Tofthagen, Cindy S

Abstract Background: Up to 50% of patients with breast cancer experience chemotherapy-inducednausea (CIN) and 95% experience fatigue. A comprehensive understanding of biological mechanisms remains elusive. Herein, we evaluated the association of CIN and fatigue with clinical and multi-omics features, including serum and stool metabolites before (T1) to after chemotherapy (T2). Methods: Patients with breast cancer (n=36) who were to receive chemotherapy, provided symptom assessment using the Memorial Symptom Assessment Scale, stool and blood samples at T1 and T2. Patients provided dietary intake data using a Dietary Screener Questionnaire at T1. Descriptive and univariate analyses evaluated associations of co-occurringsymptoms and diet with CIN and fatigue at T2. Gut microbiome was sequenced using shotgun metagenomics. Targeted metabolomics was performed on stool and serum. Shift in the abundance of taxonomic groups and metabolite levels from T1 to T2 were evaluated in association with CIN and fatigue. Results: Approximately 64% of the patients experienced CIN and 94% experienced fatigue atT2. Three gastrointestinal symptoms co-occurred with CIN and fatigue. Higher daily average intake of calcium (p=0.013) and dairy (p=0.035) were associated with CIN. Levels of hexosylceramides, ceramide, phosphatidylcholine and sphingomyelins were significantly perturbed in association with CIN and fatigue (p<0.05). Conclusion: CIN and fatigue are associated with perturbation in the sphingolipid turnover pathway, which negatively impacts functions in the gut-liver axis that include apoptosis activity and change in bile acid levels. Confirmatory studies are warranted to support the development of interventions to alleviate CIN and fatigue in patients with breast cancer receiving chemotherapy.Keywords: breast cancer; chemotherapy-induced nausea; fatigue; metabolites; sphingolipids Citation Format: Komal Preet Singh, Brenda J. Ernst, Jun Chen, Surendra Dasari, Felipe Batalini, Cindy Tofthagen, Kathryn J. Ruddy, Keenan Pituch, Linda Chlan. Perturbations in gut liver axis functions are associated with chemotherapy induced nausea and fatigue in patients with breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 6309.

ABSTRACT Background Chemotherapy‐induced peripheral neuropathy (CIPN), characterized by loss of sensation and impaired physical function, is a prevalent and debilitating side effect of chemotherapy, affecting 30%–50% of breast cancer survivors (BCS) with effects lasting years after treatment completion. Mindfulness‐based interventions are shown to be efficacious in reducing symptoms in neuropathies. This subgroup analysis examined the effect of Mindfulness‐Based Stress Reduction on Breast Cancer (MBSR(BC)) compared to Breast Cancer Education Support (BCES) or Usual Care (UC) on CIPN among BCS who received chemotherapy or chemotherapy and radiation. Methods BCS ( n = 114) were randomly assigned to the 6‐week MBSR(BC) ( n = 48), BCES ( n = 52), or UC ( n = 14) regimen. Demographic and clinical data were assessed at baseline, and CIPN was assessed using the Chemotherapy‐Induced Peripheral Neuropathy assessment tool (CIPNAT) at baseline, 6, 12, and 26 weeks. Between‐ and within‐group differences were evaluated and change over time was compared between groups. Results BCS (mean age = 52.7 years, range: 28–81 years) were primarily White and non‐Hispanic ( n = 78, 68%). The pattern of effect sizes was similar for CIPNAT symptoms and interference with improvements in CIPN for MBSR(BC) and BCES groups overtime. For both groups, the effects were larger compared to the UC. Differences tended to increase over time with significant effects observed between MBSR(BC) and UC, and between BCES and UC at weeks 12 and 26. Conclusions The findings indicate that MBSR(BC) and BCES may effectively reduce CIPN symptoms among BCS compared to UC. MBSR(BC) and BCES programs are effective non‐pharmacological interventions for CIPN that may translate into practice.

