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We conducted a Surveillance, Epidemiology, and End Results Program (SEER-18) registry analysis of classical Hodgkin lymphoma (cHL) patients more than 60 years old and compared outcomes of those diagnosed between 2006 and 2010 (cohort 1) to those identified between 2011 and 2015 (cohort 2) based on treatment era and race. Cohort 1 had a median overall survival (OS) of 4 years and cohort 2 had a median OS of 4.75 years [hazard ratio (HR): 0.92 (0.85-1.00); p = 0.052]. Non-Hispanic blacks (NHBs) had a similar 5-year OS compared to non-Hispanic whites (NHWs) of 48.6% vs. 50.2% (HR: 0.95 [0.79-1.15]; p > 0.99); on the contrary, Hispanics had worse 5-year OS of 41.8% vs. 48.6% (HR: 1.24 [1.09-1.41]; p < 0.001). NHW was the only race that had improvement in 5-year OS in 2011-2015 compared to 2006-2010 (51% vs. 46.5%, p = 0.002). In the multivariable analysis, older age, male gender, stage III-IV, unmarried status, Hispanic race, lack of chemotherapy, and diagnosis in 2006-2010 were associated with worse OS. Lymphoma was the most common cause of death in 60% of patients. In conclusion, elderly cHL patients diagnosed after 2010 had improved OS by nine months that was most prevalent in NHWs, and disparity in OS existed between NHWs and Hispanics throughout the study period.
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Enfermedad de Hodgkin , Humanos , Masculino , Anciano , Persona de Mediana Edad , Enfermedad de Hodgkin/epidemiología , Enfermedad de Hodgkin/terapia , Programa de VERF , Sistema de Registros , Población Blanca , Hispánicos o LatinosRESUMEN
Peripheral T-cell lymphomas (PTCLs) are a heterogeneous group of lymphoproliferative disorders arising from mature T cells, accounting for about 10% of non-Hodgkin lymphomas. PTCL-not otherwise specified is the most common subtype, followed by angioimmunoblastic T-cell lymphoma, anaplastic large cell lymphoma, anaplastic lymphoma kinase-positive, anaplastic large cell lymphoma, anaplastic lymphoma kinase-negative, and enteropathy-associated T-cell lymphoma. This discussion section focuses on the diagnosis and treatment of PTCLs as outlined in the NCCN Guidelines for T-Cell Lymphomas.
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Linfadenopatía Inmunoblástica , Linfoma de Células T Periférico , Linfoma de Células T , Humanos , Linfadenopatía Inmunoblástica/diagnóstico , Linfadenopatía Inmunoblástica/patología , Linfadenopatía Inmunoblástica/terapia , Linfoma de Células T/diagnóstico , Linfoma de Células T/terapia , Linfoma de Células T Periférico/diagnóstico , Linfoma de Células T Periférico/terapiaRESUMEN
ABSTRACT: Histological transformation (HT) is an exceptionally uncommon and poorly understood event where a low-grade or indolent B-cell lymphoma transforms into a more aggressive entity, typically diffuse large B-cell lymphoma (DLBCL). The pathogenesis is unclear; however, HT is associated with a worse prognosis. This article reports a unique case of marginal zone lymphoma (MZL) limited to skin/subcutis (confirmed with PET-CT) that subsequently developed DLBCL, followed by nodal MZL. We explored phenotypic, molecular genetic, and cytogenetic findings in subcutaneous MZL with HT to DLBCL and subsequent progression to systemic MZL. Shared clonal peaks between the tumors were demonstrated through immunoglobulin heavy chain PCR, and genomic microarray analysis revealed both unique genomic abnormalities and shared regions of copy-neutral loss of heterozygosity in all specimens. BCL-2 expression was present in the original subcutaneous MZL, lost on conversion to Primary cutaneous diffuse large B cell lymphoma (PCDLBCL)-NOS, and regained during subsequent transformation to systemic MZL. The PCDLBCL-NOS did not demonstrate FISH rearrangements for MYC, BCL2, and BCL6. Here, we describe the histologic, immunophenotypic, and cytogenetic abnormalities of the clonally related transformation of subcutaneous MZL, PCDLBCL-NOS, and eventual systemic MZL. The predominantly subcutaneous presentation of MZL may be associated with a more aggressive outcome and raises consideration for careful evaluation of patients who present with this pattern.
