Functional Assessment Of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity Research Articles

Prophylactic role of pentoxifylline against paclitaxel-induced neuropathy among patients with breast cancer: a randomized-controlled trial.

Paclitaxel-induced peripheral neuropathy (PN) is a significant clinical concern for which no approved treatment is currently available. The purpose of this trial was to investigate the neuro-prophylactic impact of pentoxifylline against paclitaxel-induced PN in patients diagnosed with breast cancer (BC). BC patients who were assigned to paclitaxel chemotherapy were randomly allocated to pentoxifylline or a control group for 12 weeks. The main outcomes included the assessment of PN incidence according to the defined Common Terminology Criteria for Adverse Events, quality of life (QoL) using the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT/GOG-NTx) scale, and neuropathic pain using the scale of self-reported Leeds Assessment for Neuropathic Symptoms and Signs (s-LANSS). The code of the clinical trial registration is NCT06562998. The current study included a total of 72 patients allocated into pentoxifylline arm (n = 35) and placebo arm (n = 37). By the 12th week, the prevalence of PN (grade 2 or 3) was significantly lower in the pentoxifylline arm 10/35 (28.6%) compared to 24/37 (64.9%) of the controls (P value = 0.016). The total FACT/GOG-NTx score indicated a considerably worse QoL in the control group [98.18 (10.2) vs. 81.43 (14.8) for pentoxifylline and the control group, respectively, P < 0.001] with a mean difference of -16.75 [95% confidence interval (CI): -23.97 to -9.53]. S-LANSS scale showed significantly higher scores after 6 weeks [13.72 (5.86) vs. 17.52 (3.16), P = 0.002] and 12 weeks [17.84 (4.25) vs. 23.80 (1.00), P < 0.001] for pentoxifylline and control group, respectively. In conclusion, the use of pentoxifylline showed a significant reduction in paclitaxel-induced PN, which improved their QoL.

Evaluation of the effect of pentoxifylline on the prevention of paclitaxel‑induced peripheral neuropathy in breast cancer patients: a randomized controlled study

BackgroundPaclitaxel-induced peripheral neuropathy (PIPN) is one of the most common and debilitating toxicity. Up till now, no treatment or preventive medication is recommended by guidelines. Pentoxifylline has been found to prevent PIPN in animal models. This study aimed to evaluate the tolerability and efficacy of pentoxifylline in preventing PIPN. To our knowledge, this is the first clinical trial to evaluate the potential effect of pentoxifylline on the prevention of PIPN in breast cancer (BC) patients.ResultsA simple-randomized placebo-controlled study was conducted on 60 BC patients receiving weekly paclitaxel and either pentoxifylline 400 mg twice daily (n = 30) or placebo (n = 30) for 12 weeks. Only 55 patients completed the study. The main objective was the evaluation of the effect of pentoxifylline on the incidence of PIPN which revealed no significant difference between the pentoxifylline group (85%) and the placebo group (100%). Secondary objectives included time to develop grade 2 or 3 (TTG 2/3) PIPN, the patient’s quality of life (QOL), serum tumor necrosis factor-α (TNF-α) and malondialdehyde and the tolerability of pentoxifylline. The median TTG 2/3 PIPN was not reached in the pentoxifylline group compared to 77 days (95% confidence interval of 70.91 to 83.07) in the placebo group. However, the difference did not reach significance. The assessment of the impact of PIPN on QOL was performed at baseline and at weeks 4, 8 and 12 using Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT/GOG-NTX) subscale. The magnitude of the worsening in the QOL was significantly lower in the pentoxifylline group than in the placebo group at weeks 4, 8, and 12 (p values = 0.028, 0.003, and 0.018, respectively). Analysis of the serum TNF-α and malondialdehyde revealed no significant differences between the groups. Pentoxifylline was safe, tolerable and did not affect paclitaxel toxicity.ConclusionOral pentoxifylline (400 mg twice daily) did not decrease the incidence of PIPN. However, it improved patients’ QOL significantly.Trial registration Clinical Trials.gov, NCT05189535. Registered 4 October 2021, https://classic.clinicaltrials.gov/ct2/show/NCT05189535.

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.

Evaluation of the Effect of Loratadine versus Diosmin/Hesperidin Combination on Vinca Alkaloids-Induced Neuropathy: A Randomized Controlled Clinical Trial.

