Chemotherapy-induced Peripheral Neuropathy Symptoms Research Articles

Exploring the reliability and validity of clinically-relevant outcome measures for chemotherapy-induced peripheral neuropathy.

To explore the reliability and validity of clinically-relevant outcome measures for balance (i.e., The Short Physical Performance Battery [SPPB] - Balance Subscale) and sensation (i.e., monofilament threshold testing) for use in clinical trials of chemotherapy-induced peripheral neuropathy (CIPN). Adult, post-treatment cancer survivors (N = 142) who had reported ≥ 4/10 CIPN symptom severity following neurotoxic chemotherapy were recruited from six National Cancer Institute Community Oncology Research Program (NCORP) sites associated with the University of Rochester Cancer Center NCORP Research Base. Participants completed the monofilament threshold test at the screening and baseline time points (i.e., one week apart), while the Quality of Life Questionnaire-CIPN20, Treatment-Induced Neuropathy Assessment Scale, and SPPB - Balance Subscale were completed at baseline. Test-retest reliability of the monofilament threshold testing scores was assessed using the Intraclass Correlation Coefficient (ICC). The convergent validity among monofilament threshold testing, SPPB - Balance Subscale, and CIPN patient-reported outcome (PRO) scores at baseline was assessed using Spearman's correlation. Ceiling effects were observed for SPPB-Balance Subscale scores as 113 (79.6%) respondents reported the highest score. Agreement between the screening and baseline monofilament threshold testing scores was moderate (ICC = 0.65). Monofilament threshold testing (rs Range: 0.14 - 0.21) and SPPB Balance Subscale scores (rs Range: -0.36 - -0.22) showed largely low correlations with all PRO measures. Monofilament threshold testing demonstrated moderate test-retest reliability, but low convergent validity with CIPN PROs, while the SPPB - Balance Subscale demonstrated low convergent validity with CIPN PROs and ceiling effects (i.e., highest possible score) among post-treatment cancer survivors with CIPN. Future research is needed to identify promising measures of balance and sensation loss for use in clinical trials that complement CIPN PROs to aid in the identification of clinically relevant treatments for CIPN. NCT04367490 [April 29, 2020].

The Effects of Exercise on Symptoms of Chemotherapy-Induced Peripheral Neuropathy in Cancer Survivors: A Systematic Review and Meta-Analysis.

Chemotherapy-induced peripheral neuropathy (CIPN) can cause treatment delays or discontinuation. Exercise can improve CIPN, but the effects have been inconsistent. 12 databases and 5 websites were searched from database inception to December 22, 2023, for primary studies that were reported in English and examined the effects of exercise on CIPN in cancer survivors. 20 studies (N = 1,308 total participants) were identified and reviewed. Using a random-effects model, exercise slightly improved symptoms of CIPN (Hedges's g = 0.28, Hartung-Knapp adjusted 95% confidence interval [0.12, 0.45], p = 0.002). The 95% prediction interval showed that the true effect size of future studies would likely range from -0.1 to 0.66. Frequency of performing exercise moderated the effect size, further improving symptoms. Nurses can encourage cancer survivors to engage in exercise, such as resistance training, aerobic exercise, balance training, and/or yoga. Nurses can refer cancer survivors to trained exercise specialists or provide information about finding a community exercise program for patients with cancer.

Acupuncture-related interventions improve chemotherapy-induced peripheral neuropathy: A systematic review and network meta-analysis

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.

Chemotherapy-Induced Peripheral Neuropathy: A Recent Update on Pathophysiology and Treatment.

Chemotherapy-induced peripheral neuropathy (CIPN) is a major long-lasting side effect of some chemotherapy drugs, which threatens cancer survival rate. CIPN mostly affects sensory neurons and occasionally motor neurons, causing numbness, tingling, discomfort, and burning pain in the upper and lower extremities. The pathophysiology of CIPN is not completely understood; however, it is believed that chemotherapies induce peripheral neuropathy via directly damaging mitochondria, impairing the function of ion channels, triggering immunological mechanisms, and disrupting microtubules. The treatment of CIPN is a medical challenge, and there are no approved pharmacological options. Currently, duloxetine and other antidepressants, antioxidant, anti-inflammatory, and ion-channel targeted therapies are commonly used in clinics to relieve the symptoms of CIPN. Several other types of drugs, such as cannabinoids, sigma-1 receptor antagonists, and nicotinamides ribose, are being evaluated in preclinical and clinical studies. This paper summarizes the information related to the physiology of CIPN and medicines that could be used for treating this condition.