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Linfoma de Células B de la Zona Marginal , Linfoma de Células B Grandes Difuso , Neoplasias Cutáneas , Humanos , Inmunofenotipificación , Linfoma de Células B de la Zona Marginal/genética , Linfoma de Células B de la Zona Marginal/patología , Linfoma de Células B Grandes Difuso/genética , Linfoma de Células B Grandes Difuso/patología , Tomografía Computarizada por Tomografía de Emisión de Positrones , Neoplasias Cutáneas/patologíaRESUMEN
Aim: To describe practices and outcomes in veterans with relapsed/refractory diffuse large B-cell lymphoma. Patients & methods: Using Veteran Affairs Cancer Registry System and electronic health record data, we identified relapsed/refractory diffuse large B-cell lymphoma patients completing second-line treatment (2L) in 2000-2016. Treatments were classified as aggressive/nonaggressive. Analyses included descriptive statistics and the Kaplan-Meier estimation of progression-free survival and overall survival. Results: Two hundred and seventy patients received 2L. During median 9.7-month follow-up starting from 2L, 470 regimens were observed, averaging 2.7 regimens/patient: 219 aggressive, 251 nonaggressive. One hundred and twenty-one patients proceeded to third-line, 50 to fourth-line and 18 to fifth-line treatment. Median progression-free survival in 2L was 5.2 months. Median overall survival was 9.5 months. Forty-four patients (16.3%) proceeded to bone marrow transplant. Conclusion: More effective, less toxic treatments are needed and should be initiated earlier in treatment trajectory.
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Linfoma de Células B Grandes Difuso/terapia , Adulto , Anciano , Anciano de 80 o más Años , Trasplante de Médula Ósea , Femenino , Humanos , Linfoma de Células B Grandes Difuso/mortalidad , Masculino , Persona de Mediana Edad , Recurrencia , VeteranosRESUMEN
OBJECTIVES: The aim of this systematic review is to summarize the structure, process, and outcomes of pharmacist-led collaborative medication management programs for oral antineoplastic therapies (OATs). METHODS: Included studies were peer-reviewed journal articles published in English, between January 2000 to May 2020, and reporting on pharmacist-led collaborative medication management programs for patients on OATs. To be included, studies had to report on the pharmacy practice model, pharmacist interventions, and outcomes of the medication management program. The Donabedian model informed the data extraction and summary. Two independent researchers assessed the risk of bias (confounding) for all included studies (n = 12) using the NIH tool and Cochrane ROBINS-I for observational research. RESULTS: There were 12 studies that met inclusion criteria. The structure of the programs included hiring oncology pharmacists to deliver interventions, standardized templates for electronic medical record documentation, and administrative workflow changes (e.g., automatic referrals). The most common pharmacist interventions (processes) were patient education and counseling, adverse event monitoring, and dose modifications. All studies reported one or more positive outcomes, including improved patient adherence, safety, cost savings, cost avoidance, and patient satisfaction. All included studies used an observational study designs, and the majority of studies had moderate to high risk of bias. CONCLUSION: The evidence suggests that pharmacist-led collaborative medication management programs may have beneficial clinical and economic outcomes. The implementation of these programs could be strengthened by using a conceptual framework to guide program development, implementation, and evaluation and effectiveness-hybrid study designs to assess clinical and implementation outcomes. The risk of bias should be addressed by using more robust study designs and rigorous data collection and analysis methods.
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Antineoplásicos , Servicios Farmacéuticos , Antineoplásicos/efectos adversos , Ahorro de Costo , Humanos , Administración del Tratamiento Farmacológico , Estudios Observacionales como Asunto , FarmacéuticosRESUMEN
Mycosis fungoides (MF) is the most common subtype of cutaneous T-cell lymphoma (CTCL), and Sézary syndrome (SS) is a rare erythrodermic and leukemic subtype of CTCL characterized by significant blood involvement. Although early-stage disease can be effectively treated predominantly with skin-directed therapies, systemic therapy is often necessary for the treatment of advanced-stage disease. Systemic therapy options have evolved in recent years with the approval of novel agents such as romidepsin, brentuximab vedotin, and mogamulizumab. These NCCN Guidelines Insights discuss the diagnosis and management of MF and SS (with a focus on systemic therapy).
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Linfoma Cutáneo de Células T/patología , Micosis Fungoide/diagnóstico , Neoplasias Cutáneas/patología , Guías como Asunto , Humanos , Micosis Fungoide/patologíaRESUMEN
Hepatosplenic T-cell lymphoma (HSTCL) is a rare subtype of T-cell lymphoma associated with an aggressive clinical course and a worse prognosis. HSTCL develops in the setting of chronic immune suppression or immune dysregulation in up to 20% of cases and is most often characterized by spleen, liver, and bone marrow involvement. Diagnosis and management of HSTCL pose significant challenges given the rarity of the disease along with the absence of lymphadenopathy and poor outcome with conventional chemotherapy regimens. These Guidelines Insights focus on the diagnosis and treatment of HSTCL as outlined in the NCCN Guidelines for T-Cell Lymphomas.
