Therapeutic effects of compression therapy on taxane-induced peripheral neuropathy incidence, negative emotions, and sleep disorders in patients with breast cancer.

PURPOSE: To explore the effects of compression therapy on chemotherapy-induced peripheral neuropathy (CIPN), anxiety, depression, and sleep disorders in breast cancer patients administered taxanes. METHODS: Eighty patients with breast cancer undergoing chemotherapy at Tangshan People's Hospital between October 2022 and July 2023 were randomly divided into control (n = 40) and intervention (n = 40) groups. The control group received routine care, while intervention group received compression therapy in addition to routine care (30 min before the infusion of chemotherapy drugs, patients wore surgical gloves on their hands that were one size smaller than the appropriate size and elastic socks on their feet until 30 min after the infusion). The incidence of CIPN, anxiety, depression, and sleep scores, were compared between these groups before and after compression therapy during chemotherapy cycles 2, 4, and 6. RESULTS: The general characteristics did not differ significantly between the groups (P > 0.05). The CIPN incidence, anxiety and depression scores, and sleep scores also did not differ significantly between the two groups before and after the intervention period (P > 0.05). After the fourth and sixth cycles of intervention, the incidence of CIPN (≥ 1 and ≥ 2), anxiety and depression scores, and sleep scores were significantly lower in the intervention group than in the control group (P < 0.05). CONCLUSION: Compression therapy can effectively reduce the incidence of CIPN, as well as improve the level of anxiety, depression, and sleep disorders in chemotherapy patients. Therefore, medical personnel should closely observe the physical and psychological changes in patients undergoing chemotherapy and provide corresponding preventive measures. REGISTRATION NUMBER: RMYY-LLKS-2022-054. DATE OF REGISTRATION: September 25, 2022.

Acute, long-term or non-vincristine-induced peripheral neuropathy among non-Hodgkin lymphoma survivors: Symptoms, daily activities, functional status, and quality of life.

PURPOSE: This study aimed to explore the incidence and severity of vincristine-induced peripheral neuropathy (VIPN) in non-Hodgkin lymphoma (NHL) survivors (primary aim) and its impact on daily life by comparing common cancer symptoms, functional status, and quality of life (QoL) among survivors with acute, long-term, and non-VIPN (secondary aim). METHODS: This cross-sectional study examined 144 NHL survivors. Standardized questionnaires were used to assess common cancer symptoms, functional status, and QoL with the European Organization for the Research and Treatment of Cancer - Quality of Life Questionnaire (EORTC-QLQ-C30). VIPN (Chemotherapy-Induced Peripheral Neuropathy) status was classified using EORTC-QLQ-CIPN20. A self-designed interference scale was developed to determine the impact of the VIPN on daily activities. The Kruskal-Wallis test and Spearman rank correlation were used in this study. RESULTS: Among the survivors of acute and long-term VIPN, the highest incidences and most severe symptoms were found for hand numbness and foot cramps. A significant moderate correlation was found between disturbances in daily activities and acute or long-term VIPN, including gait changes, going up or down the stairs, and imbalance-related falls. Acute and long-term VIPN survivors showed worse symptoms (fatigue, insomnia, and constipation) and lower QoL than non-VIPN survivors did. In acute VIPN, social function was significantly affected, whereas in long-term VIPN, emotional and cognitive functions were affected. CONCLUSION: Numbness and cramps should be addressed in survivors of acute and long-term VIPN. Preventing falls is recommended for NHL survivors with VIPN, and psychological support is suggested for long-term VIPN survivors.

Epidemiology and Functional Impact of Early Peripheral Neuropathy Signs in Older Adults from a General Population.

INTRODUCTION: Peripheral neuropathy (PN) becomes more common with increasing life expectancy, but general population prevalence estimates are lacking. We investigated an epidemiological distribution of signs of PN among 2,996 community-dwelling participants in Good Aging in Skåne Study, age 60-97, and their impact on physical and autonomic function. METHODS: Signs of PN were measured with Utah Early Neuropathy Scale (UENS). Associations between UENS and physical tests, pain, and dysautonomic phenomena were calculated for each sex, adjusted for age, with estimated marginal means (EMM) and odds ratios (ORs) in four UENS quantiles (Q1-Q4). RESULTS: Participants in Q4 had worse EMM for: time to complete Timed Up and Go test (Q4-Q1: male 10.8-9.6 s; female 11.7-10.2 s), 15 m Walk test (Q4-Q1: male 11.1-9.9 s; female 11.2-10.4 s), and fewer repetitions in Step test (Q4-Q1: male 15.2-17.0 steps; female 14.5-15.8 steps). Higher OR of failing one-leg balance 60 s test {male 2.5 (confidence interval [CI] 95%: 1.7-3.8); female 2.1 (1.1-3.2)}, Foam Pad Balance test (male 4.6 [CI 95%: 3.2-6.7]; female 1.8 [1.3-2.6]), and lower physical quality of life were seen in Q4 compared to Q1. Participants in Q4 had higher OR for walking aid usage, falls, fear of falling, pain, and urinary incontinence, while in males, higher OR for orthostatic intolerance, fecal incontinence, and constipation. CONCLUSIONS: In a general population, 20-25% of older adults who have highest UENS scores, a sensitive measure of early PN, express slower gait, worse balance, lower quality of life, pain, falls and fear of falling, and autonomic symptoms.