Blood biomarkers for neuroaxonal injury and astrocytic activation in chemotherapy-induced peripheral neuropathy.

Chemotherapy-induced peripheral neuropathy (CIPN) is a troublesome side effect in patients exposed to taxanes in the treatment of cancer and may affect quality of life dramatically. Here we assessed whether serum levels of neurofilament light (NfL) and tau (two neuroaxonal injury biomarkers) and glial fibrillary acidic protein (GFAP, a biomarker for astrocytic activation) correlate with the development of CIPN in the adjuvant setting of early breast cancer. Using ultrasensitive single molecule array technology, serum levels of NfL, GFAP, and tau were measured before and every 3 weeks in 10 women receiving adjuvant EC (epirubicin 90 mg/m² and cyclophosphamide 600 mg/m²) every 3 weeks × 3, followed by weekly paclitaxel 80 mg/m² × 9-12 weeks after surgery due to early breast cancer. CIPN was graded according to the NCI Common Terminology Criteria for Adverse Events (CTCAE v5.0) and the questionnaire EORTC QLQ CIPN-20. Serum levels of GFAP increased successively during cycles of EC. NfL increased instead in response to the treatment of paclitaxel. NfL and GFAP continued to rise throughout exposure of cumulatively higher doses of paclitaxel and were reduced 3 months after the end of chemotherapy. Serums levels of tau were marginally affected by exposure to chemotherapy. Women with worse symptoms of CIPN had higher concentrations of NfL than women with mild symptoms of CIPN. NfL and GFAP are promising biomarkers to identify women at risk of developing CIPN. Larger prospective studies are now needed.

Chemotherapy-Induced Peripheral Neuropathy Impacts Quality of Life and Activities of Daily Living of Brazilian Multiple Myeloma Patients.

Survival in multiple myeloma (MM) has improved in the past years with the introduction of immunomodulators and proteasome inhibitors. However, chemotherapyinduced peripheral neuropathy (CIPN) is associated with both drug classes affecting Health- Related Quality of Life (HRQoL) and activities of daily living (ADL). We evaluated CIPN in MM patients to identify associated factors and impacts on HRQoL and ADL. This is a cross-sectional study with Brazilian patients from public and private health services. Patients were interviewed using validated tools to measure CIPN and HRQoL, along with sociodemographic and clinical questions. Logistic regression was used to assess the association of CIPN with sociodemographic, clinical, and HRQoL variables. In total, 217 patients were eligible for the study. The median age was 67, 50.9% were women, 51.6% had low income, 47.5% had low education, and 55.3% attended private health services. The chemotherapy regimen most used was the combination of cyclophosphamide, thalidomide, and dexamethasone (17.5%) among the 24 types of regimens found. Most patients (90.3%) had at least one CIPN symptom: 62.7% were severe, and 51.62% were extremely bothered ADL. Numbness was the most common symptom (40.6%). CIPN was independently associated with education, hospitalization, chemotherapy, side effects, disease symptoms, and global health status in HRQoL. MM patients showed a high frequency of CIPN, which affected ADL and impaired HRQoL. Early and accurate detection of CIPN and dose management in patients with thalidomide and bortezomib-based regimens should be performed to provide better treatment outcomes and avoid permanent disabilities.

Validity of Patient-Reported Outcome Measures in Evaluating Nerve Damage Following Chemotherapy

