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.

Chemotherapy-induced peripheral neurotoxicity: single-centre prospective study.

OBJECTIVE: Chemotherapy-induced peripheral neurotoxicity (CIPN) ranges from simple paresthesia to paralysis, which may be transient or irreversible. The aim of our study was to detect CINP in our patients undergoing chemotherapy and to study the cumulative neurotoxic doses for the different drugs. METHODS: This is a cross-sectional prospective study carried out in the medical oncology department of the Habib Bourguiba University Hospital in Sfax. A survey was conducted to detect and explore possible chemo-induced peripheral neuropathy in patients undergoing known potentially neurotoxic anti-cancer treatments. RESULTS: Seventy-three patients were included in the study. The average age was 51.8 years (13-80 years). The prevalence of CIPN was 52.1%. CIPN was classified as grade I in 24 (63.2%) cases and grade II in 14 (36.8%) cases. No grade III or IV peripheral neuropathy was detected in our patients. Paclitaxel was the drug with the highest incidence of CIPN (76.9%). The chemotherapy (CT) protocols most prone to chemotherapy-induced peripheral neurotoxicity (CIPN) were based on taxanes (47.3%) and oxaliplatin (59%). Paclitaxel was the drug most likely to cause CIPN (76.9%) (p=0.031). Paclitaxel single dose per cycle of 175 mg/m2 (66.67%) was more associated with the occurrence of CIPN than 80 mg/m2 (40%), but without significant difference (p=0.437). The average cumulative dose was estimated at 315 mg/m2 for docetaxel, 474 mg/m2 for oxaliplatin and 579 mg/m2 for paclitaxel (p=0.16). CONCLUSION: The prevalence of NPCI was 51.1% in our series. Oxaliplatin and taxanes were the main contributors to this complication with cumulative dose over than 300 mg/m2.

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.

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.

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.

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.

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.

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.

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.

[Peripheral neuropathy, onycholysis and health-related quality of life in womens with breast cancer treated with taxanes. Prospective longitudinal study.] / Neuropatía periférica, onicólisis y calidad de vida en mujeres con cáncer de mama en tratamiento con taxanos. Estudio longitudinal prospectivo.

OBJECTIVE: Peripheral neuropathy and onycholysis are adverse events produced by taxanes in breast cancer that persist even after the end of treatment and negatively influence quality of life. The objectives of the study were to describe these side effects and the degree of involvement and relating them to the drug doses received. METHODS: Prospective, cross-sectional study of in 50 womens dignosed of breast cancer, treated with docetaxel and paclitaxel in Hospital Universitario Miguel Servet in Zaragoza (Aragón, Spain). CTCAE v.5.0 scale and Semes Weinsten test were used to evaluate peripheral neuropathy and onycholysis. ECOG scale was performed to measure the health-related quality of life. Study variables were evaluated before-during treatment and 1 and 6 months after finish treatment. Statistical analysis was performed using Jamovi 1.2®. For the relationship of the qualitative variables, the chi-square, Fisher's exact test, Mc's test were used. Nemar and the Odds Ratio test. Effects were considered significant if p<0.05. RESULTS: 43 subjects were included. During treatment the 9.8 presented motor neuropathy and 12.2% sensitive neuropathy, 37.2% onycholisis in upper extremities and 39.5% in lower extremities (χ2=11.3; p<0.001 / χ2=13.0; p<0.001) and 38.1% a health related quality of live limited in excessive activities (χ2=10.3; p=0.001). Post-treatment evaluation the 20.9% presented motor neuropathy and 32.6% sensitive neuropathy (χ2=3.57; p=0.059 / χ2=6.23; p=0.013), the 86% onycholisis in upper extremities and lower extremities (χ2=6.07; p=0.048 / χ2=10.1; p=0.006) and 58.5% a health related quality of live limited in excessive activities (χ2=8.47; p=0.014). 6 month later, the initials parameters were not recuperated. CONCLUSIONS: Taxanes have a negative impact on the health-related quality of life in patients, even 6 months after finishing treatment due to the peripheral neuropathy and onycholysis that they cause.

