Targeting metabolic pathways alleviates bortezomib-induced neuropathic pain without compromising anticancer efficacy in a sex-specific manner.

Introduction: Chemotherapy-induced peripheral neuropathy (CIPN) is a debilitating side effect of cancer treatment that significantly impacts patients' quality of life. This study investigated the effects of targeting metabolic pathways on bortezomib-induced neuropathic pain and tumor growth using a Lewis lung carcinoma (LLC) mouse model, while exploring potential sex differences. Methods: Male and female C57BL/6J mice were implanted with LLC cells and treated with bortezomib alone or in combination with metformin, dichloroacetate (DCA), or oxamate. Tactile allodynia was assessed using von Frey filaments. Tumor volume and weight were measured to evaluate tumor growth. Results: Metformin, DCA, and oxamate effectively attenuated bortezomib-induced neuropathic pain without compromising the anticancer efficacy of bortezomib in both male and female mice. The LLC model exhibited a paraneoplastic neuropathy-like phenotype. Significant sex differences were observed, with male mice exhibiting larger tumors compared to females. Oxamate was more effective in alleviating allodynia in males, while metformin and DCA showed greater efficacy in reducing tumor growth in females. Discussion: Targeting metabolic pathways can alleviate CIPN without interfering with bortezomib's anticancer effects. The LLC model may serve as a tool for studying paraneoplastic neuropathy. Sex differences in tumor growth and response to metabolic interventions highlight the importance of considering sex as a biological variable in preclinical and clinical studies investigating cancer biology, CIPN, and potential therapeutic interventions.

Home-based aerobic exercise feasibility in oxaliplatin-receiving newly-diagnosed cancer survivors.

PURPOSE: Physical activity (PA) is beneficial but difficult to maintain during chemotherapy. This pilot RCT explored the feasibility of the MI-Walk intervention-an 8-week motivational enhancement therapy- and home-based brisk walking intervention-among gastrointestinal (GI) cancer survivors receiving chemotherapy. METHODS: Sixty stage II-IV GI cancer survivors were recruited from 5 sites at their second infusion visit. Participants were randomized to receive PA education alone or the MI-Walk intervention: motivational enhancement therapy consisting of 3 motivational interviewing and self-efficacy-enhancing counseling sessions, a Fitbit Charge 2, exercise diaries, telephone follow-up, scripted motivational email messages, and optional weekly walking groups. RESULTS: The enrollment and completion rates were 62% and 90%, respectively. The MI-Walk participants (n = 29; mean age = 56.79, SD = 11.72; 97% white; 79% male) reported a baseline moderate-vigorous PA duration of 250.93 (SD = 636.52) min/wk. The mean MI-Walk Intervention acceptability score was 50.32 (SD = 12.02) on a scale of 14-70. Mean Fitbit and counseling helpfulness scores on a 5-point scale were 3.67 (SD = 1.43) and 3.44 (SD = 1.36), respectively. Participants' Fitbit moderate-vigorous PA 8-week averages ranged from 0 to 716.88 min/wk; 64% of participants adhered to ≥127 min/wk. Several characteristics (e.g., age, comorbidity, PA level, employment status, BMI, education level, gender, symptoms) were associated with enrollment, attrition, and intervention acceptability and adherence (p < 0.05). CONCLUSION: Enrollment and retention were adequate. The Fitbit and counseling were the most helpful. Acceptability and adherence varied based on participant characteristics; therefore, intervention tailoring and further research among cancer survivors less physically active at baseline and most in need of complex exercise intervention are needed. CLINICALTRIALS: gov NCT03515356.

Chemotherapy-Induced Peripheral Neuropathy in Patients With Gastroesophageal Cancer.

