Executing plans to enhance diversity across cancer centers in the United States: Opportunities and challenges.

BACKGROUND: Lack of diversity in the cancer research workforce persists which the new requirement for all NCI-designated cancer centers to have a Plan to Enhance Diversity (PED) seeks to address. However, it is not well understood how different cancer centers are approaching the development and execution of these plans. Our objective was to assess how cancer centers are establishing and pursuing their PED. METHODS: We conducted a cross-sectional survey of members of the Cancer Center DEI Network which includes all NCI-designated cancer centers and several emerging centers. 62 cancer centers (75% of those invited), including 58 NCI-designated cancer centers (81% of those with this designation), participated and completed a questionnaire that assessed PED leadership, major challenges, implementation strategies, and approach to evaluate PED progress. RESULTS: The most common PED challenge identified is recruiting diverse faculty (68% of centers) and the most common strategy currently used to address this is reviewing and revising faculty recruitment practices (67%). The most common approach centers are using to measure PED progress are shifts in demographics (68%), and data on the demographics of faculty, leadership, and trainees are available at 79%, 81%, and 75% of centers, respectively. CONCLUSION(S): While almost all centers have established a PED leadership structure, there is considerable variation in the approaches used to realize PED goals, and in the resources provided to support PED work. Realizing opportunities to share and implement common best practices and exemplar programs has the potential to elevate the impact of PED efforts nationally.

Safety and efficacy of peptide receptor radionuclide therapy in neuroendocrine tumors: A single center experience.

Peptide receptor radionucleotide therapy (PRRT) with 177Lu-dotatate is widely used for the treatment of patients with neuroendocrine tumors (NETs). We analyzed data from 104 patients with NETs treated with 177Lu -dotatate at a US academic center between December 2017 and October 2020 to better understand patterns of long-term efficacy, safety, and toxicity in the real-world setting. 177Lu-dotatate (200 mCi) was administered every eight weeks for four doses. The most common sites of primary disease were small intestine NETs (n = 49, 47%), pancreatic NETs (n = 32, 31%), and lung NETs (n = 7, 7%). Twenty-seven percent had Ki-67 <3%, 49% had Ki-67 between 3-20%, and 13.5% had Ki-67 >20%. The cohort had been pretreated with a median of two prior lines of treatment. Forty percent had received prior liver-directed treatment. Seventy-four percent of patients completed all four doses of treatment. The objective response rate was 18%. The median time-to-treatment failure/death was significantly longer for small-bowel NETs when compared to pancreatic NETs (37.3 months vs. 13.2 months, p = 0.001). In a multivariate model, Ki-67, primary site, and liver tumor burden ≥50% were found to independently predict time-to-treatment failure/death. Around 40% of patients experienced adverse events of ≥grade 3 severity. Treatment-related adverse events leading to discontinuation of therapy happened in 10% of patients. Preexisting mesenteric/peritoneal disease was present in 33 patients; seven of these patients developed bowel-related toxicities including two grade 5 events. We also report two cases of delayed-onset minimal change nephrotic syndrome, which occurred 14 and 27 months after the last dose of PRRT. Lastly, we describe six patients who developed rapid tumor progression in the liver leading to terminal liver failure within 7.3 months from the start of PRRT, and identify potential risk factors associated with this occurrence, which will need further study.

Development of novel pyrimidine nucleoside analogs as potential anticancer agents: Synthesis, characterization, and In-vitro evaluation against pancreatic cancer.

