Citations

e13808 Background: Cancer is a leading cause of death for Latinos. They experience higher rates than their white peers of preventable, infectious-agent-causing-cancers, such as stomach & liver cancer. Latina women have experienced a 1% rise in cancer cases since 2011 & Latino children & adolescents experience higher rates of leukemia than any other racial/ethnic group. Latinos face disparities in access to healthcare, cancer screening & treatment, medical representation & experience lower rates of survival due to late-stage cancer diagnosis. Methods: To combat these inequities & identify equitable interventions for Latino health, the Institute of Health Promotion Research & the Mays Cancer Center established the Advancing the Science of Cancer in Latinos (ASCL) Conference. The fourth ASCL Conference convened in San Antonio, TX from February 21-23, 2024. The conference objectives were 1) Examine the intersection of health equity & biological underpinnings in cancer control, prevention, and treatment 2) Foster collaborative initiatives among attendees aimed at addressing cancer-related health disparities within the Latino community. The conference hosted 286 participants (speakers, researchers, physicians, healthcare professionals, patient advocates & students). It comprised of 23 sessions (3 keynotes, 6 plenaries, 6 breakouts, 3 general sessions, 1 special session, 1 lunch panel session) featuring insights from 51 speakers, a poster session highlighting 80 research abstracts & a rapid-fire session tailored for early-career investigators. Sessions focused on multiple topics relevant to Latino cancer research, clinical trials, survivorship, patient advocacy, climate change impacts on cancer, precision medicine, health policy & social determinants of health. Results: A post-conference survey from a cohort of 48 respondents underscored high levels of satisfaction, with 90% expressing contentment regarding the conference experience. Nearly all respondents (98%) rated the relevance of conference content to Latino cancer science as excellent, with 93% regarding the conference as an exceptional platform for information exchange. Impressions regarding session quality were positive, with 90% of respondents indicating a high level of satisfaction, & all survey respondents acknowledging the objectivity, balance & absence of commercial bias in the session content. Conclusions: Results showed that the resounding positivity in attendee feedback reflects the conference's success in fostering meaningful engagement among attendees. The ASCL conference facilitated an understanding of cultural nuances and barriers specific to the Latino community, stimulating collaborative efforts aimed at enhancing Latino health outcomes. Overall, this analysis affirms the conference's success in achieving its stipulated objectives and underscores the need of having consistently coordinated research endeavors to reduce Latino health disparities.

504 Background: Axillary surgery in breast cancer is used for staging and therapeutic purposes, but axillary lymph node dissection (ALND) confers high risk of complications including lymphedema. Accordingly, trials have focused on right-sizing axillary surgery, with options ranging from complete omission of surgery, sentinel lymph node (SLN) surgery, targeted axillary dissection (TAD), or ALND. Identifying a biomarker to reliably predict nodal burden would facilitate accurate selection of surgical management. We evaluated whether the presence or absence of ctDNA in the blood pre and post NAC is associated with residual nodal burden. Methods: I-SPY2 is a prospective, multicenter NAC trial for patients with clinical stage II-III high-risk breast cancer. Patients are randomized to novel NAC agents, with pathologic complete response being the primary endpoint. As part of the trial, serial ctDNA is assessed with a highly sensitive tumor-informed assay using up to 16 patient-specific tumor mutations (Signatera) at baseline, 3 weeks, 12 weeks, and post-NAC. We determined whether ctDNA positivity or negativity post-NAC, and the change in ctDNA status baseline/post-NAC (-/-, -/+, +/+, +/-) are associated with ypN category (N0, N1, N2). Results: ctDNA status was available post-NAC in 495 patients and change in ctDNA status from baseline was available in 493. At baseline, ctDNA was detected in 