Citations

Objectives Communication barriers, such as channels, comfort, and location, can negatively impact Black prostate cancer survivors’ experiences and health outcomes after treatment. Addressing these barriers promotes a survivor-centric approach that views survivors as active partners in their care. This study explored the communication preferences of Black prostate cancer survivors, focusing on preferred channels, sources, and locations for enhanced quality of life. Design Using grounded theory methodology, we conducted engaged in-depth interviews with 7 Black prostate cancer survivors, centering on their post-treatment experiences. We analyzed participant transcripts to develop codes and themes. Communication accommodation theory (CAT) was applied to examine how survivors adapt their communication styles to navigate barriers and improve their quality of life. CAT helped identify key patterns of survivors’ convergence and divergence in their communication with healthcare providers, crucial for developing survivor-centric communication strategies. Results The analysis revealed the importance of acknowledging cultural and racial perspectives in post-treatment survivorship. Themes extracted from the transcripts included communication barriers, preferences for information channels, and favored locations for sharing information. Survivors expressed a preference for a balance between face-to-face interaction and telehealth, with environments that provide safety and support playing a key role in encouraging vulnerability and open dialogue. Inclusive healthcare practices were seen as essential in empowering Black survivors to engage in meaningful communication without feeling silenced or undervalued, thus fostering a dignified quality of life. Conclusion Tailoring post-treatment communication practices to incorporate cultural sensitivity, inclusive healthcare, and safe spaces is pivotal to supporting Black survivors. These findings provide a pathway to improving survivors’ experiences and empower them to actively shape their survivorship journey. Moreover, they highlight Black men’s need for trustworthy communication with healthcare providers and peers during the post-treatment period, emphasizing the importance of direct, personalized interactions.

Abstract Background and study aims Use of fluoroscopy in gastrointestinal endoscopy is an essential aid in advanced endoscopic interventions. However, it also raises concerns about radiation exposure. This study aimed to develop consensus-based statements for safe and effective use of fluoroscopy in gastrointestinal endoscopy, prioritizing the safety and well-being of healthcare workers and patients. Methods A modified Delphi approach was employed to achieve consensus over three rounds of surveys. Proposed statements were generated in Round 1. In the second round, panelists rated potential statements on a 5-point scale, with consensus defined as ≥80% agreement. Statements were subsequently prioritized in Round 3, using a 1 (lowest priority) to 10 (highest priority) scale. Results Forty-six experts participated, consisting of 34 therapeutic endoscopists and 12 endoscopy nurses from six continents, with an overall 45.6% female representation (n = 21). Forty-three item statements were generated in the first round. Of these, 31 statements achieved consensus after the second round. These statements were categorized into General Considerations (n = 6), Education (n = 10), Pregnancy (n = 4), Family Planning (n = 2), Patient Safety (n = 4), and Staff Safety (n = 5). In the third round, accepted statements received mean priority scores ranging from 7.28 to 9.36, with 87.2% of statements rated as very high priority (mean score ≥ 9). Conclusions This study presents consensus-based statements for safe and effective use of fluoroscopy in gastrointestinal endoscopy, addressing the well-being of healthcare workers and patients. These consensus-based statements aim to mitigate risks associated with radiation exposure while maintaining benefits of fluoroscopy, ultimately promoting a culture of safety in healthcare settings.

