Search

467 Background: Neuroendocrine, small cell, or large cell carcinoma originating from the urothelium (uro-NE/SCC/LCC) is rare. Outcomes for metastatic disease are dismal. Treatment is extrapolated from small cell lung cancer, for which immune checkpoint inhibitors (ICIs) have modest activity. Preliminary activity has been reported with ICI for uro-NE. We aimed to compare real-world progression-free survival (PFS) and overall survival (OS) between ICI-containing and non-ICI-containing regimens in the first line (1L) metastatic setting for uro-NE/SCC/LCC. Methods: We performed a retrospective study at 11 cancer centers. Patients (pts) who received systemic therapy (2011-2021) for biopsy confirmed metastatic uro-NE/SCC/LCC were included. Pts with metastasis within 6 months of (neo)adjuvant chemotherapy (CT) (n=16) were excluded from 1L analyses. Results: 102 pts with metastatic uro-NE/SCC/LCC were evaluable. 17 (16.7%) had NE histology, 81 (79.4%) SCC, and 4 (3.9%) LCC. NE/SCC/LCC was mixed with urothelial histology in 19 (18.6%). Primary tumors were most often in the bladder (84.3%, n=86), less frequently upper tract (11.8%, n=12) or urethra (3.9%, n=4). 42 pts (41.2%) were previously treated for localized disease, the rest were de novo metastatic (n=60, 58.8%). Pts who received an ICI in any line (n=61) had significantly longer OS (p=0.038) than pts that never received an ICI (n=41). As shown in the table, in the 1L, ICI-containing regimens (n=33) resulted in significantly longer PFS, but not OS or ORR compared to non-ICI regimens (n=53). Subdividing 1L regimens into ICI without CT (n=14), CT without ICI (n=53), or ICI + CT (n=19), both PFS and OS were significantly different with similar ORR. ICI w/o CT had the longest median PFS and OS with an ORR 57.1% comparable to CT regimens. Of 61 pts that received ICI in any line, 14 (23.0%) had an immune-related adverse event of any grade; 11 (18.0%) received steroids. Conclusions: This is the largest ever report of ICI for metastatic uro-NE/SCC/LCC. ICIs were associated with improved outcomes with expected added toxicity. Further prospective investigation of ICI regimens is warranted. [Table: see text]

547 Background: Despite recent therapeutic advancements for patients with mUC, including checkpoint inhibitors (CPIs), anti-FGFR and antibody-drug conjugates (ADCs), biomarker data to predict therapeutic response and identify mechanisms of resistance remain limited. Ongoing randomized clinical trials evaluating the combination of CPIs and ADCs in these pts underscore the need to develop biomarkers to better understand who might best respond to these therapies. Here, we employ a liquid biopsy approach to molecularly characterize circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA), including those isolated with Trop-2, the target of the novel drug Sacituzumab Govitecan and Datopotamab Deruxtecan. Methods: 104 blood samples serially collected from pts being treated for mUC were used for CTC collection using anti-EpCAM and Trop-2 antibodies in parallel. CTCs were isolated and stained for immune markers PD-L1 and HLA I using the VERSA (Versatile Exclusion-based Rare Sample Analysis) platform. Plasma was isolated for paired analysis of CTC and ctDNA content. CTCs were analyzed for enumeration and single-cell protein analysis. Overall survival (OS) was defined from time of sample collection, and survival analyses were performed using the Kaplan-Meier method. Results: We observed significantly shorter OS in pts with higher CTC burden (≥ 20 CTCs/7.5 mL blood) in samples captured with either EpCAM (median 34.1 vs 3.1 mo, P < 0.01) or Trop-2 (median 34.1 vs 6.2 months, P < 0.01). Furthermore, EpCAM and Trop-2 CTC burdens were higher at progression timepoints relative to responding or stable timepoints, when stratified according to treatment modality (table). Inter and intra-patient heterogeneous PD-L1 and HLA I expression and co-expression was observed on CTCs although no significant differences were seen globally between EpCAM and Trop-2 CTCs. In a cohort of pts treated with CPIs, we observed dynamic phenotypic changes in the ratio of HLA:PD-L1 that differed between EpCAM and Trop-2 CTCs. ctDNA analysis identified concordant increases in tumor fraction and acquired genomic mutations. When examined longitudinally across individual pts, these findings in tandem with changes in enumeration, suggest the emergence of different CTC subpopulations that may serve as biomarkers of resistance. Conclusions: We identify the prognostic significance of CTC enumeration with parallel EpCAM and Trop-2 CTC isolation and demonstrate the utility of a liquid biopsy assay that can detect pharmacodynamic changes in CTC burden and immune marker expression throughout the course of treatment. [Table: see text]