PURPOSE Hot flashes are a common side effect reported by men receiving androgen-deprivation therapy (ADT) for the treatment of prostate cancer. We sought to determine whether oxybutynin could improve hot flash symptoms in men with prostate cancer. PATIENTS AND METHODS Patients with prostate cancer receiving a stable regimen of ADT with at least 28 hot flashes per week were randomly assigned to receive either oxybutynin 2.5 mg twice daily, oxybutynin 5 mg twice daily, or matching placebo for 6 weeks. The primary end point was the change in patient-reported hot flash scores since baseline at 6 weeks. Additional outcomes included incidence of adverse events (AEs), changes since baseline in Hot Flash–Related Daily Interference Scale (HFRDIS) scores, and patient-reported symptoms. RESULTS Eighty-eight patients were enrolled, with the 81 participants eligible for final analysis reporting an average of 10.1 (standard deviation [SD], 5.55) hot flashes per day and an average daily hot flash score of 18.2 (SD, 13.5) included in final analysis. On average, patients on the placebo arm, 2.5 mg oxybutynin arm, and 5 mg oxybutynin arm had reductions in hot flashes/day of 2.15, 4.77 ( P = .02), and 6.89 ( P < .001), respectively. Daily hot flash scores for placebo, 2.5 mg oxybutynin, and 5 mg oxybutynin reduced by an average of 4.85, 9.94 ( P = .07), and 13.95 ( P = .002) points, respectively. No treatment-related grade 3+ AEs occurred. HFRDIS total scores improved by 14.2 and 20.7 points in the 2.5 mg ( P = .042) and 5 mg ( P < .01) oxybutynin arms, respectively, compared with a 3.1-point improvement with placebo. CONCLUSION Oxybutynin is superior to a placebo for the management of ADT-associated hot flashes in men with prostate cancer.

AbstractElectronic patient-reported outcome measures (ePROMs) can improve care for people with cancer, but effectiveness hinges on well-supported integration in clinical settings.We evaluated clinician use of specific clinical decision support (CDS) tools in the electronic health record (EHR) designed to facilitate timely, clinically appropriate responses to ePROM scores for six symptoms commonly experienced by cancer patients.The parent pragmatic trial, which took place at Mayo Clinic (Rochester, Minnesota, United States) and its affiliated community health care system between March 2019 and January 2023, evaluated the population-level effectiveness and implementation of an ePROM surveillance and EHR-facilitated collaborative care symptom management intervention. The present evaluation used a case study approach with four data sources: (1) clinician interactions with CDS tools abstracted from the EHR; (2) clinician notes identified with an institution-specific textual search tool; (3) qualitative interviews and group discussions with care teams; and (4) administrative records reviewed to identify training and outreach to care teams.EHR metrics showed very low adoption of CDS tools including alerts and symptom-specific order sets, despite educational outreach and information technology support provided to clinical care teams. Qualitative findings revealed that CDS use was not easy to integrate into busy clinical workflows and highlighted clinician perceptions that the collaborative care intervention provided additional patient support that reduced clinicians' need to utilize CDS tools. They also highlight the importance of contextual factors, including institutional priorities and EHR changes.This pragmatic clinical trial case study found limited adoption of EHR CDS tools that had been developed to increase clinicians' awareness of and responses to ePROM data. Findings suggest the need to align clinician and organizational implementation strategies, simplify CDS tools to fit practice expectations, and identify and address contextual factors that could undercut strategies like education and peer support. This may be especially important for teams who aim to iteratively evaluate and refine CDS and implementation strategies for multicomponent interventions or introduce new strategies that are responsive to barriers while maintaining scalability.

Spousal caregivers of persons living with serious illnesses experience significant emotional and social challenges related to their caregiving role. The purpose of this study was to gain a deeper understanding of how spousal caregivers perceive current and anticipated losses associated with caring for a partner living with advanced cancer. Spousal caregiver participants engaged in semistructured interviews about their caregiving experiences and subsequent changes that occurred in their lives. Caregivers experienced social changes, emotional energy investment, and relationship changes as sources of grief. Social changes involved a loss of freedom and increased isolation, while emotional energy investment manifested as suppressed emotions and fears about the future. Relationship changes encompassed both positive and negative shifts in communication and roles. Targeted interventions, such as support groups and counseling, are essential to mitigate the negative impacts of caregiving and improve the well-being of older adult spousal caregivers.