Chemotherapy-induced peripheral neuropathy (CIPN) is a substantial adverse effect of anticancer treatments. As such, the assessment of CIPN remains critically important in both research and clinic settings. To compare the validity of various patient-reported outcome measures (PROMs) with neurophysiological and sensory functional measures as the optimal method of CIPN assessment. This cohort study evaluated participants treated with neurotoxic chemotherapy across 2 cohorts using a dual-study design. Participants commencing treatment were assessed prospectively at beginning of neurotoxic treatment, midtreatment, and at the end of treatment. Participants who completed treatment up to 5 years prior were assessed cross-sectionally and completed a single assessment time point. Participants were recruited from oncology centers in Australia from August 2015 to November 2022. Data analysis occurred from February to November 2023. Neurotoxic cancer treatment including taxanes, platinums, vinca-alkaloids, proteasome inhibitors, and thalidomide. CIPN was assessed via PROMs (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire [EORTC-CIPN20], Functional Assessment of Cancer Therapy/Gynecological Cancer Group Neurotoxicity Questionnaire (FACT/GOG-Ntx), and the patient-reported outcomes version of the Common Terminology Criteria for Adverse Events [PRO-CTCAE]), neurological and neurophysiological assessment (Total Neuropathy Score and sural and tibial compound nerve amplitudes), and sensory measures (Grating orientation, Von Frey monofilament, and 2-point discrimination tasks). Core measurement properties of CIPN outcome measures were evaluated. Convergent and known-groups validity was assessed cross-sectionally following treatment completion, and responsiveness was evaluated prospectively during treatment. Neurological, neurophysiological, and sensory outcome measure scores were compared between those who reported high and low levels of CIPN symptoms using linear regressions. A total of 1033 participants (median [IQR] age, 61 [50-59] years; 676 female [65.4%]) were recruited to this study, incorporating 1623 assessments. PROMs demonstrated best ability to accurately assess CIPN (convergent validity), especially the PRO-CTCAE composite score (r = 0.85; P < .001) and EORTC-CIPN20 (r = 0.79; P < .001). PROMS also demonstrated the best ability to discriminate between CIPN severity (known-groups validity) and to detect changes at onset of CIPN development (responsiveness), especially for EORTC-CIPN20 (d = 0.67; 95% CI, 0.52-0.83), FACT/GOG-Ntx (d = 0.65; 95% CI, 0.49-0.81) and the PRO-CTCAE (d = 0.83; 95% CI, 0.64-1.02). Other measures did not achieve threshold for convergent validity (α < 0.7). Neurophysiological and sensory measures did not demonstrate acceptable responsiveness. In regression models, neurological, neurophysiological, and sensory outcome measures were significantly impaired in participants who reported high levels of CIPN symptoms compared with those who reported low levels of CIPN symptoms. In this cohort study of 1033 cancer patients, PROMs were the only measures to satisfy all 3 core measurement property criteria (convergent validity, known-groups validity, and responsiveness). These findings suggest that adoption of PROMs in clinical practice can equip clinicians with valuable information in assessing CIPN morbidity.

Patterns of Physical Therapy Referral and Subsequent Attendance Among Childhood Cancer Survivors with Chemotherapy-Induced Peripheral Neuropathy at a Regional Childhood Cancer Survivorship Clinic

ObjectivesChildhood cancer survivors are at risk for chemotherapy-induced peripheral neuropathy (CIPN). Physical therapy (PT) improves CIPN symptoms, but little is known about survivors’ PT utilization. We described characteristics of survivors with ≥ grade 2 CIPN, investigated PT referral and attendance, and described characteristics of survivors who attended and did not attend PT. MethodsChildhood cancer survivors <21 years old at cancer diagnosis and ≥2 years posttherapy, living in the United States, evaluated at a regional survivorship clinic were included in this retrospective analysis if they had motor CIPN. Symptomatic CIPN (≥grade 2 by Common Terminology Criteria for Adverse Events) and PT referral/attendance were tabulated. Patient characteristics from the medical record, and neighborhood characteristics (retrieved using survivors’ zip code from the National Neighborhood Data Archive) were described by group. ResultsAmong 91 survivors with CIPN (median 17.5 years old, 8.1 years postcancer diagnosis, 45.1% female), 35 (38.5%) had ≥ grade 2 CIPN. Survivors with ≥ grade 2 CIPN were 28.6% female, and 45.7% were <13 years old. Twenty-four (68.6%) survivors with ≥ grade 2 CIPN agreed to PT referral, and 15 (42.9%) attended PT. Among survivors who attended PT, 73.3% were <13 years old. Neighborhood characteristics of survivors included median percentage of adults without a high school diploma (6.7% PT attendees, 12.5% nonattendees), median percentage of adults who are foreign-born (11.5% PT attendees, 16.4% nonattendees), and median percentage of households with an annual income of <$15,000 (3.2% PT attendees, 6.5% nonattendees). ConclusionsWhile 68.6% of survivors with ≥ grade 2 CIPN were referred to PT, only 42.9% attended. Studies to better understand barriers to PT attendance and interventions to improve attendance are needed, especially in older survivors. Implications for Nursing PracticeNurses can play a key role in survivor education and care coordination to help optimize PT attendance.

Biological Mediators and Partial Regulatory Mechanisms on Neuropathic Pain Associated With Chemotherapeutic Agents.

