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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.
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Equidad en Salud , Neoplasias , Humanos , California , Florida , Grupos Minoritarios , Neoplasias/terapiaRESUMEN
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).
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Adenocarcinoma , Neoplasias Pancreáticas , Fármacos Sensibilizantes a Radiaciones , Humanos , Irinotecán/uso terapéutico , Neoplasias Pancreáticas/patología , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Oxaliplatino/uso terapéutico , Adenocarcinoma/patología , Terapia Neoadyuvante/métodos , Fluorouracilo/efectos adversos , Leucovorina/efectos adversos , Fármacos Sensibilizantes a Radiaciones/uso terapéutico , Ensayos Clínicos Fase II como AsuntoRESUMEN
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.
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Nanopartículas , Neoplasias Pancreáticas , Animales , Ratones , Liposomas/química , Gadolinio/uso terapéutico , Distribución Tisular , Neoplasias Pancreáticas/tratamiento farmacológico , Fluorouracilo/uso terapéutico , Nanopartículas/química , Neoplasias PancreáticasRESUMEN
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.
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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).
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A meta-analysis of randomized controlled trials (RCTs) was performed to examine the risk of everolimus discontinuation due to related and unrelated adverse events (AE) in cancer patients. Fifteen RCTs were analyzed that compared everolimus to placebo and reported discontinuation due to AE with everolimus (related and unrelated to everolimus) and placebo (unrelated to everolimus). Incidence of discontinuation with everolimus due to AE and placebo was 12.3% and 4.7% respectively. Relative risk of everolimus discontinuation due to related AE was 2.60. Risk of discontinuation varied by tumor type, however everolimus dose or concomitant chemotherapy was not significant.
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Antineoplásicos/efectos adversos , Everolimus/efectos adversos , Neoplasias/tratamiento farmacológico , Antineoplásicos/administración & dosificación , Everolimus/administración & dosificación , Femenino , Humanos , Masculino , Ensayos Clínicos Controlados Aleatorios como Asunto , Medición de RiesgoRESUMEN
Carcinomas arising from breast hamartomas are exceedingly rare. We present the first reported case of an African-American female presenting with a right breast lump and a subsequent mammogram suggestive of a hamartoma. She later underwent lumpectomy and was found to have HER2+ invasive ductal carcinoma (IDC) arising from a hamartoma. She was amenable to HER2-targeted trastuzumab, hormone therapy and adjuvant radiation but declined chemotherapy. In a review of the literature, IDC is the predominant neoplastic type found in hamartomas. The average hamartoma size at time of neoplasm diagnosis is 6.0 cm. Patients with hamartomas greater than 6.0 cm, with changes in calcification pattern; new nodules or asymmetry should be considered for additional evaluation with ultrasound, MRI and/or biopsy. HER2 status is under-reported among cases and should be evaluated in any malignancy found within hamartomas as HER-2 therapy has improved overall survival and recurrence free survival in HER2+breast cancer patients.
