Citations

Background: Chemotherapy-induced peripheral neuropathy (CIPN) from oxaliplatin and taxane drugs is a bothersome toxicity. Palmitoylethanolamide (PEA) has been reported to improve myelinated nerve fiber function in patients experiencing painful CIPN. We conducted a double-blind, placebo-controlled, randomized trial of PEA in patients with established CIPN. Methods: Eligible patients were adults who had pain, numbness, tingling, or other symptoms of CIPN for at least three months following completion of paclitaxel, oxaliplatin, or cisplatin-based chemotherapy. Study patients were randomized to one of the two treatment groups (PEA versus placebo, both administered either once or twice daily). The CIPN20 questionnaire was assessed weekly. Results: A total of 17 males and 71 females participated in the study; most had neuropathy from paclitaxel. Most (85%) finished 8 weeks of treatment. There was no suggestion that either of the PEA arms did any better than the combined placebo arms. There was no signal of significant toxicity differences between the three study arms. Quality of life outcome measures were similar between the study arms, as were cognitive function evaluations. Discussion: PEA failed to improve established CIPN. Future trials might explore whether PEA may be effective in preventing CIPN or cognitive changes based on data that suggest it may be helpful in this situation. Conclusions: PEA failed to improve established chemotherapy-induced neuropathy.

Stress is ubiquitous in our modern society and contributes to many disease states. This narrative review describes the effect of stress/distress on cancer development and progression. Seminal randomized controlled trials, systematic reviews/meta-analyses, and distress management guidelines from the National Comprehensive Cancer Network (NCCN), the American Society of Clinical Oncology (ASCO), and the Society for Integrative LinearOncology (SIO) are highlighted. We describe the physiological effects of distress, distress assessment, and management. Psychological treatments are summarized. Evidence-based lifestyle modifications and integrative therapies are reviewed in detail, including mindfulness-based techniques, yoga, guided imagery, breathing techniques, hypnosis, exercise, music therapy, qigong/Tai Chi, eye movement desensitization and reprocessing, and improving sleep and heart rate variability. Recognition and treatment of distress can improve quality of life. More research is needed to determine the effects of managing distress on cancer outcomes, as well as the best type and duration of intervention, noting that the benefits of interventions may be specific for patients with different cancer types.

Abstract BACKGROUND Fatigue is among the most common symptoms managed by patients with cancer. Hypothalamic pituitary axis dysfunction has an established role in a subset of patients with fatigue. Our primary aim was to longitudinally assess the impact of hypothalamic radiation exposure to patient self-reported fatigue. METHODS We included a sample of patients who received radiation therapy treated at a single institution from 2014-2024. The PROMIS-10 questionnaire (“How would you rate your fatigue on average,” scale 1-5) was used in standard clinical practice, with measures from 6 time points over 2 years. We performed descriptive statistics. Linear mixed models were used to assess the impact of hypothalamic radiation dose on fatigue scores. Mixed models were controlled for gender, age, time, tumor category (CNS vs. non-CNS), and modality (photon vs. proton). Models were fit with random intercepts for each Patient ID. RESULTS 1092 patients (43% female) with a median age of 54 years (range: 18-92) were included. Most patients were treated for CNS cancer (76%), with about 50% each photon and proton. Median hypothalamus radiation dose was 1306 cGy (range: 0.01-6138). Mean baseline fatigue (2.4) increased after treatment (2.7) remaining elevated at 3- and 6-months post-treatment (2.6, 2.5), returning near baseline at 1- and 2-years post-treatment (2.4, 2.3). Higher radiation dose (Estimate (SE): 0.014 (0.006), p=0.0266) and CNS cancer treatment (0.11 (0.051), p=0.0319) were significant predictors of higher fatigue in the mixed model. Male patients (-0.16 (0.042), p=0.0001) and time (-0.003 (0.0016), p=0.0398) were associated with lower fatigue. Age and treatment modality were not significant predictors of fatigue. CONCLUSIONS We found that higher hypothalamic radiation dose was related to more self-reported fatigue, which peaked by 6 months. This effect was seen more prominently in female patients and those treated for CNS disease. Treatment modality and age did not influence fatigue scores.