BACKGROUND: Chemotherapy for various stages of gastroesophageal cancer (GEC) is often neurotoxic. Chemotherapy-induced peripheral neuropathy (CIPN) impairs health-related quality of life (HRQoL). This study investigates the incidence and severity of CIPN and its association with HRQoL in patients with GEC. PATIENTS AND METHODS: Patients who received chemoradiotherapy or chemotherapy for GEC were identified from the Netherlands Cancer Registry. Patient-reported data (measured using the EORTC QLQ-CIPN20 and EORTC QLQ-C30) were collected through the Prospective Observational Cohort Study of Esophageal-Gastric Cancer Patients (POCOP) at baseline and at 3, 6, 9, 12, 18, and 24 months after treatment initiation. Linear mixed effects models were constructed to assess CIPN and the correlation between CIPN and HRQoL was analyzed using Spearman's correlation. RESULTS: A total of 2,135 patients were included (chemoradiotherapy: 1,593; chemotherapy with curative intent: 295; palliative chemotherapy: 247). In all 3 treatment groups, CIPN significantly increased during treatment (adjusted mean score of CIPN at 6 months: chemoradiotherapy, 8.3 [baseline: 5.5]; chemotherapy with curative intent, 16.0 [baseline: 5.6]; palliative therapy, 25.4 [baseline: 10.7]). For chemoradiotherapy, the adjusted mean score continued to increase after treatment (24 months: 11.2). For chemotherapy with curative intent and palliative therapy, the adjusted mean score of CIPN decreased after treatment but did not return to baseline values. CIPN was negatively correlated with HRQoL in all treatment groups, although significance and strength of the correlation differed over time. CONCLUSIONS: Because of the poor prognosis of GEC, it is essential to consider side effects of (neurotoxic) treatment. The high prevalence and association with HRQoL indicate the need for early recognition of CIPN.

Efficacy of cryotherapy in the prevention of chemotherapy-induced peripheral neuropathy: A systematic review and meta-analysis.

PURPOSE: The study investigates cryotherapy's efficacy in mitigating Chemotherapy-induced peripheral neuropathy (CIPN), an adverse effect of chemotherapy that often leads to dosage reduction or treatment discontinuation. METHOD: The study was registered with PROSPERO (CRD42023428936). A literature search was conducted using the PubMed, Embase, and Cochrane Library databases. Randomized and nonrandomized controlled trials that investigated the effects of cryotherapy on CIPN were included for systematic review and meta-analysis. The primary outcome for prevention was the incidence of CIPN. RESULTS: We identified 17 trials involving 2,851 patients. In total, 11 trials compared the incidence of CIPN between cryotherapy and control groups. Significant differences in the incidence of CIPN at the midpoint and end of chemotherapy were observed, with risk ratios (RRs) of 0.23 (95% confidence interval [CI] = 0.13 to 0.43) and 0.54 (95% CI = 0.33 to 0.88), respectively. Cryotherapy also significantly reduced the incidence of sensory CIPN, with an RR of 0.67 (95% CI = 0.49 to 0.92). Additionally, cryotherapy demonstrated a significant reduction in the incidence of CIPN in patients with gynecological cancers (RR = 0.24, 95% CI = 0.14 to 0.41). Significantly favorable global quality of life scores following chemotherapy (standardized mean difference = 1.43; 95% CI = 0.50 to 2.36) and relieved neuropathic symptoms were found with cryotherapy. CONCLUSIONS: Cryotherapy demonstrates a pronounced preventive effect against the development of CIPN, providing substantial symptomatic relief and quality of life improvements for patients undergoing chemotherapy. The administration of cryotherapy through the use of frozen gloves and socks, or continuous-flow cooling systems, optimally initiated 15 min prior to and concluded 15 min following chemotherapy, is recommended for achieving maximum therapeutic efficacy.

Modeling mechanisms of chemotherapy-induced peripheral neuropathy and chemotherapy transport using induced pluripotent stem cell-derived sensory neurons.

BACKGROUND: and Purpose: Chemotherapy-induced peripheral neuropathy (CIPN) constitutes a significant health problem due to the increasing prevalence and lack of therapies for treatment and prevention. While pivotal for routine cancer treatment, paclitaxel and vincristine frequently cause CIPN and impact the quality of life among cancer patients and survivors. Here, we investigate molecular mechanisms and drug transport in CIPN. EXPERIMENTAL APPROACH: Human sensory neurons were derived from induced pluripotent stem cells (iPSC-SNs), which were characterized using flow cytometry and immunolabeling. These iPSC-SNs were exposed to different concentrations of the two microtubule-targeting agents, paclitaxel and vincristine, with and without pre-exposure to inhibitors and inducers of efflux transporters. Neuronal networks were quantified via fluorescent staining against sensory neuron markers. Transcriptional effects of the chemotherapeutics were examined using quantitative polymerase chain reactions (qPCR). KEY RESULTS: Paclitaxel exposure resulted in axonal retraction and thickening, while vincristine caused fragmentation and abolishment of axons. Both agents increased the mRNA expression of the pain receptor, transient receptor potential vanilloid (TRPV1), and highly induced neuronal damage, as measured by activating transcription factor 3 (ATF3) mRNA. iPSC-SNs express the efflux transporters, P-glycoprotein (P-gp, encoded by ABCB1) and multidrug resistance-associated protein 1 (MPR1, encoded by ABCC1). Modulation of efflux transporters indicate that P-gp and MRP1 play a role in modulating neuronal accumulation and neurotoxicity in preliminary experiments. CONCLUSION: and Implications: iPSC-SNs are a valuable and robust model to study the role of efflux transporters and other mechanistic targets in CIPN. Efflux transporters may play a role in CIPN pathogenesis as they regulate the disposition of chemotherapy to the peripheral nervous system, and they may present potential therapeutic targets for CIPN.

