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Pancreatic cancer is projected to be the second leading cause of cancer-related death by 2030 in the US. The benefits of the most common systemic therapy for various pancreatic cancer have been masked by high drug toxicities, adverse reactions, and resistance. Using nanocarriers like liposomes to overcome these unwanted effects has become very popular. This study aimed to formulate 1,3-bis tetrahydrofuran-2yl-5FU (MFU)-loaded liposomal nanoparticles (Zhubech) and evaluate the stability, MFU release kinetics, in vitro and in vivo anticancer activities, and biodistribution. Particle size and zeta potential were determined using a particle size analyzer, while cellular uptake of rhodamine-entrapped liposomal nanoparticle (Rh0-LnP) was determined by confocal microscopy. Gadolinium hexanoate (Gd-Hex) was synthesized and entrapped into the liposomal nanoparticle (LnP) (Gd-Hex-LnP) as a model contrast agent, to evaluate gadolinium biodistribution and accumulation by LnP in vivo using inductively coupled plasma mass spec-trometry (ICP-MS). The mean hydrodynamic diameters of the blank LnP and Zhubech were 90.0 ± 0.65 nm and 124.9 ± 3.2 nm, respectively. The hydrodynamic diameter of Zhubech was found to be highly stable at 4o C and 25oC for 30 days in solution. In vitro drug release of MFU from Zhubech formulation exhibited the Higuchi model (R2 value = 0.95). Both Miapaca-2 and Panc-1 treated with Zhubech showed reduced viability, two- or four-fold lower than that of MFU-treated cells in 3D spheroids (IC50Zhubech = 3.4 ± 1.0μM vs IC50MFU = 6.8 ± 1.1μM) and organoids (IC50Zhubech = 9.8 ± 1.4μM vs IC50MFU = 42.3 ± 1.0μM) culture models. Confocal imaging confirmed high uptake of rhodamine-entrapped LnP by Panc-1 cells in a time-dependent manner. Tumor efficacy studies in PDX bearing mouse model revealed more than 9-fold decrease in mean tumor volumes in Zhu-bech treated (108 ± 13.5 mm3) compared to 5-FU treated (1,107 ± 116.2 mm3) animals respectively. This study demonstrates that Zhubech may be a potential candidate for delivering drugs for pancreatic cancer treatment.

Background: Pancreatic cancer portends a very poor prognosis. It is the third leading cause of cancer deaths in the United States. African Americans have a 50- 90% increased incidence of pancreatic cancer in comparison to other racial groups. 20% of patients with pancreatic cancer present with early-stage disease and will have a median overall survival of 2.5 years if able to undergo surgical resection. There is a desperate need to discover novel ways of treating pancreatic cancer. Understanding of the microbiome may be informative to overcoming chemotherapy resistance, toxicity and improving outcomes and disparities. The aim of this study is to (1) identify changes in the intestinal microbiota during neoadjuvant treatment of pancreatic ductal adenocarcinoma that correlate with treatment response and (2) identify changes in the intestinal microbiota during neoadjuvant treatment of pancreatic ductal adenocarcinoma that correlate with treatment toxicity in a diverse patient population. Methods: Patients with resectable or borderline resectable pancreatic cancer who are enrolled in a multi-site clinical trial (NCT03483038) receiving neoadjuvant NEO-Nali-IRI (oxaliplatin, liposomal irinotecan and 5- FU) followed by surgical resection were asked to provide stool samples and a dietary log during the following four (or five) time points: baseline, mid-therapy (after C4), at completion of chemotherapy (after C8), after radiation if applicable, and at 4-6 weeks post-operative. Participants will be given stool collection kits at clinic visits for home sample acquisition. All samples will be mailed to the University of Florida Health Cancer Center Microbiome Biorepository. Data will be collected regarding demographics, stage, medical history and concurrent medications including antimicrobics and probiotics, chemotherapy dose-reductions, delays, discontinuations, adverse events, safety adverse events, attribution of causality, and hospitalizations. Outcomes will include imaging response using RECIST criteria, CA 19-9 trend, development of metastatic disease, and the ability to proceed to definitive surgical resection. DNA will be extracted from stool and analyzed using 16S rRNA sequencing methods to determine signatures and biodiversity. Descriptive statistics and correlative analysis will be reported. Continuous and categorical variables will be compared with Student’s t-test and Chi-squared test. Multiple groups will be compared by ANOVA. Kaplan-Meier logistic regression will be performed to compare outcomes between the different microbiota groupings. Conclusion: Stool collection from a multi-site clinical trial is feasible during neoadjuvant chemotherapy for pancreatic cancer and can increase diversity of the sample population. Citation Format: Sherise Rogers, Ryan Thomas, Brain Ramnaraign, Ilyas Sahin, Jesus Fabregas, Karen Russell, Steven Hughes, Ibrahim Nassour, Kathyrn Hitchcock, Omar Kayaleh, Anita Turk, Ji-Hyun Lee, David DeRemer, Carmen Allegra, Thomas George. An exploratory analysis of the intestinal microbiome in neoadjuvant chemotherapy for pancreatic cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2186.

