a commonly used platinum-based chemotherapeutic drug known to cause CIPN, possibly by causing oxidative stress damage to primary sensory neurons. Metabotropic glutamate receptors (mGluRs) are widely hypothesized to be involved in pain processing and pain mitigation. Meclizine is an H1 histamine receptor antagonist known to have neuroprotective effects, including an anti-oxidative effect. Here, we used a mouse model of cisplatin-induced CIPN using male and female mice to test agonists of mGluR8 and Group II mGluR as well as meclizine as interventions to reduce cisplatin-induced pain. We performed behavioral pain tests, and we imaged Ca2+ activity of the large population of dorsal root ganglia (DRG) neurons in vivo For the latter, we used a genetically-encoded Ca2+ indicator, Pirt-GCaMP3, which enabled us to monitor different drug interventions at the level of the intact DRG neuronal ensemble. We found that CIPN increased spontaneous Ca2+ activity in DRG neurons, increased number of Ca2+ transients, and increased hyper-responses to mechanical, thermal, and chemical stimuli. We found that mechanical and thermal pain caused by CIPN was significantly attenuated by the mGluR8 agonist, (S)-3,4-DCPG, the Group II mGluR agonist, LY379268, and the H1 histamine receptor antagonist, meclizine. DRG neuronal Ca2+ activity elevated by CIPN was attenuated by LY379268 and meclizine, but not by (S)-3,4-DCPG. Furthermore, meclizine and LY379268 attenuated cisplatin-induced weight loss. These results suggest that Group II mGluR agonist, mGluR8 agonist, and meclizine are promising candidates as new treatment options for CIPN, and studies of their mechanisms are warranted.SIGNIFICANCE STATEMENT Chemotherapy-induced peripheral neuropathy (CIPN) is a painful condition that affects most chemotherapy patients and persists several months or longer after treatment ends. Research on CIPN mechanism is extensive but has produced only few clinically useful treatments. Using in vivo GCaMP Ca2+ imaging in live animals over 1800 neurons/dorsal root ganglia (DRG) at once, we have characterized the effects of the chemotherapeutic drug, cisplatin and three treatments that decrease CIPN pain. Cisplatin increases sensory neuronal Ca2+ activity and develops various sensitization. Metabotropic glutamate receptor (mGluR) agonist, LY379268 or the H1 histamine receptor antagonist, meclizine decreases cisplatin's effects on neuronal Ca2+ activity and reduces pain hypersensitivity. Our results and experiments provide insights into cellular effects of cisplatin and drugs preventing CIPN pain.

TPS518 Background: CIPN is an unsolved, common problem for cancer pts. CIPN greatly affects quality of life and may impact quantity of life due to dose reductions and discontinuation of beneficial therapy. No generally accepted evidence-based prevention strategies for CIPN exist. In the discipline of hand therapy (HT), there are effective science-based interventions to treat peripheral neuropathies due to injury and disease. These interventions have not been explored in patients with CIPN. Methods: Study objective is to determine if an IHT intervention based on concepts of neuroplasticity can prevent or delay time to onset of CIPN of the hands as measured by Patient Reported Outcomes &amp; Criteria for Adverse Events, version 4 (CTCAE 4.0), compared to a TOT intervention. Eligible pts have pancreatic cancer and receive nab-paclitaxel + gemcitabine containing combinations; have no prior evidence of peripheral neuropathy (PN) of the hands and are not taking duloxetine or gabapentin. Randomization is 1:1. Patient instructions on the blinded IHT or TOT activities are done by an Occupational Therapist prior to start of CTX, then reinforced at multiple follow-up sessions. Periodic assessments include standardized hand sensibility testing: QuickDASH, upper extremity provocative testing, TEN Test; plus pt reporting of CIPN onset, CTCAE-4, physical examination of peripheral sensory/motor neurologic assessment of the hands, Karnofsky Performance Status, and pain visual analogue scale. Participation in the study with a daily home program continues until onset of CIPN of the hands or if no CIPN then through completion of an 84 day schedule of chemotherapy. The number and proportion of patients without CIPN of the hands at the end of 84 days of CTX will be summarized for both intervention groups. For an 80% powered design with a medium effect size, 40 evaluable pts are needed (95% CI, alpha .05). Planned enrollment is up to 50 pts allowing for pt attrition. Study opened to enrollment 8/2016.

TPS12145 Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a common and debilitating side effect in cancer survivors that can last long after completion of neurotoxic chemotherapy. Patients with CIPN often experience neuropathy symptoms such as pain, tingling, numbness, paresthesia, and dysesthesia, which can lead to significant functional decline and diminished quality of life (QoL). Our prior study showed that more than half of breast cancer survivors who received taxane-based chemotherapy experienced persistent peripheral neuropathy symptoms for a mean duration of 5.6 years after completing chemotherapy. This outcome highlights the importance of developing effective CIPN treatments to improve cancer survivors’ QoL. Identifying nonpharmacological approaches to reduce CIPN symptoms and improve cancer survivors’ outcomes is urgently needed. Acupuncture is a widely used, minimally invasive Traditional Chinese Medicine technique that has shown promising evidence as an effective and safe treatment for CIPN. We hypothesize that acupuncture may reduce CIPN pain and improve overall CIPN symptoms in cancer survivors. Methods: We are conducting a two-arm, parallel randomized clinical trial comparing electroacupunture (EA) versus sham acupuncture (SA) in cancer survivors at Memorial Sloan Kettering Cancer Center, New York, NY. The EA arm includes a total of ten sessions of EA over eight weeks using a standardized, semi-fixed protocol developed by our group based on the previously published pilot study (NCT03183037). The SA arm includes a sham technique that uses a combination of non-acupuncture points and a non-insertion procedure in ten sessions over eight weeks. The primary outcome of this study is the Brief Pain Inventory-Short Form (BPI-SF) average pain item. The secondary outcomes are quantitative sensory testing measures and additional patient-reported outcomes that include the BPI-SF pain interference subscale, Neuropathic Pain Scale (NPS), Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT/GOG-Ntx), CIPN-20, PROMIS Global Health Scale, and Patients’ Global Impression of Change (PGIC). The primary end point is week 12 and the secondary end point is week 24; treatment effects are assessed at baseline and at weeks 4, 8, 12, 18, and 24. Eligibility criteria includes: 1) Moderate-to-severe CIPN pain, defined by a score of 4 or greater on a 0–10 numeric rating scale; 2) completion of neurotoxic chemotherapy at least three months prior to enrollment; and 3) no changes in anti-neuropathy medications within three months of enrollment. We have accrued 30 participants as of February 2022, with a total accrual target of 250 participants. Accrual completion is anticipated by December 2024. Funding resource: NIH R37 CA248563. Clinical trial information: NCT04917796.