OBJETIVO: La neuropatía periférica y la onicólisis son eventos adversos producidos por los taxanos en el cáncer de mama, que perduran incluso habiendo finalizado el tratamiento e influyendo negativamente en la calidad de vida. Los objetivos del estudio fueron describir estos efectos secundarios, midiendo el grado de afectación, y relacionarlos con las dosis de fármaco recibidas. METODOS: Se realizó un estudio observacional, longitudinal prospectivo con muestreo consecutivo inicial de concuenta mujeres con cáncer de mama en tratamiento con docetaxel y/o paclitaxel en el Hospital Universitario Miguel Servet de Zaragoza (Aragón, España). Para la valoración de la neuropatía periférica (motora y sensitiva) se utilizó la escala CTCAE v.5.0 y el test de Semmes Weinsten. La valoración de la calidad de vida relacionada con la salud se midió mediante la escala ECOG. Se realizaron valoraciones previo-durante-post y a los 6 meses de haber finalizado el tratamiento. El análisis estadístico se realizó mediante Jamovi 1.2®. Para la relación de las variables cualitativas se utilizó la chi-cuadrado, el test exacto de Fisher, el test de Mc.Nemar y el test de Odds Ratio. Los efectos se consideraron significativos si p<0,05. RESULTADOS: Se incluyeron finalmente 43 mujeres. Durante el tratamiento, el 9,8% presentó neuropatía motora y el 12,2% neuropatía sensitiva, el 37,2% onicólisis en extremidades superiores y el 39,5% en inferiores (χ2=11,3; p<0,001 / χ2=13,0; p<0,001), y el 38,1% una calidad de vida restringida a actividad exagerada (χ2=10,3; p=0,001). En la valoración postratamiento, el 20,9% presentó neuropatía motora y el 32,6% neuropatía sensitiva (χ2=3,57; p=0,059 / χ2=6,23; p=0,013), el 86% onicólisis en extremidades superiores y el 90,7% en inferiores (χ2=6,07; p=0,048 / χ2=10,1; p=0,006) y el 58,5% al menos una calidad de vida restringida a actividad exagerada (χ2=8,47; p=0,014). A los seis meses no se recuperaron los valores iniciales de evaluación. CONCLUSIONES: Los taxanos repercuten negativamente en la calidad de vida de las mujeres incluso a los seis meses tras finalizar el tratamiento debido a la neuropatía periférica y la onicólisis que provocan.

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.

Association between peripheral neuropathy and sleep quality among colorectal cancer patients from diagnosis until 2-year follow-up: results from the PROFILES registry.

PURPOSE: Studies on the association between peripheral neuropathy (PN) and patient-reported outcomes have mostly overlooked sleep quality. Therefore, we aimed to assess the association between PN and sleep quality in a population-based sample of colorectal cancer (CRC) patients up 2 years after diagnosis. METHODS: All newly diagnosed CRC patients from four Dutch hospitals were eligible for participation. Patients (N = 340) completed questionnaires about PN (EORTC QLQ-CIPN20) and sleep (PSQI) before initial treatment (baseline) and 1 and 2 years after diagnosis. RESULTS: Patients who developed sensory PN (n = 76) or motor PN (n = 79) after treatment more often reported poor sleeping scores (PSQI > 5) compared with those who did not develop SPN or MPN at 1-year (SPN: 38% vs. 261%, MPN: 37% vs. 14%) and 2-year follow-up (SPN: 38 vs. 23%, MPN: 37% vs. 18%) (all p < 0.05). Overall, results showed that among patients who did not develop SPN or MPN, sleep quality improved after baseline, while among patients with SPN or MPN, sleep quality did not improve at one and two years after diagnosis. CONCLUSIONS: Both SPN and MPN were significantly associated with the course of sleep quality among CRC patients up to 2 years after diagnosis. Clinicians should be encouraged to discuss sleep quality with their patients who either report PN or are at risk of developing PN. IMPLICATIONS FOR CANCER SURVIVORS: Improving sleep quality among survivors with PN is important, either by reducing PN symptoms or directly targeting sleep.