The present study proposed modification of 5-FU by conjugation with an acyl chloride and a 5-membered heterocyclic ring to improve its in-vitro cytotoxicity and metabolic stability. XYZ-I-71 and XYZ-I-73 were synthesized by introducing a tetrahydrofuran ring on 5-fluorocytosine (a precursor of 5-FU) and conjugation with octanoyl chloride and lauroyl chloride, respectively. The structure of the synthesized compounds was validated using NMR and micro-elemental analysis. The antiproliferative activity of the analogs was determined against MiaPaCa-2, PANC-1, and BxPC-3 pancreatic cancer cells. The analog's stability in human liver microsomes was quantified by HPLC. We found that the XYZ-I-73 (IC50 3.6 ± 0.4 µM) analog was most effective against MiaPaCa-2 cells compared to XYZ-I-71(IC50 12.3 ± 1.7 µM), GemHCl (IC50 24.2 ± 1.3 µM), Irinotecan (IC50 10.1 ± 1.5 µM) and 5-FU (IC50 13.2 ± 1.1 µM). The antiproliferative effects of this analog in Miapaca-2 cells is evident based on it having a 7-fold,3-fold, and 4-fold increased cytotoxic effect over Gem-HCl, Irinotecan, and 5-FU, respectively. On the other hand, XYZ-I-71 exhibited a 2-fold increased cytotoxic effect over Gem-HCl but a comparable cytotoxic effect to 5-FU and Irinotecan in MiaPaCa-2 cells. A similar trend of higher XYZ-I-73 inhibition was observed in PANC-1 and BxPC-3 cultures. For 48-h MiaPaCa-2 cell migration studies, XYZ-I-73 (5 µM) significantly reduced migration (# of migrated cells, 168 ± 2.9), followed by XYZ-I-71(315±2.1), Gem-HCl (762±3.1) and 5-FU (710 ± 3.2). PARP absorbance studies demonstrated significant inhibition of PARP expression of XYZ-I-73 treated cells compared to 5-FU, GemHCl, and XYZ-I-71. Further, BAX and p53 expressions were significantly increased in cells treated with XYZ-I-73 compared to 5-FU, GemHCl, and XYZ-I-71. In-vitro, metabolic stability studies showed that 80 ± 5.9% of XYZ-I-71 and XYZ-I-73 remained intact after 2 h exposure in liver microsomal solution compared to 5-FU. The XYZ-I-73 analog demonstrated a remarkable cytotoxic effect and improved in-vitro metabolic stability over the selected standard drugs and may have potential anticancer activity against pancreatic cancer.

Complete clinical remission of malignant peritoneal mesothelioma with systemic pemetrexed and bevacizumab in a patient with a BAP1 mutation.

Malignant peritoneal mesothelioma (MPeM) is a rare malignancy with historically poor prognosis. Recent research has started to reveal increasingly prevalent genetic mutations seen in this malignancy. Here, we report a case of complete clinical remission of unresectable, metastatic MPeM with systemic chemotherapy. Immunohistochemistry of our patient's malignant cytology sample showed loss of Breast Cancer Gene 1-associated protein-1 expression (BAP1). The patient had synchronous diagnoses of primary squamous cell carcinoma of the anus, benign schwannoma and meningioma. Following the completion of 18 cycles of pemetrexed and bevacizumab, the patient has remained in clinical remission for 8 months. We examine the unusual susceptibility of unresectable MPeM to systemic chemotherapy and attribute susceptibility to the molecular milieu created by mutations in multiple DNA repair pathways. We encourage increased testing for and analysis of mutations in DNA repair pathways to improve future treatment outcomes in this rare malignancy.

The Prospect of Harnessing the Microbiome to Improve Immunotherapeutic Response in Pancreatic Cancer.

Pancreatic ductal adenocarcinoma cancer (PDAC) is projected to become the second leading cause of cancer-related death in the United States by 2030. Patients are often diagnosed with advanced disease, which explains the dismal 5-year median overall survival rate of ~12%. Immunotherapy has been successful in improving outcomes in the past decade for a variety of malignancies, including gastrointestinal cancers. However, PDAC is historically an immunologically "cold" tumor, one with an immunosuppressive environment and with restricted entry of immune cells that have limited the success of immunotherapy in these tumors. The microbiome, the intricate community of microorganisms present on and within humans, has been shown to contribute to many cancers, including PDAC. Recently, its role in tumor immunology and response to immunotherapy has generated much interest. Herein, the current state of the interaction of the microbiome and immunotherapy in PDAC is discussed with a focus on needed areas of study in order to harness the immune system to combat pancreatic cancer.

Unraveling Racial Disparities in Supportive Care Medication Use among End-of-Life Pancreatic Cancer Patients: Focus on Pain Management and Psychiatric Therapies.

