The journal retracts the article “Synthetic Makaluvamine Analogs Decrease c-Kit Expression and Are Cytotoxic to Neuroendocrine Tumor Cells” [...]

Sporadic pancreatic neuroendocrine tumors (pNETs) with wild type MEN1 represent a major yet largely ignored subset whose biology and metastatic potential remain poorly understood. Because metastasis can occur despite low histologic grade and modest mutational burden, we hypothesized that metastatic competence in MEN1-wild-type pNETs reflects quantitative reinforcement of shared oncogenic pathways rather than distinct mutational processes. We profiled 75 primary low-grade pNETs by whole-exome and RNA sequencing, including 25 percent with lymph node and/or liver metastasis, and integrated genomic and transcriptomic data to connect pathway lesions with expression state. Metastatic tumors showed a slight increase in mutation frequency but conserved base-substitution spectra relative to non-metastatic cases, and adverse clinicopathologic features were enriched in Grade 2 disease. Aggregating alterations to pathways revealed broad convergence on canonical networks, with transcriptomic analyses demonstrating cohort-wide enrichment of Calcium, WNT, and KRAS/PI3K-AKT programs in metastasis. Intersection of significantly mutated genes with differentially expressed genes identified a focused 29-gene overlap, including RYR1 and ZNF273, that marks these convergent axes and distinguishes metastatic from non-metastatic tumors. Gene set enrichment confirmed preferential activation of Calcium, WNT, and PI3K-AKT signaling in metastatic tumors, consistent with a network-intensity model of progression. Finally, upstream-regulator analysis (iPathwayGuide) and gene-centric perturbation mapping (Gene2Drug) nominated candidate targeted and repurposable agents predicted to reverse the metastatic expression phenotype and flagged drugs unlikely to provide benefit, yielding a prioritized, testable therapeutic shortlist which includes fasudil and spaglumic acid. Convergent, domain-specific mutational patterns in highly mutated genes such as ZNF273 and CLCA1 define a molecular signature that could stratify metastatic risk in low-grade pNETs. Collectively, our data reframe metastasis in MEN1-wild-type low-grade pNETs as a property of pathway state rather than mutation quantity and provide a translational blueprint for biomarker-guided therapy development focused on Calcium, WNT, and KRAS/PI3K hubs.

To prospectively evaluate whether quantitative DCE-MRI can predict early chemotherapy response in pancreatic ductal adenocarcinoma (PDAC), and to assess the added value of a point-of-care portable perfusion phantom (P4) for correcting scanner-dependent errors. Fifty-four patients with biopsy-confirmed PDAC were prospectively enrolled at two institutions; 42 completed MRI scans at baseline (1 ± 1 weeks before chemotherapy) and 7 ± 2 weeks after treatment initiation. P4s were imaged concurrently to correct for scanner-dependent measurement errors. Eleven pharmacokinetic (PK) parameters were derived using Tofts, extended Tofts, and shutter speed models. Treatment response at 17 ± 4 weeks was assessed using the modified RECIST, with responders defined as patients with > 10

OBJECTIVE:The objective was to evaluate historical and contemporary trends in the terminology used to describe pancreatic head resection procedures in the English-language medical literature and to assess whether nomenclature use has changed over time and whether linguistic accuracy aligns with term prevalence. METHODS:A bibliometric analysis was conducted using a comprehensive title and abstract-based search across PubMed, Web of Science, and Cochrane databases, encompassing all available publications through December 2023. Articles were included if their titles or abstracts contained any of the following terms: "pancreatoduodenectomy," "pancreaticoduodenectomy," "duodenopancreatectomy," "Whipple procedure," "pylorus-preserving pancreatoduodenectomy," or "pylorus-preserving pancreaticoduodenectomy." There were no restrictions on article type, publication year, or original language. Duplicate entries were removed, and exact match algorithms were used to identify and quantify terminology usage across titles and abstracts. Descriptive statistics were used to analyze frequency trends by year. RESULTS:Of 28,933 identified records, 17,037 unique publications were included for analysis. From 1943 to the early 2000's, term usage was relatively balanced. However, from 2004 to 2023, "pancreaticoduodenectomy" accounted for 65.7% of all titles, and "pancreatoduodenectomy" appeared in 27.9%. The use of "duodenopancreatectomy" and other variants declined markedly. Despite grammatical and etymological evidence favoring "pancreatoduodenectomy," the less accurate "pancreaticoduodenectomy" has become increasingly dominant. CONCLUSION:Terminology describing pancreatic head resection lacks standardization, with a growing preference for a linguistically imprecise term. These inconsistencies may affect medical education, literature indexing, and the integration of terminology into data-driven systems such as electronic medical records. Standardizing language based on etymological accuracy and clinical clarity should be prioritized in surgical training, academic publishing, and health information management.