One of the most common issues caused by antineoplastic agents is chemotherapy-induced peripheral neuropathy (CIPN). In patients, CIPN is a sensory neuropathy accompanied by various motor and autonomic changes. With a high prevalence of cancer patients, CIPN is becoming a major problem for both cancer patients and for their health care providers. Nonetheless, there are lacking effective interventions preventing CIPN and treating the CIPN symptoms. A number of studies have demonstrated the cellular and molecular signaling pathways leading to CIPN using experimental models and the beneficial effects of some interventions on the CIPN symptoms related to those potential mechanisms. This review will summarize results obtained from recent human and animal studies, which include the abnormalities in mechanical and temperature sensory responses following chemotherapy such as representative bortezomib, oxaliplatin and paclitaxel. The underlying mechanisms of CIPN at cellular and molecular levels will be also discussed for additional in-depth studies needed to be better explored. Overall, this paper reviews the basic picture of CIPN and the signaling mechanisms of the most common antineoplastic agents in the peripheral and central nerve systems. A better understanding of the risk factors and fundamental mechanisms of CIPN is needed to develop effective preventive and therapeutic strategies.

Chuna Manual Therapy or Electroacupuncture with Pregabalin for Chemotherapy-Induced Peripheral Neuropathy: A Randomized Controlled Pilot Study.

Background: Chemotherapy-induced peripheral neuropathy (CIPN) is one of the most common side effects of chemotherapy, and effective treatments for CIPN are still lacking. For this reason, there is a growing interest in complementary and alternative medicine as a potential source of nonsurgical treatments for CIPN symptoms alongside pregabalin. One such option being explored is Chuna manual therapy (CMT), a traditional Korean manual therapy. Methods: This study compares the effectiveness and safety of using only pregabalin (PG) as a conventional method of treating breast and colorectal cancer patients with CIPN symptoms with a combination of both PG and electroacupuncture (EA) or CMT, while also assessing the feasibility of future large-scale clinical studies. Due to the COVID-19 pandemic, only 74 CIPN patients were recruited to this study. Twenty-five were assigned to the PG group, 26 to the PG + EA group, and 22 to the PG + CMT group for a five-week treatment and a four-week follow-up study. Results: For the primary outcome, we evaluated the mean differences in Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT/GOG-Ntx) compared to the baseline at week 5 (visit 4). Although we found that the PG + CMT group showed the biggest difference (-16.64 [95% CI: -25.16, -8.11]) compared to the PG group (-8.60 [95% CI: -14.93, -2.27]) and the PG + EA group (-6.73 [95% CI: -12.34, -1.13]), this finding lacked statistical significance (p = 0.2075). In terms of safety, two patients in the PG + CMT group reported side effects: one bruise and one headache. Conclusions: The low attrition and high adherence rates of all the groups, and the similar rates of side effects among them, support the feasibility of larger-scale follow-up studies.

Impact of chemotherapy-induced peripheral neuropathy permanence on patients' preference to discontinue chemotherapy.

12046 Background: Chemotherapy-induced peripheral neuropathy (CIPN) diminishes patients’ functional ability and quality of life; approximately 40% of patients experience CIPN symptoms 3 years after treatment. Due to the absence of effective CIPN treatments, ASCO guidelines recommend discontinuing chemotherapy in patients experiencing intolerable CIPN symptoms. Little is known about patient’s preference to continue or discontinue chemotherapy when experiencing CIPN, and whether the potential permanence of CIPN symptoms affects this decision. The objective of this prospective observational study was to determine the effect of CIPN symptom permanence on patients’ preference to discontinue chemotherapy. Methods: Patients receiving taxane and/or platinum chemotherapy for breast or colorectal cancer were enrolled in a prospective observational clinical study. Patients reported their CIPN severity using the EORTC CIPN20 patient-reported outcome questionnaire at the start of each treatment cycle. At the same time, patients were asked if they would prefer to continue or discontinue chemotherapy treatment under the hypothetical scenario that their current CIPN symptoms would be temporary or permanent. A generalized linear mixed effects model was used to determine the effect of CIPN severity, permanence, and other clinical variables on a patient’s decision to discontinue (vs. continue) chemotherapy treatment. Results: A total of 66 patients completed data collection at least one time, of whom 55 (83%) had breast cancer, 12 (18%) had metastatic disease, and 52 (79%) received a taxane. The odds a patient would prefer to discontinue chemotherapy treatment if their CIPN symptoms would be permanent (vs. temporary) were nearly 30 times greater (odds ratio (OR)=30.15, 95% confidence interval (CI): 15.73-57.79, p&lt;0.001, Table). There was a statistical trend toward preferring to discontinue chemotherapy treatment as CIPN symptom severity increased (OR=1.09, 95% CI: 1.00-1.19, p=0.063). Conclusions: The potential for CIPN symptoms to be permanent has a huge effect on whether patients want to continue or discontinue chemotherapy treatment. Additional data is needed on the incidence and predictors of permanent CIPN. More importantly, shared decision-making tools that convey the risk of permanent CIPN, and the potential risk of discontinuing chemotherapy treatment, are needed to facilitate patient-centered treatment decisions so that each patient with cancer achieves their personal treatment goals. [Table: see text]