Incidence, description, predictors, and consequences of persistent taxane-induced peripheral neuropathy.

PURPOSE OF REVIEW: This review aims to provide insights into persistent taxane-induced peripheral neuropathy (TIPN). The primary objective is to describe the incidence, predictors, and consequences of TIPN lasting at least 1 year after the end of taxane treatment. RECENT FINDINGS: Studies show varying rates of TIPN persistence, with an estimated 30-40% and 40-60% resolving by 1- and 3-year post-treatment. TIPN in the feet and motor symptoms show less resolution post-treatment. Patients who are older or have higher body weight may experience less TIPN resolution, but results may be confounded by TIPN development during treatment. Persistent TIPN negatively impacts long-term functional ability, including gait, balance, and the ability to work. It also reduces overall quality of life (QOL), particularly affecting physical and social aspects. SUMMARY: Clinicians should be aware of the potential for persistent TIPN and its impact on patients' function and QOL. Future research should focus on large prospective studies with systematic TIPN assessments during and after treatment to better understand which symptoms and patient characteristics predict resolution. This information can guide treatment decisions, balancing the need for effective chemotherapy with minimizing long-term impairments in function and QOL.

The association of clinical and patient factors with chemotherapy-induced peripheral neuropathy (CIPN) in colorectal cancer: secondary analysis of the SCOT trial.

BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) is a common adverse effect of oxaliplatin. CIPN can impair long-term quality of life and limit the dose of chemotherapy. We investigated the association of CIPN over time with age, sex, body mass index, baseline neuropathy, and chemotherapy regimen in people treated with adjuvant oxaliplatin-containing chemotherapy for colorectal cancer. PATIENTS AND METHODS: We carried out secondary analysis of data from the SCOT randomised controlled trial. SCOT compared 3 months to 6 months of oxaliplatin-containing adjuvant chemotherapy in 6088 people with colorectal cancer recruited between March 2008 and November 2013. Two different chemotherapy regimens were used: capecitabine with oxaliplatin (CAPOX) or fluorouracil with oxaliplatin (FOLFOX). CIPN was recorded with the Functional Assessment of Cancer Therapy/Gynaecologic Oncology Group-Neurotoxicity 4 tool in 2871 participants from baseline (randomisation) for up to 8 years. Longitudinal trends in CIPN [averages with 95% confidence intervals (CIs)] were plotted stratified by the investigated factors. Analysis of covariance (ANCOVA) was used to analyse the association of factors with CIPN adjusting for the SCOT randomisation arm and oxaliplatin dose. P < 0.01 was adopted as cut-off for statistical significance to account for multiple testing. RESULTS: Patients receiving CAPOX had lower CIPN scores than those receiving FOLFOX. Chemotherapy regimen was associated with CIPN from 6 months (P < 0.001) to 2 years (P = 0.001). The adjusted ANCOVA coefficient for CAPOX at 6 months was -1.6 (95% CIs -2.2 to -0.9) and at 2 years it was -1.6 (95% CIs -2.5 to -0.7). People with baseline neuropathy scores ≥1 experienced higher CIPN than people with baseline neuropathy scores of 0 (P < 0.01 for all timepoints apart from 18 months). Age, sex, and body mass index did not link with CIPN. CONCLUSIONS: A neuropathy assessment before treatment with oxaliplatin can help identify people with an increased risk of CIPN. More research is needed to understand the CIPN-inducing effect of different chemotherapy regimens.

Vitamin D Insufficiency as a Risk Factor for Paclitaxel-Induced Peripheral Neuropathy in SWOG S0221.