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Linfoma de Células T , Humanos , Linfoma de Células T/diagnóstico , Linfoma de Células T/epidemiología , Linfoma de Células T/terapia , Guías de Práctica Clínica como Asunto , PronósticoRESUMEN
Anti-programmed cell death protein 1 (PD-1) monoclonal antibodies are being increasingly tested in patients with advanced lymphoma. Following treatment, many of those patients are likely to be candidates for allogeneic hematopoietic stem cell transplant (HSCT). However, the safety and efficacy of HSCT may be affected by prior PD-1 blockade. We conducted an international retrospective analysis of 39 patients with lymphoma who received prior treatment with a PD-1 inhibitor, at a median time of 62 days (7-260) before HSCT. After a median follow-up of 12 months, the 1-year cumulative incidences of grade 2-4 and grade 3-4 acute graft-versus-host disease (GVHD) were 44% and 23%, respectively, whereas the 1-year incidence of chronic GVHD was 41%. There were 4 treatment-related deaths (1 from hepatic sinusoidal obstruction syndrome, 3 from early acute GVHD). In addition, 7 patients developed a noninfectious febrile syndrome shortly after transplant requiring prolonged courses of steroids. One-year overall and progression-free survival rates were 89% (95% confidence interval [CI], 74-96) and 76% (95% CI, 56-87), respectively. One-year cumulative incidences of relapse and nonrelapse mortality were 14% (95% CI, 4-29) and 11% (95% CI, 3-23), respectively. Circulating lymphocyte subsets were analyzed in 17 patients. Compared with controls, patients previously treated with PD-1 blockade had significantly decreased PD-1+ T cells and decreased ratios of T-regulatory cells to conventional CD4 and CD8 T cells. In conclusion, HSCT after PD-1 blockade appears feasible with a low rate of relapse. However, there may be an increased risk of early immune toxicity, which could reflect long-lasting immune alterations triggered by prior PD-1 blockade.
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Antineoplásicos/uso terapéutico , Trasplante de Células Madre Hematopoyéticas/métodos , Linfoma/terapia , Adulto , Anciano , Aloinjertos , Anticuerpos Monoclonales/uso terapéutico , Anticuerpos Monoclonales Humanizados/uso terapéutico , Terapia Combinada , Supervivencia sin Enfermedad , Femenino , Humanos , Estimación de Kaplan-Meier , Linfoma/mortalidad , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/mortalidad , Recurrencia Local de Neoplasia/terapia , Nivolumab , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Estudios Retrospectivos , Estadísticas no Paramétricas , Adulto JovenRESUMEN
BACKGROUND: Cutaneous T-cell lymphomas are rare non-Hodgkin lymphomas with substantial morbidity and mortality in advanced disease stages. We compared the efficacy of mogamulizumab, a novel monoclonal antibody directed against C-C chemokine receptor 4, with vorinostat in patients with previously treated cutaneous T-cell lymphoma. METHODS: In this open-label, international, phase 3, randomised controlled trial, we recruited patients with relapsed or refractory mycosis fungoides or Sézary syndrome at 61 medical centres in the USA, Denmark, France, Italy, Germany, the Netherlands, Spain, Switzerland, the UK, Japan, and Australia. Eligible patients were aged at least 18 years (in Japan, ≥20 years), had failed (for progression or toxicity as assessed by the principal investigator) at least one previous systemic therapy, and had an Eastern Cooperative Oncology Group performance score of 1 or less and adequate haematological, hepatic, and renal function. Patients were randomly assigned (1:1) using an interactive voice web response system to mogamulizumab (1·0 mg/kg intravenously on a weekly basis for the first 28-day cycle, then on days 1 and 15 of subsequent cycles) or vorinostat (400 mg daily). Stratification was by cutaneous T-cell lymphoma subtype (mycosis fungoides vs Sézary syndrome) and disease stage (IB-II vs III-IV). Since this study was open label, patients and investigators were not masked to treatment assignment. The primary endpoint was progression-free survival by investigator assessment in the intention-to-treat population. Patients who received one or more doses of study drug were included in the safety analyses. This study is ongoing, and enrolment is complete. This trial was registered with ClinicalTrials.gov, number NCT01728805. FINDINGS: Between Dec 12, 2012, and Jan 29, 2016, 372 eligible patients were randomly assigned to receive mogamulizumab (n=186) or vorinostat (n=186), comprising the intention-to-treat population. Two patients randomly assigned to mogamulizumab withdrew consent before receiving study treatment; thus, 370 patients were included in the safety