Citations

1089 Background: T-DXd has become an important treatment option in mBC and other malignancies. Interstitial lung disease/pneumonitis (ILD) occurred in 10-14% of pts in the DESTINY-Breast trials (0-2% G5 ILD), and with potential lower incidence/severity in earlier line settings (Krop et al, ASCO 2023). We previously reported the Mayo Clinic Rochester, MN experience with T-DXd related ILD in mBC (Hoppenworth et al, ASCO 2024). Here, we expand the data to include patients treated at all locations of the Mayo Clinic Enterprise. Methods: We retrospectively identified pts with mBC who received ≥1 dose of T-DXd across the Mayo Clinic enterprise (Rochester, MN; Mayo Clinic Health System locations in MN/WI; Scottsdale, AZ; and Jacksonville, FL) between July 2022-December 2023. Demographic, mBC characteristics, and pulmonary clinical variables were abstracted from the clinical records. Data were summarized using descriptive statistics. Diagnosis of ILD was determined by treating clinicians, and severity was approximated to CTCAE V5 based on clinical documentation. Results: 252 pts with mBC received T-DXd during the study period. The majority were Caucasian (86%) and female (99%) with a median age of 63. 91 pts (36%) were current/formers smokers and 97 (39%) had prior pulmonary comorbidities. The majority had HER2 low (155, 62%) and HR positive (164, 65%) mBC. 35 (14%) developed any grade ILD [G1: 6 (17%), G2: 13 (37%), G3: 3 (8.6%), G4: 3 (8.6%), G5: 10 (29%)], with 15 (43%) presenting with ≥G3. 29 (83%) presented with at least 1 symptom (cough or SOB). Among those with previous pulmonary toxicity, 4 (33%) had previous pneumonitis in the ILD cohort. The median prior lines of all therapies (including endocrine therapy) were 5, with a median of 3 prior lines of chemotherapy in both the ILD (range 1-13) and non-ILD cohorts (range 1-13). Median onset to any grade ILD was 7 cycles. 20 pts (57%) received steroids for ILD. 14 (40%) had a bronchoscopy, all had a CT chest, 16 (46%) were hospitalized, 7 (20%) were intubated and 1 (3%) had a lung biopsy. Pts with G5 ILD had a median of 3 lines of chemo and a median of 8 cycles prior to onset of ILD, compared to 3 lines of chemo and a median of 7 cycles for those with G1-4 ILD. G5 pts were all Caucasian females, 5 were former smokers, 5 were non-smokers, 1 had a history of pneumonitis. T-DXd was rechallenged in 4 pts (G1-2 ILD) without ILD recurrence. Conclusions: In this retrospective case series,14% of pts treated with T-DXd experienced any grade ILD (4% G5) which is in alignment with the rate observed in the pivotal DESTINY-Breast trials, though with higher rates of G5 toxicity. Among those with ILD, increased lines of therapy were not associated with increased risk. Further research is needed to correlate risk.

Abstract Introduction A previously published case report suggested that alcohol might cause false-negative results in home sleep apnea testing (HSAT) utilizing Peripheral Arterial Tonometry (PAT). Alcohol is consumed by nearly a third of people globally. Based on this, along with rapid growth in PAT HSAT utilization, we aimed to prospectively study the interaction between alcohol consumption and PAT HSAT technology. We hypothesized that alcohol use would significantly attenuate sleep disordered breathing metrics in contrast to existing literature suggesting alcohol may exacerbate sleep apnea. Methods We planned to recruit subjects (N=100) from Mayo Clinic Arizona sleep clinic who were being evaluated for sleep-disordered breathing and elected to undergo home sleep apnea testing (WatchPAT ONE). Participants were required to report social alcohol use (no more than 1-3 drinks per day). The first and second home sleep apnea test were conducted on separate nights (night 1: without alcohol; night 2: with alcohol). Patients also completed a questionnaire, detailing their normal alcohol intake as well as intake during the respective sleep tests. Statistical analysis included paired sample t-test as well as a descriptive analysis. Results A total of 75 subjects were recruited (mean age [± SD] 56.8 ± 11.9; 90.7% male; mean BMI 29.8 ± 5.8) and 56 patients completed both sleep tests. The mean apnea hypopnea index (AHI) was not statistically different (p=0.784) between night 1 and night 2 (without alcohol: 19.6/hour ± 21.0; with alcohol: 19.3 ± 21.5, respectively). Similarly, no statistically significant difference was found in the AHI during REM and NREM sleep. Conclusion Preliminary data does not suggest a statistically significant difference in AHI without or with alcohol. While no significant change in AHI was observed, this study highlights the need for further investigation into the impact alcohol may have on PAT technology. Further analyses and data enrichment are underway. Support (if any) Mayo Foundation