BACKGROUND: Prior work suggests that patients with vitamin D insufficiency may have a higher risk of chemotherapy-induced peripheral neuropathy (CIPN) from paclitaxel. The objective of this study was to validate vitamin D insufficiency as a CIPN risk factor. METHODS: We used data and samples from the prospective phase III SWOG S0221 (ClinicalTrials.gov identifier: NCT00070564) trial that compared paclitaxel-containing chemotherapy regimens for early-stage breast cancer. We quantified pretreatment 25-hydroxy-vitamin D in banked serum samples using a liquid chromatography-tandem mass spectrometry targeted assay. We tested the association between vitamin D insufficiency (≤20 ng/mL) and grade ≥3 sensory CIPN via multiple logistic regression and then adjusted for self-reported race, age, body mass index, and paclitaxel schedule (randomization to weekly or every-2-week dosing). We also tested the direct effect of vitamin D deficiency on mechanical hypersensitivity in mice randomized to a regular or vitamin D-deficient diet. RESULTS: Of the 1,191 female patients in the analysis, 397 (33.3%) had pretreatment vitamin D insufficiency, and 195 (16.4%) developed grade ≥3 CIPN. Patients with vitamin D insufficiency had a higher incidence of grade ≥3 CIPN than those who had sufficient vitamin D (20.7% vs 14.2%; odds ratio [OR], 1.57; 95% CI, 1.14-2.15; P=.005). The association retained significance after adjusting for age and paclitaxel schedule (adjusted OR, 1.65; 95% CI, 1.18-2.30; P=.003) but not race (adjusted OR, 1.39; 95% CI, 0.98-1.97; P=.066). In the mouse experiments, the vitamin D-deficient diet caused mechanical hypersensitivity and sensitized mice to paclitaxel (both P<.05). CONCLUSIONS: Pretreatment vitamin D insufficiency is the first validated potentially modifiable predictive biomarker of CIPN from paclitaxel. Prospective trials are needed to determine whether vitamin D supplementation prevents CIPN and improves treatment outcomes in patients with breast and other cancer types.

Association of cytokine gene polymorphisms with peripheral neuropathy susceptibility in people living with HIV in Greece.

Relatively little research has been done in recent years to understand what leads to the unceasingly high rates of HIV sensory neuropathy despite successful antiretroviral treatment. In vivo and in vitro studies demonstrate neuronal damage induced by HIV and increasingly identified ART neurotoxicity involving mitochondrial dysfunction and innate immune system activation in peripheral nerves, ultimately all pathways resulting in enhanced pro-inflammatory cytokine secretion. Furthermore, many infectious/autoimmune/malignant diseases are influenced by the production-profile of pro-inflammatory and anti-inflammatory cytokines, due to inter-individual allelic polymorphism within cytokine gene regulatory regions. Associations of cytokine gene polymorphisms are investigated with the aim of identifying potential genetic markers for susceptibility to HIV peripheral neuropathy including ART-dependent toxic neuropathy. One hundred seventy-one people living with HIV in Northern Greece, divided into two sub-groups according to the presence/absence of peripheral neuropathy, were studied over a 5-year period. Diagnosis was based on the Brief Peripheral Neuropathy Screening. Cytokine genotyping was performed by sequence-specific primer-polymerase chain reaction. Present study findings identify age as an important risk factor (p < 0.01) and support the idea that cytokine gene polymorphisms are at least involved in HIV peripheral-neuropathy pathogenesis. Specifically, carriers of IL1a-889/rs1800587 TT genotype and IL4-1098/rs2243250 GG genotype disclosed greater relative risk for developing HIV peripheral neuropathy (OR: 2.9 and 7.7 respectively), while conversely, carriers of IL2+166/rs2069763 TT genotype yielded lower probability (OR: 3.1), all however, with marginal statistical significance. The latter, if confirmed in a larger Greek population cohort, may offer in the future novel genetic markers to identify susceptibility, while it remains significant that further ethnicity-oriented studies continue to be conducted in a similar pursuit.

Incidence and Resolution of Eribulin-Induced Peripheral Neuropathy (IRENE) in Locally Advanced or Metastatic Breast Cancer: Prospective Cohort Study.