Background: Colorectal cancer (CRC) is the 4th most common cancer type in the US. Following CRC treatment, about 37% of CRC survivors experience symptoms associated with anxiety and depression. Additionally, psychosocial distress is especially prevalent among CRC survivors with a stoma, and those reporting CRC-induced sexual dysfunction. Pharmacotherapy is one of the mainstay treatment options for psychological distress among patients with CRC. Research has shown that racial disparities are present with the use of supportive care medications in other cancer types. However, this has not been explored with the use of psychotropic medication for patients with CRC. The purpose of this research is to evaluate the presence of racial disparities in psychotropic medication use among patients with CRC. Methods: Utilizing the National Cancer Institute Surveillance Epidemiology and End Results (NCI SEER)- Medicare linked database, our analysis included all patients with a CRC diagnosis and an active outpatient prescription claims for psychotropic medications from 2009-2018. Prescription claims were specific to patients diagnosed with CRC and stratified by self-identified race and ethnicity. Patients who were on psychotropic medications before CRC diagnosis, or unspecified race or ethnicity were excluded from the analysis. Psychotropic medications consisted of anxiolytics, antidepressants, and antipsychotic medications. Results: 136,014 participants were included in the analysis. The racial and ethnic breakdown comprised of 81.56% White, 11.22% African American (AA), 2.66% Hispanic, 4.27% Asian/Pacific Islander (API), and 0.25% Native American (NA). Results are presented as unadjusted odds ratios (OR) and 95% confidence intervals (CI). Compared to White patients, AA (OR 0.53; 95% CI 0.50-0.56), API (OR 0.50; 95% CI 0.46-0.54), Hispanic (OR 0.64; 95% CI 0.58-0.71), and NA (OR 0.59; 95% CI 0.43-0.81) patients had lower utilization of anxiolytic medications. Regarding antidepressant use, AA (OR 0.55; 95% CI 0.53-0.57), API (OR 0.46; 95% CI 0.43-0.49), Hispanic (OR 0.73; 95% CI 0.68-0.79), and NA (OR 0.78; 95% CI 0.63-0.96) had lower utilization compared to White patients. Differences in antipsychotic medication use was observed with Asian/Pacific Islanders (OR 0.71; 95% CI 0.64-0.78) and Native Americans (OR 0.49; 95% CI 0.31-0.76) compared to White patients. No other racial differences in antipsychotic medications were identified. Conclusion: The study showed that racial and ethnic disparities are present with the use of psychotropic medications among patients with CRC. Racial and ethnic minority patients had lower use for most of the drug classes evaluated. Further research is warranted to assess the potential barriers and facilitators of psychotropic medication use among patients belonging to historically minoritized racial and ethnic groups. Citation Format: MegCholack Awunti, Yi Guo, Sherise Rogers, Lisa Scarton, Diana Wilkie, John Allen. Evaluation of racial and ethnic psychotropic medication use among patients with colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1932.