247 Background: The mainstay of therapy in metastatic prostate cancer is androgen receptor (AR) signaling inhibition. However, the emergence of early castration resistance or neuroendocrine transformation is associated with poor prognosis. Reliable biomarkers are needed to identify these patients and guide selection of clinical therapy. Methods: mRNA was isolated from EpCAM-positive circulating tumor cells (CTCs) isolated from patients with CSPC, CRPC, or NEPC to measure expression of KLK2, KLK3 (PSA), TMPRSS2, FOLH1 (PSMA), synaptophysin ( SYP), and chromogranin ( CHGA). Post-hoc retrospective analysis of an institutional review board–approved prospective cohort (N = 98) was performed to identify patterns of gene expression. Samples were considered AR+ if 3 of 4 AR pathway genes ( TMPRSS2, KLK2, KLK3, and FOLH1) were positive, and were considered NE+ if either or both SYP or CHGA were positive. Blood samples from two prospective clinical trials of men with mCRPC treated with abiraterone and enzalutamide, respectively, were analyzed to confirm results. Longitudinal samples were collected from 17 patients (6 NEPC and 11 Adenocarcinoma) and cell free DNA was isolated and sequenced using a novel targeted exon panel. Results: AR and/or NE positive patients were found to have a median overall survival (OS) of 8.58 months as compared to a median OS of 29.6 months in the AR and NE negative population (p

Background: Many rural-urban indexes are utilized in United States cancer research. This variation introduces inconsistencies between studies with a rural-urban component. Recommendations to date on which index to utilize have prioritized index geographical unit over feasibility of index inclusion in analysis. We evaluated rural-urban indexes and recommend one index for use to increase comparability across studies. Methods: We assessed nine U.S. rural-urban indexes regarding their respective rural and urban code ranges; geographical unit, land area, and population distributions; percent agreement; suitability as continuous variables in analysis; and feasibility of integration into national, state, and local cancer research. We referenced 1,569 Wisconsin Pancreatic Cancer Registry patients to demonstrate how rural-urban index choice impacts patient categorization. Results: Six indexes categorized rural and urban areas. Indexes agreed on binary rural-urban designation for 88.8% of the U.S. population. As ternary variables, they agreed for 83.4%. For cancer registry patients, this decreased to 73.4% and 60.4% agreement, respectively. Rural-Urban Continuum Codes (RUCC) performed the best with ability to differentiate metropolitan, micropolitan, and rural counties, are available for retrospective and prospective studies, and can be coded continuously for analysis. Conclusions: Whether a patient was categorized as urban or rural changed depending on which index was used when applied to a cancer registry data set. We conclude that RUCC is an appropriate and feasible rural-urban index to include in cancer research, as it is standardly available in national cancer registries in its 9-code format and can be matched to patient’s county of residence for local research and it had the least amount of fluctuation of the indices analyzed. Utilizing RUCC as a continuous variable across studies with a rural-urban component will increase reproducibility and comparability of results and eliminate the choice of rural-urban index as a potential source of discrepancy between studies. Trial registration: Not applicable