Abstract Background: Calreticulin (CALR) is an endoplasmic reticulum (ER) protein that can translocate to tumor cell surfaces during partial ER stress. Surface CALR is largely absent on normal cells yet upregulated on many types of tumor cells undergoing stress, making it a tumor-specific target with potential ubiquity and application as a tumor-agnostic biomarker. Targeting surface CALR with theranostic agents could offer a novel strategy to visualize tumors and monitor treatment response. We hypothesized that de novo protein design could generate a novel CALR-specific theranostic agent. Methods: We employed the de novo protein design platform BindCraft to generate small (<10kDa) high-affinity binders against CALR. A streamlined in silico to in vitro screening pipeline enabled isolation of CALR binders within two weeks. Binding affinity and specificity were validated by biolayer interferometry (BLI) and flow cytometry. For flow cytometry, human pancreatic cancer cells were treated with doxorubicin, a known surface CALR inducer. Cells were incubated with two CALR binders for 30 minutes, followed by staining with fluorescent antibody. In a Matrigel plug model, mice bearing CALR and control plugs were injected with 100 μCi of [64Cu]Cu-NOTA-binder and imaged by dynamic PET for 1 hour followed by CT. Results: BLI against CALR identified two high affinity binders, d4 and d6, with calculated dissociation constants of 83.2 nM (kon = 512790 M-1s-1, koff = 0.04265 s-1) and 31.2 nM (kon = 551797 M-1s-1, koff = 0.01723 s-1), respectively. Flow cytometry showed both CALR binders, d4 and d6, detected increases in surface CALR of 1.6-fold and 2.1-fold, respectively, on doxorubicin-treated cancer cells compared to vehicle. PET imaging revealed significantly higher uptake of [64Cu]Cu-NOTA-d6 in CALR plugs compared to controls as early as 20 minutes post-injection, with sustained retention throughout the imaging period. At 1 hr post-injection, SUVmean of the CALR plug was (0.882±0.270) compared to (0.344± 0.048) for the control plug (p = 0.0272). [64Cu]Cu-NOTA-d6 was cleared renally with insignificant uptake in non-target organs compared to blood pool and an average blood ½-life of 4.2 minutes. Conclusions: This study demonstrates the feasibility of de novo protein design to rapidly generate high-affinity CALR-targeted binders suitable for theranostic applications. Further in vivo studies will evaluate tumor-specific uptake and long-term retention of d6 in preclinical cancer models to support its translational development as a theranostic agent. Citation Format: Luke Rathbun, Yuvasri Golivi, Rachael Guenter, J. Bart Rose, Benjamin Larimer, . De novo protein design of calreticulin binders for theranostic applications [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 5818.

