Yee, Claire

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.

Background/Aims: The Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE ® ) was developed to capture symptomatic adverse events from the patient perspective. We aim to describe statistical properties of PRO-CTCAE items and summary scores and to provide evidence for recommendations regarding PRO-CTCAE administration and reporting. Methods: Using data from the PRO-CTCAE validation study (NCT02158637), prevalence, means, and standard deviations of PRO-CTCAE items, composite scores, and mean and maximum scores across attributes (frequency, severity, and/or interference) of symptomatic adverse events were calculated. For each adverse event, correlations and agreement between attributes, correlations between attributes and composite scores, and correlations between composite, mean, and maximum scores were estimated. Results: PRO-CTCAE items were completed by 899 patients with various cancer types. Most patients reported experiencing one or more adverse events, with the most prevalent being fatigue (87.7%), sad/unhappy feelings (66.0%), anxiety (63.6%), pain (63.2%), insomnia (61.8%), and dry mouth (60.0%). Attributes were moderately to strongly correlated within an adverse event ( r = 0.53 to 0.77, all p < 0.001) but not fully concordant (κ weighted = 0.26 to 0.60, all p < 0.001), with interference demonstrating lowest mean scores and prevalence among attributes of the same adverse event. Attributes were moderately to strongly correlated with composite scores ( r = 0.67 to 0.97, all p < 0.001). Composite scores were moderately to strongly correlated with mean and maximum scores for the same adverse event ( r = 0.69 to 0.94, all p < 0.001). Correlations between composite scores of different adverse events varied widely ( r = 0.04 to 0.68) but were moderate to strong for conceptually related adverse events. Conclusions: Results provide evidence for PRO-CTCAE administration and reporting recommendations that the full complement of attributes be administered for each adverse event, and that attributes as well as summary scores be reported.

11118 Background: Lung cancer survivors experience more physical and mental challenges, heavier symptom burden, and poorer quality of life than survivors of other cancers. Many symptoms persist or worsen for survivors beyond 5 years of cancer diagnosis, referred as long-term lung cancer survivors (LTLCS). Social determinants of health (SDoH) factors negatively impact patient reported outcomes (PROs) among cancer survivors, but their role in outcomes is under reported in lung cancer survivors and unknown in LTLCS. We investigated the impact of SDoH on PROs in a 20-year prospective lung cancer cohort. Methods: Our cohort includes 19,251 lung cancer patients (cases) diagnosed from 1997 through 2016 and followed up to 27 years, of whom 4799 (25%) became LTLCS. SDoH information was obtained by a lung cancer study PRO questionnaire or an institution SDoH questionnaire. Analyzed in this report are 2982 cases and 480 controls who had a low-dose chest CT scan and were ruled out for cancer, all answered at least one PRO questionnaire (first response); and 1366 LTLCS answered 5 years after diagnosis (long-term response). Along with fatigue and dyspnea, 5 SDoH variables, i.e., financial concerns, legal concerns, family and friends support, spiritual well-being, and social activity were scored on a 0 (worst) - 10 (best) scale and dichotomized as 0-5 (deficit/worse/lower) or 6-10 (no deficit/better/higher). We also assessed employment and health-related work experience. A difference of 1.0 unit or more in score was considered clinically meaningful along with a 2-sided test P-value less than 0.05; Chi-square or Fisher’s Exact Test and Kruskal-Wallis test were used accordingly. Results: Compared to controls, cases were younger (mean age: 62 vs. 65 years, P<0.05); more women than men reported worse financial concerns (56% vs. 38%, P<0.01) and lower spiritual well-being (43% vs. 26%, P=0.04) at first response; this sex disparity reduced but remained significant at long-term. Worse dyspnea (4.4-4.8 vs. 5.6) and fatigue (4.7-4.8 vs. 5.8-5.9) were seen in cases with more financial and legal concerns compared to those with fewer concerns (Ps<0.01). Cases with higher family and friends support, spiritual well-being and social activity had less dyspnea (5.7-6.0 vs. 4.2-4.5) and fatigue (5.5-5.9 vs. 3.9-4.4) than those with lower scores (Ps<0.04). Employment and health-related work experience data were provided by 2213 responders: Comparing 1735 cases to 478 controls, a lower proportion of cases was employed (28% vs. 39%), more cases “often felt tired after work” (49% vs. 28%), and more cases had “quite a lot” of difficulty in daily work or could not work at all” (26% vs. 9%, Ps<0.01). Conclusions: We found that in lung cancer survivors, more women than men reported worse financial concerns, and lower SDoH status was correlated with worse dyspnea and fatigue, indicating SDoH-driven interventions are important to improve lung cancer survivors’ PROs.