BACKGROUND: Eribulin, a halichondrin-class microtubule dynamics inhibitor, is a preferred treatment option for patients with advanced breast cancer who have been pretreated with an anthracycline and a taxane. Peripheral neuropathy (PN) is a common side effect of chemotherapies for breast cancer and other tumors. The Incidence and Resolution of Eribulin-Induced Peripheral Neuropathy (IRENE) noninterventional postauthorization safety study assessed the incidence and severity of PN in patients with breast cancer treated with eribulin. PATIENTS AND METHODS: IRENE is an ongoing observational, single-arm, prospective, multicenter, cohort study. Adult patients (≥18 years of age) with locally advanced or metastatic breast cancer and disease progression after 1-2 prior chemotherapeutic regimen(s) for advanced disease were treated with eribulin. Patients with eribulin-induced PN (new-onset PN or worsening of preexisting PN) were monitored until death or resolution of PN. Primary endpoints included the incidence, severity, and time to resolution of eribulin-induced PN. Secondary endpoints included time to disease progression and safety. RESULTS: In this interim analysis (data cutoff date: July 1, 2019), 67 (32.4%) patients experienced any grade eribulin-induced PN, and 12 (5.8%) patients experienced grade ≥3 eribulin-induced PN. Median time to resolution of eribulin-induced PN was not reached. Median time to disease progression was 4.6 months (95% CI, 4.0-6.5). Treatment-emergent adverse events (TEAEs) occurred in 195 (93.8%) patients and serious TEAEs occurred in 107 (51.4%) patients. CONCLUSION: The rates of any grade and grade ≥3 eribulin-induced PN observed in this real-world study were consistent with those observed in phase III randomized clinical trials. No new safety findings were observed.

Comparison and development of machine learning for thalidomide-induced peripheral neuropathy prediction of refractory Crohn's disease in Chinese population.

BACKGROUND: Thalidomide is an effective treatment for refractory Crohn's disease (CD). However, thalidomide-induced peripheral neuropathy (TiPN), which has a large individual variation, is a major cause of treatment failure. TiPN is rarely predictable and recognized, especially in CD. It is necessary to develop a risk model to predict TiPN occurrence. AIM: To develop and compare a predictive model of TiPN using machine learning based on comprehensive clinical and genetic variables. METHODS: A retrospective cohort of 164 CD patients from January 2016 to June 2022 was used to establish the model. The National Cancer Institute Common Toxicity Criteria Sensory Scale (version 4.0) was used to assess TiPN. With 18 clinical features and 150 genetic variables, five predictive models were established and evaluated by the confusion matrix receiver operating characteristic curve (AUROC), area under the precision-recall curve (AUPRC), specificity, sensitivity (recall rate), precision, accuracy, and F1 score. RESULTS: The top-ranking five risk variables associated with TiPN were interleukin-12 rs1353248 [P = 0.0004, odds ratio (OR): 8.983, 95% confidence interval (CI): 2.497-30.90], dose (mg/d, P = 0.002), brain-derived neurotrophic factor (BDNF) rs2030324 (P = 0.001, OR: 3.164, 95%CI: 1.561-6.434), BDNF rs6265 (P = 0.001, OR: 3.150, 95%CI: 1.546-6.073) and BDNF rs11030104 (P = 0.001, OR: 3.091, 95%CI: 1.525-5.960). In the training set, gradient boosting decision tree (GBDT), extremely random trees (ET), random forest, logistic regression and extreme gradient boosting (XGBoost) obtained AUROC values > 0.90 and AUPRC > 0.87. Among these models, XGBoost and GBDT obtained the first two highest AUROC (0.90 and 1), AUPRC (0.98 and 1), accuracy (0.96 and 0.98), precision (0.90 and 0.95), F1 score (0.95 and 0.98), specificity (0.94 and 0.97), and sensitivity (1). In the validation set, XGBoost algorithm exhibited the best predictive performance with the highest specificity (0.857), accuracy (0.818), AUPRC (0.86) and AUROC (0.89). ET and GBDT obtained the highest sensitivity (1) and F1 score (0.8). Overall, compared with other state-of-the-art classifiers such as ET, GBDT and RF, XGBoost algorithm not only showed a more stable performance, but also yielded higher ROC-AUC and PRC-AUC scores, demonstrating its high accuracy in prediction of TiPN occurrence. CONCLUSION: The powerful XGBoost algorithm accurately predicts TiPN using 18 clinical features and 14 genetic variables. With the ability to identify high-risk patients using single nucleotide polymorphisms, it offers a feasible option for improving thalidomide efficacy in CD patients.

[A cohort study of vincristine-induced peripheral neuropathy in children]. / é•¿æ˜¥æ–°ç¢±è¯±å¯¼çš„å‘¨å›´ç¥žç»ç— å˜çš„å„¿ç«¥é˜Ÿåˆ—ç ”ç©¶.

