Citations

1586 Background: Black and Hispanic breast cancer (BC) survivors have a higher prevalence of obesity and experience less success with weight loss interventions (WLI) than White BC survivors. The BWEL trial (Alliance A011401; NCT02750826) is a phase III randomized trial evaluating the impact of a 2-year telephone-based WLI on invasive disease-free survival in participants (pts) with stage II-III HER2-negative BC and a BMI ≥ 27 kg/m 2 . At 12-months, the WLI induced significant weight loss across demographic factors, including race and ethnicity. However, Black and Hispanic pts lost less weight and completed fewer calls than White pts. Here, we evaluate intervention adherence, engagement and tool utilization in BWEL pts by race and ethnicity. Methods: BWEL randomized pts to a WLI plus health education (HE) or HE alone. WLI pts received semi-structured telephone-based health coaching, delivered in English or Spanish, and received an activity monitor and wireless scale. Pts self-reported race and ethnicity. Mean values for call duration, call density (time to complete the initial 12-week intensive intervention phase), intervention attrition, and frequency of Fitbit use and weight tracking over 12-months were compared by race and ethnicity, comparing least squares means with Tukey-Kramer adjustment for multiple comparisons with adjusted p-values. Results: Of 3181 pts randomized to the study between 08/2016 and 02/2021, 1591 pts were allocated to the WLI arm. 80.5% of pts were White, 12.8% Black, and 7.1% Hispanic. Average BMI was 34.5 (±5.7) kg/m2. Compared to White pts, Black pts had fewer days of Fitbit usage (113.6 vs. 159.8, p<0.0001) and weight tracking (77.9 vs. 135.6 days, p< 0.0001). Hispanic pts had fewer days of Fitbit usage (108.8 vs. 154.9, p= 0.001) and weight tracking (87 vs. 129.5 days, p=0.0002) compared to non-Hispanic pts. There were no differences in attrition rate, average call duration, or call density by race or ethnicity. Conclusions: In a phase III WLI trial, engagement with tools designed to support weight loss was significantly lower in Black and Hispanic pts. Future work is needed to explore ways to enhance engagement and improve weight loss outcomes for racial and ethnic minority pts. Support: U10CA180821, U10CA180882, UG1CA189823; https://acknowledgments.alliancefound.org . Clinical trial information: NCT02750826 . Measure of engagement Race Ethnicity WhiteN=1281 BlackN=204 p-value Non-HispanicN=1459 HispanicN=113 p-value Withdrew from intervention n (%) 58 (4.5%) 13 (6.4%) 0.56 70 (4.8%) 6 (5.3%) 0.51 Call Duration (min)Mean (SD) 34.5 (7.6) 34.6 (9.1) 0.99 34.6 (7.8) 33.3 (7.9) 0.25 Call density(weeks)Mean (SD) 14.2 (7.2) 14.2 (8.8) 0.99 14.2 (7.3) 14.2 (9.7) 0.99 Days of Fitbit UseMean (SD) 159.8 (132.2) 113.6 (124.7) < 0.0001 154.9 (131.8) 108.8 (125.7) 0.001 Days of weight trackingMean (SD) 135.6 (109.5) 77.9 (87.5) < 0.0001 129.5 (108.8) 87 (96.5) 0.0002