Chemotherapy-Induced Peripheral Neuropathy and Falls in Cancer Survivors Relate to Digital Balance and Gait Impairments.

Chemotherapy-induced peripheral neuropathy (CIPN) and falls can be persistent side effects of cancer treatment. Standing postural sway and gait tests with body-worn, inertial sensors provide objective digital balance and gait measures that represent several different domains controlling mobility. Specific domains of balance and gait that related to neuropathy and falls are unknown. The aim of this study was to determine which domains of balance and gait differed between cancer survivors who report (1) CIPN symptoms versus no symptoms, (2) a history of falls in the past 6 months versus no falls, and (3) prospective falls over 12 months versus no falls. Postural sway during 30 seconds of quiet standing and gait characteristics from a 7-m timed up and go test were recorded with six synchronized inertial sensors (Opals by APDM Wearable Technologies, a Clario Company) in 425 older, female cancer survivors (age: 62 ± 6 years). A principal component analysis (PCA) approach was used to identify independent domains of mobility from 15 balance and gait measures. PCA analysis revealed five independent domains (PC1 = sway amplitude, PC2 = gait pace, PC3 = sway frequency, PC4 = gait spatial-temporal, and PC5 = turning) that accounted for 81% of the variance of performance. Cancer survivors who reported CIPN symptoms had significantly higher sway frequency (PC3) than asymptomatic survivors. Past fallers had significantly larger sway area (PC1) and slower gait pace (PC2) than nonfallers. Prospective fallers showed a significantly smaller stride length (PC4) than nonfallers. Digital balance and gait measures using wearable sensors during brief standing and walking tests provide objective metrics of CIPN-related mobility impairment and fall risk that could be useful for oncology clinical trials.

Preventing chemotherapy-induced peripheral neuropathy with acupuncture, a multinational parallel randomized controlled trials project (PACT).

TPS12156 Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a significant challenge for patients (pts) with breast cancer treated with taxanes and platinum compounds. CIPN severely affects quality of life, leading to paresthesia and pain, and often results in dose modifications and discontinuation of treatment. Although preliminary trials suggest the effectiveness of acupuncture in managing existing symptoms of CIPN, the use of acupuncture to prevent CIPN is not well studied. Prior studies provide inconclusive results, underscoring the need for more rigorous investigation. We designed an international study, PACT, to evaluate the impact of acupuncture on the prevention of CIPN in breast cancer pts who undergo adjuvant or neoadjuvant taxane-based chemotherapy. Methods: PACT is a coordinated multi-national study consisting of three parallel randomized trials in USA, China, and South Korea, using the same inclusion/exclusion criteria, randomization, interventions, and validated measures. PACT is designed to evaluate the effectiveness of acupuncture in preventing CIPN in pts undergoing taxane-based chemotherapy for early-stage breast cancer. Participants include pts with newly diagnosed stage I-III breast cancer without preexisting neuropathy, scheduled for adjuvant or neoadjuvant taxane-based chemotherapy. Target enrollment is 140 pts from three sites: Dana-Farber Cancer Institute (USA) (n=100), Jiangsu Province Hospital of Chinese Medicine (China) (n = 20) and the Daegu Catholic University Medical Center (South Korea) (n=20), randomized (1:1) to the acupuncture arm or a control. The acupuncture arm receives a standardized protocol of 1-2 sessions per week for 12 weeks (total of 14 sessions). The control arm receives relaxation exercises with nature scenery videos for 14 sessions. The follow-up period for both arms is 12 weeks. Main measures include The European Organisation for Research and Treatment of Cancer (EORTC) QLQ-CIPN20, QLQ-30 and Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) CIPN items. The primary outcome measure is the change in CIPN severity, assessed using the EORTC QLQ-CIPN20 sensory subscale, between baseline and week 12, with secondary outcomes including occurrence of CIPN and maximum CIPN scores, pain, sleep quality, and overall quality of life. A planned pooled analysis of individual patient data will be performed. The ethics review committee of each site has approved the study. Today, 89 (64%) of the planned 140 participants have been enrolled. Clinical trial information: NCT05528263 , ChiCTR2200066714, KCT0008470.