Neurological injury is a crucial problem that interferes with the therapeutic use of vinca alkaloids as well as the quality of patient life. This study was conducted to assess the impact of using loratadine or diosmin/hesperidin on neuropathy induced by vinca alkaloids. Patients were randomized into one of three groups as follows: group 1 was the control group, group 2 received 450 mg diosmin and 50 mg hesperidin combination orally twice daily, and group 3 received loratadine 10 mg orally once daily. Subjective scores (numeric pain rating scale, douleur neuropathique 4, and functional assessment of cancer therapy/gynecologic oncology group-neurotoxicity (FACT/GOG-Ntx) scores), neuroinflammation biomarkers, adverse drug effects, quality of life, and response to chemotherapy were compared among the three groups. Both diosmin/hesperidin and loratadine improved the results of the neurotoxicity subscale in the FACT/GOG-Ntx score (p < 0.001, p < 0.01 respectively) and ameliorated the upsurge in neuroinflammation serum biomarkers. They also reduced the incidence and timing of paresthesia (p = 0.001 and p < 0.001, respectively) and dysuria occurrence (p = 0.042). Both loratadine and diosmin/hesperidin attenuated the intensity of acute neuropathy triggered by vinca alkaloids. Furthermore, they did not increase the frequency of adverse effects or interfere with the treatment response.

Abstract PO5-12-09: A Single-Arm Pilot Study of the Feasibility and Efficacy of Electro-Acupuncture in Subjects with Chemotherapy-Induced Peripheral Neuropathy

Abstract Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a very common dose-limiting side effect of many cancer treatments. However, the optimal treatment for CIPN remains unclear. Electroacupuncture (EA) is a non-pharmacologic treatment that combines traditional acupuncture with electrical stimulation. EA is being examined for CIPN and has shown modest benefits. Design: This is a pilot, single-center, prospective, single-arm, non-blinded study. All subjects had residual grade ≥2 CIPN after having received curative intent chemotherapy for stage I-III breast cancer, completed at least 3 months prior to study enrollment. Patients received 10 sessions of electro-acupuncture, administered by a licensed professional, over the course of 7 weeks. A sub-group of patients also had baseline and post-treatment skin punch biopsies to assess intra-epithelial nerve density (IEND). The primary objective was to determine the feasibility of completing a 10-treatment EA program in this patient population. Feasibility was defined as ≥15 subjects completing ≥8 EA treatments. Secondary endpoints included neuropathic pain, as assessed by the Brief Pain Inventory-Short Form (BPI-SF), and change in the quality of life, as assessed by the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT/GOG-NTX) subscale. Results: Twenty eligible female subjects were included in the study, with a median age of 66.5 years (range 45-81 years old). All patients received taxane chemotherapy, with 15 (75%) patients receiving weekly paclitaxel, 4 (8%) patients receiving Taxotere every 3 weeks, and 1 (2%) patient received weekly abraxane. The duration between chemotherapy completion and EA treatment initiation ranged between 4-92 months, with a median of 29 months. Eight (40%) patients were taking gabapentin, 2 (10%) on duloxetine, 1 (5%) pregabalin, and 3 (15%) on NSAIDS before and during the study. The study met its primary endpoint of feasibility, with 18 of 20 (90%) patients completing 8 or more EA sessions. Pain level, as assessed by the worst pain score on BPI-SF, improved significantly from a mean of 6.3 to 3.7, 2 weeks after completion of EA treatments (p = .0058). FACT/GOG-NTX quality of life measurement, “I am bothered by side effects of my treatment” also significantly improved from a mean score of 2.1 to 0.8 (p = .0177). There were no major adverse events (AEs) related to EA. Nine mild AEs were noted among 6 (30%) patients; localized skin biopsy site infections: G1=3, G2=3, nonlocalized cellulitis G3=1, Fatigue G1-2 =2. The localized skin biopsy site infections led to the discontinuation of further skin biopsy procedures. [We will also present data on the IEND for the nine patients who have paired before and after skin punch biopsies – this will be available at the time of the conference.] Conclusion: Electroacupuncture is a feasible treatment for CIPN. Furthermore, this pilot study did show a benefit for perceived pain and quality of life. Further studies will need to be conducted in regards to longevity of response. As larger studies in the future confirm the benefit of acupuncture, insurance payors are more likely to cover this important service. Citation Format: Nikitha Vobugari, John Paul Liang, Loni Savage, Dharamvir Jain, Kai Sun, Hanh Mai, Jenny Chang, Monica Desai, Tejal Patel, Polly Niravath. A Single-Arm Pilot Study of the Feasibility and Efficacy of Electro-Acupuncture in Subjects with Chemotherapy-Induced Peripheral Neuropathy [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-12-09.