Background: Pain management is a substantial component of the care of patients with pancreatic cancer (PC). PC-related pain occurs in up to 75% of patients at diagnosis, 90% of patients with late-stage disease, and overall is the most frequently reported adverse event in this patient population. PC-related pain is multifactorial and includes visceral, somatic, and neuropathic origins. Furthermore, PC-related pain can be disease-induced or a result of adverse side effects of treatment. PC-related pain is primarily managed by supportive care medications (SCM), including opioid and non-opioid analgesics, corticosteroids, and antiepileptics. Among these, opioids are by far the most utilized treatment. Recent evidence suggests that opioid use in PC patients is associated with increased survival. Previous literature suggests racial/ethnic differences in the use of some SCMs including opioids in patients with cancer, but there is no research confirming these findings in patients with PC. Methods: Utilizing the National Cancer Institute Surveillance Epidemiology and End Results (NCI SEER)- Medicare linked database, our analysis included all patients with a PC diagnosis and a newly initiated outpatient prescription claim for pain medications from 2009-2018. Patients who were on pain medications before PC diagnosis, or of unspecified race/ethnicity were excluded from the analysis. We assessed three separate classes of pain medications including opioids, non-opioid analgesics, and neuropathic analgesics. Prescription claims were specific to patients diagnosed with PC and stratified by self-identified race/ethnicity. Our objective was to characterize the relationship between race and receipt of pain medications in the first year following the diagnosis of PC. Results: After application of the inclusion/exclusion criteria, 71,700 patients with PC were identified and included in the analysis (White: 80.3%; Black/African American: 11.8%; Asian/Pacific Islander: 4.5%; Hispanic: 3.1%; Native American 0.25%). As compared to White patients, Black/African American (Relative Risk [RR] 0.97; 95% Confidence Interval [CI]: 0.96-0.99) and Asian/Pacific Islander patients (RR 0.88; 95% CI: 0.85-0.90) were less likely to be prescribed an opioid analgesic. Black/African American (RR 1.09; 95% CI: 1.02-1.16), Asian/Pacific Islander (RR 1.52; 95% CI: 1.41-1.65), and Hispanic (RR 1.45; 95% CI: 1.31-1.59) patients were more likely to be prescribed a non-opioid analgesic. Black/African American (RR: 1.11; 95% CI: 1.05-1.18) patients were more likely to be prescribed a neuropathic analgesic. No other differences were noted in pain medication use by race/ethnicity. Conclusion: Our study findings suggest that pain medication usage in patients with PC varies for racial/ethnic minorities as compared to White patients, in particular for Black/African Americans. Future research should explore the impact of sociocultural, and psychosocial factors on pain medication usage patterns in racial/ethnic minority patients with PC. Citation Format: John M. Allen, MegCholack Awunti, Yi Guo, Sherise Rogers, Lisa Scarton, Diana J. Wilkie. Disparities in the use of pain medication in patients with pancreatic cancer: Focus on racial and ethnic minorities [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr A026.