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Enfermedades de la Mama , Neoplasias de la Mama , Carcinoma Ductal de Mama , Hamartoma , Terapia Molecular Dirigida/métodos , Receptor ErbB-2 , Mama/diagnóstico por imagen , Enfermedades de la Mama/diagnóstico , Enfermedades de la Mama/metabolismo , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Carcinoma Ductal de Mama/diagnóstico , Carcinoma Ductal de Mama/metabolismo , Carcinoma Ductal de Mama/patología , Femenino , Hamartoma/diagnóstico , Hamartoma/metabolismo , Hamartoma/patología , Humanos , Mamografía/métodos , Persona de Mediana Edad , Invasividad Neoplásica , Estadificación de Neoplasias , Medicina de Precisión/métodos , Pronóstico , Receptor ErbB-2/análisis , Receptor ErbB-2/antagonistas & inhibidoresRESUMEN
INTRODUCTION: Pancreatic ductal adenocarcinoma (PDAC) is currently the third-leading cause of cancer-related death in the United States. African Americans (AAs) with PDAC have worse survival in comparison to other racial groups. The COVID-19 pandemic caused significant stress to the healthcare system. We aim to evaluate the pandemic's impact on already known disparities in newly diagnosed patients with PDAC in Florida. METHODS: This is a retrospective analysis of newly diagnosed patients with PDAC in the OneFlorida+ Data Trust based upon date of diagnosis: Pre-pandemic (01/01/2017- 09/30/2019), Transition (10/01/2019-02/28/2020), and Pandemic (03/1/2020-10/31/2020). Primary endpoints are time to treatment initiation and rate of surgery and secondary endpoint is survival time. Disparities due to age, sex, race, and income were also evaluated. Chi-squared or Fisher's exact test when necessary, Kruskal-Wallis test, and Kaplan-Meier analysis with log-rank test were performed to compare the differences between the comparative groups for categorical, quantitative, and survival outcomes, respectively. Multivariable regression analyses were conducted to estimate the effects of cofactors. RESULTS: 934 patients with a median age of 67 years were included. There were 47.8% females and 52.2% males; 19.4% AA, 70.2% Caucasian, 10.4% Other race; median income was $53,551. While we observed a significant reduction in the diagnosis rate of new PDAC cases during the pandemic, there were no significant differences in demographic distributions among the three cohorts. Time to treatment did not significantly change from the pre-pandemic to the pandemic, and no difference was observed across all demographics. Rate of surgery increased significantly from the pre-pandemic (35.8%) to the pandemic (55.6%). AAs in the pre-pandemic cohort had a significantly lower rate of surgery of 25.0% compared to 41.7% in Caucasians. AAs, patients ≥ 67 years, and income < $53,000 had significantly higher hazards to death and shorter median survival time (mST). CONCLUSIONS: While no differences in time to initial treatment are observed among the newly diagnosed PDAC patients, there remain significant disparities in the rate of surgery and overall survival. Observing a significant reduction in diagnosis rate and analyzing disparities can provide insight into the effect of a resource-restricting pandemic for patients with newly diagnosed PDAC.
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COVID-19 , Carcinoma Ductal Pancreático , Disparidades en Atención de Salud , Neoplasias Pancreáticas , Humanos , COVID-19/epidemiología , COVID-19/etnología , COVID-19/mortalidad , Florida/epidemiología , Femenino , Masculino , Neoplasias Pancreáticas/mortalidad , Neoplasias Pancreáticas/terapia , Neoplasias Pancreáticas/etnología , Anciano , Estudios Retrospectivos , Disparidades en Atención de Salud/etnología , Carcinoma Ductal Pancreático/terapia , Carcinoma Ductal Pancreático/mortalidad , Carcinoma Ductal Pancreático/etnología , Persona de Mediana Edad , Negro o Afroamericano/estadística & datos numéricos , Pandemias , SARS-CoV-2RESUMEN
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.
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Objective: Cancer treatment misinformation (CTM) is pervasive and impacts patient health outcomes. Cancer clinicians play an essential role in addressing CTM. We previously identified four self-reported responses that characterize the communication process clinicians engage in to address CTM. Clinicians 1) work to understand the misinformation; 2) correct the misinformation through education; 3) advise about future online searches; and 4) preserve the clinician-patient relationship. We sought to confirm and expand on the model we developed by observing cancer clinicians' communication while addressing CTM with a standardized patient (SP). Methods: 17 cancer clinicians were audio recorded in a SP encounter, in which a breast cancer SP asked three questions based on CTM. We thematically analyzed transcriptions of the recordings. Results: Clinicians used four responses with associated strategies and skills to address CTM in a standardized clinical encounter, confirming the previously developed model. The four responses were: (1) work to understand the misinformation; (2) correct the misinformation through education; (3) advise about future online searches; and (4) preserve the clinician-patient relationship. This observational approach allowed us to refine strategies within each response and identify communication skills clinicians enact to address CTM. Conclusion: These findings provide a strong foundation for the Misinformation Response Model for cancer clinicians. Future research should examine which components of the model are most effective in improving patient outcomes. Innovation: This is the first study observing clinicians' communication through simulated practice with SPs about CTM.