Infectious hematopoietic necrosis virus (IHNV) and Flavobacterium psychrophilum are major pathogens of farmed rainbow trout. Improved control strategies are desired but the influence of on-farm environmental factors that lead to disease outbreaks remain poorly understood. Water reuse is an important environmental factor affecting disease. Prior studies have established a replicated outdoor-tank system capable of varying the exposure to reuse water by controlling water flow from commercial trout production raceways. The goal of this research was to evaluate the effect of constant or pulsed reuse water exposure on survival, pathogen prevalence, and pathogen load. Herein, we compared two commercial lines of rainbow trout, Clear Springs Food (CSF) and Troutex (Tx) that were either vaccinated against IHNV with a DNA vaccine or sham vaccinated. Over a 27-day experimental period in constant reuse water, all fish from both lines and treatments, died while mortality in control fish in spring water was National Institutes of Health EEIDUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [R01GM113233]; US Department of Agriculture, Agricultural Research ServiceUnited States Department of Agriculture (USDA)USDA Agricultural Research Service [1930-32000-006] Published version This work was supported by the National Institutes of Health EEID [grant number R01GM113233]; and the US Department of Agriculture, Agricultural Research Service [Project number 1930-32000-006 Integrated Research to Improve On-Farm Animal health in Salmonid Aquaculture]. The authors alone are responsible for the content and writing of this paper. Public domain – authored by a U.S. government employee

e18524 Background: Treatment and survival disparities faced by Medicaid patients are documented for pancreatic, colon-rectosigmoid, and liver cancers at a national level. Studies show these disparities persist at academic medical centers. We assessed Medicaid treatment and survival outcomes among University of Wisconsin-Health (UWH) pancreatic, colon-rectosigmoid, and liver cancer patients to determine whether national trends persisted at this academic medical center. Methods: We included UWH registry data for 1567 pancreatic, 2313 colon-rectosigmoid, and 1027 liver cancer patients ages 18+ from 2004-2016. We performed multivariable logistic regression to estimate odds ratios (ORs) to assess insurance disparities in intended resection and Cox Proportional regression to estimate hazard ratios (HRs) to assess all-cause mortality disparities for each cancer, adjusting for age, sex, race/ethnicity, BMI, comorbidity, stage, rurality, and insurance. Results: Median overall survival was 6.5 months (range 0.1-147.5) for pancreatic, 12.8 months (0.1-167.5) for colon-rectosigmoid, and 12.5 months (0.1-168.7) for liver cancer patients. 3% of pancreatic, 5% of colon-rectosigmoid, and 9% of liver cancer patients had Medicaid Insurance. Medicaid patients were less likely to be older and non-Hispanic White than private insurance (private) patients for each cancer. Medicaid patients were diagnosed with more distant disease for colon-rectosigmoid and liver cancers and less distant disease for pancreatic cancer. Medicaid patients were less likely to receive surgery vs private patients for pancreatic (OR 0.41, 95% CI 0.16-1.08) and liver (OR 0.62, 0.26-1.49) cancers, though confidence intervals were wide. Insurance was not associated with surgery in colon-rectosigmoid cancer patients (OR 0.97, 0.48-1.97). Medicaid patients had a higher risk of death vs private patients for colon rectosigmoid cancer (HR 1.50, 1.12-2.01). Risk of death was modestly elevated for Medicaid vs private patients for pancreatic (HR 1.35, 0.97-1.87) but not liver (HR 1.07, 0.77-1.48) cancer. Conclusions: Medicaid pancreatic and liver cancer patients may be less likely to receive surgery than private patients in our one center study. Results suggested that Medicaid pancreatic and colon-rectosigmoid cancer patients may have a slightly elevated risk of death vs private patients, though this needs confirmation in larger samples. Future studies should explore at which local, state, and regional levels Medicaid pancreatic, colon-rectosigmoid, and liver cancer patients experience treatment and survival disparities vs private insurance patients. These studies, combined with Medicaid expansion studies, can guide healthcare leaders and policy makers to design context-appropriate interventions to reduce insurance-related disparities in cancer treatment and outcomes.