Background: Each year 1.4 million adults are diagnosed with diabetes, and in 2022 more than 1.9 million Americans will be diagnosed with cancer. There is a strong link between type 2 diabetes (T2D) and several types of cancer, and both conditions are known for health disparities. Unrecognized or poorly managed T2D is associated with higher staged cancer at diagnosis and cancer mortality rates with reduced overall survival. Yet, it is not standard oncology practice to test newly diagnosed cancer patients for T2D. Nurses are well positioned to facilitate testing and management of T2D.Aim: The purpose of this study was to examine the feasibility of a nurse-led intervention for adults with newly diagnosed cancer and undiagnosed T2D.Method: In a randomized feasibility pilot study conducted within a large academic medical oncology center, we used EPIC to identify adults with newly diagnosed cancer (< 3 months). The intervention group received immediate initiation of metformin and T2D management education. The standard care group received referral back to their primary care provider. The study measures included HbA1c and feasibility metrics (i.e., population availability, recruitment efficiency and sample retention).Results: Two days a week, over an 11-month timeframe, we pre-screened 379 adults (78.4% non-Hispanic White, 12.9% Black, 1.6% Asian, .5% American Indian, 7.1% other) for study eligibility. Of those pre-screened only 55 (14.5%) patients were eligible for HbA1c screening. The rest were excluded due to current use of metformin (16%), abnormal labs (AST/ALT, eGFR) (16%), or poor prognosis (e.g., pancreatic cancer or leukemia; 18%). Of the 55 patients screened, one non-Hispanic White man, one non-Hispanic White woman, and one Black woman met HbA1c ≥ 6.5% eligibility for the intervention (mean age 58.3, two patients had breast cancer and one patient had rectal cancer); one patient was randomized to the intervention group and two patients were randomized to the standard care group. The initial HbA1c for the intervention group patient was 6.7% and decreased to 5.1% after 3 months (primary endpoint). For the two standard care group patients, the HbA1c was 7.2% and 6.7% and decreased to 5.5%, 5.9%, respectively, after 3 months. No patients were lost to follow-up. All three patients indicated that they enjoyed participating in the study, the length of the study was good, and felt the study would be well received by other patients. The study was subsequently closed due to failing feasibility metrics. Conclusion: Despite study acceptability to patient, this T2D screening protocol was deemed not feasible due to recruitment inefficiency including cost, time, and personnel to screen at the point of care. Integrating routine HbA1c tests for all newly diagnosed cancer patients would simplify screening for study, which would allow another feasibility study of a promising intervention to improve management of undiagnosed T2D among newly diagnosed patients with cancer. Citation Format: Lisa Scarton, Tarah Nelson, Yingwei Yao, Shavondra Huggins, Ara Jo, LaToya J. O'Neal, Thomas J. George, Juan M. Munoz-Pena, Merry J. Markham, Martina C. Murphy, Jonathan A. Chatzkel, Sherise Rogers. Feasibility metric outcomes: A nurse-led intervention to identify and manage undiagnosed type 2 diabetes in patients with newly diagnosed cancer [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr B130.

Background: Pancreatic cancer (PC) has been associated with detrimental impacts on psychological wellbeing. Reported PC-related depression and anxiety rates are higher than in other types of cancer. A substantial component to improve psychological well-being in patients with PC is the use of drug therapy to provide symptomatic relief. The presence of racial disparities in the utilization of psychotropic medication has been reported in some cancer types. However, despite these known racial disparities and the increased psychiatric symptoms in patients with PC, there has not been an evaluation of racial disparities in psychotropic medication use among patients with PC. The purpose of this study was to describe usage patterns of psychotropic medications by race among patients diagnosed with PC. Methods: Utilizing the National Cancer Institute Surveillance Epidemiology and End Results (NCI SEER)- Medicare linked database, our analysis included all patients with a PC diagnosis and an active outpatient prescription claim for psychotropic medications from 2009-2018. Prescription claims were specific to patients diagnosed with PC and stratified by self-identified race/ethnicity. Patients who were on psychotropic medications before PC diagnosis, or unspecified race/ethnicity were excluded from the analysis. Psychotropic pharmacological agents consisted of anxiolytics, antidepressants, and anti-delirium/antipsychotic medications. Results: 71,700 participants were included in the analysis. Racial/ethnic participant breakdown included 80% White, 12% African American/Black, 4.5% Asian/Pacific Islander, 3% Hispanic, and 0.25% Native American. Results are presented as an unadjusted relative risk (RR) and 95% Confidence Interval (CI). As compared to White patients, African American/Black (RR 0.60; 95% CI 0.57-0.64), Asian/Pacific Islander (RR 0.52; 95% CI 0.48-0.58), and Hispanic (RR 0.61; 95% CI 0.55-0.67) patients had lower utilization of anxiolytics. For antidepressant medications, African American/Black (RR 0.74; 95% CI 0.71-0.77), Asian/Pacific Islander (RR 0.61; 95% CI 0.58-0.66), and Hispanic (RR 0.87; 95% CI 0.82-0.92) patients had less utilization compared to White patients. For anti-delirium/antipsychotic agents, African American/Black (RR 1.09; 95% CI 1.01-1.17) had a higher risk of utilization while Asian/Pacific Islander (RR 0.83; 95% CI 0.73-0.95) had less utilization when compared to White patients. No other differences were noted in psychotropic medication use by race/ethnicity. Conclusion: The study showed that utilization patterns of psychotropic agents in patients with PC varied by race/ethnicity. Racial/ethnic minorities had lower utilization rates for most of the drug classes except anti-delirium/antipsychotic agents in which African American/Black had higher utilization rates when compared to White patients. Further research needs to be carried out to examine social and clinical factors causing this phenomenon. Citation Format: MegCholack Awunti, Yi Guo, Sherise Rogers, Lisa Scarton, Diana Wilkie, John Allen. Evaluation of psychotropic medication usage patterns in patients with pancreatic cancer by race/ethnicity [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr A027.