A randomized phase III clinical trial of acupuncture for chemotherapy-induced peripheral neuropathy treatment (ACT).

TPS12151 Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a common and potentially dose-limiting side effect of neurotoxic chemotherapy among people who experience cancer, presenting pain, numbness, tingling, and motor weakness. CIPN worsens quality of life and disrupts active treatment regimens. Currently, duloxetine is the only ASCO-recommended painful CIPN treatment after chemotherapy completion. Still, it has undesirable side effects, i.e., fatigue, sleep disturbance, and digestive symptoms, posing a pressing need for well-tolerated, evidence-based interventions. Our pilot study demonstrated the feasibility and preliminary efficacy of acupuncture in relieving CIPN pain. Based on that, we developed the ACT trial to evaluate the effect of acupuncture on improving pain and other related symptoms among cancer survivors with CIPN pain. Methods: ACT is a prospective phase III multicenter, parallel two-arm randomized clinical trial at Dana-Farber Cancer Institute (DFCI) and Memorial Sloan Kettering Cancer Center (MSK) (ClinicalTrials.gov Identifier: NCT04917796). ACT aims to determine the efficacy of an eight-week electroacupuncture (EA) treatment vs. sham acupuncture (SA) on improving CIPN symptoms severity in cancer survivors. We plan to enroll 250 participants to detect an effect size of at least 0.45 for the primary pain outcome at 12 weeks post-randomization between EA vs. SA, with 80% power and a 1% Type I error rate, assuming a 10% loss to follow-up. Major eligibility criteria include 1) adults who have no evidence of disease or stable diseases, 2) who have completed neurotoxic chemotherapy such as platinum agents, taxanes, vinca alkaloids, and bortezomib at least three months before enrollment, and 3) who have a clinical diagnosis of CIPN with moderate to severe pain, defined as a score of at least four on the Brief Pain Inventory (BPI) average pain item. We randomly allocate participants to receive ten real or sham acupuncture treatments over eight weeks at two centers and their regional clinics. Aside from patient-reported outcome measures (i.e., BPI, Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity, EORTC Quality of Life Questionnaire-CIPN 20), we conduct quantitative sensory testing to assess changes in sensory function. The primary study endpoint is week 12, and the secondary study endpoint is week 24. Progress: 1) We are currently transitioning this trial to a multicenter trial, with DFCI being the coordinating center and MSK a subsite; 2) As of January 18, 2024, a total of 133 of the planned 250 participants have been enrolled; 3) The DSMB last reviewed the trial in December 2023, and suggested that the trial continue as planned at MSK. We anticipate initiating participant enrollment at DFCI in February 2024. Accrual completion is expected by December 2024. Clinical trial information: NCT04917796 .

A randomized phase III clinical trial of yoga for chemotherapy-induced peripheral neuropathy treatment (YCT).