Acupuncture in Multiple Myeloma Peripheral Neuropathy: A Systematic Review.

Peripheral neuropathy (PN) is a prevalent complication of multiple myeloma (MM), due to the disease itself or its treatment. Despite extensive research, the optimal treatment for multiple myeloma peripheral neuropathy (MMPN) remains unclear. Clinical practice has shown the potential efficacy of acupuncture in managing MMPN. This study aimed to conduct a comprehensive analysis of the literature to assess the effectiveness and safety of acupuncture as a treatment for MMPN. The PubMed, Web of Science, MEDLINE, Cochrane Library, and Embase databases were comprehensively searched from inception to November 1, 2023 to identify relevant studies pertaining to the use of acupuncture to treat MMPN. A total of five studies, encompassing 97 patients diagnosed with drug-related PN, were ultimately included in this analysis. The literature lacks any reports pertaining to the utilization of acupuncture for disease-related PN. ST36, LI4, SP6, and EX-LE-10 were found to be the most frequently chosen acupoints. Following acupuncture treatment, there was a consistent reduction in scores on the Visual Analogue Scale (VAS), Neuropathic Pain Scale (NPS), Brief Pain Inventory-Short Form (BPI-SF), and Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT/GOG-Ntx) among MMPN patients. The results of Nerve Conduction Velocity (NCV) tests yielded conflicting results. No severe adverse effects were reported. The use of acupuncture for disease-related PN has not been studied to date. Acupuncture is safe for drug-related PN and is helpful for relieving pain. But uncertainty exists regarding the efficacy of this approach because there is substantial heterogeneity with respect to acupuncture treatment regimens, and more high-quality studies on this topic are warranted.

Performance of the FACT-GOG-Ntx to assess chemotherapy-induced peripheral neuropathy (CIPN) in pediatric high risk Hodgkin lymphoma: report from the Children’s Oncology Group AHOD 1331 study

BackgroundChemotherapy-induced peripheral neuropathy (CIPN) is an under-recognized complication of several chemotherapy agents used as part of curative-intent therapy for Hodgkin Lymphoma (HL). In the absence of validated self- or proxy-report measures for children and adolescents, CIPN reporting has relied on clinician rating, with grading scales often restricted to severe manifestations. In a proof-of-concept study, we assessed the feasibility and psychometric performance of the Functional Assessment of Cancer Therapy-Gynecologic Oncology Group-Neurotoxicity (FACT-GOG-Ntx), a unidimensional CIPN symptom scale widely used adults with CIPN, in pediatric HL at risk for CIPN.MethodsYouth (11+ years) and parents of all children (5–17.9 years) with newly diagnosed high-risk HL enrolled on Children’s Oncology Group AHOD1331 (NCT02166463) were invited to complete the FACT-GOG-Ntx and a health-related quality of life (HRQL) measure at pre-treatment (Time 1), and during cycles 2 (Time 2) and 5 (Time 3) of chemotherapy during the first half of study accrual. Clinical grading of CIPN by providers was also assessed using the Balis Pediatric Neuropathy Scale. We evaluated Cronbach’s alpha, construct validity, and agreement between raters. Change in FACT-GOG-Ntx scores over time was assessed using a repeated measures model.Results306 patients had at least one completed FACT-GOG-Ntx with time-specific completion rates of > 90% for both raters. Cronbach’s alpha was > 0.7 for youth and parent-proxy report at all time points. Correlations between FACT-GOG-Ntx and HRQL scores were moderate (0.41–0.48) for youth and parent-proxy raters across all times. Youth and parent-proxy raters both reported worse FACT-GOG-Ntx scores at Time 3 for those who had clinically-reported CIPN compared to those who did not. Agreement between raters was moderate to high. Compared to baseline scores, those at Time 3 were significantly lower for youth (β = − 2.83, p < 0.001) and parent-proxy raters (β = − 1.99, p < 0.001).ConclusionsHigh completion rates at all time points indicated feasibility of eliciting youth and parent report. Psychometric performance of the FACT-GOG-Ntx revealed acceptable reliability, evidence of validity, and strong inter-rater agreement, supporting the use of this self- or proxy-reported measure of CIPN in youth with high-risk HL exposed to tubulin inhibitors, as part of a Phase 3 clinical trial.Clinical trial information: Clinical Trials Registry, NCT02166463. Registered 18 June 2014, https://clinicaltrials.gov/ct2/show/study/NCT02166463

A randomized trial to evaluate the preventive effect of lafutidine on chemotherapy-induced peripheral neuropathy in patients treated with carboplatin and paclitaxel for lung cancer.