Background: Socioeconomic-based treatment disparities are well-documented in pancreatic cancer in the United States. Studies have found treatment disparities by race and ethnicity, insurance, income, sex, and age. We examined 14 years of pancreatic cancer intended first course treatment data in a Midwestern state to identify state-specific disparities. Methods: Data from 8,416 pancreatic cancer patients aged over 18 diagnosed with adenocarcinoma, NOS or infiltrating duct carcinoma, NOS from 2004 to 2017 were obtained from the Wisconsin Cancer Reporting System. Adjusted logistic regression was performed to describe the association between patient characteristics and intended first course treatment. Treatment was defined as radiation, chemotherapy, or surgery, alone or in combination. The analysis was completed for all patients. It was repeated for the subset of 5,005 Medicare Patients to examine disparities by Medicare subtype. Race/ethnicity, sex, rurality, and insurance were factors of interest. Age and stage at diagnosis were included as confounders. Results: The mean overall survival of the 8,416 patients was 9.9 months. 70.5% of patients received treatment. 53% of patients were diagnosed with metastatic disease. The adjusted odds ratio of receiving treatment was 0.52 (0.41-0.65) for Non-Hispanic Black patients, 0.46 (0.24- 0.88) for Non-Hispanic Asian patients, and 0.46 (0.22-0.94) for patients categorized as ‘Other’ race/ethnicity compared to Non-Hispanic White patients. The adjusted odds ratio of receiving treatment was 0.90 (0.81-1.00) for female compared to male patients. The adjusted odds ratio of receiving treatment was 0.40 (0.29-0.54) for Medicaid patients, 0.80 (0.66-0.97) for Medicare patients, 0.44 (0.32-0.61) for Military patients, 0.18 (0.09-0.35) for Not Insured patients, and 0.24 (0.15-0.39) for Self Pay patients compared to Private Insurance patients. Among the 5,005 Medicare patients, the adjusted odds ratio of receiving treatment was 0.49 (0.35-0.68) for Non-Hispanic Black compared to Non-Hispanic White patients, 0.86 (0.76-0.98) for female compared to male patients, and 0.45 (0.33-0.62) for Medicare with Medicaid eligibility compared to Medicare, NOS patients. The adjusted odds ratio of receiving treatment was 1.42 (1.19-1.69) for Medicare patients with a supplement, NOS, 1.36 (1.11-1.66) for Medicare patients where Medicare was administered via a managed care plan, and 1.38 (1.13-1.70) for Medicare patients with a private supplement compared to Medicare, NOS patients. Rurality was not associated with treatment in either model. Conclusions: Significant race/ethnicity, sex, and insurance-based treatment disparities exist amongst Wisconsin pancreatic cancer patients. Future studies should investigate the contribution of social, clinician, and healthcare system factors that impact inequitable access to, inconsistent presentation of, and underutilization of treatment for people of color, women, and publicly insured or uninsured patients. Citation Format: Andrea M. Schiefelbein, Amy K. Taylor, Yana Puckett, Jienian Zhang, John K. Krebsbach, John M. Hampton, Amy Trentham- Dietz, Melissa C. Skala, Sharon M. Weber, John M. Eason, Noelle K. LoConte. Treatment inequity: Examining the influence of race and ethnicity, sex, and insurance on pancreatic cancer care [abstract]. In: Proceedings of the AACR Virtual Conference: Thirteenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2020 Oct 2-4. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(12 Suppl):Abstract nr PO-105.