Motor disorders related to oxaliplatin-induced peripheral neuropathy: long-term severity and impact on quality of life.

PURPOSE: Sensory chemotherapy-induced peripheral neuropathy (CIPN) is well-recognized, but motor CIPN remains understudied. This secondary analysis focused on the long-term severity and impact of motor disorders, their relation to sensory CIPN, neuropathic pain, psychological distress, and health-related quality of life (HRQoL) after oxaliplatin-based chemotherapy in colorectal cancer (CRC) survivors. METHODS: Data from a multicenter, cross-sectional study were re-analyzed to explore motor CIPN among CRC survivors up to 5 years post-chemotherapy, with no longitudinal follow-up. Questionnaires assessed sensory and motor CIPN (QLQ-CIPN20), neuropathic pain (DN4), anxiety and depression (HADS), and HRQoL (QLQ-C30). RESULTS: Among 405 CRC survivors, 31.1% had sensory CIPN as previously described. When categorizing the 405 CRC survivors based on the years since their last oxaliplatin-based chemotherapy, the motor scores derived from the QLQ-CIPN20 showed no significant difference between years (p = 0.08). Motor CIPN scores correlated with female gender, higher oxaliplatin dose intensity, sensory CIPN, and neuropathic pain. Motor CIPN also linked to decreased HRQoL and increased psychological distress. CONCLUSION: The study underscores the detrimental impact of motor disorders on CRC survivors post-oxaliplatin-based chemotherapy. Oncologists should prioritize assessing and managing motor manifestations alongside sensory symptoms to enhance post-cancer quality of life. TRIAL REGISTRATION: NCT02970526 (2016-11-22). https://classic. CLINICALTRIALS: gov/ct2/show/NCT02970526?term=NCT02970526&draw=2&rank=1 .

Ion Channel and Transporter Involvement in Chemotherapy-Induced Peripheral Neurotoxicity.

The peripheral nervous system can encounter alterations due to exposure to some of the most commonly used anticancer drugs (platinum drugs, taxanes, vinca alkaloids, proteasome inhibitors, thalidomide), the so-called chemotherapy-induced peripheral neurotoxicity (CIPN). CIPN can be long-lasting or even permanent, and it is detrimental for the quality of life of cancer survivors, being associated with persistent disturbances such as sensory loss and neuropathic pain at limb extremities due to a mostly sensory axonal polyneuropathy/neuronopathy. In the state of the art, there is no efficacious preventive/curative treatment for this condition. Among the reasons for this unmet clinical and scientific need, there is an uncomplete knowledge of the pathogenetic mechanisms. Ion channels and transporters are pivotal elements in both the central and peripheral nervous system, and there is a growing body of literature suggesting that they might play a role in CIPN development. In this review, we first describe the biophysical properties of these targets and then report existing data for the involvement of ion channels and transporters in CIPN, thus paving the way for new approaches/druggable targets to cure and/or prevent CIPN.

Cannabinoid CB2 receptors in primary sensory neurons are implicated in CB2 agonist-mediated suppression of paclitaxel-induced neuropathic nociception and sexually-dimorphic sparing of morphine tolerance.

