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The objective of the current review was to synthesize the literature on intersectionality relative to disparities across the cancer care continuum. A model to support future intersectional cancer research was proposed.Web-based discovery services and discipline-specific databases were queried for both peer-reviewed and gray literature. Study screening and data extraction were facilitated through the Covidence software platform.Among 497 screened studies, 28 met study inclusion criteria. Most articles were peer-reviewed empirical studies (n = 22) that focused on pre-diagnosis/screening (n = 19) and included marginalized racial/ethnic (n = 22) identities. Pre-cancer diagnosis, sexual orientation and race influenced women's screening and vaccine behaviors. Sexual minority women, particularly individuals of color, were less likely to engage in cancer prevention behaviors prior to diagnosis. Race and socioeconomic status (SES) were important factors in patient care/survivorship with worse outcomes among non-white women of low SES. Emergent themes in qualitative results emphasized the importance of patient intersectional identities, as well as feelings of marginalization, fears of discrimination, and general discomfort with providers as barriers to seeking cancer care.Patients with intersectional identities often experience barriers to cancer care that adversely impact screening, diagnosis, treatment, as well as survivorship. The use of an "intersectional lens" as a future clinical and research framework will facilitate a more multidimensional and holistic approach to the care of cancer patients.

Accurately predicting post-critical heat flux (CHF) heat transfer is an important but challenging task in water-cooled reactor design and safety analysis. Although numerous heat transfer correlations have been developed to predict post-CHF heat transfer, these correlations are only applicable to relatively narrow ranges of flow conditions due to the complex physical nature of the post-CHF heat transfer regimes. In this paper, a large quantity of experimental data is collected and summarized from the literature for steady-state subcooled and low-quality film boiling regimes with water as the working fluid in vertical tubular test sections. A low-quality water film boiling (LWFB) database is consolidated with a total of 22,813 experimental data points, which cover a wide flow range of the system pressure from 0.1 to 9.0 MPa, mass flux from 25 to 2750 kg/m2 s, and inlet subcooling from 1 to 70 °C. Two machine learning (ML) models, based on random forest (RF) and gradient boosted decision tree (GBDT), are trained and validated to predict wall temperatures in post-CHF flow regimes. The trained ML models demonstrate significantly improved accuracies compared to conventional empirical correlations. To further evaluate the performance of these two ML models from a statistical perspective, three criteria are investigated and three metrics are calculated to quantitatively assess the accuracy of these two ML models. For the full LWFB database, the root-mean-square errors between the measured and predicted wall temperatures by the GBDT and RF models are 5.7% and 6.2%, respectively, confirming the accuracy of the two ML models.

361 Background: TRK-950 is a first-in-class humanized antibody raised against CAPRIN-1 which we have identified as a novel and universal target for cancer therapies. TRK-950 strongly and specifically binds to various cancer cells and shows anti-tumor effects via engagement of immune cells. A series of pre-clinical studies demonstrates its potency and safety. In the phase I study of TRK-950 monotherapy (NCT02990481), it appears safe and well tolerated. No DLT was observed and MTD was not reached at doses of 3-30mg/kg IV weekly. Here, we report on select cohort of the ongoing, multicenter phase Ib study of TRK-950 combined with standard of care (SOC) regimens in patients (pts) with gastric cancer including GEJ cancer (NCT03872947). Methods: Patients with gastric or gastro-esophageal junction (GEJ) cancer and measurable disease were enrolled in phase Ib study, and received paclitaxel on D1, 8, 15 and ramucirumab on D1, 15 of 28-day cycles. In addition TRK-950 was given 10 mg/kg IV weekly. DLT was evaluated during the first cycle. Response was assessed every 2 cycles up to Cycle 6 and every 3 cycles thereafter. Primary endpoint was safety and tolerability. Secondary endpoints included overall response rate (ORR), disease control rate (DCR) per REClST v1.1. Tumor CAPRIN-1 expression was retrospectively assessed by IHC. Results: Nine patients were enrolled, median age 58 yrs; Karnofsky performance status 80 (11%), 90 (67%), 100 (22%); 89% male, 11% female; median number of prior treatments 2 [1, 4]. TRK-950 in combination with ramucirumab and paclitaxel was well tolerated with no DLTs. Most common all-grade treatment-related AEs (TRAEs) were fatigue (67%), vomiting (33%), anemia (22%), nausea (22%), diarrhea (22%), neutrophil count decreased (22%) and decreased appetite (22%). Most common grade ≥ 3 TRAE in ≥ 20% of pts were anemia (22%) and neutrophil count decreased (22%). In 9 response-evaluable pts, ORR was 55.6% and DCR was 100%. Four patients had a screening CAPRIN-1 score of 3+, and all achieved partial response. Conclusions: TRK-950 binds to a newly described target, CAPRIN-1, and has an acceptable safety and tolerability profile when combined with ramucirumab and paclitaxel in gastric cancer including GEJ cancer. Preliminary clinical activity is demonstrated in pre-treated patients with encouraging response rates, particularly enriched by the expression of CAPRIN-1. Further antitumor activity is being confirmed by limiting patients to only 1 prior treatment regimen with an eye towards a randomized trial. Clinical trial information: NCT03872947 .