160/220 (72.3%) cN0 patients and 227/273 (83.2%) cN+ patients (p=0.006). Post-NAC, ctDNA was detected in 11/220 (5%) cN0 patients and 34/273 (12.5%) cN+ patients (p=0.004). While baseline ctDNA status was not associated with ypN category, there was a significant association between post-NAC ctDNA status and ypN category. For ctDNA + patients post-NAC, 33.3% were ypN0, 31.1% were ypN1, and 35.6% were ypN2 at surgery; in contrast, for ctDNA - patients post-NAC, 67.1% were ypN0, 23.1% were ypN1, and 9.8% were ypN2 (p<0.0001). Dynamic ctDNA changes were also associated with ypN category, with significantly more ypN0 patients among ctDNA -/- or ctDNA +/- cases, and more ypN2 patients in those who did not clear ctDNA (+/+) (p=0.0001, Table). Conclusions: To our knowledge this is the first study to demonstrate a significant relationship between ctDNA and ypN category, which has important surgical implications. CtDNA negativity was associated with low likelihood of ypN2 disease, making these patients excellent candidates for SLN surgery or TAD. Ongoing analyses will incorporate receptor subtype and timing of clearance of ctDNA. CtDNA in breast cancer may help tailor surgical management of the axilla, potentially reducing patient morbidity without compromising prognostic information. ctDNA baseline/post-NAC ypN0 (n=317) ypN1 (n=116) ypN2 (n=60) ctDNA -/- (n=105) 72.4% 19.1% 8.6% ctDNA -/+ (n=1) 0.0% 100.0% 0.0% ctDNA +/+ (n=44) 34.1% 29.6% 36.4% ctDNA +/- (n=343) 65.9% 23.9% 10.2%

5022 Background: Racial disparities are evident in PCa, with Black men experiencing a higher incidence and worse survival compared to NHW patients (pts). The molecular alterations that distinguish these groups remain incompletely characterized. Herein, we investigate the clinical-genomic features that potentially contribute to the differences in outcomes between Black and NHW pts with PCa. Methods: Comprehensive next-generation sequencing of DNA (592-gene panel/whole exome) and RNA (whole transcriptome) was performed at Caris Life Sciences on PCa tissue samples (n = 5,412), collected from 2015 to 2023. Transcriptomic signatures – Androgen Receptor (AR), Neuroendocrine PCa (NEPC) scores – were calculated. Real-world overall survival (OS) data was obtained from insurance claims and was analyzed using Kaplan-Meier estimation. Results: Overall, 1,078 pts with PCa identified as Black, while 4,334 were NHW. Black pts were younger at biopsy collection than NHW pts (median age 66 vs 71 years, P < 0.001). The proportion of metastatic samples was higher in Black pts compared to NHW pts (43% vs 38%, P < 0.01). The prevalence of castrated PCa specimens was similar between Black and NHW pts (26.0% vs 25.4%, P = 0.72). Among non-castrated PCa tumors, tumors from NHW pts had more frequent alterations in TP53 , PTEN , PIK3CA , and CHEK2 , while tumors from Black pts had more SPOP and CTNNB1 mutations. In the castrate setting, TP53 and PTEN alterations were more frequent in tissue samples from NHW pts, while CDK12 and SPOP mutations were more frequent in tumors from Black pts. TMPRSS2 fusions were more prevalent in the NHW cohort across both castrated and non-castrated tumors. Tumors from Black pts had higher FOLH1 / PSMA and STEAP1 expression, elevated AR scores, but lower CD276 / B7H3 expression and NEPC scores. In the overall cohort, Black pts demonstrated a shorter median OS from diagnosis compared to NHW pts (86 vs 94 mos, P = 0.03). Black pts had a significantly longer time on treatment with enzalutamide in both the non-castrate (HR 0.82, P= 0.04) and castrate subgroups (HR 0.77, P= 0.03). Among pts with homologous recombination repair (HRR) deficiency-harboring tumors, PARP inhibitors provided a numerically longer survival benefit in Black pts than in NHW pts (21 vs 13 mos, P = 0.09). Conclusions: This multi-institutional study reveals distinct molecular profiles between Black and NHW pts with PCa. Despite having molecular features associated with better prognosis, Black men demonstrated worse survival outcomes, pointing to multifaceted determinants of disease outcomes. Notably, Black pts had improved outcomes on enzalutamide and showed potential benefit from PARP inhibitors in the presence of HRR mutations. These findings highlight genomic differences in diverse PCa populations and suggest therapeutic opportunities to address outcome disparities.