Cannabinoid CB2 agonists show therapeutic efficacy without unwanted CB1-mediated side effects. The G protein-biased CB2 receptor agonist LY2828360 attenuates the maintenance of chemotherapy-induced neuropathic nociception in male mice and blocks development of morphine tolerance in this model. However, the cell types involved in this phenomenon are unknown and whether this therapeutic profile is observed in female mice has never been investigated. We used conditional deletion of CB2 receptors to determine the cell population(s) mediating the anti-allodynic and morphine-sparing effects of CB2 agonists. Anti-allodynic effects of structurally distinct CB2 agonists (LY2828360 and AM1710) were present in paclitaxel-treated CB2f/f mice and in mice lacking CB2 receptors in CX3CR1 expressing microglia/macrophages (CX3CR1CRE/+; CB2f/f), but were absent in mice lacking CB2 receptors in peripheral sensory neurons (AdvillinCRE/+; CB2f/f). The morphine-sparing effect of LY28282360 occurred in a sexually-dimorphic manner, being present in male, but not female, mice. LY2828360 treatment (3 mg/kg per day i.p. x 12 days) blocked the development of morphine tolerance in male CB2f/f and CX3CR1CRE/+; CB2f/f mice with established paclitaxel-induced neuropathy but was absent in male (or female) AdvillinCRE/+; CB2f/f mice. Co-administration of morphine with a low dose of LY2828360 (0.1 mg/kg per day i.p. x 6 days) reversed morphine tolerance in paclitaxel-treated male CB2f/f mice, but not AdvillinCRE/+; CB2f/f mice of either sex. LY2828360 (3 mg/kg per day i.p. x 8 days) delayed, but did not prevent, the development of paclitaxel-induced mechanical or cold allodynia in either CB2f/f or CX3CR1CRE/+; CB2f/f mice of either sex. Our findings have potential clinical implications.

Safety and Efficacy of Compression Therapy to Prevent Chemotherapy-Induced Peripheral Neuropathy in Lower Extremities of Breast Cancer Patients: A Pilot Study.

Background Chemotherapy-induced peripheral neuropathy (CIPN) is a problematic adverse event for breast cancer patients receiving taxane antimitotic agents. We evaluated the effectiveness of compression therapy against CIPN in the lower extremities of breast cancer patients receiving taxanes. Methods Eligible patients scheduled for perioperative treatment with taxanes for early-stage breast cancer were enrolled. Each patient wore latex-free surgical gloves and compression socks, putting on two layers of each 15 minutes before the administration of taxanes and removing them 15 minutes after administration. Peripheral neuropathy (PN) was evaluated using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 and the Patient Neurotoxicity Questionnaire (PNQ). The primary endpoint was the incidence of CTCAE version 4.0 grade 2 or higher CIPN in the lower extremities during the entire period of perioperative chemotherapy with taxanes. Results PN assessment by CTCAE in the lower extremities, the primary outcome, showed that 13.3% developed grade 2 sensory disturbances, and 8.3% developed grade 2 motor disturbances. The incidence of CTCAE grade 2 or higher PN in the hands was 26.7% for sensory disturbances and 13.3% for motor disturbances during the entire study period. No patient had grade 3 or higher PN. No adverse events due to compression therapy were observed. Conclusion Compression of the lower extremities with compression socks tended to reduce the incidence of CIPN compared to the general incidence. Compression therapy may help prevent the development of CIPN.

Exploring Chemotherapy-Induced Peripheral Neuropathy Management Practice Patterns Among Oncology Clinicians.

OBJECTIVES: Approximately 60% of cancer survivors receiving neurotoxic chemotherapy experience chemotherapy-induced peripheral neuropathy (CIPN) (eg, hand and foot numbness, tingling, or pain). There is only one recommended pharmacological treatment (duloxetine) and one modestly beneficial nonpharmacological treatment (exercise) for CIPN. However, data suggest national guideline recommendations are not routinely practiced. Further, less is known about nurses' CIPN management practices. The purpose of this convergent mixed methods study was to explore oncology clinicians' self-reported practices and perceptions regarding CIPN prevention and management. METHODS: Oncology clinicians at three cancer centers completed a survey about their recommendations for CIPN prevention and management in practice. A subset of clinicians also participated in a semi-structured interview to explore their perspectives of and motivations for implementing CIPN assessment, prevention, and management in practice. Quantitative data were described (eg, frequency or median) and qualitative data were analyzed using inductive content analysis. RESULTS: This study (N = 44 survey responses; n = 9 interviews) resulted in four themes: (1) clinicians primarily recommend gabapentin for CIPN management and often observe cryotherapy used for CIPN prevention, but these interventions are complicated by discomfort, intolerable side effects, and efficacy concerns; (2) clinicians perceive CIPN as troublesome and desire additional information and resources regarding CIPN prevention and management; (3) CIPN-related education provided by clinicians may be limited by patient retention of the amount of education received about cancer treatment and other factors; (4) clinicians use subjective CIPN assessment to screen at each visit for common CIPN symptoms (eg, numbness or tingling) and the impact of symptoms on day-to-day activities. CONCLUSIONS: Discrepancies persist between evidence-based guidelines on CIPN management and current oncology clinician practices. IMPLICATIONS FOR NURSING PRACTICE: Clinician involvement is needed when developing education and resources to help oncology clinicians provide the most evidence-based care to potentially prevent and manage their patients' CIPN.