1543 Background: Treatment toxicity may limit the ability of cancer patients to receive all recommended cycles of therapy. Four to six cycles of docetaxel plus cyclophosphamide (TC) is a common adjuvant chemotherapy regimen for early-stage breast cancer. We assessed the impact of routine collection of patient-reported outcomes (PROs), coupled with a collaborative care model-based symptom management intervention, on the number of cycles of TC received by patients with breast cancer. Methods: The Enhanced, EHR-facilitated Cancer Symptom Control (E2C2) trial was a cluster-randomized, pragmatic clinical trial, conducted between March 2019 and January 2023 at Mayo Clinic Rochester and within the Mayo Clinic Health System in Minnesota and Wisconsin. Patients regularly reported the severity of 6 SPPADE symptoms (Sleep deficit, Pain, Physical function impairment, Anxiety, Depression, and Energy deficit/fatigue) on 11-point numerical rating scales. Each symptom score was interpreted as none to mild (0-3), moderate (4-6), or severe (7-10). The E2C2 intervention included symptom management education modules, clinician decision support aids, and the option to discuss severe symptoms with a nurse, physical therapist, or social worker. Patients with breast cancer who received at least one cycle of TC were included in this analysis. We compared the number of cycles of docetaxel and cyclophosphamide completed by patients in the control condition versus those in the intervention condition. Results: We identified 198 patients with breast cancer who received TC during the control condition and 128 who received TC during the intervention condition. Median age was 61.3 years in the control group and 60.3 years in the intervention group, and 94% and 95% were white, respectively. Those receiving treatment during the control condition, on average, completed 3.53 cycles of docetaxel, while those receiving TC during the intervention condition completed 3.77 cycles ( p = 0.014). Seventy-eight percent in the control group completed at least 4 cycles of docetaxel, compared to 84% in the intervention group. Those receiving TC during the control condition completed an average of 3.71 cycles of cyclophosphamide, compared to 3.78 cycles in the intervention condition (p = 0.231). Eighty-four percent of patients in the control group and 86% in the intervention group completed at least 4 cycles of cyclophosphamide. Conclusions: Routine PRO surveillance, coupled with guideline-based collaborative care interventions, was associated with completion of a greater number of cycles of docetaxel. These findings suggest that routine symptom surveillance and management may enhance the docetaxel tolerance profile and improve treatment adherence in patients with early-stage breast cancer, allowing for delivery of an optimized treatment course.

e20120 Background: In May 2024, the FDA approved tarlatamab, a Delta-like ligand (DLL3)/CD3-targeted bispecific T-cell engager, for patients with extensive-stage small cell lung cancer (SCLC) with disease progression following platinum-based chemotherapy and at least one other prior line of therapy. We aim to evaluate the real-world outcomes of agent. Methods: We conducted a retrospective multi-site single center analysis of adult patients who received tarlatamab at Mayo clinic sites including Arizona, Florida, Iowa, Minnesota, and Wisconsin. Data analysis was performed with Blue Sky statistics version 10.4. Results: Twenty patients with a median age 67 years (range 43-76) were included. Patients were predominantly women (55%) and all had a history of tobacco use. Metastatic disease commonly involved liver (55%) and CNS (60%). Majority (90%) had received prior PDL-1 therapy. 25% (5/20) of patients received prior gamma knife and in addition 10% (2/20) received whole brain radiation treatment in our cohort. Median time from CNS radiation and tarlatamab initiation was 4 months (range 3-28). Other characteristics, outcomes, and toxicity are presented in Table 1. Cytokine release syndrome (CRS) Grade (G) 1 was observed in 45% patients. G 2, 3 and 4 CRS were observed in 5% patients respectively. G 1 CRS was managed with acetaminophen initially followed dexamethasone 10mg or methylprednisone 1g if no improvement in 24 hours. Tocilizumab was used 20% patients for G 1,2,3 and 4 CRS depending on clinical course. Immune effector cell-associated neurotoxicity (ICANS) G 1 occurred in 10% patients, followed by G 2 in 15% and G 3 in 5% patients. ICANS was managed in a multidisciplinary fashion. All patients had resolution of CRS and ICANS. Conclusions: In this study investigating the real-world outcomes and toxicity of tarlatamab, a higher incidence of ICANS was observed than that reported in the DeLLphi-301 trial. The association between presence of CNS metastatic disease, prior CNS radiation and incidence of ICANS needs to be explored further. Mayo Clinic report of tarlatamab real world outcomes and toxicity. Patient Characteristics, Tarlatamab Outcomes and Toxicity Mayo Clinic Report DeLLphi-301 trial- Part 1 & 2 DeLLphi-301 trial- Part 3 ECOG no. (%) 2-4 4 (20) 0 (0) 0 (0) Metastatic Disease no.(%) 19 (95) 98 (98) 32 (94) Median no. of previous lines of therapy (range) 3 (2-4) 2 (1-6) 2 (2-6) Objective Response (%) 30% 40% CRS no (%) 12 (60) 49 (49) 19 (56) ICANS no (%) 6 (30) 7 (7) 4 (12) Neutropenia Grade 3 no (%) 2 (10) 6 (6) 2 (6) Fatal CRS, ICANS or Neutropenia 0 (0) 0 (0) 0 (0)