Chemotherapy-induced peripheral neuropathy (CIPN) has a significant impact on the therapeutic efficacy of chemotherapy and patients' quality of life. The aim of this study was to assess the preventive effect of lafutidine on CIPN. Patients were randomly assigned (1:1) to carboplatin and paclitaxel chemotherapy with lafutidine 10 mg twice daily (lafutidine group) or without lafutidine (control group). Peripheral neuropathy in both groups was assessed with the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 and two patient-based questionnaires, the Patient Neurotoxicity Questionnaire (PNQ) and the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT/GOG-Ntx). The primary outcome was the incidence of grade 2 or higher peripheral neuropathy in CTCAE version 5.0. The target number of cases was set at approximately 40. In total, 18 patients were screened, and 16 patients were assigned to the lafutidine group (n=9) or control group (n=7) between January 2021 and January 2023. Due to poor recruitment, the target number of cases was not reached. Grade 2 or higher neuralgia was 22.2% in the lafutidine group and 14.3% in the control group. Grade 2 or higher peripheral sensory neuropathy was 100% in the lafutidine group and 71.4% in the control group (P=0.175). Grade 3 or higher peripheral neuropathy was not detected in either group. There was no significant difference in PNQ scores between the two groups. Median FACT/GOGNtx scores after the fourth cycle tended to be lower in the lafutidine group than in the control group. There was no statistically significant difference in progression free survival (PFS) between the two groups. There were no adverse events due to lafutidine administration. Although the preventive effect of lafutidine on CIPN could not be demonstrated statistically, lafutidine FACT/GOG-Ntx scores showed a trend toward decreased neurotoxicity as chemotherapy proceeded. More reliable studies using lafutidine on the prevention of CIPN should be conducted. Japan Registry of Clinical Trials identifier: jRCTs021200031.

Cryocompression to Reduce Peripheral Neuropathy in Gynecologic Cancer: A Randomized Controlled Trial.

To investigate the efficacy of cryocompression therapy to prevent chemotherapy-induced peripheral neuropathy. This single-institution, randomized, self-controlled trial of cryocompression enrolled gynecologic cancer patients planned for five to six cycles neurotoxic chemotherapy. Exclusion criteria were prior neurotoxic chemotherapy or baseline peripheral neuropathy. Participants were randomized to cryocompression on dominant versus non-dominant hand and foot (treatment), with no intervention on the opposite side (control). Compression socks and gloves and ice bags were applied 15 minutes before, during, and 15 minutes after infusion. Primary outcome measures included the PNQ (Patient Neurotoxicity Questionnaire) and the Semmes-Weinstein monofilament test; secondary outcomes included the FACT/GOG-NTX (Functional Assessment of Cancer Therapy/Gynecologic Oncology Group - Neurotoxicity) and patient acceptability and tolerability. Sixty patients completing the study were necessary to detect a 70% reduction in the odds of PNQ grade C or higher peripheral sensory neuropathy with 80% power. Ninety-one patients were enrolled from January 2021 to October 2022; 69 were eligible for final analysis. Of the 91 patients, 64.8% were White, 30.8% were Black, and 1.1% were Hispanic or Latina. With successive cycles, more patients had sensory PNQ grade C or higher neuropathy on the control side compared with the cryocompression side. Cryocompression decreased the odds of sensory neuropathy (PNQ grade C or higher) by 46% at final visit (odds ratio 0.54, 95% CI 0.31-0.94; P =.03). There was no difference in tactile sensitivity based on the monofilament test between sides at the final visit. At the final visit, average FACT/GOG-NTX-11 (Functional Assessment of Cancer Therapy/Gynecologic Oncology Group - Neurotoxicity 11 Item Version) scores were significantly lower on the cryocompression than the control side (estimate -0.97, 95% CI -1.89 to -0.06; P =.04), as were FACT/GOG-NTX-4 (Functional Assessment of Cancer Therapy/Gynecologic Oncology Group - Neurotoxicity 4 Item Version) scores (estimate -0.35, 95% CI -0.64 to -0.05; P =.02). More than 85% of patients assessed the intervention as acceptable and tolerable. Cryocompression therapy reduces subjective chemotherapy-induced peripheral sensory neuropathy in patients who are receiving paclitaxel or cisplatin for gynecologic cancer. ClinicalTrials.gov , NCT04563130.

Efficacy of metformin in prevention of paclitaxel-induced peripheral neuropathy in breast cancer patients: a randomized controlled trial.