Cropsi study: Efficacy and safety of cryotherapy and cryocompression in the prevention of chemotherapy-induced peripheral neuropathy in patients with breast and gynecological cancer-A prospective, randomized trial.

OBJECTIVE: This study aimed to demonstrate the superiority of cryocompression over cryotherapy alone in the prevention of chemotherapy-induced peripheral neuropathy (CIPN) grade 2 or above. METHODS: This prospective randomized study was conducted between May 2020 and January 2023 in Innsbruck. Eligible patients had a diagnosis of gynecological cancer and received a minimum of 3 cycles of taxane-based CT (neoadjuvant, adjuvant or palliative therapy). Patients were randomized 1:1 to receive either cryotherapy or cryocompression on their upper extremities during chemotherapy (CT). We performed temperature measurements, two QoL questionnaires and neurological tests during CT and at follow-up 3 and 6-9 months after the completion of CT. CIPN was assessed using the CTCAE score. RESULTS: Of 200 patients recruited, both groups showed a lower prevalence of CIPN in this study compared to recent literature. In the group receiving cryotherapy, the prevalence of grade 1 CIPN was 30.1 %, and that of grade 2 CIPN or above was 13.7 %; in the group treated with cryocompression, the prevalence of grade 1 CIPN was 32.8 %, and that of grade 2 or above CIPN was 17.2 %. We found a significant reduction in temperature in the cryotherapy and cryocompression groups. Regarding the two QOL questionnaires as well as the neurological tests no significant differences were found between the two groups. CONCLUSION: Our study suggests that cryotherapy as well as cryocompression is a safe and effective way to cool patients' extremities to lower the prevalence of CIPN. Cryocompression was not more effective than cryotherapy alone in the prevention of CIPN.

Advances in Spinal Neuromodulation for Chemotherapy-induced Peripheral Neuropathy.

BACKGROUND/AIM: Chemotherapy-induced peripheral neuropathy (CIPN) continues to be a major source of chronic morbidity in patients with cancer. Current treatment options and efficacy are limited; thus, there is a need to investigate more effective therapeutic options. Spinal neuromodulation including dorsal column spinal cord stimulation (SCS) and dorsal root ganglion stimulation (DRG-S) are being explored for these patients. The purpose of this narrative review was to critically summarize and evaluate the advancements that have been made in utilizing SCS and DRG-S for CIPN. MATERIALS AND METHODS: A thorough literature search was conducted using PubMed for any research on patients with CIPN who underwent DRG-S or SCS. Studies involving patients with general cancer-related pain were not included. Only articles that were published in English, had original, extractable data, and were available on or before August 1, 2023, were included. RESULTS: This study evaluated twelve studies with a total of 13 patients that reported using SCS for CIPN and four studies with a total of 12 patients that reported using DRG-S for CIPN. Many of the studies demonstrated that DRG-S or SCS can assist in reducing opioid consumption, lowering pain scores, and improving sensory deficits. CONCLUSION: DRG-S and SCS have the potential to improve symptoms and lower medication usage in patients suffering from CIPN. Spinal neuromodulation could be considered as an alternative therapy for patients with persistent symptoms.

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

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

Pre-treatment amino acids and risk of paclitaxel-induced peripheral neuropathy in SWOG S0221.

BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) is a treatment-limiting and debilitating neurotoxicity of many commonly used anti-cancer agents, including paclitaxel. The objective of this study was to confirm the previously found inverse association between pre-treatment blood concentrations of histidine and CIPN occurrence and examine relationships of other amino acids with CIPN severity. METHODS: Pre-treatment serum concentrations of 20 amino acids were measured in the SWOG S0221 (NCT00070564) trial of patients with early-stage breast cancer receiving paclitaxel. The associations between amino acids and CIPN severity were tested in regression analysis adjusted for paclitaxel schedule, age, self-reported race, and body mass index with Bonferroni correction. The network of metabolic pathways of amino acids was analyzed using over-representation analysis. The partial correlation network of amino acids was evaluated using a debiased sparse partial correlation algorithm. RESULTS: In the primary analysis, histidine concentration was not associated with CIPN occurrence (odds ratio (OR) = 0.97 [0.83, 1.13], p = 0.72). In secondary analyses, higher concentrations of four amino acids, glutamate (ß = 0.58 [0.23, 0.93], p = 0.001), phenylalanine (ß = 0.54 [0.19, 0.89], p = 0.002), tyrosine (ß = 0.57 [0.23, 0.91], p = 0.001), and valine (ß = 0.58 [0.24, 0.92], p = 0.001) were associated with more severe CIPN, but none of these associations retained significance after adjustment. In the over-representation analysis, no amino acid metabolic pathways were significantly enriched (all FDR > 0.05). In the network of enriched pathways, glutamate metabolism had the highest centrality. CONCLUSIONS: This analysis showed that pre-treatment serum amino acid concentrations are not strongly predictive of CIPN severity. Prospectively designed studies that assess non-amino acid metabolomics predictors are encouraged.

Pharmacogenomic predictor of long-term residual chemotherapy-induced peripheral neuropathy in ovarian cancer survivors: A substudy of the GINECO Vivrovaire study.

BACKGROUND: Chemotherapy (CT) remains a backbone treatment of epithelial ovarian cancer (EOC) inducing persistent peripheral neuropathy (CIPN). Using a dedicated patient-reported outcome tool, this study investigated persistent CIPN and its pharmacogenetic predictors in a cohort of long-term EOC survivors. METHODS: Vivrovaire was a French multicenter cohort of patients with EOC free of disease 3 years after CT completion. Persistent CIPN was assessed using the FACT/GOG-Ntx4 self-questionnaire. The association of homozygous (hom) or heterozygous (het) single nucleotide polymorphisms (SNPs) in selected genes was evaluated. RESULTS: 130 patients were included with a median time from CT completion of 63 [35-180] months. The median CIPN score was 37 [18-44], with 35 (26.9%) patients reporting severe CIPN (<33). SNPs were identified as follows: CYP2C8 [hom, n = 32 (24.6%)/het, n = 99, (76.2%)]; CYP3A4 [hom, n = 0 (0%)/het, n = 8 (6.2%)], ERCC1 [hom, n = 21 (16.2%)/het, n = 57 (43.8%)], and XPC [hom, n = 45 (34.6%)/het, n = 66 (50.8%)]. In univariate analysis, the identification of ≥1 hom SNP was associated with a lower CIPN score (continuous variable; p = 0.045). Patients harboring hom or het CYP2C8_rs1934951 SNP reported more likely severe CIPN (threshold <33) score (OR 2.482; 95% CI [1.126-5.47], p = 0.024). In the multivariate analyses, age, interval from CT completion, type and number of CT courses were not significantly associated with CIPN score (OR 5.165, 95% CI [0.478-55.83], p = 0.176). CONCLUSIONS: Persistent CIPN is common among ovarian cancer long-term survivors. CYP2C8_rs1934951 SNP may be associated with severe residual CIPN in EOC survivors. More studies are warranted to identify predictive factors of CIPN.

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

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

The Association between Oxaliplatin-Induced Peripheral Neuropathy, Sociodemographic, and Clinical Characteristics with Falls in Older Adults with Colorectal Cancer.