OBJECTIVES: To study the characteristics of vincristine-induced peripheral neuropathy (VIPN) in children with acute lymphoblastic leukemia (ALL) and the factors influencing the development of VIPN. METHODS: The children with ALL, aged 1-18 years, who were treated with CCCG-ALL2015 or CCCG-ALL2020 regimen in the Affiliated Hospital of Guizhou Medical University from January 2018 to February 2022 were enrolled as subjects. According to the influence of age on risk, the children were divided into 1-10 years group with 91 children and >10 years group with 29 children. VIPN was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (5th edition), and the incidence rate, severity, and type of VIPN were compared between different groups. RESULTS: A total of 120 children were enrolled in this study, among whom 56 (46.7%) developed VIPN. The >10 years group had a significantly higher incidence rate of VIPN than the 1-10 years group (69% vs 40%, P<0.05). Among the 56 children with VIPN, 12 (21%) had grade 3 VIPN or above, and 44 (79%) had grade 2 VIPN. There were 77 cases of autonomic nerve symptoms (59.7%), 42 cases of peripheral nerve injury (32.5%), and 10 cases of cranial nerve injury (7.8%). There were no significant differences in the severity and type of VIPN between the groups with different ages, sexes, degrees of risk, or treatment regimens (P>0.05). The results of binary logistic regression analysis showed that age is the influencing factor for the occurrence of VIPN (P>0.05). CONCLUSIONS: There is a relatively high incidence rate of VIPN in children with ALL, with the highest incidence rate of autonomic nervous symptoms. The incidence of VIP in children over 10 years old is relatively high.

The association between sociodemographic, clinical, and potentially preventive therapies with oxaliplatin-induced peripheral neuropathy in colorectal cancer patients.

PURPOSE: The purpose of this retrospective cohort study was to evaluate whether several potentially preventive therapies reduced the rate of oxaliplatin-induced peripheral neuropathy (OIPN) in colorectal cancer patients and to assess the relationship of sociodemographic/clinical factors with OIPN diagnosis. METHODS: Data were obtained from the Surveillance, Epidemiology, and End Results database combined with Medicare claims. Eligible patients were diagnosed with colorectal cancer between 2007 and 2015, ≥ 66 years of age, and treated with oxaliplatin. Two definitions were used to denote diagnosis of OIPN based on diagnosis codes: OIPN 1 (specific definition, drug-induced polyneuropathy) and OIPN 2 (broader definition, additional codes for peripheral neuropathy). Cox regression was used to obtain hazard ratios (HR) with 95% confidence intervals (CI) for the relative rate of OIPN within 2 years of oxaliplatin initiation. RESULTS: There were 4792 subjects available for analysis. At 2 years, the unadjusted cumulative incidence of OIPN 1 was 13.1% and 27.1% for OIPN 2. For both outcomes, no therapies reduced the rate of OIPN diagnosis. The anticonvulsants gabapentin and oxcarbazepine/carbamazepine were associated with an increased rate of OIPN (both definitions) as were increasing cycles of oxaliplatin. Compared to younger patients, those 75-84 years of age experienced a 15% decreased rate of OIPN. For OIPN 2, prior peripheral neuropathy and moderate/severe liver disease were also associated with an increased hazard rate. For OIPN 1, state buy-in health insurance coverage was associated with a decreased hazard rate. CONCLUSION: Additional studies are needed to identify preventive therapeutics for OIPN in cancer patients treated with oxaliplatin.

The effects of daily dose and treatment duration of metformin on the prevalence of vitamin B12 deficiency and peripheral neuropathy in Chinese patients with type 2 diabetes mellitus: A multicenter cross-sectional study.

AIMS: To evaluate the prevalence of vitamin B12 deficiency in Chinese patients with type 2 diabetes mellitus receiving metformin treatment and to investigate the effects of metformin daily dose and treatment duration on the prevalence of vitamin B12 deficiency and peripheral neuropathy (PN). MATERIALS AND METHODS: In this multicenter cross-sectional study, 1027 Chinese patients who had been taking ≥1000 mg/day metformin for ≥1 year were enrolled using proportionate stratified random sampling based on daily dose and treatment duration. Primary measures included the prevalence of vitamin B12 deficiency (<148 pmol/L), borderline B12 deficiency (148 pmol/L-211 pmol/L), and PN. RESULTS: The prevalence of vitamin B12 deficiency, borderline deficiency, and PN were 2.15%, 13.66%, and 11.59%, respectively. Patients receiving ≥1500 mg/day metformin had significantly higher prevalence of borderline vitamin B12 deficiency (16.76% vs. 9.91%, p = .0015) and serum B12 ≤221 pmol/L (19.25% vs. 11.64%, p < .001) than patients receiving <1500 mg/day metformin. No difference was found in prevalence of borderline vitamin B12 deficiency (12.58% vs. 15.49%, p = .1902) and serum B12 ≤221 pmol/L (14.91% vs. 17.32%, p = .3055) between patients receiving metformin for ≥3 and <3 years. Patients with vitamin B12 deficiency had numerically higher PN prevalence (18.18% vs. 11.27%, p = .3192) than patients without it. Multiple logistic analyses revealed that HbA1c and metformin daily dose were associated with the prevalence of borderline B12 deficiency and B12 ≤221 pmol/L. CONCLUSIONS: High daily dosage (≥1500 mg/day) played an important role in metformin-associated vitamin B12 deficiency while not contributing to the risk of PN.