BACKGROUND: Supportive care medication use differences may contribute to racial disparities observed in health-related quality of life in patients with pancreatic cancer. METHODS: In this observation study using the Surveillance, Epidemiology, and End Results-Medicare linked database, we sought to examine supportive care medication use disparities in patients with pancreatic cancer from 2005 to 2017 by race and ethnicity. RESULTS: Among 74,309 patients included in the final analysis, racial and ethnic disparities in the use of supportive care medications were identified. After adjustment for confounding factors and compared with non-Hispanic Whites, minorities had significantly less use of opioids [Black: adjusted OR (aOR), 0.84; 95% confidence interval (CI), 0.79-0.88; Asian: aOR, 0.84; 95% CI, 0.79-0.90), and skeletomuscular relaxants (Black: aOR, 0.90; 95% CI, 0.82-0.99; Hispanic: aOR, 0.82; 95% CI, 0.74-0.91; Asian: aOR, 0.59; 95% CI, 0.51-0.68), and increased use of non-opioid analgesics (Hispanic: aOR, 1.16; 95% CI, 1.01-1.14; Asian: aOR, 1.37; 95% CI, 1.26-1.49). Racial and ethnic minorities had less use of antidepressants (Black: aOR, 0.56; 95% CI, 0.53-0.59; Hispanic: aOR, 0.77; 95% CI, 0.73-0.82; Asian: aOR, 0.47; 95% CI, 0.44-0.51), anxiolytics (Black: aOR, 0.78; 95% CI, 0.74-0.82; Hispanic: aOR, 0.66; 95% CI, 0.62-0.71; Asian: aOR, 0.52; 95% CI, 0.48-0.57), and antipsychotics (Hispanic: aOR, 0.90; 95% CI, 0.82-0.99; Asian: aOR, 0.84; 95% CI, 0.74-0.95). CONCLUSIONS: Racial and ethnic disparities in the use of supportive care medications among patients with pancreatic cancer were observed, with the differences unexplained by sociodemographic factors. IMPACT: Future studies should identify strategies to promote equitable use of supportive care medications among racial minorities and explore factors that may influence their use in these populations.

Prognosis and Treatment Outcomes of Bone Metastasis in Gallbladder Adenocarcinoma: A SEER-Based Study.

BACKGROUND: Gallbladder carcinoma (GBC) is a rare, aggressive malignancy comprising 0.5% of gastrointestinal cancers. It has poor survival outcomes due to its insidious onset, lack of standardized screening, and limited therapies. Advanced-stage diagnosis with liver, lymph node, and peritoneal metastasis is common, while bone metastasis is rare. The knowledge on bone metastasis in GBC is limited to case reports and small series, and its clinical significance is largely unexplored. METHODS: The study extracted the demographic and clinical variables of patients with metastatic (M1) gallbladder adenocarcinoma from the Surveillance, Epidemiology, and End Results (SEER) database between 2011 and 2020. Descriptive statistics were used to analyze the demographic characteristics. The multivariate Cox regression analysis was used to calculate the hazard ratio. The overall survival (OS) was assessed using the Kaplan-Meier method, and the log-rank test was utilized to compare the survival between the groups. RESULTS: A total of 2724 patients were included in the study. A total of 69% of the patients were female, and the median age was 68 (range 24-90+). A total of 7.4% of the patients had bone metastasis on diagnosis. The multivariate Cox analysis identified bone metastasis as an independent mortality risk factor in metastatic GBC (HR 1.50, p < 0.001). The patients were divided into two age groups: a younger age group (18-74 years) and an older age group (75+ years). In the younger group, the median OS with and without bone metastasis was 3 and 5 months, respectively (p < 0.0001). In the older age group, there was no significant difference in the OS between the patients with and without bone metastasis (p = 0.35). In the younger group who were treated with chemotherapy, the patients with bone metastasis had a significantly worse OS (median OS 5 months vs. 8 months, p < 0.0001). In the untreated group, the patients with bone metastasis in the younger age group had a significantly worse OS (median OS 1 month vs. 2 months, p = 0.014). In the patients with bone metastasis, those who did not receive chemotherapy had a significantly worse OS than those who were treated with chemotherapy in both age groups (younger age group: median OS 1 month vs. 5 months, p < 0.0001 and older age group: median OS 1 month vs. 5 months, p = 0.041). CONCLUSIONS: Our findings suggest that the presence of bone metastasis in gallbladder adenocarcinoma is an independent prognostic factor associated with unfavorable survival outcomes in the younger age group (18-74 years). However, in the older age group (75+ years), the presence of bone metastasis did not impact the survival. Treatment with chemotherapy was associated with extended survival in all patients. Thus, early detection and aggressive management of bone metastasis, including the consideration of chemotherapy, may be crucial in improving the OS and quality of life for individuals with gallbladder adenocarcinoma.