3040 Background: EVEREST-2 is a first-in-human, phase 1/2 trial to assess the safety and efficacy of A2B694, an autologous, logic-gated Tmod CAR T therapy targeted to MSLN, which is normally expressed in the mesothelium and can be upregulated in many solid tumors. A2B694 is designed to overcome challenges of on-target, off-tumor toxicity that have limited other MSLN-targeted approaches by combining a CAR-activating receptor targeting MSLN with a blocker CAR that recognizes HLA-A*02, to distinguish between normal and tumor cells (Tokatlian, et al. J Immunother Cancer. 2022). Methods: Adults with recurrent unresectable, locally advanced, or metastatic cancers with MSLN expression who have progressed after standard-of-care therapy are eligible for EVEREST-2. Enrollment to EVEREST-2 and collection of T-cells occurs through the ongoing prescreening study BASECAMP-1 (NCT04981119). When clinically appropriate, A2B694 is manufactured from cryopreserved T cells, and patients undergo lymphodepletion before A2B694 infusion. The dose-escalation phase is evaluating the safety and tolerability of A2B694 to identify the recommended phase 2 dose (RP2D). Dose escalation was started at 1x10 8 Tmod positive cells (dose level [DL] 1) and will increase up to 14x10 8 in combination with low-dose IL-2 (DL 5). The dose-expansion phase will confirm RP2D and collect biomarker data to further characterize A2B694. Results: As of January 15, 2025, 5 participants (median age: 60 years; range, 50-84) have enrolled on EVEREST-2 and received A2B694 at DLs 1-2; participants had ovarian cancer (n = 3), pancreatic cancer (n = 1), and non-small cell lung cancer (n = 1) and had received a median of 4 prior lines of therapy (range, 1-7). Lymphodepleting chemotherapy was well tolerated with no significant cytopenias observed. The most common adverse events were lymphopenia (7 [14.6%]) and decreased appetite (6 [12.5%]). There were no dose-limiting toxicities, cytokine release syndrome, nor related neurotoxicity. One participant was admitted to the hospital for decreased appetite. No long-term toxicities have been noted up to 7.5 months post-infusion. Of the participants who have received A2B694, 5 were efficacy evaluable at DLs 1-2. A2B694 was detected post-infusion in the peripheral blood in all patients. Additionally, A2B694 was detected in an abdominal tumor biopsy from a patient with pancreatic cancer 42 days post-infusion. Conclusions: The logic-gated approach was successful at reducing toxicity seen with prior MSLN-targeted CAR T therapies, and A2B694 showed successful CAR T expansion and tumor infiltration. The maximum tolerated dose has not been reached, and results from the dose-escalation phase continue to determine the RP2D. Clinical trial information: NCT06051695 .

e16408 Background: A2B530 is a logic-gated CEA-targeting Tmod CAR T therapy being evaluated in the EVEREST-1 (NCT05736731) phase 1/2 study. Tmod CAR T therapy addresses challenges of on-target, off-tumor toxicity that have limited application of CAR T therapy to solid tumors (Tabernero, et al. J Clin Oncol. 2017); through use of a CEA-targeted CAR-activating receptor combined with a blocking receptor recognizing HLA-A*02, A2B530 can distinguish between tumor and normal cells (Sandberg, et al. Sci Transl Med. 2022). Methods: Patients with unresectable locally advanced or metastatic solid tumors expressing CEA and tumor-associated HLA-A*02 LOH are enrolled through the ongoing prescreening study BASECAMP-1 (NCT04981119). Eligible patients undergo leukapheresis and, when clinically appropriate, A2B530 is manufactured for the EVEREST-1 study. Patients undergo lymphodepletion before A2B530 infusion. The phase 1 dose escalation will evaluate safety, tolerability, manufacturing feasibility, and biomarkers starting at 1x10 8 Tmod positive cells (dose level [DL] 1) up to 6x10 8 cells and higher doses of lymphodepleting chemotherapy (LDC; DL 5). After the recommended phase 2 dose has been established, dose expansion will confirm safety and activity. Results: As of January 15, 2025, 14 total participants were enrolled on EVEREST-1 and had received A2B530 infusion at DLs 1-5, 4 (29%) with pancreatic (PANC) and 10 (71%) with colorectal cancer. Median age was 57 years (range, 34-76), with a median of 2 prior lines of therapy (range, 1-6). LDC was well tolerated: neutropenia nadired at days 7-10, with recovery in all patients, and no significant episodes of prolonged cytopenia. There were no dose-limiting toxicities, grade > 3 serious adverse events (AEs), or episodes of related neurotoxicity. Most gastrointestinal AEs occurred early and were grade 1 or 2. One patient in DL 2 (2x10 8 cells) experienced possible grade 2 cytokine release syndrome (CRS), which started on day 15 and resolved with supportive therapy within 2 days; later the CRS diagnosis was confounded by a positive blood culture from the participant’s central line. The low rate of CRS is consistent with the low levels of serum cytokines measured up to 28 days post-infusion. Central response assessment has been completed for the 6 participants in DLs 1-2, with a partial response observed in 1 of 3 (33%) of participants with PANC. Peak expansion shows a possible dose response. Conclusions: Treatment with A2B530 was well tolerated, showing potential clinical efficacy and a potential dose response, although these are initial results. Maximum tolerated dose has not been reached, and dose escalation continues to determine the optimal phase 2 dosing of this treatment regimen. Clinical trial information: NCT05736731 .