TPS4169 Background: Cyclin dependent kinases (CDKs) are serine/threonine kinases that are responsible for phosphorylating the intracellular proteins that coordinate cell-cycle progression. The Cancer Genome Atlas (TCGA) molecular analysis of esophageal/gastroesophageal junction (E/GEJ) carcinomas has highlighted significant dysregulation of CDKN2A, the gene coding for the tumor suppressor p16, through deletion, mutation or epigenetic silencing in up to 76% of cases and the associated significant upregulation of the CDK4/6-Cyclin D-axis (The Cancer Genome Atlas Research Network. Integrated genomic characterization of oesophageal carcinoma. Nature 2017). Preclinical experiments demonstrated that single agent abemaciclib has potent antitumor efficacy both in vitro and in vivo in esophageal adenocarcinoma with direct pathway inhibition (Kosovec J et al. CDK4/6 dual inhibitor abemaciclib demonstrates compelling preclinical activity against esophageal adenocarcinoma: a novel therapeutic options for a deadly disease. Oncotarget 2017 Nov 1;8[59]). Significant activity was seen in the OE33 (p=0.048) and FLO1 (p=0.043) esophageal cancer cell lines while western blot revealed downregulation of Cyclin D, phospho-pRb, E2F1, and Cyclin A2 (Kosovec J et al, 2017). In vivo experiments , utilizing the Levrat model of end-to-side esophagojejunostomy performed on Sprague-Dawley rats demonstrated that 78.9% of animals given abemaciclib demonstrated >20% tumor volume decrease (placebo 0%). Post treatment comparison between placebo and abemaciclib of qRT-PCR gene expression demonstrated downregulation of pathway correlates, including CDK4 (p=0.023), CDK6 (p=0.068), E2F1 (p=0.005), Rb1 (p=0.067), Cyclin D (p=0.031), and Cyclin A (p=0.039) (Kosovec J et al, 2017). The JPBJ phase 1b study has previously demonstrated the safety of combining abemaciclib with ramucirumab in NSCLC. Methods: Subjects with previously treated metastatic esophageal or gastroesophageal junction adenocarcinomas are eligible for this study which is currently open and enrolling patients. Squamous cell and mixed histology with neuroendocrine features are excluded. A total of 30 patients will be enrolled across 3 sites at Baylor University Medical Center in Dallas, The Allegheny Health Network in Pittsburgh and at Johns Hopkins Hospital in Baltimore. The primary objective is to describe the safety profile of abemaciclib (150mg po bid) and ramucirumab (8mg/kg iv every 2 weeks) in this patient population as assessed according to Common Terminology Criteria for Adverse Events version 4.0. Secondary objectives are to assess response rate, progression free and overall survival. In addition, we will determine the rate of stable disease at 3 months post targeted therapy. Correlative studies investigating changes in the expression of selected serum/tissue genomic markers of interest will be performed. Clinical trial information: NCT04921904.

Social determinants of health (SDOH) are strongly linked to individual and population health outcomes. Hospitals and health systems are in a unique position to initiate or partner on community-wide efforts address SDOH. However, such efforts typically require collaboration with other healthcare and local community organizations since SDOH affect more than just medical care. Despite studies that have identified specific organizational and environmental factors associated with hospital-community partnerships, the role of social capital and community health needs as drivers of such partnerships remains unexplored. This study examines whether hospital partnerships with community organizations in the United States are driven predominantly by community social capital or the prevailing health needs of the community, and whether these drivers are similar for overall partnerships as well as for partnerships with individual organizations. We use 2020 data from the American Hospital Association, US County Health Rankings, and Social Capital Project and employ ordinary least-squares (OLS) regression and logit models to assess the relationship between social capital, community health needs and hospital-community partnerships to address SDOH. Our results indicate that for community social capital was significantly and positively associated with total hospital partnerships (β = 0.05, p = 0.01). We also found that community social capital was significantly more likely to be associated with hospitals' partnerships with local/state public health agencies, schools, law enforcement agencies, other healthcare providers, and organizations that assist with food insecurity. On the other hand, community health needs were not associated with total partnerships and had limited associations with hospital partnerships with individual organizations. Overall, this research suggests that social capital is a critical determinant of hospital partnerships with community organizations, and hospitals may seek partnerships with organizations that allow them to address community health issues outside of their own expertise since such partnerships and collaborative efforts can help address SDOH and manage population health.