Dysmetabolism-related Early Sensory Deficits and Their Relationship With Peripheral Neuropathy Development.

AIM: To investigate the association of early peripheral sensory dysfunction (EPSD) identified through quantitative sensory testing (QST) with factors related to a dysmetabolic status in individuals with and without type 2 diabetes (T2DM) without peripheral neuropathy (PN), and the impact of those factors on PN development. METHODS: A total of 225 individuals (117 and 108 without and with T2DM, respectively) without PN based on clinical and electrophysiological criteria were analyzed. Comparative analysis was conducted between those identified as "healthy" and those with EPSD based on a standardized QST protocol. A total of 196 were followed-up over a mean of 2.64 years for PN occurrence. RESULTS: Among those without T2DM, apart from male sex, height, and higher fat and lower lean mass, only higher insulin resistance (IR; homeostatic model assessment for IR: odds ratio [OR], 1.70; P = .009; McAuley index OR, 0.62, P = .008), was independently associated with EPSD. In T2DM, metabolic syndrome (OR, 18.32; P < .001) and skin advanced glycation end-products (AGEs; OR, 5.66; P = .003) were independent predictors of EPSD. In longitudinal analysis, T2DM (hazard ratio [HR], 3.32 vs no diabetes mellitus; P < .001), EPSD (adjusted HR, 1.88 vs healthy; P = .049 adjusted for diabetes mellitus and sex), higher IR and AGEs predicted PN development. Among the 3 EPSD-associated sensory phenotypes, "sensory loss" was most strongly associated with PN development (adjusted HR, 4.35; P = .011). CONCLUSION: We demonstrate for the first time the utility of a standardized QST-based approach in identifying early sensory deficits in individuals with and without T2DM. These are associated with a dysmetabolic status signified by IR markers, metabolic syndrome, and higher AGEs, which in turn are shown to influence PN development.

Peripheral Neuropathy in Older People Is Associated with Reduced Life Expectancy.

INTRODUCTION: We analyzed data from a prospective cohort of older primary care patients to determine whether the presence of peripheral neuropathy (PN) was associated with premature mortality and to investigate potential mechanisms. METHODS: PN was defined as the presence of 1 or more bilateral lower extremity sensory deficits detectable by physical examination. Mortality was determined from key contacts and Internet sources. Statistical models were used to evaluate the association between PN and mortality. RESULTS: Bilateral lower extremity neurological deficits were common, reaching 54% in those 85 and older. PN was strongly associated with earlier mortality. Mean survival time for those with PN was 10.8 years, compared with 13.9 years for subjects without PN. PN was also indirectly associated through impaired balance. CONCLUSIONS: In this relatively healthy cohort of older primary care patients, PN detectable by physical examination was extremely common and strongly associated with earlier mortality. One possible mechanism involves loss of balance, though our data were insufficient to determine whether poor balance led to injurious falls or to less-specific declines in health. These findings may warrant further studies to determine the causes of age-associated PN and potential impact of early detection and balance improvement and other fall prevention strategies.

Persistent weekly paclitaxel-induced peripheral neuropathy in early breast cancer patients enrolled in a randomized trial of cryotherapy.

Chemotherapy-induced peripheral neuropathy (CIPN) is a serious side effect of weekly paclitaxel-based chemotherapy for breast cancer, that can persist for years. Cryotherapy therapy is effective for preventing early CIPN, but its protective effect on persistent CIPN is uncertain. This is a cross-sectional study conducted as an ancillary analysis of a randomized trial investigating the preventive effect of cryotherapy on CIPN in breast cancer patients receiving weekly paclitaxel-based chemotherapy (UMIN000034966). Eligible patients were evaluated for CIPN at more than a year after completion of the chemotherapy (persistent CIPN). CIPN was defined as a 6 or more points reduction from baseline in the Functional Assessment of Cancer Therapy-Neurotoxicity (FACT-NTX) score. The incidence of early and persistent CIPN was compared between cryotherapy and control groups. Thirty-eight patients were examined for both early and persistent CIPN. The median time from completion of the weekly paclitaxel-based chemotherapy to the questionnaire for persistent CIPN was 2.3 (1.3-3.1) years. In all 38 patients, persistent CIPN was demonstrated in 10 (26.3%), respectively. There was a numerical, however not significant, reduction in the incidence of persistent CIPN (15.8% vs 36.8%, P = .1) in the cryotherapy group compared with the control group, respectively. In multivariate logistic regression analysis, age ≥ 65 was a substantial risk factor for persistent CIPN (HR: 14.7, 95%CI: 1.7-130.7, P = .01). In breast cancer patients receiving adjuvant weekly paclitaxel-based chemotherapy, cryotherapy resulted in a numerical, however not significant, reduction in the incidence of persistent CIPN and age>=65 was a risk factor for persistent CIPN.