Background/Objectives: The peak oxygen consumption (VO2) during cardiopulmonary exercise testing (CPET) is a strong predictor of all-cause mortality. The cardiac output, a key determinant of VO2, can be assessed using resting echocardiographic parameters. The heart rate recovery and ventilatory efficiency (VE/VCO2 slope) from CPET offer additional insights into cardiovascular fitness. Methods: This study aimed to identify resting echocardiographic parameters that predict the percentage of predicted peak VO2, heart rate recovery, and VE/VCO2 slope in a general cardiology population. This retrospective analysis included 1909 patients who underwent echocardiography within 3 months of CPET from 2017 to 2022. Patients with potentially confounding co-morbid conditions were removed. Spearman correlations were used to compare 19 echocardiographic parameters to peak VO2, heart rate recovery, and the VE/VCO2 slope, followed by multiple linear regression of peak VO2. Results: Eleven echocardiographic parameters correlated with peak VO2, with the strongest correlations seen with the left ventricular stroke volume index (R = 0.284, p < 0.001), mitral valve medial annular a’ wave velocity (R = 0.142, p < 0.0001), and mitral E-to-e’ ratio (R = −0.117, p < 0.0001). The left ventricular diastolic parameters and mitral E/A ratio correlated strongly with the heart rate recovery and VE/VCO2 slope. The multiple linear regression analysis identified the left ventricular mass index, stroke volume index, mitral valve E wave velocity, tricuspid valve regurgitation peak systolic velocity, tricuspid lateral annular systolic velocity S’, and left atrial volume index as independent predictors of peak VO2 (R2 = 0.191). Conclusions: The left ventricular stroke volume, diastolic function, and RV systolic function markers are significant predictors of cardiopulmonary fitness, aiding clinical decision-making in patients without CPET data.

The effectiveness of in-person psychological interventions for chronic pain populations has been widely studied. The current retrospective pilot study evaluates the effectiveness of a 10-week integrative telehealth pain group intervention consisting of cognitive, behavioral, mindfulness, and lifestyle strategies on anxiety, depression, pain catastrophizing, pain interference, and pain intensity. Participants at a large multidisciplinary hospital are referred internally from various medical departments within the hospital. The present study consists of data from 9 group cohorts from October 2020 to June 2022. The study included 86 patients, with 52 completing all 10 weeks of the intervention with post-questionnaire data available. Measures assessing anxiety, depression, pain catastrophizing, pain interference, and pain intensity at baseline and at the completion of the intervention. A series of paired samples t-tests were used to assess change in each outcome measure from baseline to after completion of the program. All the outcome variables including anxiety, depression, pain interference, pain intensity, and pain catastrophizing showed statistically significant reductions after the intervention compared to baseline assessments. There were no significant differences in any of the demographic variables (age, gender, ethnicity, education level) or chronic pain condition between participants who did and did not complete the program. Preliminary data suggest that this 10-week integrative telehealth pain group intervention significantly lowered anxiety, depression, pain catastrophizing, pain interference, and pain intensity from pre- to post-intervention. Larger, randomized controlled studies are needed to validate these results.