Abstract Disclosure: M.D. Hurtado: None. E. Tama: None. D. Hodge: None. A. Weston: None. S. Fahad: None. K. Ruddy: None. J. Olson: None. F. Coach: None. R. Carter: None. S. D'Andre: None. A. Acosta: Consulting Fee; Self; Amgen Inc. Grant Recipient; Self; Vivus USA, Novo Nordisk. C. Shufelt: None. Background: Breast cancer (BC) is the most common cancer in women. Weight gain after treatment for early-stage BC is associated with a higher risk of recurrence. Excess adiposity is also a major risk factor for cardiovascular disease, the leading cause of non-BC related death in BC survivors. This study aimed to describe weight trends in a large cohort of BC survivors and to identify predictors of weight gain after BC diagnosis. Methods: This was a retrospective study of BC survivors from the prospectively consented Mayo Clinic Breast Cancer Registry, which has enrolled >10,000 patients seen at least once at Mayo Clinic Rochester for a BC diagnosed within the prior year. We extracted data on weights at baseline, and years 1, 4, and 6 after BC diagnosis to generate longitudinal weight trajectory curves on the change from baseline. Weights were either reported by patients in the registry questionnaires or extracted from the electronic health records. We identified BC survivors with weight gain >10% from baseline weight at years 1, 4, and 6. We then conducted univariable logistic regression analyses to identify predictors of >10% weight gain. Variables considered included: demographics, anthropometrics, BC clinical and pathologic characteristics, BRCA 1 and 2 genetic mutation status, and treatment (surgery, neoadjuvant or adjuvant chemotherapy, and/or radiotherapy). Results: We included 4744 BC survivors, mostly white (95%) and non-Hispanic (91%), with a mean age and weight at BC diagnosis of 58 ± 13 years and 76 ± 18 kg. Most patients had clinical stage I (43%) and ER+ and PR+ BC (83% and 76%, respectively). Most patients underwent breast preserving surgery (62%), half received radiation (54%), one third (36%) received systemic chemotherapy, and two thirds (61%) received endocrine therapy. At one year after BC diagnosis the average weight change was negligible compared to baseline (mean difference -0.2 ± 8 kg), but there were small but significant average increases by years 4 and 6 (0.5 ± 9 kg, p=0.002; and 0.8 ± 10 kg, p<0.001; respectively). At years 1, 4, and 6, the percentage of BC survivors gaining >10% of their baseline weight was 10%, 15%, and 18%, respectively. Baseline characteristics associated with >10% weight gain at 6 years included lower baseline weight (p<0.001), younger age at BC diagnosis (p<0.001), more advanced clinical and pathologic BC stage (p=0.008), ER+ and PR+ tumor biology (p=0.02 for both), BRCA2 mutation (p<0.001), mastectomy (compared to breast preserving surgeries, p=0.008), the use of systemic chemotherapy treatment (p<0.001), and the use of endocrine therapy (p=0.03). Conclusion: While most BC survivors do not experience weight gain after survivorship, 1 out 5 may experience excessive weight gain of more than 10%. Baseline anthropometric and BC-related variables are associated with excessive weight gain and could be used as predictors of weight gain in this population. Presentation: 6/3/2024

Background: Patients have been known to use cannabinoids for treating established chemotherapy-induced peripheral neuropathy (CIPN) based on anecdotal information and retrospective reports suggesting that such might be beneficial. In response, a double-blinded, placebo-controlled, randomized, pilot clinical trial was developed to evaluate whether resultant data would support a phase III trial for testing whether a cannabidiol (CBD) cream might improve CIPN. Methods: Forty patients with established CIPN were randomized, in a double-blinded manner, to topical CBD or a placebo cream. The study product was applied for 2 weeks, followed by a crossover for 2 weeks. Neuropathy was evaluated using the European Organization of Research and Treatment of Cancer (EORTC)–CIPN20, the Chemotherapy-Induced Peripheral Neuropathy Assessment Tool, and the Global Impression of Change instruments. Side effects were recorded by symptom diaries. Results: The EORTC-CIPN20 scores were similar in the patients receiving CBD versus the placebo. Likewise, the toxicity scores were similar in patients who received the CBD versus the placebo. Conclusions: This pilot trial did not support that the studied CBD isolate cream improved painful established CIPN. It was well tolerated overall. Clinical Trial Registration Number: NCT05388058