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BACKGROUND: Lack of diversity in the cancer research workforce persists, which the new requirement for all National Cancer Institute (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 Diversity, Equity and Inclusion Network, which includes all NCI-designated cancer centers and several emerging centers. A total of 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 is shifts in demographics (68%), and data on the demographics of faculty, leadership, and trainees are available at 79%, 81%, and 75% of centers, respectively. CONCLUSIONS: Almost all centers have established a PED leadership structure, however, 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.
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Instituciones Oncológicas , Diversidad Cultural , National Cancer Institute (U.S.) , Humanos , Estados Unidos , Estudios Transversales , Instituciones Oncológicas/organización & administración , Instituciones Oncológicas/estadística & datos numéricos , Encuestas y Cuestionarios , Liderazgo , Neoplasias/epidemiología , Masculino , Femenino , Investigación Biomédica/organización & administraciónRESUMEN
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.
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Tumores Neuroendocrinos , Octreótido , Receptores de Péptidos , Humanos , Tumores Neuroendocrinos/radioterapia , Tumores Neuroendocrinos/patología , Tumores Neuroendocrinos/metabolismo , Masculino , Femenino , Persona de Mediana Edad , Anciano , Octreótido/análogos & derivados , Octreótido/uso terapéutico , Octreótido/efectos adversos , Octreótido/administración & dosificación , Receptores de Péptidos/metabolismo , Adulto , Resultado del Tratamiento , Compuestos Organometálicos/uso terapéutico , Compuestos Organometálicos/efectos adversos , Compuestos Organometálicos/administración & dosificación , Anciano de 80 o más Años , Radiofármacos/uso terapéutico , Radiofármacos/efectos adversos , Radiofármacos/administración & dosificación , Neoplasias Pancreáticas/radioterapia , Neoplasias Pancreáticas/patología , Estudios RetrospectivosRESUMEN
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.
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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.
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Neoplasias Pulmonares , Mesotelioma Maligno , Mesotelioma , Neoplasias Peritoneales , Humanos , Bevacizumab/uso terapéutico , Pemetrexed/uso terapéutico , Neoplasias Pulmonares/patología , Mesotelioma Maligno/tratamiento farmacológico , Mesotelioma/tratamiento farmacológico , Mesotelioma/genética , Mesotelioma/diagnóstico , Neoplasias Peritoneales/tratamiento farmacológico , Neoplasias Peritoneales/genética , Neoplasias Peritoneales/patología , Mutación , Ubiquitina Tiolesterasa/genética , Ubiquitina Tiolesterasa/uso terapéutico , Proteínas Supresoras de Tumor/genéticaRESUMEN
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.
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Antineoplásicos , Negro o Afroamericano , Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Negro o Afroamericano/genética , Carcinoma Ductal Pancreático/tratamiento farmacológico , Carcinoma Ductal Pancreático/etnología , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/patología , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/etnología , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patología , Farmacogenética , Terapia Molecular Dirigida/métodosRESUMEN
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.
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Manejo del Dolor , Neoplasias Pancreáticas , Humanos , Anciano , Estados Unidos/epidemiología , Calidad de Vida , Disparidades en Atención de Salud , Medicare , Muerte , Neoplasias Pancreáticas/tratamiento farmacológicoRESUMEN
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.
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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.
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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.
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Adenocarcinoma , Neoplasias Duodenales , Humanos , Anciano , Antígeno Carcinoembrionario , Estudios Retrospectivos , Estudios de Cohortes , Biomarcadores de Tumor , Pronóstico , Antígeno CA-19-9 , Carbohidratos , Antígeno Ca-125RESUMEN
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.