e16457 Background: Patients with inoperable stage II-III pancreatic cancer commonly undergo sequential stereotactic body radiation therapy (SBRT) and chemotherapy. However, there is variability in clinical outcomes, and the predictors of high-risk patients with rapid tumor progression (within 3 months) and poor overall survival (OS) despite treatment are not well characterized. We developed a radiomic (imaging-derived features) signature (RS) that predicts rapid progression. We then investigated clinical characteristics, including pathologic features and treatments received, and RS in a combined analysis to develop and validate the highest-performing model to predict OS from the time of SBRT initiation. We identified the most predictive feature from the combined model that best predicts OS. Methods: In our retrospective study, we examined a cohort of 124 stage II-III pancreatic cancer patients who underwent sequential SBRT and systemic chemotherapy and had pre-treatment pancreatic protocol computed tomography (CT) imaging. We examined 10 clinical features and extracted 900 radiomic features from each segmented tumor per patient using PyRadiomics. Dividing our cohort into training and test sets (60:40), we built a prediction model for rapid tumor progression using radiomic data on the training set (n = 74), applying a LASSO-based algorithm for feature selection and 5-fold cross-validation for parameter optimization. We validated the model performance on the held-out test set (n = 50) and generated the RS for predicting rapid progression. We examined the performance of clinical features and RS in predicting OS in univariate and multivariate Cox regression models. Results: Analysis on our cohort (57 men, 67 women; mean age 67 ± 11 years) generated a 43-feature RS that predicted rapid tumor progression (AUC 0.83, 95% CI: 0.70–0.94) in the test set. High RS was a significant predictor of mortality with hazard ratio (HR) 2.22 (95% CI: 1.32–3.73, p = 0.003) within the first year and 2.85 (95% CI: 1.35–6.03, p = 0.006) thereafter. Non-intensive chemotherapy increased only early mortality risk (HR 1.95, 95% CI: 1.08–3.53, p = 0.03), while older age was significant in later years (HR 1.80, 95% CI: 1.02–3.15, p = 0.04). Conclusions: CT-derived RS accurately predicted rapid tumor progression in stage II-III pancreatic cancer patients undergoing SBRT sequentially with chemotherapy. High RS was the strongest prognostic indicator for increased mortality risk, suggesting its utility for guiding treatment or selection for clinical trials.

TPS4616 Background: Osseous metastases (OM) occur in approximately 30% patients with advanced RCC. Despite therapeutic advances, OM are associated with poor survival and risk of symptomatic skeletal events (SSEs). Cabozantinib targets multiple tyrosine kinases, including vascular endothelial growth factor (VEGF) receptors and MET (Mesenchymal-Epithelial Transition factor), which are overexpressed in OM, contributing to cabozantinib’s enhanced bone activity. Radium-223, an alpha-emitting bone-seeking radioisotope, prolongs survival in men with metastatic castration-resistant prostate cancer to the bone. Building on this therapeutic approach targeting OM, our pilot study of radium-223 with VEGF inhibition in RCC with OM has also shown safety, improvement in circulating bone turnover markers, and early efficacy (McKay et al, CCR 2018). To address the unmet need to improve SSE rates and outcomes in RCC and OM, we designed a study investigating cabozantinib with or without radium-223 in patients with RCC with OM (NCT04071223). Methods: This is an open-label, multicenter randomized phase-2 study. Key inclusion criteria include metastatic RCC of any histology with ≥1 OM, at least 1 OM without prior radiation, any number of prior therapies, and Karnofsky performance status ≥ 60%. Use of a bone protecting agent is required unless contraindicated. Patients are randomized 1:1 to cabozantinib with (Arm A) or without (Arm B) radium-223. The starting dose of cabozantinib for Arm A is 40 mg by mouth daily to be escalated to 60 mg daily after cycle 1 (1 cycle = 28 days) if no persistent grade 2 or grade ≥3 toxicity. Radium-223 is administered at a fixed dose of 1.49 