Background: Paclitaxel-induced peripheral neuropathy (PN) is a serious clinical problem with no approved drug for prevention. This study aimed to examine the neuroprotective effect of metformin against paclitaxel-induced PN in breast cancer patients. Methods: Patients with confirmed breast cancer diagnosis who were planned to receive paclitaxel were randomized to receive either metformin or placebo. Both groups received the standard chemotherapy protocol for breast cancer. Patients started metformin/placebo 1week before paclitaxel initiation and continued study interventions thereafter for nine consecutive weeks. The primary outcome was the incidence of development of grade two or more paclitaxel-induced sensory PN. The PN was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE). Patients' quality of life (QoL) was assessed by the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACTGOG-Ntx) subscale. Pain severity was measured by the Brief Pain Inventory Short Form (BPI-SF). Serum levels of nerve growth factor (NGF) and neurotensin (NT) were measured at baseline and at the end paclitaxel treatment. Results: A total of 73 patients (36 in the metformin arm and 37 in the control arm) were evaluated. The cumulative incidence of development of grade two or more PN was significantly lower in the metformin arm (14 (38.9%) than the control arm (28 (75.7%); p = 0.001). At the end of paclitaxel treatment, patients' QoL was significantly better in the metformin arm [median (IQR) FACTGOG-Ntx subscale of (24.0 (20.5-26.5)] compared to the control arm (21.0 (18.0-24.0); p = 0.003). The metformin arm showed lower "average" and "worst" pain scores than those detected in the control arm. At the end of the paclitaxel treatment, there was a significant difference in the median serum NGF levels between the two arms, favoring metformin (p < 0.05), while NT serum levels were deemed comparable between the two study arms (p = 0.09). Conclusion: The use of metformin in breast cancer patients offered a marked protection against paclitaxel-induced PN, which translated to better patient QoL. Clinical Trial Registration: https://classic.clinicaltrials.gov/ct2/show/NCT05351021, identifier NCT05351021.

Effect of Cilostazol on Preventing Paclitaxel-Induced Neuropathy in Patients with Breast Cancer: A Randomized Controlled Trial.

Paclitaxel-induced peripheral neuropathy is a significant clinical problem can markedly deteriorate patient's quality of life (QoL). Preclinical evidence exists about the preventive capacity of cilostazol against peripheral neuropathy. However, this hypothesis has not yet been clinically investigated. This proof-of-concept study evaluated the effect of cilostazol on the incidence of paclitaxel-induced peripheral neuropathy in patients with non-metastatic breast cancer. This study is a parallel randomized placebo-controlled trial. Patients (n=69) with breast cancer scheduled to receive paclitaxel 175 mg/m2 biweekly were randomized to either cilostazol group who received cilostazol tablets 100 mg BID, or to control group who received placebo instead. The primary endpoint was the incidence of paclitaxel-induced neuropathy evaluated through common terminology criteria for adverse event (NCI-CTCAE) version 4. Secondary endpoints included assessment of the patient's QoL by the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT-GOG-NTx) subscale. Exploratory outcome measures included changes in serum levels of biomarkers namely nerve growth factor (NGF), and neurofilament light chain (NfL). The incidence of grade two, and three peripheral neuropathies were significantly lower in the cilostazol group (40%) compared to control group (86.7%) (P < 0.001). The incidence of clinically significant worsening in neuropathy related QoL was higher in control group compared to cilostazol group (P = 0.001). A higher percent increase from baseline in serum NGF was observed in the cilostazol group (P = 0.043). The circulating levels of NfL deemed comparable between the two arms at the end of the study (P = 0.593). Adjunctive use of cilostazol may be considered as a novel option that might reduce the incidence of paclitaxel-induced peripheral neuropathy and improve the patients' QoL. Future larger clinical trials are warranted to confirm these findings.

Validation of the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group Neurotoxicity Questionnaire for the Latin American Population.