Florida-California Cancer Research, Education and Engagement (CaRE2) Health Equity Center: Structure, Innovations, and Initial Outcomes.

INTRODUCTION: The Florida-California Cancer Research, Education, and Engagement (CaRE2) Health Equity Center is a triad partnership committed to increasing institutional capacity for cancer disparity research, the diversity of the cancer workforce, and community empowerment. This article provides an overview of the structure, process innovations, and initial outcomes from the first 4 years of the CaRE2 triad partnership. METHODS: CaRE2 serves diverse populations in Florida and California using a "molecule to the community and back" model. We prioritize research on the complex intersection of biological, environmental, and social determinants health, working together with scientific and health disparities communities, sharing expertise across institutions, bidirectional training, and community outreach. Partnership progress and outcomes were assessed using mixed methods and four Program Steering Committee meetings. RESULTS: Research capacity was increased through development of a Living Repository of 81 cancer model systems from minority patients for novel cancer drug development. CaRE2 funded 15 scientific projects resulting in 38 publications. Workforce diversity entailed supporting 94 cancer trainees (92 URM) and 34 ESIs (32 URM) who coauthored 313 CaRE2-related publications and received 48 grants. Community empowerment was promoted via outreaching to more than 3000 individuals, training 145 community cancer advocates (including 28 Community Scientist Advocates), and publishing 10 community reports. CaRE2 members and trainees together have published 639 articles, received 61 grants, and 57 awards. CONCLUSION: The CaRE2 partnership has achieved its initial aims. Infrastructure for translational cancer research was expanded at one partner institution, and cancer disparities research was expanded at the two cancer centers.

A phase II study of neoadjuvant liposomal irinotecan with 5-FU and oxaliplatin (NALIRIFOX) in pancreatic adenocarcinoma.

For patients with localized pancreatic cancer with minimal vascular involvement, optimal survivability requires a multidisciplinary approach of surgical resection and systemic chemotherapy. FOLFIRINOX is a combination chemotherapy regimen that offers promising results in the perioperative and metastatic settings; however, it can cause significant adverse effects. Such toxicity can negatively impact some patients, resulting in chemotherapy discontinuation or surgical unsuitability. In an effort to reduce toxicities and optimize outcomes, this investigation explores the safety and feasibility of substituting liposomal irinotecan (nal-IRI) for nonliposomal irinotecan to improve tumor drug delivery and potentially reduce toxicity. This regimen, NALIRIFOX, has the potential to be both safer and more effective when administered in the preoperative setting.

For patients with pancreatic cancer with little to no cancer near the blood vessels, the best life expectancy usually requires surgery and chemotherapy. FOLFIRINOX is a chemotherapy medicine that offers promising results for both patients getting surgery and for patients with widespread disease. However, it can cause harmful side effects. The side effects can be so bad that the chemotherapy has to be stopped or that surgery is no longer possible. In order to reduce the harmful side effects and improve outcomes, this investigation looks into the safety and practicality of using a different version of one of the medicines. The different version hopes to improve drug delivery and reduce harmful side effects. This regimen, NALIRIFOX, can be safer and more effective in patients awaiting surgery. Clinical Trial Registration: UF-STO-PANC-004 (NCT03483038) (ClinicalTrials.gov).

National adoption of neoadjuvant chemotherapy: paradigm shift in the treatment of pancreatic cancer.

BACKGROUND: The historical standard of care in treating operable pancreatic cancer via upfront surgery has been challenged recently using a neoadjuvant approach. The aim of the study is to examine the national practice patterns in the management of pancreatic cancer with an emphasis on the trends of neoadjuvant systemic therapy use. METHODS: This is a cross-sectional time-series study using the National Cancer Database from 2006 to 2019. Patients who underwent resection for stage I-II pancreatic adenocarcinoma were selected. RESULTS: Overall, 25% of patients had neoadjuvant chemotherapy, 49% had surgery followed by adjuvant chemotherapy and 26% had surgery alone. The rate of neoadjuvant chemotherapy has increased from 11% in 2006 to 43% in 2019. There was a decrease in the rate of surgery followed by chemotherapy from 48% to 38%, and a decrease in the rate of surgery alone from 41% to 19%. The rate of radiation therapy use has decreased over time, as has the resection rate, while median overall survival has steadily improved over the years. CONCLUSIONS: In 2019, the rate of using neoadjuvant systemic therapy overtook the rate of surgery first followed by adjuvant systemic therapy, marking a pragmatic national shift in the clinical management of pancreatic cancer.