Implantable Cardioverter Defibrillators (ICDs) are essential for managing life-threatening arrhythmias but can impact patients’ quality of life (QoL), mood, and sexual health. Although QoL may improve shortly after implantation, factors such as age, psychological state, and ICD shocks can influence long-term outcomes. Anxiety, depression, and fears around physical and sexual activity are common among ICD patients, yet the depth of these effects remains underexplored. This cross-sectional, correlational study examined associations between QoL, mood, and sexual health in 30 adult ICD patients (ages 27–83) within 3 years postimplantation, recruited from a Southeastern U.S. academic medical center. Participants completed the SF-36, Profile of Mood States, and Multidimensional Sexuality Questionnaire. Spearman’s correlations indicated that lower QoL was significantly associated with higher mood disturbance (rho = −0.645, p < .001) and lower sexual health (rho = 0.535, p = .005), though no significant link was found between mood disturbance and sexual health (rho = −0.279, p = .168). Multiple linear regression confirmed that QoL was influenced by both mood and sexual health. Post-hoc power analysis using EpiData verified that the sample size ( n = 30) provided 90% power with a 5% error rate. These findings underscore the importance of addressing emotional and sexual well-being in ICD patient care. Targeted interventions could improve outcomes, but further research with larger samples is needed to deepen understanding of these relationships.

This study aimed to explore contextual elements of the cancer experience that are consistently distressing and/or psychologically traumatic, as well as explore perceptions of Accelerated Resolution Therapy® (ART®) and its influence on the cancer experience. Using a qualitative descriptive design, semi-structured interviews were completed by 12 participants following the completion of ART. Interview data were analyzed using content analysis to identify major themes and patterns. Four themes included: (a) Cancer as the straw that broke the camel’s back, (b) ART® is different from previous therapy, (c) Don’t need to always be looking in the rearview mirror, and (d) Importance of early psychological intervention. Participants perceived that ART® was different and potentially more effective than other types of therapy they had previously received. Results support the diagnosis of cancer and the cumulative effects of previous life events and cancer-related stressors as traumatic events.

ABSTRACTBackgroundAn estimated one‐third of cancer survivors suffer from post‐traumatic stress (PTS) symptoms. PTS is associated with high levels of cancer distress, anxiety, and depression. Few evidence‐based treatments are available for PTS. Accelerated Resolution Therapy (ART) is a form of trauma‐focused psychological therapy that has been found to be both safe and effective at alleviating post‐traumatic stress symptoms, psychological distress, anxiety and depressive symptoms in non‐cancer populations.MethodsThe purpose of this single arm, pilot study was to examine the preliminary efficacy of ART for alleviating post‐traumatic stress symptoms, cancer distress, depressive symptoms and anxiety among cancer survivors, as well as to evaluate baseline characteristics of persons most likely to respond to ART. Participants were provided with five ART sessions and outcome variables were assessed at enrollment, immediately following ART, and 30 days post ART. Paired t‐tests were used to examine differences between scores at each time point. Associations between the PCL‐5 score from baseline to post 30‐day visit were assessed and other variables were examined using univariate linear regression.ResultsIn a sample of 20 cancer survivors, statistically significant decreases in PTS symptoms (p < 0.0001), cancer distress (p < 0.0001), anxiety (p = 0.0002), and depression (p < 0.0001) from pre to post intervention were present. These improvements remained 30 days post‐intervention. Higher baseline PCL‐5 scores, as well as higher scores on two subscales of the cancer distress measure were associated with response to treatment.ConclusionsFindings suggest that ART is an effective therapeutic intervention for reducing PTS symptoms and cancer distress among cancer survivors.

The objective of this manuscript is to present the protocol of a study aiming to test the effects of Accelerated Resolution Therapy® (ART) on pre-loss grief and prolonged grief among older adult family caregivers. This study also aims to better understand predictors of response to ART®, and cognitive processes that occur among grieving individuals following ART®. Design: The study is a double-blinded, randomized clinical trial. Setting: This study takes place at both inpatient and outpatient palliative care and hospice programs at two Mayo Clinic sites. Participants: Participants include older adult ( ≥ 60 years) immediate family members who are primary caregivers of someone with an advanced illness and life expectancy of less than 12 months. Intervention: Participants are randomized to either the ART® intervention group or the attention control group. In the ART® intervention, caregivers engage in imaginal exposure, lateral eye movements, and imagery rescripting via 4 sessions lasting 1-1.5 hours each. The attention control group receives a standard social work intervention, including education, resources, and active listening, which is matched for time and attention. Both interventions will longitudinally follow caregivers from active caregiving into bereavement. Outcomes Measured: The primary outcomes of pre-loss grief and prolonged grief will be measured with the Pre-Loss Grief 12 item (PG-12-R) before the care recipient’s death, and with the Prolonged Grief-13 (PG-13-R) afterwards.