TPS12152 Background: Chemotherapy-induced peripheral neuropathy (CIPN) is common and debilitating among cancer survivors receiving neurotoxic chemotherapy, which can cause functional disabilities and significantly increase the risk of falls. There are limited approaches to managing CIPN symptoms and related functional limitations. Our pilot study demonstrated yoga therapy's feasibility and preliminary efficacy in improving CIPN pain and functional outcomes. We developed the YCT trial to assess the effect of yoga therapy on improving pain and balance symptoms among cancer survivors with CIPN pain. Methods: YCT is a prospective phase III multicenter, parallel three-arm randomized clinical trial at Dana-Farber Cancer Institute (DFCI) and Memorial Sloan Kettering Cancer Center (MSK) (ClinicalTrials.gov Identifier: NCT05121558). YCT aims to determine the efficacy of an eight-week yoga treatment vs. education control (EC) vs. usual care (UC) in improving CIPN pain and balance in cancer survivors. We plan to enroll and randomize 268 participants (2:1:1) to yoga, EC, and UC groups to detect an effect size of at least 0.48 for the primary pain outcome at eight weeks post-randomization between yoga vs. EC, with 80% power and a 2.5% Type I error rate, assuming 12% attrition by week 8 and 20% attrition by week 24. Major eligibility criteria include 1) adults who have no evidence of disease or stable diseases, 2) who have completed neurotoxic chemotherapy such as platinum agents, taxanes, vinca alkaloids, and bortezomib at least three months before enrollment, 3) who have a clinical diagnosis of CIPN with moderate to severe pain, defined as a score of at least four on the Brief Pain Inventory (BPI) average pain item, and 4) who experience self-identified CIPN balance difficulty. Eligible subjects in the yoga arm will receive hourly gentle therapeutic yoga classes taught by protocol-trained oncology yoga instructors, twice weekly for eight weeks, and practice home-based yoga. Subjects in the EC arm will receive hourly education classes taught by protocol-trained healthcare instructors twice weekly for eight weeks. Subjects in the UC arm will continue usual care for eight weeks. We offer free yoga sessions for participants in control groups after study completion. Aside from patient-reported outcome measures (i.e., BPI, FACT/GOG-Ntx, QLQ-CIPN 20), we measured functional improvements by functional reach, timed up-and-go, and chair-to-stand tests. We also conducted quantitative sensory testing to assess changes in sensory function. Progress: 1) We are transitioning this trial to a multicenter trial, with DFCI being the coordinating center and MSK a subsite; 2) As of January 18, 2024, 104 of the planned 268 participants have been enrolled. We anticipate initiating participant enrollment at DFCI in February 2024. Anticipated accrual completion: March 2025. Clinical trial information: NCT05121558 .

Intervensi Non Farmakologis untuk Memperbaiki Status Fungsional Pasien Kanker dengan Chemotherapy-Induced Peripheral Neuropathy (CIPN)

This study aims to identify non-pharmacological interventions that can improve the functional status of cancer patients with chemotherapy-induced peripheral neuropathy (CIPN). The research method uses a systematic review through literature searches from 4 databases: SAGE, PUBMED, SCIENCE DIRECT, and PROQUEST. The research results show that from 12 research articles, non-pharmacological interventions to improve functional status in CIPN can be grouped into physical and non-physical interventions. Physical interventions include physical exercise and stimulation, while non-physical interventions are through self-management. In conclusion, physical intervention effectively reduces the pain scale and sensory symptoms of CIPN, which improves the patient's functional status and quality of life. However, in some literature, it is stated that a combination with pharmacological therapy can reduce CIPN complaints. Keywords: CIPN, Non-Pharmacological Intervention, Functional Status

Cured but not well-haematological cancer survivors' experiences of chemotherapy-induced peripheral neuropathy in everyday life: a phenomenological-hermeneutic study.

To explore haematological cancer survivors' experience of chemotherapy-induced peripheral neuropathy (CIPN) in everyday life. Data were generated by means of individual semi-structured interviews with 12 haematological cancer survivors who experience CIPN after completion of treatment. Data were analysed using thematic analysis. The thematic analysis yielded an in-depth description of the experience of CIPN symptoms and the influence of the symptoms on everyday life as being unwell despite being cured. Four main themes emerged from the analysis: (1) A diffuse and contradictory sensation which is impossible to ignore in everyday life, (2) Not feeling well, even though I'm cured, (3) Living with CIPN, despite limitations, and (4) An invisible companion, that everybody knows about. The findings shows that survival from haematological cancer does not always equal well-being, as experiencing CIPN has extensive consequences on everyday life. CIPN affects haematological cancer survivors' transition to an ordinary everyday life, with disturbances in the physical function, daily activities, social relationships, psychological aspects, and work ability. As a diffuse and contradictory symptom, CIPN appears as an invisible companion that leads to a feeling of being alone. A better and deeper understanding of haematological cancer survivors' experience of CIPN in everyday life may improve communication, guidance, and treatment of CIPN symptoms. The results suggest a need for interventions and strategies to accommodate the gap in practice and to address the impact of CIPN in everyday life.

Impact of exercise on chemotherapy-induced peripheral neuropathy in survivors with post-treatment primary breast cancer.