Background: There are limited evidence-based data to guide treatment recommendations for breast cancer (BC) patients ≥80 years (P80+). Identifying and addressing unmet needs are critical. Aims: Advocate-BREAST80+ compared the needs of P80+ vs. patients < 80 years (P80−). Methods: In 12/2021, a REDCap survey was electronically circulated to 6918 persons enrolled in the Mayo Clinic Breast Disease Registry. The survey asked about concerns and satisfaction with multiple aspects of BC care. Results: Overall, 2437 participants responded (35% response rate); 202 (8.3%) were P80+. P80+ were less likely to undergo local regional and systemic therapies vs. P80− (p < 0.01). Notably, P80+ were significantly less satisfied with information about the short and long-term side effects of BC therapies and managing toxicities. P80+ were also less likely to have participated in a clinical trial (p < 0.001) or to want to do so in the future (p = 0.0001). Conclusions: Although P80+ experienced less anxiety and symptom-related distress compared with P80−, they were significantly less satisfied with information regarding the side effects of BC therapies and their management. P80+ were significantly less likely to have participated in a clinical trial or be open to considering this option. Future studies should address educational needs pertaining to side effects and barriers to research participation in P80+.

TPS1647 Background: The majority of patients with primary and secondary central nervous system (CNS) malignancy develop cognitive impairment, fatigue, and mood-related symptoms. Radiotherapy has been shown to contribute to symptom burden often limiting quality of life and functional status. The development of interventions mitigating neurocognitive toxicity requires an accurate assessment of function and symptom burden. Formal neuropsychological evaluation is resource and time intensive, and often challenging to incorporate in routine clinical practice. There is a critical need to accurately assess cognition without causing undue burden to cancer patients while evaluating the efficacy of interventions that can be scaled and implemented at a population level. Methods: To adequately assess the neurocognitive function and related symptoms in patients with CNS malignancy we have designed an open-label decentralized clinical trial that will randomize patients who received intracranial radiation for primary or metastatic brain tumors in a 1:1 allocation to a therapy targeting radiation-related toxicity (metformin shipped to patient home) plus health promotion with a wearable device vs. health promotion with a wearable device alone. Participants will be stratified based on tumor type (glioblastoma vs. other glioma vs. brain metastases vs. meningioma) and age (<70 vs. 70+ years). Participants will be provided a wearable device for monitoring health status. Participants will undergo serial remote cognitive assessments with the Mayo Test Development Through Rapid Iteration, Validation and Expansion platform (Mayo Test Drive). Remote reported symptom collection via patient surveys and remote neurologic examination by telehealth will also be incorporated. Cognitive assessments and symptom surveys will be designed for completion on a smartphone, tablet, or computer device. Health data will be collected from the wearable device, including the number of steps per day and sleep quality/duration. Participants receiving metformin will utilize device apps to report medication adherence and adverse events. Study-related laboratory assessments will be completed remotely and transmitted electronically. This decentralized clinical trial will provide real-world cognitive and quality-of-life data for patients with primary and metastatic brain tumors while providing preliminary data on the effectiveness of device-based health promotion with or without metformin for treating radiation-related cognitive decline. Results gained from this study will guide future trials in neuro-oncology and other fields. This study is expected to open in March 2024.

Abstract Glioblastoma (GBM) is the most common and aggressive form of brain tumor in adults. Despite maximal surgical resection, irradiation, and chemotherapy, median overall survival (OS) for recurrent GBM (rGBM) remains at only 30 weeks. GBM tumors have an immune-suppressive microenvironment with low numbers of tumor-infiltrating lymphocytes (TILs). Interleukin 7 (IL-7) plays a key role in T cell homeostasis and survival, with IL-7 inducing T cell expansion in lymphopenic conditions. Efineptakin alfa (NT-I7), a long-acting IL-7, has been shown to increase effector CD8 T cells and reduce suppressor T-regulatory cells in murine GBM models, with subsequently improved OS. We recently completed a Phase I study in newly diagnosed GBM patients which showed that NT-I7 is safe, well-tolerated, and increased absolute lymphocyte counts (ALCs), and determined maximum tolerated dose for Phase II. We hypothesized that NT-I7 may not only mitigate GBM treatment-associated immune suppression, but also potentiate the effect of immune checkpoint blockade, leading to an increase in TILs and improved survival. The purpose of this study is to evaluate the safety and efficacy of combining NT-I7 and pembrolizumab in rGBM patients. This is an open-label, single arm one-stage Phase II study of NT-I7 and pembrolizumab as neoadjuvant and adjuvant therapy with surgery for adult patients with rGBM. We plan to enroll 30 evaluable patients, including a 6-patient safety run-in. The primary endpoint is the 9-month OS rate. Secondary endpoints include progression-free survival, objective response rate, changes in ALC, and adverse events profile. The correlative endpoints include studies to assess the anti-glioma immune response, changes in T cell subsets and functionality, peripheral cytokine quantification, and immunohistochemical analysis of GBM tissue. Longitudinal cerebrospinal fluid proteomics is optional. This study opened in Jan 2023. Six (6) of the planned thirty (30) patients had been enrolled by time of submission.