Abstract Background: Pancreatic ductal adenocarcinoma (PDAC) is currently the fourth leading cause of cancer-related deaths in the United States and is projected to increase within the next decade due to its poor prognosis and increasing incidence. There is an urgent need to develop more effective therapeutic options and detection strategies to improve survival outcomes for PDAC patients. Calreticulin (CALR), an endoplasmic reticulum protein, is known to translocate to the cell surface following cellular stress. Surface-expressed CALR holds promise for cancer detection or therapeutic delivery. To explore this potential, we performed high-throughput screening to identify compounds which induce surface CALR expression. Methods: Two human PDAC cell lines (Panc1, MIA Pa Ca-2) were engineered using the Nano-Glo HiBiT Extracellular Detection System to stably integrate HiBiT into the CALR gene. A high throughput screen for surface CALR-inducing compounds was performed at the National Center for Advancing Translational Sciences (NCATS). Cell lines expressing HiBiT-CALR were treated with approximately 3,000 drugs from the Mechanism interrogation PlatEs (MIPE) library for 24 or 48 hours and then assessed for cell viability using CellTiter-Glo and surface CALR levels by luminescence. Surface HiBiT-CALR and cell viability signals were quantified using a ViewLux microplate imager and automated processes utilizing the XTS Staubli UniVAL robotic system. The top ten drugs demonstrating high CALR signal (AUC) with minimal toxicity were validated for surface CALR induction by flowcytometry. Cells were also analyzed for viability using MTT assay, with P < 0.05 considered significant. Results: Out of the compounds evaluated, 102 compounds showed increased CALR surface expression and were selected for secondary screening, from which ten were further chosen for in-lab validation. Among these, bisindolylmaleimide IV and AEM1 were identified to reliably increase CALR. Flow cytometry analysis confirmed significant increases in live surface CALR+ cells, with bisindolylmaleimide IV (1.1µM) increasing CALR by 1.7-fold in MIA Pa Ca-2 and 1.32-fold in Panc1, while AEM1 (10µM) increased CALR by 7-fold in MIA PaCa-2 and 3.7-fold in PANC-1. Viability assays confirmed low cytotoxicity for bisindolylmaleimide IV (1.1 µM), with 77% and 84% cell viability observed in MIA PaCa-2 and PANC-1 cells, respectively. Similarly, AEM1 (10 µM) showed 81% viability in MIA PaCa-2 and 76% in PANC-1 cells. Conclusion: Our results identified the potential of two novel drugs, bisindolylmaleimide IV and AEM1, as promising candidates for enhancing surface CALR expression, offering new avenues for PDAC detection and tumor specific delivery of therapies. Citation Format: Yuvasri Golivi, Steven D. Forsythe, Rachael Guenter, Faris Zaibaq, Michele Ceribelli, Craig Thomas, J. Bart Rose. High throughput screening identifies novel drugs for calreticulin surface translocation in pancreatic ductal adenocarcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 6425.

Background: Prior studies have shown substantial regional variation in pancreatic cancer incidence and mortality. Understanding how environmental exposures and social vulnerability shape these geographic patterns may reveal actionable drivers of disease burden. Methods: County-level incidence and mortality data (2017–2022) were obtained from the NIH State Cancer Profiles and CDC Environmental Public Health Tracking Network. Age-adjusted rates were linked with environmental (particulate matter (PM₂.₅), arsenic), behavioral (smoking, obesity, binge drinking), and social vulnerability (social vulnerability index[ SVI]) metrics. Spatial autocorrelation (Global Moran’s I) and hotspot analysis (Getis-Ord Gi*) were performed in ArcGIS Pro. Linear regression, SVI domain decomposition, and urban–rural interaction modeling was conducted to evaluate regional associations between social and environmental determinants and pancreatic cancer incidence and mortality (or whatever you want it to say here). Geographically weighted regression (GWR) assessed regional heterogeneity. Results: Among 3,143 U.S. counties, the national median age-adjusted incidence rate was 13.8 per 100,000 (IQR 12.4–15.3), with significant spatial clustering (Moran's I = 0.47, p < 0.001). Incidence hotspots concentrated in the Deep South, Appalachia, and the industrial Midwest. Median age-adjusted mortality was 7.65 per 100,000 (IQR 0.0–12.2; Moran's I = 0.42, p < 0.001), extending into Arkansas, Tennessee, and the Carolinas. Counties with elevated mortality showed disproportionately higher social vulnerability and environmental exposures. In multivariable analyses (n = 1,683 counties), incidence was independently associated with PM₂.₅ (β = 0.87, p < 0.001) and obesity (β = 0.79, p < 0.001). Mortality was independently associated with SVI (β = 5.18, p < 0.001), PM₂.₅ (β = 0.46, p < 0.001), and alcohol consumption (β = 13.59, p = 0.014). The model explained 16–18% of geographic variance. Conclusion: Pancreatic cancer burden clusters in distinct regions due to intersecting environmental, behavioral factors and SVI.