Abstract Introduction: Black men experience a significant burden and face greater hurdles in the prevention, detection, treatment, and survival of prostate cancer (CaP). To address barriers and systemic issues associated with CaP, we have established Community Living Lab (CoLLab) Learning Health Systems through a partnership with the American Legion Post (ALP) and Mayo Clinic. The focus is on providing comprehensive prostate health resources, education, amenities, and community health services (REACH). This initiative represents a proactive approach to addressing health disparities in prostate cancer prevention, detection, and treatment to improve CaP health equity for Black men. This study has three primary aims: (1) Co-develop a user-centric CoLLab Learning Health System with collaborating ALPs, (2) Evaluate the impact of the CoLLab Learning Health System using a pretest-posttest design, and (3) Explore the feasibility of replicating the CoLLab Learning Health System in Black communities nationally. Methods: Three ALPs in Northeast Florida are currently included in this pilot study. The study timeline spans 30 months, from October 2023 to March 2026. The target recruitment is 150 Black men aged 30 to 80 years. Community Health Workers (CHWs) are currently recruiting participants to complete the ALP Neighborhood assessment four times over 12 months to measure changes in CaP-related knowledge, attitudes, health beliefs, perceived control, intentions, and cues to action. Participants will be able to access prostate health REACH services at the designated ALPs through education, navigation, and support services. The program will be continuously evaluated for continuous improvement. The reach of the prostate health REACH services, including extent and patterns of use, demographics of participants reached, and successful navigation for social determinants of health (SDOH), clinical trials, and healthcare, will be evaluated. Additionally, participation in the Community Research Registry, indicating interest in being matched with clinical trials at Mayo Clinic, will be assessed. Results: To date, we have trained 10 CHWs for the study who will serve as community navigators to provide REACH services at their designated ALPs. We have had 49 Black men recruited into the study, and they have completed the baseline assessment at various events held at the ALPs. CaP survivors support group, led by ALP, has begun providing survivorship support services, including healthcare navigation, wellness programs, and grocery distribution to Black men and their households in the community surrounding the ALPs. Conclusion: The CoLLab initiative represents a proactive approach to addressing health disparities and improving outcomes for Black men in CaP prevention, detection, treatment, and survivorship. This study represents a crucial step towards eliminating CaP disparities experienced by Black men, contributing to improved health equity and outcomes in this population. Citation Format: Floyd B Willis, Collisa Mahin, Opeyemi O Bolajoko, Caleb Ramirez, Shannon Pressey, Shaina Flynn, Arnold J Merriweather, Toshiko Moultrie, Vermelle Smith, Wayne Ford, Derry Green. Utilizing Community Living Labs (CoLLab) to address prostate cancer disparities in Black men: An innovative partnership with the American Legion Post and Mayo Clinic [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr B073.

Abstract Introduction: In an effort to ensure an all-inclusive initiative that would close the disparity gap among the immigrant communities in Florida, we developed a pilot project under the Inclusive Cancer Care Research Equity (iCCaRE) for Black Men Consortium with generous support from the Mayo Clinic Comprehensive Cancer Center (MCCCC). The objective is to train cancer advocates to engage their communities and develop and implement cancer prevention and screening navigation programs. The central hypothesis for this program is that community-driven cancer advocacy will significantly improve cancer awareness, knowledge, prevention, risk reduction, screening uptake, and early detection among Black immigrants. Methods: We collaborated with immigrant communities’ leaders to brainstorm on the current state of healthcare access and disparities experienced by Black immigrants and to set program and research priorities through listening sessions. Cancer advocates were trained to engage their communities to (1) develop and implement cancer risk reduction and education programs using train-the-trainer approach, (2) mobilize the resources within the community for cancer health promotion, prevention, and screening strategies, (3) partner with key stakeholders to accomplish targeted objectives; (4) raise funds to support advocacy activities; and (5) develop and successfully organize community-centered programs. Results: We are currently working with 10 Black immigrant organizations, including immigrant churches across different ethnicities, including Nigeria, Ghana, Cameroon, Liberia, South Africa, Haiti, Jamaica, and across different cities in the United States. Eighteen community cancer advocates, including breast and prostate cancer survivors, caregivers, and community influencers, were trained to engage the immigrant communities in cancer risk reduction and research in Florida using multiple channels, including in-person community programs and online engagement approaches. We have engaged 720 immigrants in cancer risk reduction education and the need to participate in research during advocate-led in-person community outreaches. We currently have 26 immigrants who have volunteered in the Mayo Clinic Community Research Registry. The program is ongoing, and we anticipate that more than 750 will be engaged, and 100 will volunteer to be registered in the Mayo Clinic Community Research Registry. Conclusion: Advocate-led advocacy in immigrant communities will provide evidence for compelling arguments about the feasibility and availability of the Black immigrant population for robust and sustainable research and program engagements to eliminate disparity and advance cancer health equity. Citation Format: Opeyemi O. Bolajoko, Caleb Ramirez, Shannon Pressey, Noreen A. Stephenson, Vinessa A. Gordon, Binta Onyibe, Kingsley Efe, Austin Okaiwele, Mubo Oloruntobo, Brittany M. Norris, Folakemi T. Odedina. Cancer health equity and research advocacy program among immigrant communities [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr B002.