Do peripheral neuropathies differ among immune checkpoint inhibitors? Reports from the European post-marketing surveillance database in the past 10 years.

Although the immunotherapy advent has revolutionized cancer treatment, it, unfortunately, does not spare cancer patients from possible immune-related adverse events (irAEs), which can also involve the peripheral nervous system. Immune checkpoint inhibitors (ICIs), blocking cytotoxic T-lymphocyteassociated protein 4 (CTLA-4), programmed cell death protein 1 (PD-1), or programmed cell death ligand 1 (PD-L1), can induce an immune imbalance and cause different peripheral neuropathies (PNs). Considering the wide range of PNs and their high impact on the safety and quality of life for cancer patients and the availability of large post-marketing surveillance databases, we chose to analyze the characteristics of ICI-related PNs reported as suspected drug reactions from 2010 to 2020 in the European real-world context. We analyzed data collected in the European pharmacovigilance database, Eudravigilance, and conducted a systematic and disproportionality analysis. In our study, we found 735 reports describing 766 PNs occurred in patients treated with ICIs. These PNs included Guillain-Barré syndrome, Miller-Fisher syndrome, neuritis, and chronic inflammatory demyelinating polyradiculoneuropathy. These ADRs were often serious, resulting in patient disability or hospitalization. Moreover, our disproportionality analysis revealed an increased reporting frequency of PNs with tezolizumab compared to other ICIs. Guillain-Barré syndrome is a notable potential PN related to ICIs, as it is associated with a significant impact on patient safety and has had unfavorable outcomes, including a fatal one. Continued monitoring of the safety profile of ICIs in real-life settings is necessary, especially considering the increased frequency of PNs associated with atezolizumab compared with other ICIs.

Chemotherapy-induced peripheral neuropathy in the detroit research on cancer survivors (ROCS) cohort.

PURPOSE: Improved life expectancy has increased the likelihood for long-term complications from chemotherapy among cancer survivors. One burdensome complication is chemotherapy-induced peripheral neuropathy (CIPN). We evaluated rates of CIPN outcomes in the Detroit Research on Cancer Survivorship (ROCS) cohort. METHODS: The population included 1,034 African American (AA) survivors who received chemotherapy for breast, colorectal, lung or prostate cancer. CIPN prevalence was based on initial occurrence of worsening of self-reported pain, numbness or tingling after chemotherapy. Current CIPN included symptoms still present at the time of the survey, and persistent CIPN symptoms were present 12 or more months post-chemotherapy. CIPN severity was ranked as mild, moderate or severe. Logistic regression was utilized to evaluate sociodemographic and clinical factors associated with the various categories of CIPN. RESULTS: CIPN prevalence was 68%, with 53% current and 52% persistent. The symptom severity distribution based on prevalent CIPN included 32.2% mild, 30.8% moderate, and 36.9% severe. Factors associated with prevalent CIPN (odds ratio, 95% confidence interval) included primary cancer site (breast: 3.88, 2.02-7.46); and (colorectal: 5.37, 2.69-10.73), lower risk for older age at diagnosis (0.66, 0.53-0.83) and divorced/separated marital status (2.13, 1.42-3.21). Current CIPN was in addition, associated with more advanced stage disease trend (1.34, 1.08-1.66) and greater number of co-morbid medical conditions trend (1.23, 1.09-1.40), as was persistent CIPN. Severity of prevalent CIPN was associated with history of arthritis (1.55, 1.06-2.26) and severity of persistent CIPN with higher BMI (1.58, 1.07-2.35). CONCLUSIONS: CIPN is a common and persistent complication in AA cancer survivors. Further research is needed to improve our understanding of CIPN predictors in all groups of cancer survivors.

The association of peripheral neuropathy detected by monofilament testing with risk of falls and fractures in older adults.