321 Background: The phase III CheckMate 577 study resulted in adjuvant nivolumab becoming a new standard of care for patients with completely resected E/GEJ cancer with residual pathologic disease post neoadjuvant chemoradiotherapy. We evaluated if neoadjuvant nivolumab (N) or nivolumab/relatlimab (N/R) combined with chemoradiotherapy (CRT) can further improve patient outcomes. Methods: Patients with stage II/III E/GEJ carcinoma eligible for curative resection were treated with standard of care regimen of carboplatin (AUC2), paclitaxel (50mg/m2), RT 41.1Gy in 23 fractions and an Ivor-Lewis esophagectomy (E/MIE) 6-10 weeks after last CRT/IO dose. Patients on arm A (n=16) received 2 cycles of induction N (240mg q2 wks) plus three additional cycles of N on week 1, 3 and 5 of CRT. After safety and feasibility evaluation of arm A, patients on arm B (n=16) received N (240mg q 2 wks) plus R (80mg q 2 wks) following the same schedule. The primary endpoints of the study were safety and feasibility. Secondary endpoints include pCR, MPR (

335 Background: There is a critical need to develop effective therapeutic approaches for patients with esophageal cancer, a leading cause of cancer mortality. Recently, immune checkpoint blockade (ICB) has demonstrated modest survival benefit in gastroesophageal cancer patients. Epigenetic therapies, including DNA methyltransferases (DNMT) and histone deacetylases (HDACs), have shown to enhance tumor immune recognition by directly upregulating antigen presentation and by activation of type-1 interferon response triggered by cytoplasmic double-stranded RNA, a phenomenon known as viral mimicry. In other cancer models, epigenetic therapy has shown early promise by enhancing the effectiveness of ICB via addictive antiproliferative effects, enhanced immune activation and reversal of T cell exhaustion towards a memory-effector T-cell phenotypes. Methods: Esophagojejunostomy was performed to induce gastroduodenojejunal reflux in rats, leading to development of EAC. At 32 weeks postop, animals were randomized into eight treatment and control groups: placebo ± radiation, epigenetic treatment ± radiation, immunotherapy treatment ± radiation, and concurrent epigenetic and immunotherapy ± radiation. Animals underwent three 14 day cycles of epigenetic treatment or placebo. Each cycle consisted of one week of DNMT treatment or placebo at a dose of 0.5mg/kg, followed by one week of HDAC treatment or placebo at a dose of 2mg/kg. Animals received one 3mg/kg dose of PD1 inhibitor or placebo on day 12 of each cycle. Safety and efficacy were evaluated via objective health assessments, change in tumor volume, immunofluorescent labeling and RT-PCR. Results: Seventy of 74 randomized animals reached study end-point with no significant differences in mortality observed across groups (p = 0.556). There were no significant differences in observed health scores or weights between all groups (p = 0.431 and p = 0.882, respectively). Pre to posttreatment, mean MRI tumor volume increased by 263.1% and 90.9% in the placebo and the placebo plus radiation groups, respectively. The largest tumor reduction was observed in the concurrent treatment groups, 84.5% and 61.8% with and without radiation, respectively. Additionally, independent epigenetic and immunotherapy treatments with or without radiation also exhibited decrease in tumor volume, but to a lesser extent than the concurrent regimens (p = 0.005). Immunofluorescent labeling demonstrated a significant increase in CD3+ CD8+ T cells in all treatment groups compared to placebo (p = < 0.001). Gene expression displayed upregulation of CD206 (p = 0.002), TNFα (p = < 0.001), and Arg1 (p = < 0.001) in treatment arms compared to placebo. Conclusions: This study establishes addictive antitumor efficacy and enhanced immune sensitization for a concurrently sequenced treatment, combining epigenetic therapy and radiation with immunotherapy, to treat EAC.