119 Background: Race and ethnicity-based treatment and survival disparities are documented for pancreatic cancer. Studies cite patient genetic, biological, and social factors and differences across treatment centers and geographical areas that may contribute to disparities. We investigated treatment and survival disparities for a cohort of 1,569 pancreatic cancer (PC) patients at the local level within a National Cancer Institute-designated comprehensive cancer center. Methods: Data from 1,569 PC patients aged over 18 diagnosed with adenocarcinoma, NOS or infiltrating duct carcinoma, NOS from 2004 to 2016 who received some or all of their care at the University of Wisconsin Carbone Cancer Center were included in the study. Sequential models of adjusted Cox proportional hazard regression were performed to describe the association between race/ethnicity and overall survival. Model I included age, sex and race/ethnicity; model II added BMI, Charlson Comorbidity Index and stage; model III added rurality, treatment course and payer. Treatment course, defined as the receipt of chemoradiation, surgery with/without chemoradiation, or no treatment, rurality, and insurance status were factors of interest. Results: 38.6% of patients were diagnosed with metastatic disease. Overall survival was 11.6 months. Non-Hispanic black (NHB) patients experienced an 88% increased risk of death (95% CI: 23%-188%) and patients categorized as other race/ethnicity experienced a 32% (10%-60%) increased risk of death compared to NH white (NHW) patients in model II. After adding treatment course and insurance status, the hazard ratio for NHB patients decreased to 1.41 (0.92-2.17) and other race/ethnicity patients decreased to 1.27 (1.05-1.53) compared to NHW Patients. Medicaid patients had an adjusted hazard ratio of 1.41 (1.01-1.95) and unknown/uninsured patients had an adjusted hazard ratio of 1.62 (1.71-4.02) compared to managed care patients. Incarcerated patients had an adjusted hazard ratio of 1.28 (0.98-1.67) compared to managed care patients. Conclusions: To reduce disparities across race/ethnicity and insurance status, organizations should invest in financial support programs for patients in need and monitor treatment courses for people of color, underinsured or uninsured patients to verify access to treatment, equitable treatment, and adherence to treatment guidelines. Future studies should investigate the contribution of clinician and healthcare system bias to race and ethnicity-based cancer disparities.

e19063 Background: Trends in oncology examine the influence of rural characteristics on cancer patient (pt) treatment and outcomes. Current definitions of rurality are broad and varied, with multiple standardized definitions. Few analyses exist to compare definitions and quality in assessing oncologic outcomes. We aim to determine which index is most suitable to define rurality in cancer research. Methods: 1,567 pancreatic cancer pts from the University of Wisconsin Cancer Registry, representing 84 Midwestern counties and 452 zip codes, were assigned rurality codes based on three indices spanning 1983-2013: Rural-Urban Continuum Code (RUCC), Rural-Urban Commuting Areas (RUCA), and Index of Relative Rurality (IRR). RUCC and IRR were assigned to pts at the county level and RUCA at the zip level. Pt rurality was compared across the three indices and over time via the median and interquartile range and inspected visually with violin plots. We compared indices with Spearman’s Rank Order Correlation (SROC). Results: RUCC 2003, RUCA 2004 (zip), and IRR 2000 were concordant in terms of metropolitan, micropolitan, and rural designations for 66.9% (1,049) of pancreatic cancer registry pts. The rural designation for almost one-third (489, 31.2%) of pts was discordant by one or two levels across the three indices (i.e. classified as metropolitan in one index and micropolitan or rural in another). SROC was 0.73 between RUCC 2003 and RUCA 2004 (zip) indices, 0.82 between IRR 2000 and RUCA 2004 (zip), and 0.85 between RUCC 2003 and IRR 2000. Across the 84 counties of registry pts’ residence, the median and interquartile range of RUCC decreased from 6 (3-7) in 1983 to 4 (2.25-6) in 2013 and of IRR decreased from 0.49 (0.44-0.53) in 2000 to 0.49 (0.43-0.53) in 2010. Across the 452 zip codes, RUCA decreased from 4 (1-10) in 1998 to 3 (1-8) in 2004. Pts’ median RUCC decreased from 3 (2-6) in 1983 to 3 (2-4) in 2013, median RUCA (zip) decreased from 2 (1-7) in 1990 to 1 (1-6) in 2000, and IRR remained constant at 0.42 (0.38-0.49) in 2000 and 2010. Conclusions: RUCC is preferable for state-level cancer studies incorporating rurality as it best distributes pts across the rural-urban interface compared to RUCA (skews urban) and IRR (skews central). County boundaries (RUCC) are consistent over time versus zip (RUCA) and census tract (RUCA). Our findings suggest that while the extremes of rural and urban are well-defined, rurality as a continuum is inconsistently measured. Researchers should continue to incorporate other measures of vulnerability to achieve health equity.