Effects of Clinical and Tumor Characteristics on Survival in Patients with Hepatocellular Carcinoma with Bone Metastasis.

Background: Advanced hepatocellular carcinoma (HCC) generally has a dismal prognosis. Bone metastases from HCC are infrequent, with a poorer prognosis. However, the survival influencing factors are not yet well understood. Aim: The aim of the present study was to assess the clinical features and tumor characteristics of HCC patients with bone metastasis. Methods: A cohort of 170,576 adult patients with HCC was studied using the National Cancer Database (NCDB) spanning from 2010 to 2019, and within this group, 5285 patients (3.1%) were diagnosed with bone metastasis. We performed the Kaplan-Meier method to calculate the median overall survival (OS). We included demographics (age at diagnosis, gender, race, insurance status), comorbidity score, and treatment characteristics. Results: Of a total of 5285 HCC patients with bone metastasis, 86.2% were male and 61.2% were non-Hispanic white. Most patients (55.1%) were below 65, and 89% had a total Charlson-Deyo comorbidity score of under 3. Among patients with known tumor grade, 24.8% had well-differentiated tumors, and 36.1% had poorly differentiated tumors. Chemotherapy was administrated to 39.5% of patients. In univariate analysis, patients with well-differentiated tumors had better OS compared to poorly differentiated tumors (5.4 months vs 3.0 months, p = 0.001). Patients who received single or multiagent chemotherapy were significantly associated with improved OS compared to patients who did not receive chemotherapy (7.0 and 8.5 months vs 1.94 months, respectively). We also found mortality difference between age, comorbidity scores, facility types and race groups. Conclusion: In this cohort analysis of NCDB data, we found better OS in treatment receipt, lower tumor grade, younger age, non-Hispanic Black and Hispanic race, treatment at academic facility and lower comorbidity score in HCC patients with bone metastasis. The study results may have a consequential impact on the treatment decisions for HCC patients with bone metastasis.

A nurse-led intervention in patients with newly diagnosed cancer and Type 2 diabetes: A pilot randomized controlled trial feasibility study.

BACKGROUND: Undiagnosed Type 2 diabetes (T2D) has been associated with advanced stage cancer at diagnosis, higher mortality, and lower long-term all-cause survival. This was a RCT pilot study to examine the feasibility of a nurse-led T2D intervention for adults with newly diagnosed cancer (≤3 months), and T2D, undiagnosed or untreated with medication, conducted at an outpatient oncology clinic affiliated with a large academic institution. METHODS: Participants needed to meet the eligibility criteria including a HbA1c level between 6.5% and 9.9%. Randomization was 1:1 to a 3-month intervention that consisted of nursing-led diabetes education and immediate initiation of metformin versus referral to primary care for usual care (control). RESULTS: Three hundred and seventy nine patients were screened using EHR, 55 agreed to participate, and 3 had eligible HbA1c levels and were randomized in the study. Primary reasons for study exclusion included life expectancy ≤2 years (16.9%), current use or inability to tolerate metformin (14.8%), and abnormal labs that contraindicated metformin use (13.9%). CONCLUSION: This study was not feasible due to recruitment inefficiencies, but acceptable to all who qualified.

Importance of carbohydrate antigen (CA 19-9) and carcinoembrionic antigen (CEA) in the prognosis of patients with duodenal adenocarcinoma: a retrospective single-institution cohort study.

BACKGROUND: Duodenal adenocarcinoma (DA) is a rare malignancy without validated tumor markers. In practice, carcinoembryonic antigen (CEA) and carbohydrate antigen (CA 19-9) are often used in the management of DA, though their prognostic value is unknown. MATERIALS AND METHODS: A single-institution retrospective review included patients diagnosed with biopsy-confirmed adenocarcinoma of the duodenum between 2006 and 2021. Peri-ampullary tumors were excluded. Levels of CA 19-9 and CEA were collected as continuous variables and were analyzed as binary variables: normal vs. high, using the maximum normal value as a cut-off (normal Ca 19-9 <35 U/ml; CEA <3 ng/ml). Survival analysis was conducted using Kaplan Meier curves, log-rank test and Cox proportional hazards model. RESULTS: There were 68 patients included in the final analysis. Median age was 67 years old and median follow-up time was 22.2 months. CA 19-9 and CEA were elevated in 36.8% and 48.5% of patients, respectively. A concomitant elevation of both tumor markers was associated with worsened OS (HR 2.140, 95% CI: 1.114-4.112; p = 0.019). After controlling for age and sex on multivariate analysis, elevation in both CA 19-9 ≥35 and CEA ≥3.0 remained significantly associated with increased mortality (HR 2.278, 95% CI: 1.162-4.466; p = 0.016). CONCLUSIONS: In summary, CA 19-9 and, to a lesser extent, CEA, show promise as prognostic markers in DA. Larger studies are needed to validate their use and to evaluate their performance as markers of recurrence.