Antibody production by B cells has emerged as an important factor in regulating antitumor immunity with both suppressive and promotive roles in cancer. However, the specific effect of antibody deficiency during development of pancreatic ductal adenocarcinoma (PDAC) has not been explored. To address this question, we crossed the well-established KPC mouse model to mice lacking all circulating immunoglobulin (Ig) due to genetic ablation of both Ig secretion and Ig class switching (KPC-μSAID mice). KPC-μSAID mice exhibited a two-fold acceleration in tumor formation, a two-fold reduction in median survival, and increased liver metastases versus KPC-WT control mice. Immunofluorescence analysis of pancreatic tissues from antibody-sufficient KC- and KPC-WT mice showed that IgG was predominantly localized within the extracellular matrix (ECM). Furthermore, in both KC- and KPC-μSAID mice, ECM density and podoplanin+ cancer-associated fibroblasts (CAFs) were significantly reduced. In the KPC-μSAID tumor microenvironment (TME), intratumoral myeloid-derived suppressor cells (MDSC) were also increased, while CD4+ and CD8+ T cells decreased, relative to tumor-bearing KPC-WT mice, with macrophage exhibiting a mixed polarization phenotype. These findings were recapitulated in antibody subclass-deficient, KPC-AID mice, suggesting a potentially novel function of IgG in suppressing PDAC progression by directly or indirectly regulating pancreatic fibrosis and the density of the ECM.

Abstract Background: Pancreatic ductal adenocarcinoma (PDAC) develops within a dense, heterogeneous tumor microenvironment (TME) in which collagen and hyaluronic acid (HA) shape tissue architecture, biomechanics, and therapeutic response. Although mouse PDAC models are widely used, their ability to recapitulate human extracellular matrix (ECM) organization remains uncertain. This study aimed to quantitatively compare ECM composition and spatial topology in human PDAC versus a commonly used mouse model. Methods: Tissue sections from primary human PDAC (n=6) and a syngeneic PDAC mouse model (n=3) were stained with H&E and a dual Picrosirius Red (collagen) and Alcian Blue (HA) protocol. The mouse model was generated by subcutaneous implantation of 2838c3 cells into C57BL/6 mice under approved protocols, with tumors resected at ∼100 mm3. High-resolution brightfield images were acquired under identical conditions using Agilent Lionheart. Quantitative analyses across 63 histomorphometric and spatial parameters, including area fractions, edge-to-core localization, and texture, were performed using the CerFlux PEER AI/ML imaging and analytics platform and cross-validated in Fiji. Texture and spatial order were quantified using gray-level co-occurrence matrix features and Moran’s I. Results: Human PDAC exhibited balanced ECM composition (collagen=0.16±0.04; HA=0.18±0.04), whereas mouse tumors showed HA enrichment and collagen depletion (collagen=0.04±0.002; HA=0.26±0.09). Edge mapping revealed proportionate collagen and HA in human samples (edge ratio=0.9±0.46) but 4-fold peripheral collagen enrichment in mouse tumors (edge ratio=4.3±1.3). Human tumors demonstrated higher entropy (collagen=8.1±0.2; HA=7.9±0.2) and substantial HA autocorrelation (Moran’s I=0.58±0.22; 0.60±0.42), reflecting heterogeneous, regionally clustered desmoplasia. Mouse tumors displayed reduced entropy (∼7.8) and lower Moran’s I (0.32±0.05; 0.17±0.01), indicative of ordered, capsule-like ECM organization. Principal component analysis distinctly segregated species: PC1 (42%) collagen-HA balance, with human samples scoring positive and mouse samples negative; PC2 (21%) textural heterogeneity versus edge-localized order. Conclusions: These findings show that the murine PDAC model fails to reproduce the balanced collagen-HA composition and spatially disordered desmoplasia of human PDAC, instead forming an HA-rich, collagen-depleted core encased in an ordered collagen capsule with markedly lower stromal entropy and autocorrelation. These findings highlight the limitations of mouse models, particularly subcutaneous tumor models, and underscores the need for human-relevant new approach methods (NAMs) for translational therapeutic studies. Citation Format: Rachael Guenter, Libby A. Boykin, Khidr Kishan K. Budhwani, Brahma Mubarak K. Budhwani, Chelsea L. Crawford, J. Bart Rose, Karim I. Budhwani. Bridging the translational gap: Critical TME differences between human PDAC and mouse models [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 763.