Mutations in the PINK1 and PRKN genes are the most frequent genetic cause of early-onset Parkinson disease. The pathogenic p.R275W substitution in PRKN is the most frequent substitution observed in patients, and thus far has been characterized mostly through overexpression models that suggest a possible gain of toxic misfunction. However, its effects under endogenous conditions are largely unknown. We used patient fibroblasts, isogenic neurons, and post-mortem human brain samples from carriers with and without PRKN p.R275W to assess functional impact. Immunoblot analysis and immunofluorescence were used to study mitophagy activation, and mitophagy execution was analyzed by flow cytometry of the reporter mitoKeima. The functional analysis was accompanied by structural investigation of PRKN p.R275W. We observed lower PRKN protein in fibroblasts with compound heterozygous p.R275W mutations. Isogenic neurons showed an allele-dose dependent decrease in PRKN protein. Lower PRKN protein levels were accompanied by diminished phosphorylated ubiquitin and decreased MFN2 modification. Mitochondrial degradation was also allele-dose dependently impaired. Consistently, PRKN protein levels were drastically reduced in human brain samples from p.R275W carriers. Finally, structural simulations showed significant changes in the closed form of PRKN p.R275W. Our data suggest that under endogenous conditions the p.R275W mutation results in a loss-of-function by destabilizing PRKN.

Purpose: The purpose of this study was to evaluate and compare the anatomic characteristics of eyes with Fuchs endothelial corneal dystrophy (FECD) with eyes without FECD. Methods: This study was a retrospective chart review performed at an academic medical center. Patients with FECD were identified through a search of the electronic medical records. Eligible patients underwent Scheimpflug imaging and optical biometry and were compared with age and sex-matched control subjects who underwent similar testing in preparation for cataract surgery. Several measurements of the cornea, anterior chamber, and eyes were evaluated using multivariable linear regression models and multivariable logistic regression models. Results: A total of 404 eyes (202 eyes with FECD and 202 control eyes) were included in this study. Compared with controls, eyes with FECD had shallower AC depths, lower AC volumes, and narrower angles. Conversely, the spherical equivalent before cataract surgery, corneal pachymetry, and corneal volume were higher in eyes with FECD. On Scheimpflug imaging analysis, these anatomical differences were present in FECD eyes with and without corneal edema. After adjusting for sex, these differences remained statistically significant. Shorter axial length was found to be statistically significant in male eyes but not in female eyes with FECD. Conclusions: This study reports new ocular characteristics in FECD eyes with and without edema. Optical biometry and Scheimpflug imaging established that the anatomic findings in eyes with FECD were not simply due to the larger volume of an edematous cornea but rather unique to eyes with FECD. These findings will provide reliable, normative data for future studies examining surgical, medical, and anatomical factors in FECD.