population. Mogamulizumab therapy resulted in superior investigator-assessed progression-free survival compared with vorinostat therapy (median 7·7 months [95% CI 5·7-10·3] in the mogamulizumab group vs 3·1 months [2·9-4·1] in the vorinostat group; hazard ratio 0·53, 95% CI 0·41-0·69; stratified log-rank p<0·0001). Grade 3-4 adverse events of any cause were reported in 75 (41%) of 184 patients in the mogamulizumab group and 76 (41%) of 186 patients in the vorinostat group. The most common serious adverse events of any cause were pyrexia in eight (4%) patients and cellulitis in five (3%) patients in the mogamulizumab group; and cellulitis in six (3%) patients, pulmonary embolism in six (3%) patients, and sepsis in five (3%) patients in the vorinostat group. Two (67%) of three on-treatment deaths with mogamulizumab (due to sepsis and polymyositis) and three (33%) of nine on-treatment deaths with vorinostat (two due to pulmonary embolism and one due to bronchopneumonia) were considered treatment-related. INTERPRETATION: Mogamulizumab significantly prolonged progression-free survival compared with vorinostat, and could provide a new, effective treatment for patients with mycosis fungoides and, importantly, for Sézary syndrome, a subtype that represents a major therapeutic challenge in cutaneous T-cell lymphoma. FUNDING: Kyowa Kirin.
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Anticuerpos Monoclonales Humanizados/administración & dosificación , Antineoplásicos Inmunológicos/administración & dosificación , Inhibidores de Histona Desacetilasas/administración & dosificación , Linfoma Cutáneo de Células T/tratamiento farmacológico , Micosis Fungoide/tratamiento farmacológico , Síndrome de Sézary/tratamiento farmacológico , Vorinostat/administración & dosificación , Anciano , Anticuerpos Monoclonales Humanizados/efectos adversos , Antineoplásicos Inmunológicos/efectos adversos , Australia , Esquema de Medicación , Resistencia a Antineoplásicos , Europa (Continente) , Femenino , Inhibidores de Histona Desacetilasas/efectos adversos , Humanos , Japón , Linfoma Cutáneo de Células T/mortalidad , Linfoma Cutáneo de Células T/patología , Masculino , Persona de Mediana Edad , Micosis Fungoide/mortalidad , Micosis Fungoide/patología , Recurrencia Local de Neoplasia , Estadificación de Neoplasias , Supervivencia sin Progresión , Síndrome de Sézary/mortalidad , Síndrome de Sézary/patología , Factores de Tiempo , Estados Unidos , Vorinostat/efectos adversosRESUMEN
BACKGROUND: Preclinical studies suggest that Reed-Sternberg cells exploit the programmed death 1 (PD-1) pathway to evade immune detection. In classic Hodgkin's lymphoma, alterations in chromosome 9p24.1 increase the abundance of the PD-1 ligands, PD-L1 and PD-L2, and promote their induction through Janus kinase (JAK)-signal transducer and activator of transcription (STAT) signaling. We hypothesized that nivolumab, a PD-1-blocking antibody, could inhibit tumor immune evasion in patients with relapsed or refractory Hodgkin's lymphoma. METHODS: In this ongoing study, 23 patients with relapsed or refractory Hodgkin's lymphoma that had already been heavily treated received nivolumab (at a dose of 3 mg per kilogram of body weight) every 2 weeks until they had a complete response, tumor progression, or excessive toxic effects. Study objectives were measurement of safety and efficacy and assessment of the PDL1 and PDL2 (also called CD274 and PDCD1LG2, respectively) loci and PD-L1 and PD-L2 protein expression. RESULTS: Of the 23 study patients, 78% were enrolled in the study after a relapse following autologous stem-cell transplantation and 78% after a relapse following the receipt of brentuximab vedotin. Drug-related adverse events of any grade and of grade 3 occurred in 78% and 22% of patients, respectively. An objective response was reported in 20 patients (87%), including 17% with a complete response and 70% with a partial response; the remaining 3 patients (13%) had stable disease. The rate of progression-free survival at 24 weeks was 86%; 11 patients were continuing to participate in the study. Reasons for discontinuation included stem-cell transplantation (in 6 patients), disease progression (in 4 patients), and drug toxicity (in 2 patients). Analyses of pretreatment tumor specimens from 10 patients revealed copy-number gains in PDL1 and PDL2 and increased expression of these ligands. Reed-Sternberg cells showed nuclear positivity of phosphorylated STAT3, indicative of active JAK-STAT signaling. CONCLUSIONS: Nivolumab had substantial therapeutic activity and an acceptable safety profile in patients with previously heavily treated relapsed or refractory Hodgkin's lymphoma. (Funded by Bristol-Myers Squibb and others; ClinicalTrials.gov number, NCT01592370.).
