Factors Associated with Quality of Life in Cancer Patients Experiencing Chemotherapy-Induced Peripheral Neuropathy (CIPN) : Scoping review

60 Background: Chemotherapy-induced peripheral neuropathy (CIPN) is common in cancer patients (pts). CIPN impacts quality of life (QoL) and causes emotional distress and treatment (Tx) delays. No agents are recommended for prevention and one agent is recommended for Tx of CIPN (ASCO Guidelines, 2014). Limited data exist about pt experiences with CIPN. The study goal was to understand pt experiences related to CIPN. Methods: An online, 67-question survey was completed by pts with breast or lung cancer. All had chemotherapy and self-reported moderate (mod) or severe CIPN within the past 2 years (mild CIPN excluded). Pts rated CIPN symptom frequency, socioemotional wellness, and impact on a 6- or 7-point scale (depending on item) and bothersomeness on a 5-point scale. Results were not analyzed by chemotherapy type. Results: Respondents had early breast cancer (EBC; n = 114), metastatic breast cancer (MBC; n = 96), or lung cancer (LC, all stages; n = 65). All EBC and MBC and 72% of LC pts were women; > 80% were White. Moderate CIPN existed in 63%, 67%, and 82% of EBC, MBC, and LC pts; severe CIPN occurred in 37%, 33%, and 18%, respectively. CIPN severity was associated with reduced QoL. Very/extremely bothersome effects on QoL occurred in 63% severe CIPN (n = 86) and 15% mod CIPN (n = 189) pts. Almost all EBC (94%) and two-thirds of MBC and LC pts had persistent CIPN. Symptoms included foot (97%)/hand (88%) numbness/tingling, foot (92%)/hand (81%) discomfort, foot/leg pain (85%), and joint pain (83%). Pts reported reduced physical function, productivity, and socioemotional wellness. Receiving information before Tx was linked with greater chance of mod vs severe CIPN. More pts with mod vs severe CIPN (37% vs 21%) received information about CIPN before chemotherapy. Having healthcare providers (HCPs) ask about symptoms was linked with a greater chance of mod vs severe CIPN. More pts with mod vs severe CIPN (28% vs 17%) had HCPs ask about CIPN symptoms. Conclusions: Learning about CIPN before chemotherapy was associated with a lower chance of severe CIPN. Early and ongoing communication with pts about risks, manifestations, and importance of reporting CIPN may limit severe CIPN and preserve QoL specifically with regards to socioemotional wellness.

SP66 Chemotherapy induced neuropathic pain. Clinical diagnosis and treatment

Objective To integrate relevant qualitative studies and to evaluate the experience of chemotherapy-induced peripheral neuropathy (CIPN) systematically in cancer patients. Methods Relevant qualitative studies were retrieved from PubMed, Embase, Web of Science, Science Direct, PsycINFO and Chinese databases such as CNKI, Wanfang, VIP and SinoMed from when they were founded to July 31, 2018. The Joanna Briggs Institute (JBI) 's qualitative study quality evaluation standards was used to evaluate the literature, and the converging integration method was used to integrate the results. Results Totally 6 studies were included, and they boiled down to 19 results, 8 types and 4 integration results. Integration result 1: CIPN was an indefinite symptom experience, which was complex and mainly reflected by unclear CIPN symptoms, lack of information support for patients and low reporting rates. Integration result 2: CIPN was misunderstood by patients as an unimportant risk which was mainly reflected as patients' low risk awareness of CIPN, lack of attention to CIPN from medical workers and thus low evaluation rates of CIPN. Integration result 3: CIPN affected patients' quality of life severely, as reflected by its effects on patients' daily life and emotional disturbance. Integration result 4: CIPN was a characteristic of cancer survivors as reflected by uncertainty of drug treatment in patients and their adaptation to the symptoms when the symptoms were mitigated or controlled. Conclusions The symptoms of CIPN is complex. Medical workers' evaluation capacity and patients' self-management shall be enhanced so as to mitigate CIPN symptoms and improve the overall quality of life of patients. Key words: Chemotherapy; Peripheral chemotherapy; Psychological experience; Qualitative study; Systematic evaluation