BACKGROUND: In persons with diabetes, annual screening for peripheral neuropathy (PN) using monofilament testing is the standard of care. However, PN detected by monofilament testing is common in older adults, even in the absence of diabetes. We aimed to assess the association of PN with risk of falls and fractures in older adults. METHODS: We included participants in the Atherosclerosis Risk in Communities (ARIC) Study who underwent monofilament testing at visit 6 (2016-2017). Incident falls and fractures were identified based on ICD-9 and ICD-10 codes from active surveillance of all hospitalizations and linkage to Medicare claims. We used Cox models to assess the association of PN with falls and fractures (combined and as separate outcomes) after adjusting for demographics and risk factors for falls. RESULTS: There were 3617 ARIC participants (mean age 79.4 [SD 4.7] years, 40.8% male, and 21.4% Black adults), of whom 1242 (34.3%) had PN based on monofilament testing. During a median follow-up of 2.5 years, 371 participants had a documented fall, and 475 participants had a documented fracture. The incidence rate (per 1000 person-years) for falls or fractures for participants with PN versus those without PN was 111.1 versus 74.3 (p < 0.001). The age-, sex-, and race-adjusted 3-year cumulative incidence of incident fall or fracture was significantly higher for participants with PN versus those without PN (26.5% vs. 18.4%, p < 0.001). After adjusting for demographics, PN remained independently associated with falls and fractures (HR 1.48, 95% CI 1.26, 1.74). Results were similar for models including traditional risk factors for falls, when falls and fractures were analyzed as separate outcomes, and after adjustment for competing risk of death. CONCLUSIONS: PN, as measured by monofilament testing, is common in older adults and associated with risk of falls and fracture. Screening with monofilament testing may be warranted to identify older adults at high risk for falls.

Patient Characteristics Associated With Chemotherapy-Induced Peripheral Neuropathy Severity in a Phase II Clinical Trial: A Retrospective Analysis.

INTRODUCTION: Chemotherapy-induced peripheral neuropathy (CIPN) can lead to chemotherapy dose reduction, delay, and discontinuation, and has limited effective prevention strategies. Our study aimed to identify patient characteristics associated with CIPN severity during weekly paclitaxel chemotherapy in people with early-stage breast cancer. METHODS: We retrospectively collected baseline data including participants' age, gender, race, body mass index (BMI), hemoglobin (regular and A1C), thyroid stimulating hormone, Vitamins (B6, B12, and D), anxiety, and depression up to 4 months prior to their first paclitaxel treatment. We also collected CIPN severity by Common Terminology Criteria for Adverse Events (CTCAE) after chemotherapy, chemotherapy relative dose density (RDI), disease recurrence, and mortality rate at the time of the analysis. Logistic regression was used for statistical analysis. RESULTS: We extracted 105 participants' baseline characteristics from electronic medical records. Baseline BMI was associated with CIPN severity (Odds Ratio [OR] 1.08; 95% CI, 1.01-1.16, P = .024). No significant correlations were observed in other covariates. At median follow-up (61 months), there were 12 (9.5%) breast cancer recurrences and six (5.7%) breast cancer-related deaths. Higher chemotherapy RDI was associated with improved disease-free survival (DFS, OR 1.025; 95% CI, 1.00-1.05; P = .028). CONCLUSIONS AND RELEVANCE: Baseline BMI may be a risk factor for CIPN and suboptimal chemotherapy delivery due to CIPN may negatively impact disease-free survival in patients with breast cancer. Further study is warranted to identify mitigating lifestyle factors to reduce incidences of CIPN during breast cancer treatment.

Impact of Adjuvant FOLFOX on Quality of Life and Peripheral Neuropathy Incidence in Patients With Gastric Cancer: A Prospective Cohort Study.

OBJECTIVES: Perioperative and adjuvant chemotherapy have demonstrated clinical benefits in localized gastric cancer. Nevertheless, the reports on their effects on patient's health-related quality of life (HRQoL) are scarce. Here, we prospectively assessed quality of life and the incidence of chemotherapy-induced peripheral neuropathy (CIPN) in a cohort of patients treated with adjuvant FOLFOX. METHODS: Localized stomach or gastroesophageal junction adenocarcinoma patients who underwent curative resection were recruited at a single center. All patients received adjuvant FOLFOX6, and HRQoL and CIPN were assessed using the European organization for research and treatment of cancer quality life (EORTC) C30 and the EORTC CIPN20 questionnaires, respectively. Clinically significant deterioration of HRQoL was also assessed as a coprimary outcome in a longitudinal analysis. RESULTS: We recruited a total of 63 patients. Median age was 62.5 years, and 75% had stomach tumors. Twenty-four weeks after the start of treatment, the probability of being free from HRQoL deterioration and CIPN was 29% (95% confidence interval [CI] 18%-42%) and 6% (95% CI 2%-17%), respectively. Five-year disease-free survival was 45% (95% CI 24%-64%) and 5-year overall survival was 63% (95% CI 48%-76%). CONCLUSIONS: Adjuvant FOLFOX is associated with a high rate of long-term survival in localized gastric cancer; nevertheless, it has detrimental effects on patients' quality of life.