Abstract Introduction: Chimeric antigen receptor T-cell (CAR-T) therapy is an established treatment modality for the management of refractory and/or relapsed non-Hodgkin lymphoma (NHL). Despite restrictions on granulocyte colony-stimulating factor (G-CSF) use in registration clinical trials due to potential worsening of cytokine release syndrome (CRS), G-CSF is often prescribed for neutrophil recovery post-CAR-T in clinical practice. We conducted a retrospective study to assess the association between G-CSF use and the safety and efficacy of CAR-T. Methods: Following Institutional Review Board approval, we retrospectively analyzed NHL patients receiving commercial CD19-targeted CAR-T across Mayo Clinic sites (Arizona, Florida, and Minnesota) between October 2017 and May 2023. Demographics, labs, and post CAR-T events were collected. Electronic medical records were reviewed for G-CSF exposure within Day 1 - 100 post-CAR T. Differences by G-CSF status were examined using a Chi-square test and Kruskal Wallis tests. Hazard ratios (HR) and 95% confidence intervals (CI) for overall survival (OS) were calculated using Cox model. Results: Among 270 CAR-T patients; 106 received G-CSF within 30 days and 164 did not. Median age was 56.9 with G-CSF and 58.3 without G-CSF. Most were male (75.2% G-CSF, 62.6% no G-CSF). Diffuse large B cell lymphoma was the predominant NHL subtype (67.0% G-CSF, 65.2% no G-CSF). G-CSF within 30 days was not associated with reduced incidence of neutropenic fever (11.7% G-CSF vs 9.9% no G-CSF, p = 0.6593) or documented infection (22.1% vs 18.3%, p = 0.4439). G-CSF correlated with decreased profound neutropenia duration (ANC &lt; 100 μL, 0 vs 2 days, p &lt; 0.0001) and incidence within 30 days ( 31.7% vs 60.4%, p &lt; 0.0001) as well as incidence of protracted profound neutropenia (&gt; 7 days, 3.8% vs 22.8%, p &lt; 0.0001). G-CSF was associated with a higher incidence of cytopenias between days 30 -100: severe neutropenia (ANC &lt; 500/uL, 28.8% vs 15.2%, p = 0.0075), severe anemia (Hb &lt; 8 g/dL, 21% vs 9.7%, p = 0.0114), and severe thrombocytopenia (Plt &lt; 50 g/L, 35.2% vs 20.9%, p = 0.0099). Logistic regression analysis showed that none of the examined covariates, including prior autologous stem cell transplant, ECOG PS score, and receipt of bridging therapy, were associated with severe neutropenia likelihood. G-CSF was associated with a higher CRS incidence (89.6% vs 79.9%, p = 0.0343), but grade 3 CRS or higher (4.7% vs 3.7%, p = 0.6675) was no different. No difference in complete response rates (66% vs 61.1%, p = 0.4707) or 2-year OS (p = 0.523) was observed between the 2 groups. Conclusion: G-CSF within 30 days was associated with reduced duration and incidence of profound neutropenia without a significant impact on incidence of neutropenic fever or documented infections. There was a signal of association between G-CSF and increased incidence of low-grade CRS and delayed cytopenias (day 30-100) that warrants confirmation in larger studies. Citation Format: Lay She Ng, Claire I. Yee, Radhika Bansal, Mohamed A. Kharfan-Dabaja, Grzegorz S. Nowakowski, Allison C. Rosenthal, Javier Munoz, Januario Castro, Wern Lynn Ng, Hemant S. Murthy, Yi Lin, Matthew R. Buras, Madiha Iqbal, Yucai Wang, Talal Hilal. Impact of G-CSF on safety and efficacy of CAR T-cell therapy in non-Hodgkin lymphoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6327.