Chemotherapy-induced peripheral neuropathy (CIPN) is a common adverse effect of neurotoxic anticancer drugs that may affect quality of life (QoL). Purpose: The purposes of this study were to: assess the levels of CIPN, anxiety, depression, CIPN–related QoL, and general QoL; and identify the factors related to CIPN–related QoL and general QoL in patients with advanced lung cancer (LC) receiving platinum-based chemotherapy. This cross-sectional study examined patients with advanced LC who received platinum-based chemotherapy from the thoracic oncology inpatient wards of a medical center in northern Taiwan. Structured questionnaires were used to measure patients’ CIPN (European Organization for Research and Treatment of Cancer quality of life questionnaire–chemotherapy–induced peripheral neuropathy 20), anxiety (Hospital Anxiety and Depression Scale Depression Scale [HADS]), depression (HADS), CIPN-related QoL (Functional Assessment of Cancer Therapy /Gynecologic Oncology Group-Neurotoxicity subscale [FACT/GOG–Ntx]), and general QoL (Functional Assessment of Cancer Therapy–General Input [FACT-G]). Of 93 patients with advanced LC, 53.8% reported CIPN–sensory impairment and 47.3% reported CIPN–motor impairment. The most common CIPN symptoms were difficulty getting or maintaining an erection (only for men > 65 years) and difficulty in climbing stairs or getting up out of a chair. Poor CIPN–related QoL (FACT/GOG–Ntx) was associated with more CIPN–sensory and more CIPN–motor impairment. Poor general QoL (FACT-G) was associated with a higher level of depression, a higher level of anxiety, and receipt of more chemotherapy cycles. More than half of LC patients report impairment related to CIPN, calling for holistic treatment to improve QoL.

Chemotherapy-induced peripheral neuropathy (CIPN) affects approximately 50% of patients who receive chemotherapy. CIPN often results in dose reductions, therapy discontinuation, and long-term neurological impairment. Despite existing studies, identifying high-risk populations remains challenging, particularly in patients with diabetes, diabetic neuropathy, and those undergoing corticosteroid therapy. We sought to evaluate the key risk factors associated with CIPN by analyzing patient demographics, comorbidities, and chemotherapy regimens, with a specific focus on diabetes-related variables in order to inform early identification and prevention strategies. Retrospective, single-center, observational cohort study. Academic tertiary care cancer center. Adult patients who received chemotherapy between January 2016 and December 2023 were identified through electronic medical records. Patients with CIPN were defined by the International Classification of Disease, Tenth Revision G62.0 diagnosis code (drug-induced polyneuropathy) and an associated diagnosis of "painful peripheral neuropathy." Extracted data included demographics (age, body mass index [kg/m2], race/ethnicity), clinical variables (alcohol use, corticosteroid use, diabetes-related factors), and chemotherapy regimen details. Descriptive statistics, Wilcoxon rank sum, c2/Fisher's exact tests, and multivariable logistic regression were performed. Institutional review board (IRB) approval was obtained (IRB exemption #2024-0139). Among 36,949 patients, significant CIPN risk factors included older age (40-80 years, P < 0.0001), women (odds ratio [OR] 1.89; P < 0.0001), non-Hispanic/non-Latino ethnicity (OR 1.29; P < 0.0001), and corticosteroid use (OR 2.01; P < 0.0001). African American patients had lower odds of CIPN than White patients (OR 0.78; P < 0.0001). Diabetic neuropathy was strongly associated with increased CIPN risk (OR 5.35; P < 0.0001). Alcohol use was inversely associated with CIPN (OR 0.75; P < 0.0001). Several chemotherapy agents also showed significant associations. Our study is limited by its retrospective design, potential misclassification bias in CIPN diagnosis, and reliance on electronic medical records. Alcohol use data were frequently missing or unspecified, limiting interpretation. Key CIPN risk factors include age, race/ethnicity, corticosteroid use, and diabetic neuropathy. Alcohol use appeared inversely associated with CIPN, though causality remains unclear. Individualized patient assessments and proactive management strategies may help reduce CIPN incidence and improve outcomes in patients with cancer who are receiving chemotherapy.