732 Background: Ampullary carcinoma (AC) is a rare malignancy arising from the ampulla of Vater which has a more favorable prognosis compared to other pancreatic malignancies. Current guidelines favor surgical resection followed by adjuvant therapy for average risk patients (pts), however the type of regimen as well as other perioperative treatment modalities are still being explored. The objective of this retrospective study aims to provide insight into the management of locoregional disease. Methods: Pathology records from Mayo Clinic (AZ, FL, MN) denoting AC between 2010 to 2024 were searched using Mayo Data Explorer and selected for retrospective review. Pt demographics, treatment courses, and next generation sequencing (NGS) data were collected. Statistical analysis was conducted using SAS version 9.04. Results: A total of 137 pts (62% male, n = 85) were identified with median age 66 years old. Histologic subtypes were 54% pancreatobiliary (44/81), 40% intestinal (32/81), 6% mixed (5/81), with 56 pts unknown. Stages at diagnosis were 81% resectable (111/137), 11% locally advanced (15/137), and 8% metastatic (11/137). Nearly all (93%, n = 103/111) pts with localized disease had resection with a 97% R0 resection rate (100/103). Majority (68%, n = 75/111) of resectable pts had perioperative chemotherapy with 5-FU or gemcitabine-based regimens (24%, n = 18/75 neoadjuvant vs. 76%, n = 57/75 adjuvant). Perioperative chemoradiation was given in 17% (19/111) of pts. At median follow up of 30.5 months, recurrence rates were 40% (41/103), primarily to the liver (18/41). Median recurrence free survival (RFS) was 29.3 months (95% CI 24.7 – NE). Median overall survival (OS) has not been reached. The 5-year RFS and OS rates were 0.37 (95% CI 0.25 - 0.55) and 0.69 (95% CI 0.58 - 0.82), respectively. Univariate analysis showed no difference in OS with the addition of neoadjuvant or adjuvant chemotherapy or chemoradiation. Somatic NGS testing showed pathogenic mutations in 90% of pts (63/70): 57% KRAS (36/63; 44% G12D, 19% G12V, 8% G12C, 8% G12D, 19% others); 13% homologous recombination (HR) (8/63); 6% ERRB2 /Her2 amplification (4/63), and 5% mismatch repair (MMR) (3/63). Conclusions: AC has a favorable prognosis in resectable pts. However, high recurrence rates indicate the need for better systemic therapies and improved selection of pts who would benefit from these treatments. Future research should focus on refining perioperative strategies to enhance outcomes and reduce recurrence.

PURPOSE Pancreatic acinar cell carcinoma (PACC) is a rare and aggressive form of pancreatic cancer that originates in the acinar cells of the exocrine pancreas. In this study, we aimed to investigate the clinical and molecular characteristics of patients with PACC at our institution. METHODS This was a retrospective study of patients with PACC seen at Mayo Clinic between 2002 and 2023. Baseline patient characteristics, tumor pathology, treatment strategies used, and survival outcomes were analyzed. Kaplan-Meier curves were estimated using newsurv macros in SAS. RESULTS The study included a total of 65 patients with PACC. The median age at diagnosis was 66 years. Almost half of the patients (48%) presented with resectable/borderline-resectable disease (n = 28). Five-year overall survival (OS) for resectable/borderline-resectable, locally advanced/unresectable, and metastatic disease were 72.0%, 21.6%, and 20.9%, respectively. Somatic and germline next-generation sequencing identified numerous potentially actionable targets including homologous recombination (43% somatic, 33% germline), RAF alterations (29% somatic), and mismatch repair (14% somatic). CONCLUSION Our findings underscore the heterogeneity and aggressive nature of PACC. Despite the improved prognosis for patients with resectable/borderline-resectable disease, OS remains poor, particularly for those with locally advanced or metastatic disease. The identification of actionable molecular targets in a significant proportion of patients highlights the potential for personalized therapeutic approaches. Future research should focus on tailored treatment strategies to exploit these molecular vulnerabilities, which may offer new options for improving outcomes in this rare malignancy.

Abstract Dementia caregivers are at heightened risk for developing mental and physical health problems. Interventions designed to protect caregiver health often create additional demands on time and energy (e.g., exercise programs). Technology-based interventions (e.g., remote monitoring) can be effective, scalable, and do not add greatly to caregiver burden. Through a collaboration with a local technology company, Care Daily, we conducted two randomized controlled trials to evaluate People Power Caregiver (PPCg), a system of sensors in the home connected to cloud-based AI that alerts caregivers about worrisome deviations from normal patterns (e.g., care-recipient’s falls, wandering). Across two studies (study 1: 9-month duration with professional installation of PPCg; study 2: 6-month duration with caregiver self-installing the PPCg using remote tech support), 284 caregivers were recruited; 261 completed initial study deployment (e.g., system installation); and 235 completed the entire study protocol. Use of PPCg was associated with (a) reduced caregiver anxiety in study 1; (b) greater protection from declines in sleep efficiency in studies 1 and 2. These findings underscore the promise of technology-based intervention to mitigate health problems in dementia caregivers. However, challenges and complexities in recruitment (e.g., remote consenting both caregivers and care recipients), retention (e.g., due to changes in home environment or caregiving status), system installation (e.g., working with caregivers with less experience using technology), data quality assurance (e.g., invalid sensor data) as well as our efforts to overcome these challenges have been instructive. Lessons learned from these studies can provide useful guidance for future large-scale, technology-based interventions for dementia caregivers.