INTRODUCTION:Racial disparities in pancreatic adenocarcinoma mortality may stem from differences in chemotherapy response. This study examines potential disparities between Black and White patients' responses to adjuvant chemotherapy. METHODS:Using the National Cancer Database (2010-2019), we analyzed Black and White patients with pancreatic adenocarcinoma who underwent surgery with or without adjuvant therapy. Patients receiving neoadjuvant therapy, radiation, with American Joint Committee on Cancer stage >4, or missing data were excluded. A race-stratified landmark survival analysis was performed at 6 mo post surgery using Kaplan-Meier and Cox proportional hazards models. RESULTS:Among 22,898 surgical patients, 20,434 were White (89%) and 2464 were Black (11%) and the median follow-up was 19.9 mo. Black patients were younger (65.6 versus 69.0 y), more often female (58% versus 48%), and had higher Charlson-Deyo Comorbidity Index (CCI) scores (≥3: 6.0% versus 4.6%) than White patients. Black patients were less likely to receive adjuvant therapy (58% versus 61%). At 6 mo post surgery, 18,977 patients were alive, with 65% receiving chemotherapy. Cox analysis revealed a significant survival benefit from adjuvant therapy in White patients (hazard ratio = 0.90, 95% confidence interval = 0.87-0.95, P < 0.01); a similar effect was not seen in Black patients (hazard ratio = 0.96, 95% confidence interval = 0.84-1.09, P = 0.52). CONCLUSIONS:Although overall survival is similar, adjuvant chemotherapy was associated with improved survival only in White patients. The lack of observed benefit in Black patients may indicate underlying biological differences warranting further study.

Single domain antibodies, often known as nanobodies, are versatile molecules with therapeutic and diagnostic applications, but they are primarily developed through immunization of camelids. This approach is not scalable by automation, not effective for non-immunogenic or toxic antigens, and prevents the use of modified scaffolds for altered pharmacokinetic properties. Synthetic libraries allow for pre-selection of a single domain framework tailored to its intended downstream use. One area of interest for these biologic vectors is radiopharmaceuticals. Ideal radiopharmaceutical pharmacokinetic properties differ from most traditional therapeutics, as short plasma circulation and rapid kidney clearance are necessary to avoid dose-limiting organ radiation. Although there are a growing number of nanobody radiopharmaceuticals in clinical trials, their frameworks and corresponding pharmacokinetic properties vary. One potential method for improving the development of novel single domain antibody radiopharmaceuticals is through synthetic libraries based on nanobodies with proven clinically acceptable pharmacokinetics. We developed a modular synthetic nanobody phage display vector based on the scaffold of the 2Rs15d nanobody that allows for manipulation of the binding and framework regions. Using this vector, we created a library of nanobodies with a randomized CDR2 containing over 1.7×10 6 unique sequences/µL. As a proof-of-concept, we panned the library for nanobodies binding calreticulin (CALR), a protein critical in immunogenic cell death. One isolated clone, Cal3, has a measured affinity of 140 nM for CALR and is cross-reactive with mouse and human CALR. Using positron emission tomography (PET) imaging, the radiolabeled 64 Cu-NOTA-Cal3 demonstrated CALR binding in vivo , representing the first reported synthetic nanobody characterized by PET imaging. This study demonstrates the feasibility of building and panning synthetic libraries for high-affinity radiopharmaceutical nanobodies as an alternative to immunized camelid libraries.