Background Chemotherapy-induced peripheral neuropathy is a common adverse effect of chemotherapeutic treatment and is associated with decreased quality of life. The aim of this study was to evaluate the validity and reliability of the neurotoxicity subscale of the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT/GOG-Ntx) for the Chilean population. Methods A cross-sectional study in which 101 participants with haematologic, colorectal, breast, gastric, gynaecological, and other types of cancer completed the FACT/GOG-Ntx. Content validity (n = 14 health professionals evaluated the subscale in four categories: test-retest reliability (n = 20 patients), dimensionality, internal consistency, and concurrent validity and discriminant validity. In all analyses, p < 0.05 was considered significant. Results There was an agreement among the evaluators for all categories of the subscale (Kendall's coefficient, W = 0.4, p < 0.01) and moderate to high intrarater reliability (intraclass correlation coefficient = 0.7–0.9). Of the 11 original items that make up the subscale, none was eliminated. The factor analysis generated four factors that represented 72.2% of the total variance. Cronbach's α was 0.8 for the 11 items. Women showed greater compromise in emotional well-being and neurotoxicity symptoms compared with men, and age was directly correlated with the questions ‘I have difficulty hearing' (r = 0.2, p = 0.019) and ‘I feel a noise or buzzing in my ears' (r = 0.2, p = 0.03). Conclusion The Chilean version of the FACT/GOG-Ntx neurotoxicity subscale is a valid and reliable scale for evaluating neurotoxicity symptoms in adult cancer survivors in Latin America. The scales also adequately distinguish between sex-based well-being among the afflicted population.

A Case Report of Chemotherapy-Induced Peripheral Neuropathy Treated with Modified &lt;italic&gt;Guibi-tang&lt;/italic&gt;

Objective: The purpose of this study was to report the effectiveness of modified &lt;i&gt;Guibi-tang&lt;/i&gt; in a patient suffering from chemotherapy-induced peripheral neuropathy (CIPN).Methods: A 54-year-old Korean female patient diagnosed with recurrent ovarian cancer had CIPN with other symptoms, such as anorexia, dyspepsia, insomnia, etc. She was diagnosed with Simbiyangheo and hence treated with a modified &lt;i&gt;Guibi-tang&lt;/i&gt;. Neuropathic symptoms were assessed using a numerical rating scale (NRS) and a sensory score. Quality of life was assessed using the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group Neurotoxicity (FACT/GOG-Ntx).Results: After 14 days of treatment, the patients showed a decrease in NRS for bilateral limb pain and improvement in other symptoms, such as general weakness, insomnia, dizziness, and headache. Quality of life also increased.Conclusion: Modified &lt;i&gt;Guibi-tang&lt;/i&gt; may be considered an optional treatment for CIPN if the patient is diagnosed with Simbiyangheo. Further studies are needed to confirm this finding.

Analysis of peripheral neuropathy (PN) using clinician- and patient-reported outcomes (ClinRO and PRO) in the POLARIX study.

7561 Background: PN is an identified risk of anti-microtubule agents, including polatuzumab vedotin and vincristine. POLARIX (NCT03274492), a Phase III randomized, double-blind, placebo-controlled study comparing Pola-R-CHP with R-CHOP, demonstrated improved progression-free survival (PFS) with Pola-R-CHP (Tilly et al. NEJM 2022). Here, we evaluate the impact of Pola-R-CHP vs R-CHOP on PN using ClinRO and PRO data. Methods: Patients with previously untreated diffuse large B-cell lymphoma (DLBCL) received Pola-R-CHP or R-CHOP. ClinRO data were based on PN grading according to the NCI CTCAE v4.0. PRO data were generated from assessment of patient-reported PN symptoms at baseline and Day 1 of each cycle using the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group – Neurotoxicity (FACT-GOG/NTX) subscale, ranging from 0–44, with higher scores representing lower levels of PN (minimal clinically important difference: 1.38–3.68 [Cheng et al. Health Qual Life Outcomes 2020]). Results: At baseline, ClinRO and PRO symptom scores showed low PN burden (Table). Overall incidence of PN was comparable between treatment arms (Pola-R-CHP: 52.9%; R-CHOP: 53.9%); most events were grade 1, and incidence of grade 2 (Pola-R-CHP: 12.2%; R-CHOP: 15.5%) and grade 3 (Pola-R-CHP: 1.6%; R-CHOP: 1.1%) events were comparable between treatment arms. FACT-GOG/NTX survey completion was high in both arms (96% at baseline; &gt;80% at other timepoints). When evaluated by cycle, ClinRO and PRO demonstrated that more patients experienced earlier onset PN with R-CHOP than with Pola-R-CHP (Table), with ̃10% more R-CHOP- than Pola-R-CHP-treated patients having clinician-reported PN in Cycle (C) 2–5, and a ̃+1-point difference (i.e. fewer symptoms) in PRO symptom scores in C3–6 with Pola-R-CHP vs R-CHOP; by C8+, and during follow up, rates and symptoms of PN were similar. PN symptoms resulted in fewer dose reductions (3.9% vs 8.2%) and drug discontinuations (0.7% vs 2.1%) with Pola-R-CHP vs R-CHOP. Duration of PN was similar for both treatments. Conclusions: In the POLARIX study, Pola-R-CHP did not result in different rates or severity of PN vs R-CHOP. According to ClinRO and PRO data, PN occurred later following initial exposure to Pola-R-CHP than to R-CHOP, and there were fewer dose modifications with Pola-R-CHP than with R-CHOP. Overall, the risk of PN was manageable. Clinical trial information: NCT03274492. [Table: see text]

A randomized phase III clinical trial of acupuncture for chemotherapy-induced peripheral neuropathy (CIPN) in cancer survivors.