Evaluation of Anticancer Activity of Zhubech, a New 5-FU Analog Liposomal Formulation, against Pancreatic Cancer.

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 cancers have been masked by high drug toxicities, adverse reactions, and resistance. The use of nanocarriers such as liposomes to overcome these unwanted effects has become very popular. This study aims to formulate 1,3-bistertrahydrofuran-2yl-5FU (MFU)-loaded liposomal nanoparticles (Zhubech) and to evaluate itsstability, release kinetics, in vitro and in vivo anticancer activities, and biodistribution in different tissues. Particle size and zeta potential were determined using a particle size analyzer, while cellular uptake of rhodamine-entrapped liposomal nanoparticles (Rho-LnPs) 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 LnPs in vivo using inductively coupled plasma mass spectrometry (ICP-MS). The mean hydrodynamic diameters of blank LnPs 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 4 °C and 25 °C 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 spheroid (IC50Zhubech = 3.4 ± 1.0 µM vs. IC50MFU = 6.8 ± 1.1 µM) and organoid (IC50Zhubech = 9.8 ± 1.4 µM vs. IC50MFU = 42.3 ± 1.0 µM) culture models. Confocal imaging confirmed a high uptake of rhodamine-entrapped LnP by Panc-1 cells in a time-dependent manner. Tumor-efficacy studies in a PDX bearing mouse model revealed a more than 9-fold decrease in mean tumor volumes in Zhubech-treated (108 ± 13.5 mm3) compared to 5-FU-treated (1107 ± 116.2 mm3) animals, respectively. This study demonstrates that Zhubech may be a potential candidate for delivering drugs for pancreatic cancer treatment.

Review of genetic and pharmacogenetic differences in cytotoxic and targeted therapies for pancreatic cancer in African Americans.

Pancreatic ductal adenocarcinoma (PDAC) is currently the third leading cause of cancer mortality and the incidence is projected to increase by 2030. Despite recent advances in its treatment, African Americans have a 50-60% higher incidence and 30% higher mortality rate when compared to European Americans possibly resulting from differences in socioeconomic status, access to healthcare, and genetics. Genetics plays a role in cancer predisposition, response to cancer therapeutics (pharmacogenetics), and in tumor behavior, making some genes targets for oncologic therapeutics. We hypothesize that the germline genetic differences in predisposition, drug response, and targeted therapies also impact PDAC disparities. To demonstrate the impact of genetics and pharmacogenetics on PDAC disparities, a review of the literature was performed using PubMed with variations of the following keywords: pharmacogenetics, pancreatic cancer, race, ethnicity, African, Black, toxicity, and the FDA-approved drug names: Fluoropyrimidines, Topoisomerase inhibitors, Gemcitabine, Nab-Paclitaxel, Platinum agents, Pembrolizumab, PARP-inhibitors, and NTRK fusion inhibitors. Our findings suggest that the genetic profiles of African Americans may contribute to disparities related to FDA approved chemotherapeutic response for patients with PDAC. We recommend a strong focus on improving genetic testing and participation in biobank sample donations for African Americans. In this way, we can improve our current understanding of genes that influence drug response for patients with PDAC.

Atezolizumab plus tivozanib for immunologically cold tumor types: the IMMCO-1 trial.

Immune checkpoint inhibitor therapy represents a significant advance in cancer care. The interaction between PD-1 and PD-L1 induces immune tolerance and the inhibition of this interaction is an effective treatment strategy for numerous malignancies. Despite its demonstrated potential, immunotherapy is not clinically effective in immunogenically 'cold' tumors such as pancreatic cancer, prostate cancer and neuroendocrine tumors. Through the inhibition of VEGF, it may be possible to potentiate the effect of immune checkpoint blockade in tumors that have traditionally shown a lack of clinical response to immunotherapy. This signal-seeking, single-arm, prospective clinical trial aims to determine the objective response of tivozanib and atezolizumab in advanced immunogenically cold solid tumors. Clinical Trial Registration: NCT05000294 (ClinicalTrials.gov).