e24080 Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a major yet poorly understood side effect of cancer treatment, leading to symptoms including numbness, tingling and pain. It can lead to cessation of effective treatment, long-term functional disability and reduced quality of life. Despite this, there is currently little understanding of its impact. Methods: The aim of the study was to investigate the impact of neurotoxic chemotherapy side effects on the lives of cancer survivors. Data was collected via an online survey covering demographics, cancer diagnosis and treatment, CIPN and other side effects of chemotherapy, using standardised measures to assess comorbidities, quality of life, physical activity, pain and CIPN symptoms. Results: Data was analysed from 986 respondents who were treated with neurotoxic therapies (83% female, 16% male), with mean age 59 years ( SD 10.7 years). A majority of respondents were treated for breast cancer (59%), 14% for colorectal cancer and 11% for multiple myeloma. Chemotherapy types received included paclitaxel (32%), docetaxel (32%) and oxaliplatin (13%), and respondents completed treatment a mean of 3.6 years ago. The majority of respondents (80%) reported experiencing neuropathic symptoms after finishing chemotherapy, with 77% reporting current CIPN. Those with CIPN reported functional impacts, with 23% reporting moderate to severe problems with hand function and 28% reporting moderate to severe walking difficulties. CIPN was second most commonly rated as the treatment side effect having the greatest impact, following fatigue. Respondents with high levels of current CIPN symptoms had poorer quality of life, more comorbid health conditions, higher BMI and more often received multiple neurotoxic chemotherapies than those with low levels of CIPN symptoms. In addition, respondents who reported meeting government physical activity guidelines had lower CIPN and higher quality of life scores than those who did not meet the guidelines. Regression analyses investigating the association between quality of life and clinical and sociodemographic characteristics resulted in a model with comorbid health conditions, CIPN symptoms, years since treatment, age and physical activity as significant predictors of quality of life. Conclusions: These findings suggest that CIPN has a lasting impact on cancer survivors, leading to decreases in quality of life, often occurring alongside poorer general health. This impact supports the need for further research to improve assessment, prevention and treatment.

Background: Chemotherapy Induced Peripheral Neuropathy (CIPN) is a debilitating side effect associated with many antineoplastic chemotherapeutic agents including cytotoxic and targeted agents. It significantly impacts cancer patients’ quality of life during treatment, and may cause lasting neuropathy and shorten treatment regimen, potentially impacting clinical benefit. The pathology of CIPN is complex and still not completely understood. Damages to nerve cells are believed to be directly resulting from the antineoplastic agents’ cytotoxicity, and inflammation and the immune system are believed to be involved as well. Evidence suggests that intervention of certain GPCRs (e.g., cannabinoid receptors and others) may be useful as potential treatments. Altered neuronal sphingolipid metabolism has been linked to neuropathic pain and elevated plasma levels of sphingosine-1-phosphate (S1P) have also been associated with patients receiving chemotherapy and developing CIPN; therefore, modulating S1P levels may also be a potential treatment. Method: BXQ-350 is a nanovesicle of Saposin C, an allosteric activator of sphingolipid metabolism, that lowers systemic S1P; Saposin C has been reported to activate certain GPCRs, including GPR37. BXQ-350 was investigated in an adult Phase 1 dose-escalation safety study in heavily pretreated all-comer cancer patients with advanced solid malignancies (NCT02859857). The cytoprotective properties of BXQ-350 against multiple agents known to induce CIPN were investigated in vitro in neuronal PC12 cells and BXQ-350’s CIPN mitigation properties were investigated in vivo in a CIPN preclinical model. Results: A pancreatic cancer patient with chronic CIPN at time of enrollment in the Phase 1 study spontaneously reported a significant improvement of her neuropathic symptoms shortly after receiving BXQ-350; several patients had similar improvements. Results from preclinical experiments in PC12 cells revealed that BXQ-350 at concentration as low as 50 nM protected cells from oxaliplatin, paclitaxel, bortezomib or MMAE and promoted neurite growth. BXQ-350 was subsequently investigated in a murine oxaliplatin-induced CIPN preclinical model, showing a dose-dependent reduction of thermal and mechanical allodynia correlating with decreasing systemic S1P levels. Conclusions: Preclinical results demonstrated that BXQ-350 was highly effective at protecting neuronal cells from antineoplastic agents known to induce CIPN and prevent CIPN in a preclinical model. These results appeared to support the clinical observation that BXQ-350 alleviated CIPN symptoms in several patients soon after receiving BXQ-350. Additional studies are on-going. Citation Format: Nikhil Wilkins, Tim Stephens, Robin Furnish, Charlie Cruze, Darren Wolfe, Gilles H. Tapolsky, Ray Takigiku. BXQ-350 may protect peripheral nerves from the direct cytotoxicity of chemotherapeutic agents leading to chemotherapy induced peripheral neuropathy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3042.