Abstract Background and Aims Accurate differentiation of cardiac amyloidosis (CA) from phenotypic mimics remains challenging using current clinical and echocardiographic techniques. The accuracy of a novel artificial intelligence (AI) screening algorithm for echocardiography-based CA detection was assessed. Methods Utilizing a multisite, multiethnic dataset (n = 2612, 52% CA), a convolutional neural network was trained to differentiate CA from phenotypic controls using transthoracic apical four-chamber video clips. External validation was conducted globally across 18 sites including 597 CA cases and 2122 controls. Classification accuracy was assessed on the entire external validation dataset, and subgroup analyses were performed both on technetium pyrophosphate scintigraphy referrals, and individuals matched for age, sex, and wall thickness. Model accuracy was also compared with the transthyretin CA score and the increased wall thickness score within a subset of older heart failure with preserved ejection fraction patients with increased wall thickness. Results Cardiac amyloidosis patients and controls displayed similar age, sex, race, and comorbidities. After the removal of uncertain AI predictions (13%), model discrimination and classification were excellent for the entire external validation dataset [area under the receiver operating characteristic curve (AUROC) 0.93, sensitivity 85%, specificity 93%], irrespective of CA subtype (sensitivity: light-chain = 84%, wild-type transthyretin = 85%, and hereditary transthyretin = 86%). Performance was maintained in subgroup analysis in patients clinically referred for technetium pyrophosphate scintigraphy imaging (AUROC 0.86, sensitivity 77%, specificity 86%) and matched patients (AUROC 0.92, sensitivity 84%, specificity 91%). The AI model (AUROC 0.93) also outperformed transthyretin CA score (AUROC 0.73) and increased wall thickness (AUROC 0.80) scores. Conclusions This AI screening model—using only an apical four-chamber view—effectively differentiated CA from other causes of increased left ventricular wall thickness.

Purpose: Chronic dizziness and imbalance is often difficult to rehabilitate based on the complex set of systems involved. Recently, transcutaneous vagus nerve stimulation (tVNS) has been investigated as a noninvasive means to reduce symptoms associated with vestibular impairment, chronic dizziness, and neurological conditions affecting balance control. The purpose of this integrative review is to examine available data describing therapeutic efficacy and proposed mechanisms of tVNS in adult patients with dizziness and imbalance. Method: PubMed, Europe PMC, and Google Scholar searches were conducted using the following search terms from 1987 to 2024: “vagal nerve stimulat*” OR “vagus nerve stimulat*” OR “transcutaneous vagus nerve stimulat*” OR “tVNS” AND “dizziness,” “vertigo.” Articles were imported for screening and review through Rayyan. Articles discussing the use of tVNS to study metrics related to vestibular and balance function in adult humans were selected for full-text review. Results: Eleven articles were identified as meeting the inclusion criteria and are classified according to the neurotological class studied and level of evidence provided. Available data show that tVNS may benefit patients with dizziness and imbalance based on subjective metrics including quality of life and reduction in dizziness handicap. Less-controlled case study evidence suggests that additional benefit from tVNS may manifest in changes to vestibulo-ocular reflex function. Conclusion: Although tVNS exposure has provided variable degrees of benefit in both subjective (e.g., quality of life) and objective (e.g., changes in vestibulo-ocular reflex function and gait) contexts, the degree to which distinct mechanisms can explain these benefits is unclear.

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

Objective Present the rationale for the development of a new, patient-facing vital sign for adult hearing. Study Design Structured A3 process. Setting Fourteen virtual meetings and two in-person meetings held between May 2021 and June 2022. Main Outcome Measure(s) Identification and refinement of a countermeasure to develop and imbed a hearing health vital sign for adult hearing. Results Through a rigorous, structured A3 process, the Hearing Health Collaborative identified and refined the rationale for and the qualities associated with a public-facing vital sign for adult hearing loss. Specifically, such a vital sign must embody five qualities: simple, accessible, stable, inclusive, and meaningful. These qualities together would ensure that a hearing health vital sign would be useful not only as a screening tool but also as an instrument to guide next steps in workup and potentially treatment. Conclusions Successful identification and implementation of a hearing metric or “vital sign” for the presence of adult hearing loss, using precedent convention of other medical diseases, may help reframe public perceptions surrounding hearing loss, improve awareness and literacy regarding the presence of the disease, and prompt action to seek diagnostic assessment.