BACKGROUND AND OBJECTIVES: Stereotactic radiosurgery (SRS) with neoadjuvant embolization is a treatment strategy for brain arteriovenous malformations (AVMs), especially for those with large nidal volume or concomitant aneurysms. The aim of this study was to assess the effects of pre-SRS embolization in AVMs with an associated intracranial aneurysm (IA). METHODS: The International Radiosurgery Research Foundation AVM database from 1987 to 2018 was retrospectively reviewed. SRS-treated AVMs with IAs were included. Patients were categorized into those treated with upfront embolization (E + SRS) vs stand-alone SRS (SRS). Primary end point was a favorable outcome (AVM obliteration + no permanent radiation-induced changes or post-SRS hemorrhage). Secondary outcomes included AVM obliteration, mortality, follow-up modified Rankin Scale, post-SRS hemorrhage, and radiation-induced changes. RESULTS: Forty four AVM patients with associated IAs were included, of which 23 (52.3%) underwent pre-SRS embolization and 21 (47.7%) SRS only. Significant differences between the E + SRS vs SRS groups were found for AVM maximum diameter (1.5 ± 0.5 vs 1.1 ± 0.4 cm 3 , P = .019) and SRS treatment volume (9.3 ± 8.3 vs 4.3 ± 3.3 cm 3 , P = .025). A favorable outcome was achieved in 45.4% of patients in the E + SRS group and 38.1% in the SRS group ( P = .625). Obliteration rates were comparable (56.5% for E + SRS vs 47.6% for SRS, P = .555), whereas a higher mortality rate was found in the SRS group (19.1% vs 0%, P = .048). After adjusting for AVM maximum diameter, SRS treatment volume, and maximum radiation dose, the likelihood of achieving favorable outcome and AVM obliteration did not differ between groups ( P = .475 and P = .820, respectively). CONCLUSION: The likelihood of a favorable outcome and AVM obliteration after SRS with neoadjuvant embolization in AVMs with concomitant IA seems to be comparable with stand-alone SRS, even after adjusting for AVM volume and SRS maximum dose. However, the increased mortality among the stand-alone SRS group and relatively low risk of embolization-related complications suggest that these patients may benefit from a combined treatment approach.

Breast cancer imposes a significant burden globally. While the survival rate is steadily improving, much remains to be elucidated. This observational, single time point, multiomic study utilizing genomics, proteomics, targeted and untargeted metabolomics, and metagenomics in a breast cancer survivor (BCS) and age-matched healthy control cohort (N = 100) provides deep molecular phenotyping of breast cancer survivors. In this study, the BCS cohort had significantly higher polygenic risk scores for breast cancer than the control group. Carnitine and hexanoyl carnitine were significantly different. Several bile acid and fatty acid metabolites were significantly dissimilar, most notably the Omega-3 Index (O3I) (significantly lower in BCS). Proteomic and metagenomic analyses identified group and pathway differences, which warrant further investigation. The database built from this study contributes a wealth of data on breast cancer survivorship where there has been a paucity, affording the ability to identify patterns and novel insights that can drive new hypotheses and inform future research. Expansion of this database in the treatment-naïve, newly diagnosed, controlling for treatment confounders, and through the disease progression, can be leveraged to profile and contextualize breast cancer and breast cancer survivorship, potentially leading to the development of new strategies to combat this disease and improve the quality of life for its victims.

TPS2699 Background: Despite the success in hematologic cancers, chimeric antigen receptor (CAR) T-cell therapies are challenging to implement in solid tumors owing to a lack of tumor-specific targets that discriminate cancer from normal cells. MSLN expression normally is limited to the mesothelium of major body cavities but can be upregulated in diverse solid tumor types (TCGA 2022), making it a potential target for cancer therapy. MSLN-targeted cell approaches, including CAR T-cell and T-cell receptor fusion therapies, have shown promising clinical activity; however, on-target, off-tumor toxicity including fatal events have occurred (1-3). A2B694 is an autologous logic-gated, MSLN-targeted Tmod CAR T-cell therapy that addresses the challenges of on-target, off-tumor toxicity by combining 2 CARs: an activating and blocking receptor. The activator recognizes MSLN present on the surface of both tumor and normal cells; the blocker binds HLA-A*02 and prevents CAR T-cell activity. Thus, in patients with both germline HLA-A*02 and tumor-associated HLA-A*02 LOH, the blocker prevents on-target, off-tumor toxicity on normal cells owing to retained HLA-A*02 expression (4). Through this unique discriminatory mechanism, A2B694 may provide a therapeutic window to treat patients with MSLN-expressing solid tumors exhibiting HLA-A*02 LOH. Methods: EVEREST-2 (NCT06051695) is a first-in-human, phase 1/2, open-label, nonrandomized study to evaluate the safety and efficacy of A2B694 in adults with recurrent unresectable, locally advanced, or metastatic cancers with MSLN expression, including non-small cell lung cancer, colorectal cancer, pancreatic cancer, ovarian cancer, mesothelioma, or other solid tumors with MSLN expression. Eligible patients should have received ≥1 line of prior therapy such as checkpoint inhibitor, molecular targeted, or chemotherapy. Enrollment to EVEREST-2 occurs through the prescreening study BASECAMP-1 (NCT04981119), which identifies patients with tumor-associated HLA-A*02 LOH via next-generation sequencing (Tempus AI, Inc.). Eligible patients enroll in the BASECAMP-1 study and undergo leukapheresis. A2B694 is manufactured from cryopreserved T cells when clinically appropriate for patients. The primary objective of phase 1 is to evaluate the safety and tolerability of A2B694 and identify the recommended phase 2 dose (RP2D). The dose-expansion phase will confirm RP2D and collect biomarker data to further characterize A2B694. Phase 2 will assess overall response rate per RECIST v1.1. 1. Beatty, et al. Gastroenterology. 2018. 2. Haas, et al. Mol Ther. 2023. 3. Hong, et al. ESMO 2021. Abstract 9590. 4. Hamburger, et al. Mol Immunol. 2020. Clinical trial information: NCT06051695 .