336 Background: The high incidence of esophageal adenocarcinoma (EAC) remains a major clinical challenge as majority of these cases are diagnosed at advanced stages, with poor survival outcomes. Emerging evidence indicate intriguing associations between unique microbial profiles and cancer pathogenesis. More recent data also indicates the potential clinical significance of specific microbial signatures as diagnostic and prognostic biomarkers. However, to date, no studies have systematically interrogated circulating metagenome profiling in EAC patients, particularly as non-invasive, early detection, surveillance and prognostic classifiers that may improve the current management paradigms. Methods: Metagenome sequencing was performed on 81 serum specimens collected from 51 EAC, 10 high grade dysplasia (HGD), 10 Barretts’s esophagus (BE), and 10 gastro-esophageal reflux disease (GERD) patients, respectively. Sequencing reads were classified using Bracken and MetaPhlAn3 to determine relative abundance between various classes. The Linear Discriminant Analysis effect size (LEfSe) method was performed to identify potential conserved and discrete microbial profiles between groups. Logistic regression and Kaplan-Meier analyses were used to build a model according to clinical and metagenomic classifiers to examine the diagnostic and prognostic potential of the identified metagenomic signature. Results: A significant loss of alpha and beta diversity was identified in serum specimens from EAC patients. We observed a shift in microbial taxa between each group – at the phylum, genus, and species level – with Lactobacillus sakei as the most prominent species in GERD vs. other patient groups. Interestingly, LEfSe analysis identified a complete loss of Lactobacillus ( L.Sakei and L. Curvatus), Collinsella stercoris and Bacteroides stercoris, but conversely a significant increase in Escherichia coli in patients with EAC. Finally, we developed a metagenome panel that discriminated EAC from GERD patients with an AUC value of 0.89 (95% CI, 0.78 – 0.95), and this panel in conjunction with the TNM stage was a robust predictor of overall survival (≥24 months; AUC = 0.84 [95% CI 0.66 – 0.92]) and an accompanying hazard ratio (HR) of 6.23 (95% CI, 2.65 – 14.46, P

333 Background: Esophageal adenocarcinoma (EAC) is a leading cause of cancer deaths. Pexidartinib, is a multi-gene tyrosine kinase inhibitor, targeting FLT3, KIT and CSF1R. In particular, pexidartinib by targeting CSF-1R down modulates macrophage mediated pro-survival tumor signaling. Recently, CSF-1R inhibitors have successfully shown to enhance antitumor activity of PD-1/PD-L1 inhibitors by suppressing tumor immune evasion, in multiple solid tumors. Methods: Seventy-two rats underwent an end-to-side esophagojejunostomy to induce gastroesophageal reflux, resulting in EAC carcinogenesis. At 32 weeks postoperatively, tumor bearing animals were randomized to a dose of 30mg/kg of pexidartinib or vehicle control, 5 days on and 2 days off (14 day cycle), for a total of 3 cycles. A PD-1 inhibitor, AUNP-12, at a dose of 3mg/kg or placebo, was administered on day 12 of each cycle. At 38 weeks postoperatively animals were euthanized. Safety and efficacy was evaluated by objective health assessments, pre and posttreatment MRI, RT-PCR, immunofluorescent labeling and a serum cytokine assay. Results: The pexidartinib +/- PD-1 inhibitor (Px+P and Px-P) groups demonstrated no significant difference in daily weight change (p = 0.98) or in mortality (p = 0.59) when compared to vehicle control (V+P and V-P) groups. On post-mortem serum analysis AST (p = 0.01) and ALT (p = 0.001) were elevated, while albumin (p = 0.57) and BUN/creatinine ratio (p = 0.09) were reported within normal ranges, when comparing treatment to placebo groups. Pre to posttreatment, mean MRI tumor volume decreased by 37% and 54% in the Px-P and Px+P animals and increased by 147% and 88% in the V+P and V-P animals, respectively (p = < 0.0001). Overall response rate was 69% and 87% in Px-P and Px+P animals compared to 21% and 13% in V-P and V+P animals, respectively (p = < 0.0001). Downstream gene expression demonstrated upregulation of TNF-α (p = 0.003), IFN-γ (p = 0.002) and IL-6 (p = 0.0001) and downregulation of IL-13 (p = 0.051), IL-10 (p = 0.051), TGF-β (p = 0.024) and Arg-1 (p = 0.0003), in treatment vs. placebo animals. Increased apoptosis (Cas-3 p = 0.0005) and reduced proliferation (Ki-67 p = < 0.0001) were reported in the treatment animals. Higher CD3+CD8+ T cell densities and CD86/CD206 macrophage ratio was reported in treatment groups compared to placebo (p = < 0.0001). Serum cytokine levels significantly displayed upregulation of TNF-α and IFN-γ and downregulation of IL-4 and IL-10 in the treatment animals compared to the placebo. Conclusions: Overall, this study established a promising combinatorial strategy using a CSF-1R inhibitor to overcome resistance to PD-1/PD-L1 axis blockade in an esophageal cancer model, providing the rationale for future clinical strategies.