Introduction: Pancreatic neuroendocrine tumors (pNETs) are slow growing, malignant tumors that show different survival outcomes by race. Current size-based guidelines were largely developed in White patients. Our aim was to investigate tumor size and incidence of lymph node metastasis (LNM) between White and Asian pNET patients to evaluate generalizability of established guidelines. Methods: Using the National Cancer Database (NCDB), we conducted a multi-institutional analysis of patients with low grade, resected, nonfunctional, sporadic, non-metastatic pNETs. Chi-squared tests were implemented to determine correlation between PTS and LMN incidence as well as race and LMN incidence. A logistic regression model was utilized to determine correlation between LMN, tumor size, and race. Overall survival was assessed using the Kaplan-Meier method. Results: A total of 4977 pNET patients (205 Asian and 4772 White) were included in our analysis. Asian patients presented with smaller tumors (3.0 cm vs 3.9 cm, p = 0.029) but when grouped by size, there was no difference in the distribution (p = 0.77). White patients demonstrated a higher incidence of lymph node metastasis at presentation compared to Asian patients (27% vs 19%, p = 0.013), a higher likelihood of an R0 resection (95.3% vs. 89.3 %, p < 0.0001). Within both populations, tumor size (<2 cm, 2-3 cm, and >3 cm) positively correlated with incidence of LNM (11.5 %, 24.6 %, and 39.1 %). No difference of LNM was seen between racial cohorts at PTS <3 cm, however, Asian patients were less likely to exhibit LNM at PTS >3 cm (28.2 % and 39.5 %, p = 0.04). Overall survival was not significantly different between racial groups (p = 0.92). Conclusion: Size based surgical resection guidelines for pancreatic neuroendocrine tumors based on a predominantly White patient population may not be generalizable to the Asian population. Within this population, we found the risk of lymph node metastasis did not increase at similar rates with increasing primary tumor size.

Targeted agents, such as nanobodies, can be covalently linked to radionuclide chelators for theranostics. Nanobodies are single-domain immunoglobulin variable regions with a short blood half-lives and high specificity. Calreticulin (CALR) is endoplasmic reticular (ER) protein that translocates to the cell surface upon induction with certain agents, namely doxorubicin. We hypothesized surface CALR on tumors could be targeted using a novel nanobody after induction with doxorubicin. Studies were conducted using in vitro and in vivo models of pancreatic ductal adenocarcinoma (PDAC). Surface CALR expression was determined by western blot on fractionated lysates, flow cytometry, or immunofluorescence (IF). Doxorubicin was administered by intraperitoneal injection to mouse models of PDAC. The anti-CALR nanobody was developed via the panning of a synthetic nanobody phage display library. The top CALR-binding nanobody was confirmed by ELISA, immunohistochemistry (IHC), and flow cytometry. For in vivo studies, the nanobody was conjugated with the chelator NOTA and radiolabeled with 64Cu. PET images were acquired 1-hour after injection. Significance was determined using an independent t-test and p values < 0.05 were considered statistically significant. PDAC cells treated with doxorubicin showed peak surface CALR expression between 24 and 48 hours. Flow cytometry revealed that 61.7% of live PDAC cultured cells treated for 24 hours expressed surface CALR, compared to 2.2% in controls (p < 0.001). In a subcutaneous syngeneic PDAC mouse model, two doses of doxorubicin 48 hours apart significantly increased surface CALR, with 30.4% of live-cells expressing CALR in treated tumors versus 1.5% in controls (p < 0.001). Similarly, doxorubicin-treated tumors from a PDAC patient derived xenograft (PDX) model had a 6.7-fold increase in live-cells expressing surface CALR compared to controls (p < 0.01). IF confirmed a 1.4-fold increase in CALR expression in doxorubicin-treated tumors from the subcutaneous PDAC mouse model (p < 0.01) and a 1.7-fold increase in the PDAC PDX model (p < 0.01). Our anti-CALR nanobody has an apparent 37 nM affinity for recombinant CALR and successfully detected surface CALR by IHC and flow cytometry. In vivo PET imaging showed significant increased uptake of the 64Cu-NOTA-nanobody in tumors from doxorubicin-treated mice over controls, with no significant changes in heart, kidney, or liver accumulation by PET quantification and flow cytometry (p < 0.05). Systemic doxorubicin treatment induces CALR surface translocation in tumors that can be successfully targeted with a radiolabeled nanobody for PET imaging. Targeting chemotherapy-induced surface CALR using our radiolabeled nanobody could provide a theragnostic strategy for the detection and treatment of PDAC. Rachael Guenter, Yuvasri Golivi, Lucinda Hall, Amro Abdelrahman, Chloe La Prairie, Caleb Miller, Tejeshwar C. Rao, Danielle M. Carlson, Mark J. Truty, Benjamin Larimer, J. Bart Rose. Detection of tumor cell surface calreticulin after doxorubicin treatment using a novel radiolabeled nanobody [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 574.