688 Background: PACC is a rare malignancy originating from the exocrine pancreas, accounting for less than 1% of all pancreatic cancers. Due to the rarity of the disease entity, there is a paucity of data to guide treatment decisions. This retrospective study aims to provide additional clinical characteristics and outcomes to aid in future treatment decisions. Methods: Pathology records from Mayo Clinic (AZ, FL, MN) patients (pts) denoting acinar or mixed-acinar cell carcinoma were searched between 2002 to 2023 and selected for retrospective review. Pt demographics, treatment courses, and next generation sequencing (NGS) were collected. Results: A total of 62 pts (74% male, n = 46) were identified with median age 64 years old. Histologic subtypes were 67% pure acinar cell carcinoma (42/62), 24% mixed acinar-neuroendocrine (15/62), and 8% mixed acinar-adenocarcinoma (5/62). AJCC stages at diagnosis were 34% stage I/II (21/62), 16% stage III (10/62), and 50% stage IV (31/62). Early-stage disease was treated with upfront surgical resection (81%, 17/21). Locally advanced disease received neoadjuvant therapy (NAT) followed by surgical resection (80%, 8/10). FOLFIRINOX was most often chosen as NAT (65%, 11/17), while others received gemcitabine-based NAT. The R0 resection rate was 86%. The 3 and 5-year survival estimates for stage III were 90.9% (95% CI: 75.4 – 100%) and 67.3% (95% CI: 42.3 – 100%), respectively. The 3 and 5-year survival estimates for stage IV were 36.6% (95% CI: 18.6 – 71.9%) and 29.3% (95% CI: 13.1 – 65.5%), respectively. Median survival time for stage IV was 3 years. Somatic NGS testing was done in 24 pts with alterations found in: homologous recombination (HR) in 42% (10/24); RAF alterations in 25% (6/24); mismatch repair (MMR) in 13% (3/24; none of them with MMR germline mutations), 1 ETV6-NTRK3 fusion, and 1 FGFR mutation. Germline NGS testing was done in 21 pts and alterations in HR were seen in 33% (7/21) of pts. This led to additional therapeutic options in 46% (11/24) of pts. Conclusions: Unlike PDAC, PACC is a genomically diverse disease, with potentially targetable alterations in RAF, HRD, and MMR genes, offering additional therapeutic options for significant number of pts. In addition, more than one-third of the pts harbored germline mutations in HR genes. Therefore, somatic and germline testing should be considered for any pt diagnosed with PACC.

ObjectivesThere is an absence of data in the literature regarding methods to improve the patient experience during the performance of awake in‐office laryngeal injections. This study sought to evaluate whether the use of local anesthetic or a vibrating instrument decreased overall pain experienced by patients with laryngeal dystonia, frequently referred to as spasmodic dysphonia (SD), undergoing transcervical botulinum toxin injections.MethodsThis was an unblinded, prospective randomized control trial with a crossover design where each patient received transcutaneous transcricothyroid injection of botulinum toxin with alternating use of no anesthesia, local anesthesia (2% lidocaine in 1:100,000 epinephrine), and vibrating instrument in three consecutive laryngeal injections to treat adductor SD. Patients were randomized to the order they received these treatments. Patients measured pain on a 0–10 visual analogue scale (VAS) and selected their preferred technique after receiving all three analgesic modalities.ResultsThirty‐two patients completed the study. There was no statistically significant difference in pain between the three analgesic techniques (p = 0.38). The most preferred analgesic technique was the vibrating wand (44% (14/32)). Lidocaine was the second most preferred (37% (12/32)) and 19% (6/32) of patients preferred nothing. When combining the wand and nothing groups, 63% of patients preferred one of these two methods (95% exact CI: 44%–79%).ConclusionThere was no statistically significant difference in median pain experienced by patients during laryngeal botulinum toxin injection between these different analgesic modalities. More than half of the patients selected a preference for a technique that did not include lidocaine. This data supports individualization of analgesia during transcutaneous laryngeal injections.Level of Evidence2 Laryngoscope, 134:2277–2281, 2024

Abstract There are striking differences among caregivers of people with dementia (PWDs) in how their health and well-being changes during active caregiving; however, less is known about these differences after caregiving has ended. One important factor influencing caregiver health is the emotional quality of the caregiver-PWD relationship. The present study evaluated caregivers’ emotional connection to the PWD (during caregiving) and associations with caregivers’ depression both concurrently (N = 326 active caregivers) and longitudinally (n = 91 former caregivers). Active caregivers described a recent time they felt connected to the PWD, and their responses were transcribed verbatim. Caregivers’ emotional connection to the PWD was operationalized by summing the number of positive and negative emotion words from the transcripts using text analysis software and dividing each figure by the total number of words in the response. Results indicated that neither positive nor negative emotional language was significantly correlated with caregivers’ concurrent depression. However, two-wave latent change score modeling revealed that caregivers’ greater positive emotional language (adjusting for caregivers’ baseline depression and negative emotional language) predicted steeper declines in depression (i.e., improvements in depression trajectories) after the death of the PWD (ß = -.11, SE(ß) = 0.04, p = .033). Negative emotional language was not significantly associated with changes in caregivers’ depression. This finding highlights positive emotion expressed by caregivers when describing their connection with the PWD as a potential resilience factor and underscores the important role that positive emotional qualities of the caregiving relationship play in improving caregivers’ mental health after caregiving ends.