Background: Addition of taxanes to adjuvant chemotherapy provides survival benefit in patients with early breast cancer (EBC). Intensifying adjuvant regimens with taxanes leads to increased toxicity, including higher rates of sensory peripheral neuropathy (sPN). Prevalence of chemotherapy induced peripheral neuropathy (CIPN) in trials varies with reported rates of 15 - 30%. Up to 15% of patients report persistent CIPN 1-3 years post treatment with associated adverse impact on quality of life (QOL). There is limited data reporting rates of CIPN and QOL beyond 3 years. We assessed rates of persistent sPN in real world patients with EBC treated with adjuvant taxanes and its effect on QOL. Methods: Patients who received adjuvant taxane for EBC at a metropolitan health service in the preceding 10 years were identified from hospital records and invited to participate. Data was collected at a single time point using the EORTC Quality of Life (QLQ30) and Chemotherapy-Induced Peripheral Neuropathy (CIPN20) questionnaires. Demographic, co-morbid and treatment details were collected from medical records. Raw scores were linearly transformed to a 0 to 100 scale with higher scores indicating higher functioning, QOL and levels of symptomatology. Prevalence was determined using a binary model of no or any sPN and cases grouped into no/mild or moderate/severe for further analysis. Groupwise comparisons were performed with parametric and non-parametric tests. Analysis of covariance was used to fit models incorporating comorbid factors such as diabetes with time point of assessment as the covariate. Results: 176 of 250 questionnaires were returned, a response rate of 71%. Median age was 59 (range 30-88 years) with 52% of respondents receiving paclitaxel vs 47% docetaxel containing regimens. Median time from completion of taxane was 30 months (range 6-120 months). 11 patients (6%) had known diabetes and 50 (26%) had at least one other known risk factor for neuropathy. The prevalence of CIPN across all time points was 74.4%, much higher than seen in historical trials. Table 1: Incidence of sensory neuropathy (all grades) by time from chemotherapyTime bracket (months)N= (176)PN (%)No PN (%)6-246352 (82.5)11 (17.5)25-486347 (74.6)16 (25.4)49-1205032 (64%)18 (36%) QOL scores were lower in patients with moderate/severe sPN, with a median global QOL scaled score of 50 vs 75 in patient with no/mild sPN (p = 0.0062). Increasing sPN score was associated with lower QOL score controlling for time from chemotherapy (standardised beta co-efficient -0.28). In an analysis of covariance, diabetes was the only significant comorbid factor associated with higher sPN scores. In the final model incorporating diabetes, miscellaneous other sPN risk factors and time from chemotherapy, diabetes was associated with increased sPN scores with a small effect size (p = 0.03). Paclitaxel was associated with higher sPN scores than docetaxel (p 0.0001) with significant interaction of paclitaxel with diabetes independent of other sPN risk factors and time from chemotherapy (p = 0.02). Paclitaxel was associated with higher sPN scores in diabetic patients (adjusted mean score in diabetic patients 46.7 v 20.9 in non-diabetic receiving paclitaxel, p = 0.001). Conclusion: CIPN is significantly more prevalent in this real world cohort than reported in historic data, with persistent sPN having a negative correlation with QOL out to 10 years. Higher rates of paclitaxel-associated sPN in diabetic patients could inform decision making on adjuvant chemotherapy. Citation Format: Elizabeth F Blackley, Megan G Kesper, Peter Savas, Bianca Devitt. Long-term incidence of taxane induced peripheral neuropathy in early breast cancer patients, a real world, single centre experience exploring effects on health related quality of life [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-17-06.