Various social determinants of health (SDOH) metrics, also known as area-based social measures, are utilized to evaluate access to cancer care and to explain disparities in outcomes. Little prior work has compared the validity of these various geographic metrics. We reviewed all patients surgically treated for PNETs (2006-2022) at a single comprehensive cancer center. We collected patient demographics including self-reported race (White or Black), billing addresses, tumor characteristics and area-based social measures. We then compared between- and within-race differences to understand accuracy across different geographic levels. One hundred seventy-nine patients were included; 49 (27%) Black, a median age of 60.3 years and 86 (48%) females. At the block group/census tract level, compared to White patients, Black patients lived in neighborhoods with lower educational attainment, lower income, higher rates of uninsurance, higher overall social vulnerability index (SVI), and higher area deprivation index (ADI) (all P < 0.05). These differences, however, were masked when examining county-level area-based social measures. Compared to census block group/tract-level data, for White patients, zip code-level metrics underestimated income and overestimated uninsurance level (P < 0.05). County-level metrics underestimated White patients' income and education level but overestimated poverty, uninsurance rate and SVI (all P < 0.05). For Black patients, zip code-level metrics overestimated poverty and uninsurance rates (P < 0.05); the only inaccurate county-level metric was overestimation of SVI (P < 0.001). Black patients with PNETs experience more vulnerable area-based social measures, a disparity which may be hidden when analyzing large geographic metrics.

BACKGROUND:Pancreatic ductal adenocarcinoma (PDAC) is aggressive with a poor prognosis, and racial disparities persist despite care advances. The impact of socioeconomic status on mediating these disparities, remain unclear. METHODS:We used the SEER-17 database to create a cohort of PDAC patients diagnosed between 2005 and 2019. We examined the association between race and all-cause mortality along with a race-stratified Kaplan-Meier analysis on low-income (<$40K) and high-income (>$75K) subgroups. RESULTS:The cohort included 118,514 patients. Black patients experienced worse survival compared to White patients (HR:1.10, 95 ​%CI:1.08-1.13, p ​< ​0.001). Three-year survival rate was 9.8 ​% (95 ​%CI: 9.4-10.1) for White patients in high-income areas, compared to 8.7 ​% (95 ​%CI: 7.8-9.8) for Black patients (p ​< ​0.01). White patients in low-income areas had a survival rate of 6.3 ​% (95 ​%CI: 5.4-7.4), compared to Black patients: 5.0 ​% (95 ​%CI: 3.5-7.0) (p ​< ​0.01). CONCLUSIONS:Our study shows significantly poorer survival rates for Black individuals, even with high socioeconomic status, compared to White counterparts, highlighting persistent racial disparities in PDAC outcomes.