Incidence and risk factors associated with development of oxalipatin-induced acute peripheral neuropathy in colorectal cancer patients.

INTRODUCTION: Oxaliplatin utilized in colorectal neoplasms treatment could induce acute peripheral neuropathy (APN) which is a dreadful and frequent adverse event. The objective of this study is to estimate incidence of APN induced by oxaliplatin cumulative incidence in cancer patients colorectal and to describe the distribution of the APN incidence according to demographic and clinical characteristics, as well as according to oxaliplatin cumulative dose. MATERIAL AND METHODS: This is a prospective descriptive study which took place from June to December 2018 at the Salah Azaiz Institute, Tunis. Demographic data, clinical data and data on oxaliplatin administration were collected from patient interview, medical files and pharmaceutical databases. RESULTS: The APN (grade 1, grade 2 and grade 3) cumulative incidence during the period of six months of follow up was 86% (95% CI [0.7815-0.9132]). While 38.3% (95% CI [0.29-0.48]) of the patients had grade 2 or 3 neuropathy. The search for factors associated with the risk of grade 2 and 3 NAP revealed trend significant association with diabetes (adjusted RR = 5.7 (IC95% [0.9- 37.3]; p = 0.07). Moreover, there was significant association with oxaliplatin cumulative dose (≥421 mg/m2) to increase the risk of APN grade 2 and 3 (adjusted RR = 7.8; [2.7-22.7]; p = 0.0001). Furthermore, significant association with obesity to increase the risk of APN grade 2 and 3 (adjusted RR = 5.3 [1.1- 25.4]; p = 0.04) was found. Among the patients included, 31.1% experienced oxaliplatin dose reduction and in the majority of cases this reduction is due to neurotoxicity (90.9%). CONCLUSION: The high incidence of oxaliplatin-induced APN remains an embarrassing and handicapping side effect. Our study has shown that oxaliplatin cumulative dose (≥421 mg/m2), diabetes and obesity are risk factor for the development of grade 2 and 3 APN.

Metabolic and lifestyle risk factors for chemotherapy-induced peripheral neuropathy in taxane and platinum-treated patients: a systematic review.

PURPOSE: Chemotherapy-induced peripheral neurotoxicity (CIPN) is a common dose-limiting toxicity of cancer treatment causing functional impairment and impacting quality of life. Effective prevention and treatment of CIPN are lacking, and CIPN risk factors remain ill-defined. Metabolic syndrome and associated conditions have emerged as potential risk factors, due to their high prevalence and independent association with nerve dysfunction. This systematic review aimed to investigate the association between these common metabolic-lifestyle factors and CIPN. METHODS: Searches were undertaken using Medline, Embase, CINAHL, Scopus, and Web of Science databases, with additional studies identified from bibliographic references cited by original and review articles. Articles that analyzed metabolic-lifestyle risk factors associated with CIPN for patients treated with platinum- or taxane-based chemotherapy were included. RESULTS: Searches identified 6897 titles; 44 articles had full text review, with 26 studies included. Overall incidence of neuropathy ranged from 16.9 to 89.4%. Obesity had the most consistent patient-oriented evidence as a risk factor for CIPN, with moderate evidence suggesting diabetes did not increase CIPN incidence or severity. A limited number of studies supported an association with low physical activity and greater CIPN risk. CONCLUSIONS: Comorbidities and lifestyle factors, particularly obesity and low physical activity, may contribute to the development of CIPN. The implementation of sensitive outcome measures in large-scale clinical trials is required to further elucidate CIPN risk factors and evaluate if changes in lifestyle would improve long-term CIPN outcomes for cancer survivors. IMPLICATIONS FOR CANCER SURVIVORS: Better understanding of CIPN risk profiles may inform personalized medicine strategies and help elucidate pathophysiological mechanisms which could be targeted for neuroprotection.