e23143 Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a common, long-term side effect of many antineoplastic agents and has a detrimental impact on patients (pts)’ quality of life and functional activities of daily living. Currently, preventive measures and treatment options for CIPN are quite limited. OnLife is a dietary supplement that contains a patented mixture of fatty acids with anti-inflammatory, neuroprotective and antinociceptive properties. Methods: The STEFANO study – an observational, prospective, two-cohort, multicenter study of dietary supplementation – was designed to evaluate the potential of OnLife to improve CIPN in adult pts with completed neo-/adjuvant chemotherapy and manifest CIPN (grade 1-3) (Cohort A: colon cancer, oxaliplatin-containing therapy; cohort B: breast cancer, paclitaxel therapy). Pts received OnLife for 3 months. The primary objective – assessment of changes in CIPN – was evaluated by comparing the severity of sensory and motor CIPN according to CTCAE v4.03 before, during and after treatment with OnLife. Secondary endpoints included patient-reported experience of symptoms and functional limitations related to CIPN. Descriptive statistics were used to analyze data. Results: In total, 75 breast cancer pts with paclitaxel-induced and 71 colon cancer pts with oxaliplatin-induced peripheral neuropathy, respectively, received OnLife. Based on physician-rated CTCAE grades, 21.3% of breast cancer pts and 12.7% of colon cancer pts had a sustained improvement of sensory CIPN after OnLife treatment. Concerning motor CIPN, the proportions were 12.0% and 9.9%, respectively. According to patient-reported outcomes, 45.3% of breast cancer pts and 23.9% of colon cancer pts had less symptoms and functional limitations related to sensory CIPN after OnLife treatment. Concerning motor CIPN, the proportions were 32.0% and 22.5%, respectively. Conclusions: STEFANO provides indications of the potential of OnLife to reduce severity of objective and subjective CIPN-related symptoms. Therefore, it is a promising agent to meet the unmet medical need of management options for patients with established CIPN. Clinical trial information: NCT03065478.

Chemotherapy-induced peripheral neuropathy (CIPN) is often an overlooked side effect, affecting cancer patients' quality of life. Improving this requires an in-depth understanding of how patients perceived their CIPN experience, which this study had explored. This study also sought to identify potential barriers to current CIPN management among Malaysian cancer patients. Semi-structured one-to-one interviews were conducted among cancer patients who had a confirmed diagnosis of CIPN from one hospital and a local cancer organization. Interviews were conducted until theme saturation was achieved (N = 22). Interviews were audio-recorded, transcribed verbatim, and analysed using thematic analysis. Three main themes emerged: manageable CIPN experiences impacting activities of daily living despite limited awareness, current conventional treatments of CIPN were partially effective with side effects, and explorative of alternative treatment options for CIPN. The study results indicated that patients experienced CIPN, which was considerably mild and impacted their life activities to a small extent. The limited information provided about CIPN contributed to a sense of uncertainty among patients. They emphasized the importance of more accessible information and education about CIPN and its management. Although the conventional management of CIPN was able to partly control symptoms, patients experienced side effects from the prescribed medications. Interestingly, patients expressed openness to explore new treatments to help them cope better with CIPN. These findings highlighted the need for a comprehensive, patient-centred approach to CIPN management. Insights from patient experiences could guide the development of educational interventions, such as patient's assessment form on CIPN experiences and awareness activities to enhance CIPN care.