Our purpose was to investigate the associations between oxaliplatin-induced peripheral neuropathy (OIPN), sociodemographic, and clinical characteristics of older colorectal cancer patients with falls. The study population consisted of older adults diagnosed with colorectal cancer obtained from the Surveillance, Epidemiology, and End Results database combined with Medicare claims. OIPN was defined using specific (OIPN 1) and broader (OIPN 2) definitions of OIPN, based on diagnosis codes. Extensions of the Cox regression model to accommodate repeated events were used to obtain overall hazard ratios (HR) with 95% confidence intervals and the cumulative hazard of fall. The unadjusted risk of fall for colorectal cancer survivors with vs. without OIPN 1 at 36 months of follow-up was 19.6% vs. 14.3%, respectively. The association of OIPN with time to fall was moderate (OIPN 1, HR = 1.37, 95% CI: 1.04, 1.79) to small (OIPN 2, HR = 1.24, 95% CI: 1.01, 1.53). Memantine, opioids, cannabinoids, prior history of fall, female sex, advanced age and disease stage, chronic liver disease, diabetes, and chronic obstructive pulmonary disease all increased the hazard rate of fall. Incorporating fall prevention in cancer care is essential to minimize morbidity and mortality of this serious event in older colorectal cancer survivors.

The association of chemotherapy-induced peripheral neuropathy with reduced executive function in chemotherapy-treated cancer survivors: A cross-sectional study.

INTRODUCTION: Chemotherapy-induced peripheral neuropathy (CIPN) is common and disabling among cancer survivors. Little is known about the association of CIPN with other measures of the nervous system's integrity, such as executive dysfunction. We compared measures of executive function in older chemotherapy-treated cancer survivors with and without CIPN. MATERIALS AND METHODS: This cross-sectional study enrolled 50 chemotherapy-treated cancer survivors (65.6 ± 11.5 years, 88% female) post-chemotherapy treatment who were previously referred for outpatient rehabilitation at the request of the cancer survivor or a medical provider. Twenty-two participants (44%) had CIPN defined by patient-reported distal paresthesia or numbness, which began with chemotherapy and continued to the time of cognitive testing. Measures of executive function included Trails-B, Stroop, and rapid reaction accuracy (RRA) and were evaluated between cancer survivors with and without CIPN using t-tests. Multivariable models were then used to determine whether CIPN was an independent determinant of the measures of executive function (Trails-B, Stroop Incongruent, and RRA). Models were adjusted for age, sex, history of anxiety, and benzodiazepine use due to their known associations with CIPN and executive function. RESULTS: Cancer survivors with CIPN (CIPN+) had reduced executive function compared to survivors without CIPN (CIPN-) on Trails-B (CIPN+: 84.9 s ± 44.1 s, CIPN-: 59.1 s ± 22.5 s, p = 0.01), Stroop (CIPN+: 100.6 s ± 38.2 s, CIPN-: 82.1 s ± 17.3 s, p = 0.03), and RRA (CIPN+: 60.3% ± 12.9%, CIPN-: 70.6% ± 15.7%, p = 0.01). There were no differences in cancer stage severity or functional status by patient report or sit-to-stand function. The association between CIPN and reduced executive function was found in multivariable models after adjusting for age, sex, anxiety, and benzodiazepine use for Trails-B (ß:17.9, p = 0.046), Stroop (ß:16.9, p = 0.02), and RRA (ß:-0.072, p = 0.03). DISCUSSION: In this population, CIPN is associated with reduced executive function in older cancer survivors treated with chemotherapy. Future research is required to further understand this preliminary association, the causality, and the potential risk factors.

A retrospective cohort study describing chemotherapy-induced peripheral neuropathy in Non-Hodgkin lymphoma patients treated with EPOCH ± R: does HIV status matter?

The frontline immuno-chemotherapy regimen for HIV-associated non-Hodgkin Lymphoma is dose-adjusted EPOCH ± R (etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab). Chemotherapy-induced peripheral neuropathy (CIPN), caused by vincristine, is a common adverse effect of EPOCH ± R, negatively impacting long-term patient outcomes. The primary objective of this study was to determine the incidence of CIPN, stratified by HIV status, in patients treated with EPOCH ± R. A retrospective cohort study at a tertiary referral comprehensive cancer center evaluated patients treated with EPOCH ± R from 2011 to 2018. The final sample included 27 patients with HIV compared to 279 without HIV (total n = 306). Overall, the incidence of CIPN was 29.4% (n = 90), including 5 with HIV (18.5%) and 85 without HIV (30.5%). Propensity scores were used to match patients by HIV status. Although no relationship was found between HIV status and neuropathy, CIPN affects too many undergoing treatments for lymphoma, supporting future investigations to minimize toxicities.

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

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