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Anticuerpos Monoclonales/administración & dosificación , Antineoplásicos/administración & dosificación , Enfermedad de Hodgkin/tratamiento farmacológico , Inmunoterapia , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Adulto , Anticuerpos Monoclonales/efectos adversos , Antineoplásicos/efectos adversos , Brentuximab Vedotina , Femenino , Enfermedad de Hodgkin/metabolismo , Enfermedad de Hodgkin/terapia , Humanos , Inmunoconjugados/uso terapéutico , Quinasas Janus/metabolismo , Masculino , Persona de Mediana Edad , Nivolumab , Proteína 2 Ligando de Muerte Celular Programada 1/metabolismo , Receptor de Muerte Celular Programada 1/metabolismo , Recurrencia , Células de Reed-Sternberg/efectos de los fármacos , Factores de Transcripción STAT/metabolismo , Trasplante de Células MadreRESUMEN
Natural killer (NK)/T-cell lymphomas are a rare and distinct subtype of non-Hodgkin's lymphomas. NK/T-cell lymphomas are predominantly extranodal and most of these are nasal type, often localized to the upper aerodigestive tract. Because extranodal NK/T-cell lymphomas (ENKL) are rare malignancies, randomized trials comparing different regimens have not been conducted to date and standard therapy has not yet been established for these patients. These NCCN Guidelines Insights discuss the recommendations for the diagnosis and management of patients with ENKL as outlined in the NCCN Guidelines for T-Cell Lymphomas.
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Linfoma de Células T/diagnóstico , Linfoma de Células T/terapia , Manejo de la Enfermedad , Humanos , Linfoma de Células T/etiologíaAsunto(s)
Veteranos/estadística & datos numéricos , Macroglobulinemia de Waldenström/tratamiento farmacológico , Adenina/análogos & derivados , Adenina/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Clorhidrato de Bendamustina/uso terapéutico , Bortezomib/uso terapéutico , Clorambucilo/uso terapéutico , Ciclofosfamida/uso terapéutico , Dexametasona/uso terapéutico , Doxorrubicina/uso terapéutico , Humanos , Estimación de Kaplan-Meier , Piperidinas/uso terapéutico , Prednisona/uso terapéutico , Supervivencia sin Progresión , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Rituximab/uso terapéutico , Resultado del Tratamiento , Vidarabina/análogos & derivados , Vidarabina/uso terapéutico , Vincristina/uso terapéutico , Macroglobulinemia de Waldenström/mortalidadRESUMEN
An increasing number of women are being cared for within the Veterans Health Administration (VA). However, the demographics and trends of women with breast cancer at the VA has not been documented. We describe the demographics and breast cancer characteristics of the 4445 women enrolled in the VA and reported to the Department of Veterans Affairs Central Cancer Registry diagnosed with breast cancer from 1995 to 2012. The cases of breast cancer per year increased over time to 365 in 2012. Black women represented only 16% of women diagnosed with breast cancer in the VA in 1995-1999 but increased to 25% by 2010-2012 (P<0.001). The median age at diagnosis in 1995-1999 was 58.4 and decreased to 56.8 by 2010-2012 (P<0.02). The fraction of breast cancers that were node negative was 45% in 1995-1999 and increased to 64% in 2010-2012; correspondingly, women presented at an earlier stage in more recent years (P<0.001). Urban women with breast cancer cared for within the VA are more likely to be younger (P=0.04) and nonwhite (P<0.001) compared with rural women, but the breast tumor characteristics appear similar. Oncology physicians at the VA must be prepared to care for breast cancer among women as the number of cases is growing. With only 365 women diagnosed with breast cancer at the VA as per year 2012 and nearly 150 treating VA facilities, the number of breast cancer patients seen by a particular physician could be quite low, and this fact suggests a need for an evaluation of the quality and outcomes of breast cancer care at the VA.