Abstract Disclosure: S. Fansa: None. W. Ghusn: None. E. Tama: None. B. Nicolalde: None. D. Anazco: None. S. D'Andre: None. S. Faubion: None. C. Shufelt: None. A. Acosta: None. M.D. Hurtado: None. Background: Aromatase inhibitors (AIs) block estrogen synthesis and are used as adjuvant treatment for breast cancer. AIs are associated with weight gain that can lead to increased cardiometabolic risk, thereby affecting health and survivorship quality in these patients. The role of anti-obesity medications (AOMs) in patients using AIs has not been studied. We sought to investigate weight loss outcomes to AOMs in patients taking AIs for breast cancer treatment. Methods: This is a matched case-control retrospective cohort study of breast cancer survivors on AI using FDA-approved AOMs (AI/AOM group). We compared their weight loss outcomes with a group of female patients with obesity, without a history of breast cancer or AI use, on AOMs (AOM group). We matched patients by age and body mass index (BMI). Exclusion criteria: AOM initiation prior to AI therapy, ≤3 months of AOM use, history of bariatric surgery, active malignancy, or pregnancy. Primary endpoint: total body weight loss % (TBWL%) at 12 months. Secondary endpoints: TBWL% at 3 and 6 months and % of patients achieving categorical TBWL ≥5%, ≥10% and ≥15% at 12 months. We used Pearson χ2 and unpaired t-test to compare baseline characteristics and outcomes between groups, and univariate analyses to estimate the contribution of variables to TBWL% in the AI/AOM group. We present results as mean ± standard deviation. Results: We included 99 patients: 63 in the AI/AOM group (63.5±10 years, BMI 34.4±7.0 kg/m2) and 36 in the AOM group (60.4±8.7 years, BMI 36.3±6.9 kg/m2). Liraglutide, semaglutide and phentermine were the only AOMs used. There was no difference in the frequency of use of these three AOMs among both groups (p= 0.1). AI/AOM group had a lower TBWL% compared to the AOM group during follow-up: 3.7± 4.3% vs. 5.6 ± 4.1% (p= 0.03) at 3 months, 3.9± 4.3% vs. 9.5± 4.7% (p&lt; 0.0001) at 6 months, and 5.2± 5.3% vs. 10.5± 6.8% (p&lt; 0.0001) at 12 months. Although the AI/AOM group was more likely to use lower doses of AOMs (p= 0.0004), TBWL% differences persisted among groups at 12 months after adjusting for AOM dosing (p&lt; 0.0001). There was no difference in nutritional and behavioral modification sessions among groups (p=0.06 and p=0.9, respectively). At 12 months, the percentage of patients achieving ≥5%, ≥10%, and ≥15% TBWL was greater in the AOM group compared to the AI/AOM group: ≥5% TBWL, 85.7% vs. 50.0% (p&lt; 0.0001); ≥10%, 57.1 vs. 20.0% (p&lt; 0.0001); and ≥15%, 28.6 vs. 5.0% (p&lt; 0.0001); respectively. We found no predictors of TBWL% at 12 months in the AI/AOM group. Conclusion: Weight loss outcomes in breast cancer survivors on AIs taking AOMs are poorer compared to patients without breast cancer history and not taking AIs. Studies are needed to assess the mechanisms behind the different weight loss response to AOMs in women taking AIs, which we hypothesize may relate to AIs’ anti-estrogenic effect on lean and fat mass. Presentation: Friday, June 16, 2023

Abstract Breast cancer survivors may experience significant after effects from diagnoses of breast cancer and cancer directed therapies. This review synthesizes the evidence about optimal management of the sequelae of a diagnosis of breast cancer. It describes the side effects of chemotherapy and endocrine therapy and evidence based strategies for management of such effects, with particular attention to effects of therapies with curative intent. It includes strategies to promote health and wellness among breast cancer survivors, along with data to support the use of integrative oncology strategies. In addition, this review examines models of survivorship care and ways in which digital tools may facilitate communication between clinicians and patients. The strategies outlined in this review are paramount to supporting breast cancer survivors’ quality of life.