microcurie/kg IV every 28 days x 6 doses. The starting dose for cabozantinib in Arm B is 60 mg daily. The primary endpoint is SSE-free survival. Secondary endpoints include safety, progression-free survival, overall survival, time to first SSE, objective response rate, time to subsequent anti-cancer therapies, quality of life (QoL) measures, and correlative analyses including liquid biopsy and tumor tissue analysis. The study is designed to have 85% power to detect an improvement in 6-month SSE-free survival rate from 65% to 78% with one-sided α = 0.05 significance. To ensure 124 evaluable patients, target accrual is 134 (67 per arm). The group-sequential design includes a safety run-in and an interim analysis for futility when 50% of the expected number of events have been observed. The safety run-in, performed in the first 12 patients randomized to combination therapy, did not demonstrate dose limiting toxicities. Final data analysis will occur when 99 events have been observed. The study was activated in July 2020 and accrual is ongoing throughout the National Clinical Trials Network (NCTN). Continued site participation and enrollment are essential to evaluate this therapeutic strategy. Clinical trial information: NCT04071223 .

4568 Background: The 2IR immune response score was initially developed using bulk RNA sequencing of pre-treatment tissue from ImVigor 210 and CheckMate 275 trials, however these trials enrolled patients (pts) with pure urothelial carcinoma (pUC) histology. Patients with hsUC often exhibit worse response to immune checkpoint inibitors (ICI) than patients with pUC. Here, we evaluated the 2IR score as a prognostic or predictive biomarker in real-world pts with hsUC. Methods: Specimens from pts with pUC (n = 1677) and hsUC (n = 417) were profiled at Caris Life Sciences (Phoenix, AZ) using next generation sequencing (NGS) of DNA and RNA. HsUC histologies included majority ( > 50%) squamous (n = 340), sarcomatoid (n = 51), neuroendocrine (n = 20), and micropapillary (n = 6) component. 2IR was calculated by comparative RNA expression of 10 adaptive immune genes and 39 pro-tumorigenic genes. Tumors were classified as 2IR-Low (2IR ≤ -0.5), -Mid (-0.5 < 2IR < 0), and -High (2IR ≥ 0), as previously described (Wang et al., 2022). Spearman correlation analysis was utilized to compare 2IR with tumor mutation burden (TMB), interferon score (IFN) and the tumor microenvironment (TME) cell fractions estimated using quanTIseq. Clinical outcomes included real-world overall survival (rwOS) from ICI start to last contact and time on treatment (ToT) with pembrolizumab, obtained via matched insurance claims data and calculated using Kaplan-Meier methods, while Hazard ratio (HR) was calculated by Cox proportional model. Results: For patients with hsUC, distribution of 2IR score was High 5.76%, Mid 33.3%, and Low 60.9%. Median 2IR score was significantly lower in squamous (-0.60, p < 0.0001) and sarcomatoid UC (-0.82, p < 0.0001) compared to pUC (-0.41) and significantly higher in neuroendocrine UC (-0.15, p = 0.003). Among patients with hsUC, median rwOS was significantly longer for patients with high/mid 2IR score compared to low 2IR score (25.3 [10.9-39.3] months vs. 8.7 [6.2-11.3] months; HR 0.52, 95% CI 0.34 – 0.78, p = 0.0017). ToT with pembrolizumab was also significantly longer for high/mid 2IR score compared to low 2IR score (3.0 [1.4-5.5] months vs. 2.1 [1.4-3.3] months; HR 0.68, 95% CI 0.46-1.00, p = 0.0471). Similar to pUC, 2IR score in patients with squamous UC was positively associated with CD8 T cell infiltration (r = 0.39; p < 0.0001), IFN score (r = 0.41, p < 0.0001), and TMB (r = 0.20, p < 0.001) and negatively associated with M1 macrophage infiltration (r = -0.25, p < 0.0001). 2IR scores in hsUC correlated positively but not significantly with mutations in TP53 (Median: -0.59 vs -0.62, p = 0.067) and PIK3CA (Median: -0.56 vs -0.61, p = 0.172) and negatively with mutations in CDKN2A (Median: -0.67 vs -0.59, p = 0.052). Conclusions: In a real-world cohort of patients with hsUC, we show the 2IR score may be prognostic for rwOS and predictive for pembrolizumab ToT. Prospective studies are needed to further validate this biomarker for use in this population.