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.

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

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.

Health-Related Quality of Life in Cancer Survivors with Chemotherapy-Induced Peripheral Neuropathy: A Randomized Clinical Trial

Chemotherapy-induced peripheral neuropathy (CIPN) is a common, debilitating adverse effect of neurotoxic chemotherapy that significantly worsens the quality of life of cancer survivors. Survivors of solid tumors with persistent moderate-to-severe CIPN defined as numbness, tingling, or pain rated ≥4 on an 11-point numeric rating scale (NRS) were randomized in a 1:1:1 ratio to 8 weeks of real acupuncture (RA) versus sham acupuncture (SA) versus usual care (UC). We previously reported the primary endpoint (NRS); here we report the following health-related quality of life endpoints: Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT/GOG-Ntx), Hospital Anxiety and Depression Scale (HADS), Insomnia Severity Index (ISI), and Brief Fatigue Inventory (BFI). For each endpoint, the mean changes from baseline and 95% confidence intervals were estimated within each arm and compared between arms using linear mixed models. We enrolled 75 survivors of solid tumors with moderate-to-severe CIPN into the study. Compared with baseline, at week 8, FACT/GOG-Ntx, HADS anxiety, and ISI scores significantly improved in RA and SA, but not in UC. Compared with UC, at week 8, FACT/GOG-Ntx scores significantly increased in RA and SA arms indicating improved CIPN-related symptoms and quality of life (p=.001 and p=.01). There was no statistically significant difference between RA and SA. There was no difference in HADS depression or BFI among RA, SA, and UC at weeks 8 and 12. Acupuncture may improve CIPN-related symptoms and quality of life in cancer survivors with persistent CIPN. Further large sample size studies are needed to delineate placebo effects. The authors conducted a randomized sham acupuncture- and usual care-controlled clinical trial to evaluate the impact of acupuncture on health-related quality of life outcomes in patients with solid tumors with chemotherapy-induced peripheral neuropathy (CIPN). Statistically significant improvements in quality of life, anxiety, insomnia, and fatigue were achieved with 8 weeks of real acupuncture when compared with baseline, without statistically significant differences between real and sham acupuncture. These findings suggest that acupuncture may be effective for improving CIPN-related symptoms and quality of life and reducing anxiety and insomnia in cancer survivors with persistent CIPN, with further study needed to delineate placebo effects.

Acupuncture Relieved Chemotherapy-Induced Peripheral Neuropathy in Patients with Breast Cancer: A Pilot Randomized Sham-Controlled Trial

Chemotherapy-induced peripheral neuropathy (CIPN) is a disabling side effect caused by neurotoxic chemotherapy. This randomized controlled trial aimed to evaluate the effect of manual acupuncture on CIPN. Twenty eligible breast cancer patients receiving taxane chemotherapy treatment were recruited and randomly divided into verum acupuncture and sham acupuncture groups. Each group received 15 treatments over 9 weeks. Quantitative tactile detection thresholds were measured using Semmes–Weinstein monofilament testing (SWM). The World Health Organization Quality of Life scale (WHOQOL-BREF), the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT/GOG-Ntx), and the Brief Pain Inventory-Short Form (BPI-SF) were measured before and after treatment. The between-group comparison of SWM revealed that the verum acupuncture group had more improvement of touch perception thresholds compared to the sham acupuncture group. The average pain severity in the BPI-SF of the verum acupuncture group was significantly lower than that of the sham acupuncture group. There were no significant differences in the FACT/GOG-Ntx trial outcome index and WHOQOL-BREF scores between the acupuncture and sham groups. The results suggest that acupuncture can alleviate the neuropathic pain of CIPN and improve touch perception thresholds.