e17063 Background: Chemotherapy-induced peripheral neuropathy (CIPN20) after curative treatment for testicular germ cell tumors (GCTs) has been previously reported. The impact of CIPN on long-term quality of life (QOL) in GCT survivors remains unclear. Herein, we aimed to evaluate chemotherapy-induced peripheral neuropathy (CIPN20) in association with QOL in GCT survivors. Methods: European Organisation for Research and Treatment of Cancer (EORTC) CIPN20, QLQ-C30 and Functional Assessment of Cancer Therapy-Cognitive Function (FACT-Cog) questionnaires were prospectively completed by GCT survivors (N = 153) at National Cancer Institute in Slovakia during their annual follow-up. The median follow-up was 10 years (range 4-25). Upon obtaining the scores from each questionnaire per recommended guidelines, each score from QLQ-C30 and FACT-Cog was correlated with CIPN defined as high or low (above and below median) as obtained from CIPN20. Results: GCT survivors with CIPN high reported impairment in quality of life in QLQ-C30. The global health status was lower in survivors with high vs low CIPN (mean score ± SEM: 66.5 ± 1.9 vs. 86.2 ± 1.8, P &lt; 0.00001). Survivors with CIPN high reported substantially worse physical, role, emotional, cognitive and social functioning compared to CIPN low (all P &lt; 0.00001). CIPN high survivors perceived more fatigue, nausea, pain, dyspnoea, appetite loss and more sleeping disorders compared to CIPN low (all P &lt; 0.0001). Higher burden of CIPN was associated with more financial problems vs CIPN low (mean score ± SEM: 19.6 ± 2.6 vs. 6.67 ± 2.3, P = 0.0002). Cognitive impairment was higher in all FACT-Cog domains including the overall cognitive function score (all P &lt; 0.001) for CIPN high. Spearman analysis has confirmed negative correlations of CIPN20 overall score with QLQ-C30 global health status (R = -0.54, P &lt; 0.0001) and with FACT-Cog overall cognitive function score (R = -0.52, P &lt; 0.0001). Conclusions: CIPN is a powerful predictor of disturbances in QOL and cognitive functioning among GCT survivors. Physicians should never over-treat patients unnecessarily and novel therapies with lower burden of late toxicity should be researched

The purpose of this study was to examine the mediation of psychological distress in the relationship between disturbance in ADL from chemotherapy induced peripheral neuropathy and quality of life in order to provide a basis for planning nursing interventions to improve the quality of life in cancer patients. A purposive sample of 130 patients treated with chemotherapy were recruited in the cross-sectional survey design. Data were collected using self-report questionnaires. The instruments were the Chemotherapy Induced Peripheral Neuropathy Assessment Tool (CIPNAT), Hospital Anxiety Depression Scale (HADS), and Functional Assessment of Cancer Therapy-General (FACT-G). The mean score for disturbance in ADL from chemotherapy induced peripheral neuropathy was 3.30. Overall quality of life was 2.48. The mean score was 1.04 for psychological distress. The prevalence was 35.4% for anxiety and 47.7% for depression. There were significant correlations among the three variables, disturbance in ADL from chemotherapy induced peripheral neuropathy, psychosocial distress, and quality of life. Psychosocial distress had a complete mediating effect (β=-.74, p<.001) in the relationship between disturbance in ADL from chemotherapy induced peripheral neuropathy and quality of life (Sobel test: Z=-6.11, p<.001). Based on the findings of this study, nursing intervention programs focusing on disturbance of ADL management, and decrease of psychological distress are highly recommended to improve quality of life in cancer patients.