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Neoplasias de la Mama/epidemiología , Salud de los Veteranos , Veteranos , Salud de la Mujer , Neoplasias de la Mama/etnología , Femenino , Humanos , Persona de Mediana Edad , Sistema de Registros , Factores de Riesgo , Estados Unidos/epidemiología , United States Department of Veterans AffairsRESUMEN
PURPOSE: Outpatient infusions are commonly missing in Veterans Health Affairs (VHA) pharmacy dispensing data sets. Currently, Healthcare Common Procedure Coding System (HCPCS) codes are used to identify outpatient infusions, but concerns exist if they correctly capture all infusions and infusion-related data such as dose and date of administration. We developed natural language processing (NLP) software to extract infusion information from medical text infusion notes. The objective was to compare the sensitivity of three approaches to identify infliximab administration dates and infusion doses against a reference standard established from the Veterans Affairs rheumatoid arthritis (VARA) registry. METHODS: We compared the sensitivity and positive predictive value (PPV) of NLP to that of HCPCS codes in identifying the correct date and dose of infliximab infusions against a human extracted reference standard. RESULTS: The sensitivity was 0.606 (0.585-0.627) for HCPCS alone, 0.858 (0.842-0.873) for NLP alone, and 0.923 (0.911-0.934) for the two methods combined, with a PPV of 0.735 (0.716-0.754), 0.976 (0.969-0.983), and 0.957 (0.948-0.965) for each method, respectively. The mean dose of infliximab was 433 mg in the reference standard, 337 mg from HCPCS, 434 mg from NLP, and 426 mg from the combined method. CONCLUSIONS: HCPCS codes alone are not sufficient to accurately identify infliximab infusion dates and doses in the VHA system. The use of NLP significantly improved the sensitivity and PPV for estimating infusion dates and doses, especially when combined with HCPCS codes.
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Atención Ambulatoria/métodos , Atención Ambulatoria/normas , Anticuerpos Monoclonales/administración & dosificación , Healthcare Common Procedure Coding System/normas , Procesamiento de Lenguaje Natural , United States Department of Veterans Affairs/normas , Humanos , Infliximab , Infusiones Intravenosas , Estudios Longitudinales , Pacientes Ambulatorios , Estudios Prospectivos , Sistema de Registros/normas , Estados Unidos/epidemiologíaRESUMEN
Piperlongumine (PL), isolated from the fruit of Long pepper, Piper longum, is a cancer-inhibiting compound that selectively kills tumor cells while sparing their normal counterparts. Here we evaluated the efficacy with which PL suppresses malignant B cells derived from a newly developed, double-transgenic mouse model of human endemic Burkitt lymphoma (BL), designated mCD40-LMP1/iMyc(Eµ). PL inhibited tumor cell proliferation in a concentration-dependent manner and induced apoptosis of neoplastic but not normal B cells. Treatment with PL resulted in downregulation of EBV-encoded LMP1, cellular Myc, constitutive NF-κB activity, and a host of LMP1-Myc-NF-κB-regulated target genes including Aurka, Bcat1, Bub1b, Ccnb1, Chek1, Fancd2, Tfrc and Xrcc6. Of note, p21(Cip1)-encoding Cdkn1a was suppressed independent of changes in Trp53 mRNA levels and p53 DNA-binding activity. Considering the central role of the LMP1-NF-κB-Myc axis in B-lineage neoplasia, these findings further our understanding of the mechanisms by which PL inhibits B-lymphoma and provide a preclinical rationale for the inclusion of PL in new interventions in blood cancers.