A Case Report of Chemotherapy-Induced Peripheral Neuropathy Treated with Warm Needling

Objective The purpose of this study is to report the effects of warm needling in a patient with cancer who had chemotherapy -induced peripheral neuropathy (CIPN). Methods A 46-year-old Korean female outpatient diagnosed with malignant ovarian cancer was treated with warm needling therapy on the foot acupuncture points for CIPN. Neuropathic symptoms and quality of life were assessed using the numeric rating scale (NRS) and the functional assessment of cancer therapy/Gynecologic Oncology Group neurotoxicity (FACT/GOG-NTX) score. Results After 6 months of treatment, the patient showed a reduction in the severity of CIPN symptoms and an improvement in the quality of life, although the severity of symptoms fluctuated as the patient underwent chemotherapy sessions. Conclusion This study suggests that warm needling may be an effective treatment for CIPN. Keywords: warm needling, acupuncture, chemotherapy, neuropathy, CIPN

Abstract PS9-51: Secondary outcomes in a randomized controlled trial of acupuncture versus sham acupuncture and usual care in solid tumor survivors with chemotherapy-induced peripheral neuropathy

Abstract Background: Chemotherapy-induced peripheral neuropathy (CIPN) is the most common and debilitating long-term adverse effect of neurotoxic chemotherapy and it significantly worsens cancer survivors’ quality of life. In a previously reported randomized controlled trial, we showed that real acupuncture is more effective in reducing persistent CIPN symptoms compared to usual care, with a trend of greater CIPN pain reduction compared to sham acupuncture (Bao et al, JAMA Netw Open, 2020). Here, we report secondary outcomes in this trial. Patients and Methods: Solid tumor survivors with persistent moderate to severe CIPN (symptoms of numbness, tingling, or pain rated ≥4 on a numeric rating scale [NRS]) were randomized to three arms: 1) Eight weeks of real acupuncture (RA); 2) eight weeks of sham acupuncture (SA); and 3) usual care (UC). The secondary endpoints were Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT/GOG-Ntx), Hospital Anxiety and Depression Score (HADS), and Insomnia Severity Index (ISI). For each endpoint, the mean changes from baseline and 95% confidence intervals (CI) were estimated within each arm and compared between arms using linear mixed models.Results: We enrolled and randomized 75 solid tumor survivors (53% breast cancer) with moderate to severe CIPN to the study. Compared to baseline, at week 8, FACT/GOG-Ntx, HADS anxiety, and ISI scores significantly improved in both RA and SA arms, but not in the UC arm (Table 1). At week 8, FACT/GOG-Ntx scores significantly increased in both RA and SA arms when compared with UC (p=0.001 and 0.007), indicating improved CIPN related symptoms and quality of life. There was no statistically significant difference between RA and SA arms, p=0.498. When comparing RA and SA with UC, we found no statistically significant difference in changes from baseline in HADS anxiety and ISI. Conclusions: Our study showed acupuncture may be effective in improving CIPN symptoms and reducing anxiety and insomnia in cancer survivors with persistent CIPN. Further large sample size studies are needed to delineate possible placebo effects from SA. Table 1. Secondary Outcomes in RA, SA, and UC Arms and Changes From BaselineReal Acupuncture(n=27)Sham Acupuncture (n=24)Usual Care (n=24)OutcomeWeekMean (95% CI)Change from Baseline,Mean (95% CI)Mean (95% CI)Change from Baseline,Mean (95% CI)Mean (95% CI)Change from Baseline,Mean (95% CI)FACT/GOG-Ntx024.41 (21.38, 27.44)NA25.13 (21.91, 28.34)NA27.01 (23.80, 30.22)NA828.60 (25.52, 31.67)4.19 (2.39, 5.99)***28.42 (25.19, 31.66)3.30 (1.45, 5.15)***26.61 (23.32, 29.89)-0.40 (-2.35, 1.54)HADS Anxiety06.61 (4.98, 8.25)NA7.66 (5.93, 9.39)NA6.52 (4.79, 8.25)NA85.61 (3.95, 7.27)-1.00 (-1.99, -0.01)*6.64 (4.89, 8.38)-1.02 (-2.03, -0.01)*6.76 (4.99, 8.53)0.24 (-0.81, 1.29)ISI012.93 (10.24, 15.61)NA12.46 (9.61, 15.31)NA10.17 (7.32, 13.02)NA810.63 (7.88, 13.37)-2.30 (-3.99, -0.61)**10.20 (7.33, 13.07)-2.26 (-3.99, -0.53)*8.96 (6.05, 11.87)-1.21 (-3.01, 0.60)Table Symbols: *, p &amp;lt; 0.05; **, p &amp;lt; 0.01; ***, p &amp;lt; 0.001 Citation Format: Ting Bao, Ray Baser, Crystal Lin, Qing Li, Lauren Piulson, Iris Zhi. Secondary outcomes in a randomized controlled trial of acupuncture versus sham acupuncture and usual care in solid tumor 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 PS9-51.