Background: Pancreatic cancer portends a very poor prognosis. It is the third leading cause of cancer deaths in the United States. African Americans have a 50- 90% increased incidence of pancreatic cancer in comparison to other racial groups. 20% of patients with pancreatic cancer present with early stage disease and will have a median overall survival of 2.5 years if able to undergo surgical resection. There is a desperate need to discover novel ways of treating pancreatic cancer. Understanding of the microbiome may be informative to overcoming chemotherapy resistance, toxicity and improving outcomes and disparities. The aim of this study is to (1) identify changes in the intestinal microbiota during neoadjuvant treatment of pancreatic ductal adenocarcinoma that correlate with treatment response and (2) identify changes in the intestinal microbiota during neoadjuvant treatment of pancreatic ductal adenocarcinoma that correlate with treatment toxicity in a diverse patient population. Methods: Patients with resectable or borderline resectable pancreatic cancer who are enrolled in a multi-site clinical trial (NCT03483038) receiving neoadjuvant NEO-Nali-IRI (oxaliplatin, liposomal irinotecan and 5- FU) followed by surgical resection were asked to provide stool samples and a dietary log during the following four (or five) time points: baseline, mid-therapy (after C4), at completion of chemotherapy (after C8), after radiation if applicable, and at 4-6 weeks post-operative. Participants will be given stool collection kits at clinic visits for home sample acquisition. All samples will be mailed to the University of Florida Health Cancer Center Microbiome Biorepository. Data will be collected regarding demographics, stage, medical history and concurrent medications including antimicrobics and probiotics, chemotherapy dose-reductions, delays, discontinuations, adverse events, safety adverse events, attribution of causality, and hospitalizations. Outcomes will include imaging response using RECIST criteria, CA 19-9 trend, development of metastatic disease, and the ability to proceed to definitive surgical resection. DNA will be extracted from stool and analyzed using 16S rRNA sequencing methods to determine signatures and biodiversity. Descriptive statistics and correlative analysis will be reported. Continuous and categorical variables will be compared with Student’s t-test and Chi-squared test. Multiple groups will be compared by ANOVA. Kaplan-Meier logistic regression will be performed to compare outcomes between the different microbiota groupings. Conclusion: Stool collection from a multi-site clinical trial is feasible during neoadjuvant chemotherapy for pancreatic cancer and can increase diversity of the sample population. Citation Format: Sherise Rogers, Ryan Thomas, Brian Ramnaraign, Ilyas Sahin, Jesus Fabregas, Karen Russell, Steven Hughes, Ibrahim Nassour, Kathryn Hitchcock, Omar Kayaleh, Anita Turk, Ji-Hyun Lee, David DeRemer, Carmen Allegra, Thomas George. An exploratory analysis of the intestinal microbiome in neoadjuvant chemotherapy for pancreatic cancer [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer; 2022 Sep 13-16; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2022;82(22 Suppl):Abstract nr B037.