Introduction: Phase I trials are designed to evaluate the safety and tolerability of new treatments. Review of adverse events (AEs) experienced by trial participants is a critical aspect of these early phase trials. Current practice for safety and tolerability data collection is for clinicians to evaluate AEs using the Common Terminology Criteria for Adverse Events (CTCAE). Past work has demonstrated that clinicians may miss or underreport symptomatic AEs. The Patient-Reported Outcomes version of the CTCAE (PRO-CTCAE) is an item library of questions for patients to self-report symptomatic AEs in clinical trials that is complementary to the CTCAE. PRO-CTCAE offers a patient-centric method for capturing symptomatic AEs, which may be missed or underreported by clinicians. The PRO-CTCAE library includes questions using patient friendly terms to assess frequency, severity, and interference of symptomatic AEs on 0-4 verbal descriptor scales (e.g., severity is rated by patients as none, mild, moderate, severe, or very severe). The goal of the current work was to demonstrate how to incorporate AE information from PRO-CTCAE and CTCAE into a Phase I dose review report. Methods: We used data from a Phase I clinical trial of patients with relapsed or refractory acute myeloid leukemia. Therapy was administered on 28-day cycles. Patients completed questionnaires on an electronic device on days 1, 8, 15, and 22 of the first cycle of treatment. Through iterative feedback from clinicians and statisticians, we developed an example dose review report. The report summarized data for one dose level in which 4 patients were treated. These 4 patients comprised the first patient cohort enrolled in the available Phase I clinical trial. The report was intended to be representative of the type of report that would be reviewed to make a decision about the next dose level for a new cohort of patients. Results: The final dose review report included narratives for each patient generated by the statistical team based on patient-reported and physician-graded AEs in cycle 1, tabular summaries integrating CTCAE and PRO-CTCAE, and novel graphical presentation of PRO-CTCAE and CTCAE, including swimmer plots and butterfly plots for symptoms listed as dose limiting toxicity criteria. In this cohort, 3/4 (75%) patients had at least one grade 3+ AE, as assessed by CTCAE, and 4/4 (100%) patients had at least one score 3 symptomatic AE, as assessed by PRO-CTCAE. All 4/4 (100%) patients had at least one reported symptom on the PRO-CTCAE that was not captured by CTCAE or was reported at a lower grade by CTCAE. Multiple versions of the example dose review report were presented to the study team and iterative feedback was solicited from clinicians and statisticians. Feedback highlighted the usefulness of narratives and patient-level graphical displays. Narratives within the dose review report were refined to focus on treatment emergent AEs, minimizing text and succinctly presenting baseline symptoms where relevant. Symptom-level graphics of combined PRO-CTCAE scores and CTCAE grades were preferred over graphics consolidating data for multiple symptoms. Final graphics and report will be presented. Conclusions: We demonstrated that PRO-CTCAE, which captures patient-reported symptoms, complements traditional AE reporting and that reporting PRO-CTCAE and CTCAE jointly in a Phase I dose level report can provide a more complete picture of safety and tolerability in the Phase I setting.

Introduction: Metabolic equivalents (METs), a measure of energy use during a specified exercise intensity, and volume of oxygen consumed (VO2) are key measurements in cardiopulmonary exercise tests (CPETs). METs are traditionally converted to VO2 via multiplying METs by 3.5 ml/kg/min when VO2 data is not available, due to the fact that the latter requires more-expensive, accurate measurements of volume of inspired and expired oxygen and CO2. However, it is unclear which populations have significant variation between peak METs and peak VO2. Research Question: In a general cardiology population, do older women have a weaker relationship between peak METs and peak VO2? Methods: We present a retrospective study analyzing the relationship of peak METs and peak VO2 achieved on a CPET. Patients presenting to the cardiology clinic who received a CPET from 2017-2022 were included. Patients with severe valvular dysfunction, congenital heart disease, prior coronary artery bypass grafting, or ejection fraction < 50% were removed to limit confounding. A Spearman correlation coefficient was calculated for the whole sample comparing peak METs and peak VO2. Subsequently, a subgroup of women age 65 or greater were compared to the general sample by a fisher’s z transformation. Results: 1907 patients were included. There was a strong positive correlation between peak VO2 and peak METs in the whole sample (r(1860) = 0.914), p<0,001), shown in Figure 1. Women age 65 or greater had a weaker correlation (r(190)=0.808, p<0.0001) compared to the those who were not (r(1668) = 0.915, p<0.0001; z = -5.656, p<0.001), shown in Figure 2. Conclusions: Peak METs and peak VO2 have an extremely strong positive correlation in a general cardiology population. However, these relationships weaken for women age 65 or greater. METs are an accurate, cost-effective proxy measurement of VO2 in a general population, however may lack reliability for certain demographics.