Background Chemotherapy induced peripheral neuropathy (CIPN) is one of the most common dose-limiting side effects seen among patients with early stage breast cancer and received taxane-containing regimens. The primary clinical manifestation of CIPN is sensory neuropathy such as numbness, tingling and pain in hands and feet, which negatively affect the patient’s quality of life (QoL). Although in most patients, CIPN improves over time, in a subset of patients, it remains a substantial debilitating problem, significantly affecting QoL. To date, there are no effective prevention strategies- or sufficient treatment due to the limited understanding of CIPN pre-disposing factors or pathophysiology. We hypothesize that a multimodal integration of biomarkers with CIPN progression analysis will be required to understand the pathophysiology and to consistently predict patient susceptibility. Further, we hypothesize that this multimodal approach may be leveraged to identify targets for CIPN treatment and/or prevention. This abstract describes the study protocol used to explore this hypothesis. Objective This study is designed to 1) identify genetic, transcriptional, epigenetic, metabolic, inflammatory biomarkers predictive of CIPN development among patients with early stage breast cancer receiving a taxane containing therapy; 2) With these biomarkers, develop an algorithm to identify patients who are at risk of developing CIPN before or during taxane therapy. Methods This is a longitudinal, multicenter, observational study. Patients with early-stage breast cancer who are receiving a taxane-containing (paclitaxel, docetaxel or nab-paclitaxel) treatment regimen, without preexisting peripheral neuropathy are eligible. Estimated enrollment is 400 patients. Demographic and clinical data are collected after patients consent to participate. Molecular data and patient reported outcomes (PRO) are collected prior to initiation of taxane therapy, the 4th, 8th, and 12th week of taxane therapy, and at 3, 6, and 9 months after completion of taxane therapy. Blood samples are collected for molecular data which include genetic, transcriptional, epigenetic (DNA-methylation), and metabolic data. PRO are assessed using (i) the European Organization for Research and Treatment of Cancer CIPN20 questionnaire, (ii) the Brief Pain Inventory, (iii) the Pain Catastrophizing Scale, and (iv) the PRO Measurement System for anxiety, depression and pain interference. Initial data analysis will characterize the association of biomarkers in each modality (e.g., genetic, epigenetic, etc.) with the presence or absence of CIPN, and machine learning will be used to build candidate biomarker signatures to predict CIPN before and during taxane treatment. Two distinct multi-modal prediction models will be constructed: 1) a pre-treatment model to predict risk of developing CIPN, and 2) an on-treatment model to predict the onset of CIPN. The goal is to develop a parsimonious, clinically translatable model for robust and accurate predictions of taxane-induced CIPN. Trial Status: Active, 135 subjects enrolled. Trial Centers: 1) Cleveland Clinic Foundation (8 regional sites in Ohio and 1 in Florida); 2) Huntsman Cancer Institute, University of Utah Research Funding: National Institute of Neurological Disorder and Stroke. Grant No.: 1R61NS113258-01A1 Citation Format: Mei Wei, Anukriti Sharma, Ken Johnson, Bihua Bie, courtney hershberger, Alper Sen, Emily E. Rhoades, Chi-Fan Hocking, George Budd, N. Lynn Henry, Charis Eng, Joseph Foss, daniel rotroff. Protocol Description of Genetics and Inflammatory Markers to predict Chemotherapy-Induced Peripheral Neuropathy among Early Stage Breast Cancer Patients Receiving Taxane Therapy – GENIE Study [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr OT1-17-01.