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Dioxolanos/farmacología , Genes myc , Linfoma de Células B/patología , Proteínas de la Matriz Viral/fisiología , Animales , Línea Celular Tumoral , Linfoma de Células B/genética , Ratones , Ratones Endogámicos C57BL , FN-kappa B/metabolismoRESUMEN
Importance: Racial and ethnic disparities in prostate cancer are poorly understood. A given disparity-related factor may affect outcomes differently at each point along the highly variable trajectory of the disease. Objective: To examine clinical outcomes by race and ethnicity in patients with nonmetastatic castration-resistant prostate cancer (nmCRPC) within the US Veterans Health Administration. Design, Setting, and Participants: A retrospective, observational cohort study using electronic health care records (January 1, 2006, to December 31, 2021) in a nationwide equal-access health care system was conducted. Mean (SD) follow-up time was 4.3 (3.3) years. Patients included in the analysis were diagnosed with prostate cancer from January 1, 2006, to December 30, 2020, that progressed to nmCRPC defined by (1) increasing prostate-specific antigen levels, (2) ongoing androgen deprivation, and (3) no evidence of metastatic disease. Patients with metastatic disease or death within the landmark period (3 months after the first nmCRPC evidence) were excluded. Main Outcomes and Measures: The primary outcome was time from the landmark period to death or metastasis; the secondary outcome was overall survival. A multivariate Cox proportional hazards model, Kaplan-Meier estimates, and adjusted survival curves were used to evaluate outcome differences by race and ethnicity. Results: Of 12â¯992 patients in the cohort, 826 patients identified as Hispanic (6%), 3671 as non-Hispanic Black (28%; henceforth Black), 7323 as non-Hispanic White (56%; henceforth White), and 1172 of other race and ethnicity (9%; henceforth other, including American Indian or Alaska Native, Asian, Native Hawaiian or Other Pacific Islander, unknown by patient, and patient declined to answer). Median time elapsed from nmCRPC to metastasis or death was 5.96 (95% CI, 5.58-6.34) years for Black patients, 5.62 (95% CI, 5.11-6.67) years for Hispanic patients, 4.11 (95% CI, 3.96-4.25) years for White patients, and 3.59 (95% CI, 3.23-3.97) years for other patients. Median unadjusted overall survival was 6.26 (95% CI, 6.03-6.46) years among all patients, 8.36 (95% CI, 8.0-8.8) years for Black patients, 8.56 (95% CI, 7.3-9.7) years for Hispanic patients, 5.48 (95% CI, 5.2-5.7) years for White patients, and 4.48 (95% CI, 4.1-5.0) years for other patients. Conclusions and Relevance: The findings of this cohort study of patients with nmCRPC suggest that differences in outcomes by race and ethnicity exist; in addition, Black and Hispanic men may have considerably improved outcomes when treated in an equal-access setting.
Asunto(s)
Neoplasias de la Próstata Resistentes a la Castración , Veteranos , Humanos , Masculino , Antagonistas de Andrógenos/uso terapéutico , Negro o Afroamericano/estadística & datos numéricos , Estudios de Cohortes , Etnicidad , Neoplasias de la Próstata Resistentes a la Castración/diagnóstico , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Neoplasias de la Próstata Resistentes a la Castración/epidemiología , Neoplasias de la Próstata Resistentes a la Castración/etnología , Neoplasias de la Próstata Resistentes a la Castración/mortalidad , Estudios Retrospectivos , Veteranos/estadística & datos numéricos , Blanco/estadística & datos numéricos , Hispánicos o Latinos/estadística & datos numéricos , Indio Americano o Nativo de Alaska/estadística & datos numéricos , Asiático/estadística & datos numéricos , Nativos de Hawái y Otras Islas del Pacífico/estadística & datos numéricosRESUMEN
BACKGROUND: The Enhancing Quality of Prescribing Practices for Older Veterans Discharged from the Emergency Department (EQUIPPED) program developed an audit and feedback health information technology (IT) solution with the intent to replace the in-person academic detailing service provided by the program. The EQUIPPED dashboard provides emergency department (ED) providers with a personalized view of their prescribing performance. OBJECTIVES: Here, we analyze the association between ED provider characteristics and viewership of the EQUIPPED dashboard, adding insight into strategies for addressing barriers to initial use. METHODS: We performed a retrospective analysis of EQUIPPED dashboard viewership among four Veterans Affairs (VA) EDs. We extracted quantitative data from user interaction logs to determine evidence of dashboard use. Provider characteristics and baseline potentially inappropriate medication (PIM) prescribing rate were extracted from the VA's Corporate Data Warehouse. Logistic regression was used to examine the association between dashboard use and provider characteristics. RESULTS: A total of 82 providers were invited to receive audit and feedback via the EQUIPPED dashboard. Among invited providers, 40 (48.7%) had evidence of at least 1 dashboard view during the 1-year feedback period. Adjusted analyses suggest that providers with a higher baseline PIM prescribing rate were more likely to use the dashboard (odds ratio [OR]: 1.22; 95% confidence interval [CI]: 1.01-1.47). Furthermore, providers at ED site D were more likely to use the dashboard in comparison to the other sites (OR: 9.99; 95% CI: 1.72-58.04) and reportedly had the highest site-level baseline PIM rate. CONCLUSION: Providers with lower PIM prescribing rates (i.e., <5%) receive communication from an integrated dashboard reminder system that they are "optimal prescribers" which may have discouraged initial attempts to view the dashboard. Site D had the highest baseline PIM rate, but further qualitative investigation is warranted to better understand why site D had the greatest users of the dashboard.