A Scoping Review on the Relationship between Race/Ethnicity and the Receipt of Supportive Care Medications during Cancer Treatment: Implications for the Clinical Pharmacist.

There is surmounting levels of evidence on the health disparities within cancer treatment in the United States (US). Most of the research focused on cancer specific factors including anticancer incidence, screening, treatment and follow-up, and clinical outcomes such as overall survival (OS). Less is known about the disparities present with supportive care medication use in cancer patients. Supportive care utilization during cancer treatment has been linked to improved quality of life (QoL) and OS among patients. The goal of this scoping review is to summarize findings of current literature on the relationship between race and ethnicity and the receipt of supportive care medications during cancer treatment for pain and chemotherapy-induced nausea and vomiting (CINV). This scoping review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA-ScR) guidelines. Our literature search included quantitative studies, qualitative studies, and grey literature written in the English language with clinically relevant outcomes pertaining to pain and CINV management in cancer treatment published from 2001-2021. Articles that met the predefined inclusion criteria were considered for inclusion in the analysis. The initial search yielded 308 studies. Following de-duplication and screening, 14 studies met the predefined inclusion criteria, with majority of the studies being quantitative studies (n=13). Collectively, results were mixed results regarding the presence of racial disparities for supportive care medication use. Half of the studies (n=7) supported this finding whereas, the other half (n=7) did not identify any racial disparities. In our review, multiple studies illustrate the existence of disparities in the use of supportive care medications in some cancer types. Clinical pharmacists should strive to eliminate supportive medication use disparities as part of a multidisciplinary team. In order to develop strategies to prevent supportive care medication use disparities in this population, further research and analysis of external factors that influence them are needed.

Chemotherapy is associated with improved survival in a national cohort of stage IV pancreatic adenosquamous carcinoma.

Background: Pancreatic adenosquamous carcinoma (PASC) is a rare cancer that often presents with advanced disease and carries a grim prognosis. PASC is defined by the presence of at least 30% malignant squamous cells in the presence of malignant ductal adenocarcinoma. The utility of chemotherapy in the setting of metastatic disease is unknown. Methods: In this cross-sectional analysis, patients with stage IV PASC diagnosed between 2006 and 2016 were abstracted from the National Cancer Data Base. Patients were then categorized according to whether they received chemotherapy. Multivariable logistic regression analysis was done to determine the odds of receiving palliative chemotherapy. Overall survival analysis was performed using Kaplan-Meier analysis. A Cox proportional hazard multivariable model was generated to account for potential confounders. Results: There were 698 patients with metastatic PASC available for analysis, including 400 patients (57.3%) who received chemotherapy and 298 patients (42.3%) who did not receive chemotherapy. Median overall survival was significantly longer for patients who received chemotherapy (5.2 vs. 1.5 months, P<0.001; HR 0.328, 95% CI: 0.272-0.397). Compared to patients who did not receive chemotherapy, patients who received chemotherapy were younger (mean 62.6 vs. 70.1 years old; P<0.001) and more likely to have no comorbidities (72.0% vs. 58.7%; P<0.001). In multivariate analysis, chemotherapy was the only factor independently associated with improved survival. Conclusions: This is the largest study on PASC conducted to date and the first to evaluate whether chemotherapy is associated with improved survival for patients with metastatic disease. We found that palliative chemotherapy was associated with significant prolongation of life. However, overall prognosis remained dismal despite chemotherapy and novel treatment approaches are needed to improve long-term survival.

Immunotherapy Management in Special Cancer Patient Populations.

Patients with autoimmune disorders, multiple comorbidities, poor performance status, advanced age, and infection with SARS-CoV-2 (COVID-19) each represent unique subgroups of patients with cancer to whom little is known of the effects, benefits, and complications of checkpoint inhibitor (CPI) therapy. Although prospective trials are lacking in these populations, retrospective data and cohort series suggest that these patients can safely receive and benefit from CPI therapy. Here, we review the relevant data available and offer clinical recommendations in managing these complex patients with CPI therapy, where otherwise indicated.