Abstract IntroductionFungal infections, particularly in the Midwest, can often be asymptomatic and may mimic primary lung cancer. This case illustrates pulmonary histoplasmosis in an 80-year-old woman with a history of lung cancer highlighting the diagnostic challenges presented when both conditions coexist.Case SummaryAn 80-year-old woman (prior smoking history of 47-pack-years) with synchronous lung cancers (poorly differentiated non-small cell carcinoma with squamous differentiation in the left lower lobe and squamous cell carcinoma in the right lower lobe) previously underwent radiation therapy to both lesions. She was admitted for shortness of breath and cough and was initially diagnosed with pneumonia based on CT findings. Despite multiple courses of antibiotics, her symptoms persisted over 2 months, improving only temporarily with a short course of prednisone. A follow-up CT revealed increasing confluent thick-walled cavitation in the posterior right upper lobe and superior segment of the right lower lobe concerning for cavitating/necrotizing pneumonia versus possible cancer progression. A PET-CT scan (Fig.1A) showed significant FDG uptake in the right upper lobe lesion and mild uptake in mediastinal lymph nodes complicating the differentiation between cancer and infection. Bronchoscopy with biopsy of an endobronchial lesion in the posterior segment of right lower lobe revealed necrotizing granulomatous inflammation (Fig.1B) with GMS stain showing the presence of fungal organisms suggestive of histoplasmosis. Histoplasma PCR from bronchoalveolar lavage was also positive. She was subsequently started on antifungal therapy for a planned one-year treatment course. DiscussionHigh positron emission tomography (PET) avidity in chest imaging is often linked to aggressive tumors but can also indicate benign conditions such as fungal infections. A “flip-flop sign” on PET imaging, where nodal activity surpasses that of a lung nodule, is typically seen in benign lung lesions, particularly fungal infections. However, infections and inflammatory conditions may also show high PET avidity mimicking malignancy. Endobronchial lesions, common in lung cancer, are less frequently associated with infections. In patients with a history of cancer, active lung infection, and PET-avid lesions without the flip-flop sign, invasive testing is usually required to differentiate between infection and malignancy. In this case, our patient with a history of lung cancer and a PET-avid lung lesion was found to have pulmonary histoplasmosis after invasive testing highlighting the need for comprehensive evaluation.ConclusionThis case emphasizes the importance of considering fungal infections in the differential diagnosis of PET-avid pulmonary lesions, particularly in patients with a history of malignancy.

PURPOSE Sertoli-Leydig cell tumors (SLCTs) are rare sex cord-stromal tumors, representing <0.5% of all ovarian tumors. We analyze the role of germline DICER1 status in outcomes of ovarian SLCT. METHODS Patients with SLCT were enrolled in the International Pleuropulmonary Blastoma/ DICER1 Registry and/or the International Ovarian and Testicular Stromal Tumor Registry. Medical records were systematically abstracted, and those with known germline DICER1 status were selected for analysis. RESULTS Of 162 patients with SLCT, 60% had a germline DICER1 pathogenic or likely pathogenic (P/LP) variant. The adjusted 3-year recurrence-free survival (RFS) was 87.2% (95% CI, 79.4 to 95.8) for patients with a germline DICER1 P/LP variant compared with 78.1% (95% CI, 66.4 to 91.9) for those without a germline DICER1 P/LP variant ( P = .043). The adjusted 3-year and 5-year overall survival (OS) was 93.9% (95% CI, 87.3 to 100.0) for those with a germline DICER1 P/LP variant compared with the 3-year OS of 91.3% (95% CI, 83.4 to 100.0) and the 5-year OS of 78.2% (95% CI, 63.8 to 95.9) for those without a germline DICER1 P/LP variant ( P = .021). Among patients with a germline DICER1 P/LP variant, the risk of a subsequent, nonrecurrent event was 36.2% (95% CI, 21.4 to 48.1) within 10 years. Previous/concurrent and subsequent neoplasms were rare among those without a germline DICER1 P/LP variant. CONCLUSION This cohort study of patients with SLCT demonstrated that those with germline DICER1 P/LP variants had superior RFS and OS even when adjusting for other prognostic factors. Beyond prognostic implications of a germline DICER1 P/LP variant, germline testing helps identify patients at risk of subsequent neoplasms, including metachronous SLCT.