Asunto(s)
Comunicación , Servicio de Urgencia en Hospital , Humanos , Retroalimentación , Estudios Retrospectivos , Alta del PacienteRESUMEN
Mycosis Fungoides (MF) is a rare T-cell lymphoma and evidence on treatment practices, and outcomes are limited. We evaluated changes in practice patterns and corresponding effects on overall survival (OS) in MF using a cross-sectional study of patients diagnosed with MF from 2004 to 2016 in the National Cancer Database. Outcomes evaluated included patterns of care and OS across treatment eras. We found factors associated with chemotherapy use included male gender, treatment from 2004 to 2010 and stage III-IV disease. Factors associated with radiotherapy receipt included stage I-II disease, nonacademic treatment centers, male gender, non-black race, and Medicare status. Immunotherapy use was associated with treatment from 2004 to 2010 and stage III-IV disease. After propensity score matching, there was no OS difference among patients with stage I-II disease between 2004-2010 and 2011-2016. However, amongst patients with stage III-IV disease, OS was significantly improved in those treated from 2011 to 2016.
Asunto(s)
Micosis Fungoide , Neoplasias Cutáneas , Anciano , Estudios Transversales , Humanos , Masculino , Medicare , Micosis Fungoide/diagnóstico , Micosis Fungoide/terapia , Estadificación de Neoplasias , Pronóstico , Estudios Retrospectivos , Neoplasias Cutáneas/patología , Tasa de Supervivencia , Estados Unidos/epidemiologíaRESUMEN
PURPOSE: Veterans prescribed oral antineoplastic therapies (OATs) by community providers outside the Veterans Health Administration (VA) may lack access to comprehensive medication management. To address this, our multidisciplinary team developed and implemented a pharmacist-led telehealth medication management program for veterans prescribed OATs by community providers. SUMMARY: The program exclusively uses telehealth to connect veterans with a dedicated board-certified clinical oncology pharmacist who provides comprehensive medication management. The program is based on established pharmacy models found in the research literature. We developed a standard operating procedure, communication templates, patient education materials, and a suite of health information technology tools to help streamline pharmacy processes. The Consolidated Framework for Implementation Research was used to design implementation strategies to promote the adoption of the program. In the first year, 64 veterans from 3 VA medical centers were enrolled in the program. The oncology clinical pharmacist performed 342 encounters and 101 interventions. The program saved an estimated $200,724 in medication-related costs. The veterans we surveyed reported high levels of satisfaction with the pharmacy services provided by the program. CONCLUSION: The delivery of comprehensive medication management through telehealth is feasible from a healthcare system perspective and beneficial for patients. The board-certified oncology clinical pharmacist provided remote pharmacy services to Veterans across three sites in a large and rural service area for the VA. The program realized several benefits, including positive clinical outcomes, high levels of patient satisfaction, and cost savings on medication-related costs.
Asunto(s)
Antineoplásicos , Telemedicina , Veteranos , Humanos , Administración del Tratamiento Farmacológico , Satisfacción del Paciente , FarmacéuticosRESUMEN
PURPOSE: There are growing efforts to integrate patient-reported outcome (PRO) data into electronic health records (EHRs) to bring together disparate sources of patient information and improve medical care. PRO measures can be used to assess cancer symptom presence and severity. Integrating PRO tools in EHRs can alert providers to address symptoms, which is an essential component of comprehensive oncology care. METHODS: We modified a PRO used to measure cancer and end-of-life symptoms, the Edmonton Symptom Assessment System to create the Veteran Symptom Assessment System (VSAS). VSAS was implemented as an integrated PRO as part of the Veterans Administration EHR system and was used at hematology-oncology clinics in Veteran Administration (VA) medical centers in the Southeast. RESULTS: From 2013 to 2014, VSAS was introduced, underwent usability testing and modifications, and was finally implemented in the EHR. Between 2015 and 2019, VSAS was administered 43,883 times in 9,058 patients. Eighty-nine percent of Veterans were male, 11% were female, 52% identified as non-Hispanic White, and 43% identified as African American. Fatigue, shortness of breath with exertion, and pain were most frequently reported initially (68%, 48%, and 45%, respectively) and were most frequently rated as severe (27%, 16%, and 17%, respectively). In patients diagnosed with stage IV cancer, higher symptom burden was significantly associated with shorter overall survival. The majority of Veterans with longitudinal measurements experienced improvement in symptoms, most frequently in severe symptoms. CONCLUSION: To our knowledge, this is the first large-scale implementation of a PRO system, integrated in the VA EHR, in ambulatory patients with cancer and blood disorders. The integration of VSAS within the VA EHR is a significant demonstration and a necessary requirement for current and future systemic initiatives in cancer symptom management.