TPS2677 Background: Despite the success in hematologic malignancies, CAR T therapies face significant challenges in solid tumors due to the lack of tumor-specific targets that distinguish cancer from normal cells. EGFR plays a critical role in oncogenesis across several cancers and is often upregulated (TCGA 2022). While monoclonal antibodies targeting EGFR have demonstrated efficacy, these approaches are often limited by on-target, off-tumor toxicities, such as skin rash, which constrains dose escalation and efficacy (Macdonald, et al. J Am Acad Dermatol . 2015). A2B395 is an allogeneic, logic-gated, EGFR-targeted Tmod CAR T therapy designed to address these limitations and provide a convenient and consistent off-the-shelf option. This therapy incorporates 2 CARs: an activator targeting EGFR, and a blocker targeting HLA-A*02. The activator recognizes EGFR on both tumor and normal cells, while the blocker inhibits CAR T activity against normal cells with preserved HLA expression and decreases the risk for graft-versus-host disease (Hamburger, et al. Mol Immunol . 2020). To address potential host-vs-graft response, an shRNA expression module targeting B2M is included in the Tmod construct, which significantly reduces major histocompatibility complex class I levels and subsequent host immune response (DiAndreth, et al. Clin Immunol. 2022). Importantly, the Tmod system is modular and adaptable to multiple targets. Initial data on autologous Tmod CAR T therapy suggest reduced off-tumor toxicity and encouraging clinical efficacy (Grierson, et al. SITC 2024. Abstract 588). A2B395 represents a novel approach for EGFR-expressing solid tumors with HLA-A*02 LOH. Methods: DENALI-1 (NCT06682793) is a phase 1/2, open-label, nonrandomized study evaluating the safety and efficacy of A2B395 in adults. 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 via next-generation sequencing (Tempus AI, Inc.). Key inclusion criteria include histologically confirmed recurrent unresectable, locally advanced, or metastatic cancers associated with EGFR expression, including colorectal, non-small cell lung, squamous cell head and neck, triple negative breast, and renal cell cancers. Patients must have received ≥1 line of prior therapy, such as a checkpoint inhibitor, molecular targeted therapy, or chemotherapy. The primary objective of phase 1 is to evaluate safety, tolerability, and the recommended phase 2 dose (RP2D) using a Bayesian optimal interval design for dose escalation. The dose-expansion phase will confirm RP2D and collect biomarker data. Phase 2 will assess overall response rate per RECIST v1.1. Clinical trial information: NCT06682793 .

Objective Aneurysm wall enhancement (AWE) is a potential biomarker of inflammation within the aneurysm wall that has been correlated with a higher risk of rupture. Aspirin (ASA) may decrease AWE due to its anti-inflammatory properties. We aimed to assess the effect of ASA on AWE in an animal model and a cohort of patients with unruptured intracranial aneurysms (UIAs). Methods Three rabbits with elastase-induced aneurysms were exposed to ASA for 8 weeks and three rabbits were used as controls. 3 T high-resolution magnetic resonance imaging (HR-MRI) was performed at 7 days and 8 weeks to evaluate changes in AWE through histological and immunohistological analyses. Additionally, we evaluated AWE in patients who underwent imaging with a 3 T HR-MRI protocol. ASA exposure was defined as daily intake of 81 mg for at least six months prior to HR-MRI. AWE was quantified using three-dimensional AWE maps and histograms. Results Among rabbits exposed to ASA, the mean AWE was lower at 8 weeks compared to the controls (2.11 vs 2.15, p = 0.13). Immunostaining of the aneurysm wall in rabbits that received ASA revealed a reduced expression of CD68 + or cyclooxygenase-2 + cells, compared to the controls. A total of 99 patients with 120 UIAs were included in the HR-MRI analysis of UIAs. UIAs exposed to ASA (22/120) had significantly lower median AWE than those that were not exposed (0.60 vs 0.72, p = 0.032). Conclusion ASA therapy is associated with an objective reduction in AWE, suggesting a potential role in lowering the risk of aneurysm rupture.