Highlight: Chemotherapy induces neurotoxicity through DNA crosslink, impaired calcium homeostasis, mitochondrial damage, increased reactive oxygen species, pro-inflammatory cascade, axon degeneration, and programmed cell death. CIPN has a primary impact on the sensory neuron. CIPN is diagnosed based on the patient's history, chemotherapy history, and neurologic examination. Some pharmacological and non-pharmacological treatments are hypothesized to reduce CIPN symptoms, but only duloxetine is recommended. ABSTRACT Chemotherapy-induced peripheral neuropathy (CIPN) is the most common and severe neurological side effect of many commonly used chemotherapy agents. It affects more than 60% of cancer patients. Approximately 30%–40% of patients have persistent symptoms five months or longer after stopping treatment. Even years after completing chemotherapy, some patients still experience CIPN symptoms. CIPN increases the annual cost of healthcare, leads to detrimental dose reduction and even cessation of treatment, and severely affects cancer survivors’ quality of life. Chemotherapy induces neurotoxicity through a variety of mechanisms that lead to neuronal cell damage or cell death. This mechanism of neurotoxicity varies depending on the specific agent. CIPN is characterized predominantly by sensory axonal peripheral neuropathy. Motor and autonomic symptoms may appear, but less frequently. To diagnose CIPN, a thorough patient's history and neurological examination are required. The current approach to CIPN management focuses on managing the symptoms of neuropathic pain and reducing or stopping the chemotherapy agent when CIPN manifests. There is no proven or advised prophylaxis therapy for CIPN. The point of this review was to talk about how some commonly used chemotherapy agents (such as platinum-based compounds, taxanes, vinca alkaloids, bortezomib, and thalidomide) cause CIPN, how to diagnose it, and the newest treatments that are available.

BackgroundPatients commonly experience chemotherapy-induced peripheral neuropathy (CIPN) as an adverse effect from chemotherapies, such as taxanes. In some patients, CIPN symptoms are severe and significantly impact their quality of life. Gaining a deeper understanding of how patient factors change over time, and identifying predisposing patient factors for CIPN susceptibility, could provide opportunities to mitigate the risk of CIPN and improve patient outcomes.MethodsA total of 229 patients with breast cancer receiving taxane chemotherapy completed study visits over 12 months. Data from patient reported outcomes (PROs) were collected from validated questionnaires to assess CIPN, anxiety, depression, weight, physical function, and sleep disturbance. Wilcoxon signed-rank tests were conducted to evaluate changes in PROs between timepoints (pre-treatment, on-treatment, post-treatment). Logistic regression was used to compare PROs between CIPN and non-CIPN groups at each time point, after adjustment for age, race, and pre-treatment CIPN score. Results were adjusted for multiple comparisons using a false discovery rate (FDR) procedure (FDR P < .05). A random forest model using 19 patient features was employed to build a CIPN predictive model.ResultsOut of 229 patients, 75% developed CIPN. Higher depression scores were associated with CIPN development across the three time periods: pre-treatment (OR = 1.20, FDR P = 5.3 × 10−3), on-treatment (OR = 1.32, FDR P = 4.4 × 10−4), and post-treatment (OR = 1.24, FDR P = 4.3 × 10−3). Similarly, pre-treatment PROMIS physical function T scores were lower among patients who developed CIPN (FDR P = 1.30 × 10−2), on-treatment (FDR P = 5.78 × 10−6) and post-treatment (FDR P = 8.7 × 10−5). On treatment anxiety scores were higher on-treatment in patients experiencing CIPN (OR = 1.30, FDR P = 4.3 × 10−3). Patients with obesity were 3.78 times more likely to develop CIPN compared to those with normal weight (FDR P = 3 × 10−3). Patients with CIPN did not report experiencing higher levels of sleep disturbance (FDR P > .05). The random forest predictive model reached an accuracy of 84% with body mass index (BMI), physical function score and general anxiety score as the most important predictors.ConclusionThese findings indicate that those experiencing CIPN were more likely to report reduced physical functioning, increased anxiety and depression, and have higher BMIs. As new multi-modal approaches are developed for CIPN, pre-treatment physical functioning, BMI and other patient reported measures may provide predictive ability.