Lack of health insurance is a serious problem in the United States. Using data from the 1996 Medical Expenditure Panel Survey, this paper examines how insurance varies between black, white, and Latino adults. Because Latino subgroups are not homogeneous, the paper also compares the factors associated with health insurance status for Mexican and Puerto Rican adults. Results indicate that access to private health insurance for Latino adults was more closely associated with workplace characteristics than employment itself. Time lived in the United States was a major factor associated with being uninsured for Mexican adults, while language barriers were a major factor limiting Puerto Rican individuals' access to private health insurance. The paper suggests two approaches for decreasing uninsurance among Latino adults: (1) strengthening the link between employment and private health insurance and (2) addressing disparities in access to public coverage for racial and ethnic groups, including recent immigrants.

Access to health insurance and protection against expenditures for medical care are of special concern to diabetic patients in the United States. This study examines some information on the extent and breadth of public and private health insurance for individuals with diabetes, as well as some estimates of their use of health-care services and their mean expenses for this care. About 12% of all diabetic patients < 65 yr old (∼311,000 individuals) were uninsured throughout 1977, a rate not much different from that for the rest of the United States population. Those with diabetes who are uninsured tend to be younger, Black or Hispanic, in excellent or good health, and live outside of metropolitan areas and in the South or West. As expected, diabetic patients use more medical care than others of their age and sex, and their medical expenses are also much higher, particularly in younger age groups. In 1977, average total medical-care expenses for people with diabetes were $1514 compared with $548 for the rest of the population. They and their families paid ∼ 20% out of pocket (∼ $355). Their health insurance premiums were not much different from those without diabetes, averaging ∼ $1000 in 1977 for those under age 65. The private insurance coverage for diabetic patients was similar to that for others, although slightly fewer had major medical coverage than the general population.

Prologue: Within the American medical care system, the Veterans Administration (VA) operates a vast subsystem that is charged by law with caring for the health care needs of veterans of the armed services. Outlays to finance this enterprise of 172 medical centers, forty-nine satellite or independent outpatient clinics, and 195,000 employees consumed some $8 billion in fiscal 1983. Even in an era of austerity, the VA has proven resilient politically, handily dispensing with any designs the Reagan administration may have had to check its growth. The future, though, remains less clear. The implications of an aging society have been receiving an increasing amount of attention in the last several years. Although much of the discussion has focused on the viability of Social Security and Medicares Hospital Insurance Trust Fund, the VA has focused its concern on the aging veteran. Specifically, what impact will the growing population of aging veterans have on the comprehensive services offered by the VA medical c...

The enhancer landscape is dramatically restructured as naive preimplantation epiblasts transition to the post-implantation state of primed pluripotency. A key factor in this process is Otx2, which is upregulated during the early stages of this transition and ultimately recruits Oct4 to a different set of enhancers. In this study, we discover that the acetylation status of Oct4 regulates the induction of the primed pluripotency gene network. Maintenance of the naive state requires the NAD-dependent deacetylase, SirT1, which deacetylates Oct4. The activity of SirT1 is reduced during the naive-to-primed transition; Oct4 becomes hyper-acetylated and binds to an Otx2 enhancer to induce Otx2 expression. Induction of Otx2 causes the reorganization of acetylated Oct4 and results in the induction of the primed pluripotency gene network. Regulation of Oct4 by SirT1 may link stem cell development to environmental conditions, and it may provide strategies to manipulate epiblast cell state., National Institutes of Health (U.S.), Glenn Foundation for Medical Research, American Cancer Society

Determinants of health insurance choices are estimated from a logit model and data from the National Medical Care Expenditure Survey. Employees offered a choice between traditional health insurance plans chose the high option and the low option in roughly equal numbers. About a quarter of the employees who were offered enrollment in an HMO selected the HMO in preference to a traditional plan. Prices figured significantly in both types of decisions, with the choice between traditional plans about twice as sensitive to prices as the decision to enroll in an HMO. Comprehensive hospital benefits and superior catastrophic protection also appeared to be important factors in the choice of health insurance plans.

Renewed national interest in market forces to promote more efficient and cost-conscious behavior by patients and providers increasingly focuses on the structure of private health insurance benefits. Two features of procompetitive legislative proposals are considered: a ceiling on tax-free employer insurance premiums and offering greater choice of insurance plans. The interests of efficiency and equity invoke different kinds of risks and transfers; no single institutional approach is likely to yield the promised benefits.