Chemotherapy-induced peripheral neuropathy (CIPN) is a debilitating side effect of neurotoxic chemotherapy. Exercise activates neuromuscular function and may improve CIPN. We examined the association between exercise and CIPN symptoms in breast cancer survivors. In a retrospective cross-sectional study, we included patients completing a survey assessing exercise exposure and neuropathy symptoms in a tertiary cancer center survivorship clinic. We evaluated exercise duration and intensity using a standardized questionnaire quantified in metabolic equivalent tasks (MET-h/wk). We defined exercisers as patients meeting the National Physical Activity Guidelines' criteria. We used multivariable logistic regressions to examine the relationship between exercise and CIPN and if this differed as a function of chemotherapy regimen adjusting for age, gender, and race. We identified 5444 breast cancer survivors post-chemotherapy (median age 62years (interquartile range [IQR]: 55, 71); median 4.7years post-chemotherapy (IQR: 3.3, 7.6)) from 2017 to 2022. CIPN overall prevalence was 34% (95% confidence interval [CI]: 33%, 36%), 33% for non-taxane, and 37% for taxane-based chemotherapy. CIPN prevalence was 28% (95% CI: 26%, 30%) among exercisers and 38% (95% CI: 37%, 40%) among non-exercisers (difference 11%; 95% CI: 8%, 13%; p < 0.001). Compared to patients with low (<6 MET-h/wk) levels of exercise (42%), 11% fewer patients with moderate (6-20.24 MET-h/wk) to high (>20.25 MET-h/wk) levels of exercise reported CIPN. Exercise was associated with reduced prevalence of all CIPN symptoms regardless of chemotherapy type. CIPN may persist several years following chemotherapy among patients with breast cancer but is significantly reduced by exercise in a dose-dependent manner.

Implementation of personalized multidisciplinary neuropathy management program for chemotherapy-induced peripheral neuropathy symptoms in breast cancer patients

Objective To construct a personalized multidisciplinary neurotoxicity management program for chemotherapy-induced peripheral neuropathy (CIPN) symptoms in breast cancer patients and evaluate its application effects. Methods A retrospective analysis was conducted on clinical data of 133 breast cancer chemotherapy patients admitted to our hospital from January 2022 to January 2024. Based on the nursing protocols received, patients were divided into a control group (n = 66) and an intervention group (n = 67). The control group received conventional nursing interventions, while the intervention group received personalized nursing interventions in addition to the control group interventions. The nursing programs were carried out during chemotherapy. A comparison was made between the two groups before chemotherapy and 3 months after chemotherapy in terms of the degree of neuropathy, cancer-related fatigue, negative emotional status, and symptom management knowledge, attitudes, and practices (KAP). Results The intervention group showed significantly lower neuropathy severity (FACT/GOG-Ntx), cancer-related fatigue (CFS), and negative emotions (PHQ-9, GAD-7) scores after chemotherapy compared to the control group (p < 0.05). Additionally, the intervention group exhibited higher scores for symptom management knowledge, beliefs, and behaviors (p < 0.05). Conclusion Personalized multidisciplinary neurotoxicity management program significantly improved neuropathy severity, reduced cancer-related fatigue and negative emotions, and enhanced symptom management knowledge, attitudes, and practices among breast cancer patients undergoing chemotherapy.

Effects of taxane-induced peripheral neuropathy on hand dexterity impairment: evaluation of quantitative and subjective assessments.

Chemotherapy-induced peripheral neuropathy (CIPN) commonly involves hand dexterity impairment. However, the factors affecting hand dexterity impairment are unknown and there is currently no established treatment. The purpose of the current study was to clarify factors influencing hand dexterity impairment in taxane-induced peripheral neuropathy using subjective and objective assessments. We assessed patient characteristics, treatment-related factors, subjective symptoms of CIPN (Patient Neurotoxicity Questionnaire [PNQ]), psychological symptoms, and upper limb dysfunction (Quick Disabilities of the Arm, Shoulder and Hand [Quick DASH]). Quantitative assessments were pinch strength, sensory threshold, hand dexterity impairment, and grip force control. Multiple regression analysis was performed using hand dexterity impairment as the dependent variable and age and PNQ, Quick DASH, and control of grip force as independent variables. Forty-three breast cancer patients were included in the analysis. Hand dexterity impairment in taxane-induced peripheral neuropathy patients was significantly correlated with age, grip force control, and PNQ sensory scores (p < 0.008). Multiple regression analysis demonstrated that PNQ sensory scores and grip force control were significantly associated with hand dexterity impairment (p < 0.01). Subjective symptoms (numbness and pain) and grip force control contributed to impaired hand dexterity in taxane-induced peripheral neuropathy.