TPS2698 Background: Chimeric antigen receptor (CAR) T-cell therapies for treating solid tumors are challenging due to a lack of tumor-specific targets that discriminate cancer from normal cells. Previous studies using CEA T-cell receptors and T-cell engagers have resulted in dose-limiting, on-target, off-tumor toxicities (1,2). A2B530 is an autologous logic-gated, CEA-targeted Tmod CAR T-cell therapy that addresses the challenges of on-target, off-tumor toxicity by combining a CAR-activating receptor with a blocking receptor to discriminate tumor from normal cells (3). The activator recognizes CEA on the surface of both tumor and normal cells while specificity for tumor cells is provided by a blocker that binds HLA-A*02. In patients with both germline HLA-A*02 and tumor-associated HLA-A*02 LOH, the blocker prevents on-target, off-tumor toxicity on normal cells owing to retained HLA-A*02 expression (4). HLA-A*02 LOH can be detected using next-generation sequencing (Tempus AI, Inc.). With this definitive discriminator target, A2B530 can potentially provide a therapeutic window to treat patients with CEA-expressing solid tumors exhibiting HLA LOH. Methods: EVEREST-1 (NCT05736731) is a seamless, phase 1/2, open-label, nonrandomized study to evaluate the safety and efficacy of A2B530 in adult patients. Patients are enrolled through BASECAMP-1 (NCT04981119), a master prescreening study that identifies patients with HLA LOH at any time in the course of their disease. BASECAMP-1–eligible patients undergo leukapheresis and, when clinically appropriate, their banked T cells are manufactured for the EVEREST-1 study. The key inclusion criteria include histologically confirmed recurrent unresectable, locally advanced, or metastatic cancers associated with CEA expression: non-small cell lung, colorectal, or pancreatic cancers. Patients should have received ≥1 line of prior therapy such as checkpoint inhibitor, molecular targeted, or chemotherapy. The primary objective of phase 1 is to evaluate the safety and tolerability of A2B530 and determine the recommended phase 2 dose (RP2D). The dose-escalation portion is based on the Bayesian optimal interval design. The dose-expansion phase will confirm RP2D and collect biomarker data to further characterize A2B530. Phase 2 will assess overall response rate per RECIST v1.1. As of January 29, 2024, 8 patients have been enrolled on EVEREST-1. A2B530 was successfully manufactured for all patients, and all patients have received A2B530 infusion, with the first patient dosed in May 2023. Dose escalation is ongoing. 1. Parkhurst, et al. Mol Ther. 2022. 2. Tabernero, et al. J Clin Oncol. 2017. 3. Hamburger, et al. Mol Immunol. 2020. 4. Sandberg, et al. Sci Transl Med. 2022. Clinical trial information: NCT05736731 .