Ritter, John

Abstract RATIONALE: The diagnosis of Pulmonary Embolism (PE) is associated with high mortality and morbidity. In patients with cancer, high-risk pulmonary emboli further escalate these risks. Ensuring access to the necessary resources for appropriate intervention is crucial for improving patient outcomes. However, the resource-intensive nature of managing multiple life-threatening conditions can create barriers for certain demographic populations, leading to disparities in outcomes. To address this issue, we explored mortality trends among diverse groups based on gender, ethnicity, and geographical background in the United States from 1999-2000. METHODS: We obtained mortality data from death certificate queries in the Centers for Disease Control and Prevention Wide-range Online Data for Epidemiologic Research database. Queries included all decedents with the underlying cause of death being PE (I26) in patients with a diagnosis of cancer (C00 – C97). Age-adjusted mortality rates (AAMR) per 100,000 people were compared across demographic populations, and 95% Confidence Intervals were standardized to the year 2000. Log-linear regression models were utilized to assess temporal mortality shifts and calculate annual percentage change (APC) from 1999 to 2020. RESULTS: A total of 179483 PE-related deaths was reported in patients with cancer. The AAMR increased from 2.14 [2.08-2.19] in 1999 to 3.05 [3.00-3.11] in 2020. The cumulative AAMR was 2.42 [2.41-2.43] with an average APC of +1.56% (p<0.001). The mortality rate accelerated following the year 2016, with the years prior having an APC of +0.69%, (p<0.001) and the years following having an APC +5.33% (p<0.001). A higher mortality was observed in males (AAMR 2.71 [2.69-2.73]) than females (2.20 [2.18-2.21]), in rural communities (AAMR 2.50 [2.47-2.53]) compared to urban communities (AAMR 2.38 [2.37-2.40]), and in non-Hispanic (AAMR 2.48 [2.47-2.49]) populations over Hispanic populations (AAMR 1.45 [1.42-1.48]). Mortality was highest in the Black population (AAMR 3.65 [3.60-3.69]), followed by White population (AAMR 2.33 [2.32-2.34]), American Natives (AAMR 1.43 [1.33-1.54]), and Asian (AAMR 1.04 [1.00-1.08]). Geographically, Midwest (AAMR 2.58 [2.56-2.61]) had the highest mortality while the South (AAMR 2.26 [2.24-2.28]) had the lowest mortality. CONCLUSIONS: We identified significant disparities in mortality related to pulmonary embolism (PE) among cancer patients across different demographic populations. Further investigation into these healthcare inequities is essential for addressing the disparities affecting various groups.

Abstract Background: Bladder cancer patients with lower socioeconomic status (SES) often present with more aggressive disease and face poor outcomes, likely due to complex interactions with risk factors linked to lower SES. However, little is known about the effect of low SES on bladder tumor biology at the molecular level. This study sought to characterize better the impact of low SES on the bladder tumor microenvironment. Methods: This is a retrospective analysis of 93 patients (63 male and 30 female) ranging from age 33 to 92 presenting to the University of Arizona Cancer Center with bladder cancer from 2016-2023. Each patient's neighborhood level of SES was scored using the Area Deprivation Index on a scale of 1-100, with 1 representing the highest SES and 100 the least. These patients were then split into tertile 1: 1-33 (T1: N=16), tertile 2: 34-67 (T2: N=43), and tertile 3: 68-100 (T3: N=34), and each patient’s tumor microenvironment and mutational landscape was characterized and compared utilizing NGS (592, NextSeq; WES, NovaSeq) and WTS Sequencing (NovaSeq) (Caris Life Sciences, Phoenix, AZ). Statistical significance was determined using chi-square and Mann-Whitney U (p<0.05). Results: Our study had no significant difference between age, sex, and race between the three tertiles. Hispanic ethnicity was significantly higher in T3 (26.5%) when compared to T2 (7%) and T1 (0%), p=0.013. The frequency of TMB-H (>10 mutations/megabase) was significantly lower in T3 (15.6%) when compared to T2 (51.2%, p=0.02) and T1 (50%, p=0.01). There was significantly less T cell CD8+ infiltration in tertile 3 (0.02%) when compared to T2 (0.43%, p=0.04) and T1 (0.37%, p=0.08), and less dendritic cell infiltration in T3 (0%) when compared to T2 (0.1%, p=0.13) and T1 (0.64%, p=0.008). T regulatory cells were lower in T3 (1.37%) compared to T2 (2.13%, p=0.09) and T3 (2.02%, p=0.24). IHC-PD-L1 and gene expression for immune checkpoint genes, MHC-Class I, and MHC-Class II did not vary significantly between tertiles. KMT2C-mt was highest in T2 (21.1%) compared to T1 (3.12%, p=0.03) and T3 (6.67%). There was no other significant differences in mutation prevalence between the three tertiles. Discussion: In our study, lower SES bladder cancer patients had a lower amount of CD8+ cells, dendritic cell infiltration, and a low frequency of TMB-H, indicating a lower level of adaptive immune response present in the tumor microenvironment. Lower levels of adaptive immune activity have been associated with more aggressive tumor behavior and worse outcomes in bladder cancer patients. These findings provide a partial explanation of the molecular mechanisms underlying the poor prognosis observed in low SES patients with bladder cancer. Larger-scale studies exploring the impact of SES on tumor biology are essential as they hold significant therapeutic and preventive implications. Citation Format: Tom Marco, Kenneth Barker, Jesse Ritter, Numaan Mahmood, Rishab Srivastava, Amith Rao, Isaac Zarif, Ricardo Estrada Mendizabal, Sachin Deshmukh, Edgar Tapia, Jose Guillen-Rodriguez, Juan Chipollini, Alejandro Recio-Boiles. The effects of socioeconomic deprivation on the tumor microenvironment of bladder cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 7392.