Survival Outcomes by Race and Ethnicity in Veterans With Nonmetastatic Castration-Resistant Prostate Cancer.

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 12 992 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.

Use of a Medication Safety Audit and Feedback Tool in the Emergency Department Is Affected by Prescribing Characteristics.

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.

A comprehensive SEER registry analysis of elderly patients with classical Hodgkin lymphoma based on treatment era and race.

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.

Developing the VA Geriatric Scholars Programs' Clinical Dashboards Using the PDSA Framework for Quality Improvement.

BACKGROUND: Involving clinician end users in the development process of clinical dashboards is important to ensure that user needs are adequately met prior to releasing the dashboard for use. The challenge with following this approach is that clinician end users can undergo periodic turnover, meaning, the clinicians that played a role in the initial development process may not be the same individuals that use the dashboard in future. OBJECTIVES: Here, we summarize our Plan, Do, Study, Act (PDSA)-guided clinical dashboard development process for the VA Geriatric Scholars Program (GSP) and the value of continuous, iterative development. We summarize dashboard adaptations that resulted from two PDSA cycles of improvement for the potentially inappropriate medication dashboard (PIMD), one of many Geriatric Scholars clinical dashboards. We also present the evaluative performance of the PIMD. METHODS: Evaluation of the PIMD was performed using the system usability scale (SUS) and through review of user interaction logs. Routine end users that were Geriatric Scholars and had evidence of 5 or more dashboard views were invited to complete an electronic form that contained the 10-item SUS. RESULTS: The proportion of Geriatric Scholars that utilized the PIMD increased for each iterative dashboard version that was produced as a byproduct from feedback (31.0% in 2017 to 60.2% in 2019). The overall usability of the PIMD among routine users was found to be above average (SUS score: 75.2 [95% CI 70.5-79.8]) in comparison to the recommended standard of acceptability (SUS score: 68) CONCLUSION: The solicitation of feedback during dashboard orientations led to iterative adaptations of the PIMD that broadened its intended use. The presented PDSA-guided process to clinical dashboard development for the VA GSP can serve as a valuable framework for development teams seeking to produce well-adopted and usable health information technology (IT) innovations.

Improved overall survival over time in advanced stage mycosis fungoides: a cross-sectional study.

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.

Histological Transformation and Clonal Relationship of Subcutaneous Marginal Zone B-Cell Lymphoma and Diffuse Large B-Cell Lymphoma.

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.

Integration of Patient-Reported Outcome Measures in the Electronic Health Record: The Veterans Affairs Experience.

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.

T-Cell Lymphomas, Version 2.2022, NCCN Clinical Practice Guidelines in Oncology.

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.

Development and implementation of a pharmacist-led telehealth medication management program for veterans receiving oral antineoplastic therapies through the MISSION Act.

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.

Phase 1/2 study of intratumoral G100 (TLR4 agonist) with or without pembrolizumab in follicular lymphoma.

Intratumoral injection of G100, a toll-like receptor 4 (TLR4) agonist, was shown pre-clinically to stimulate anti-tumor immune responses and tumor regression. This open-label, multicenter, phase 1/2 trial evaluated the safety, tolerability, and preliminary efficacy of intratumoral G100 injections following localized low-dose radiation in patients with follicular lymphoma (ClinicalTrials.gov #NCT02501473). The study was comprised of a G100 dose escalation (5 or 10 µg/dose, or 20 µg/dose for large tumors); a randomized component comparing G100 to G100 plus pembrolizumab; and G100 20 µg/dose expansion. Adverse events grade ≥3 were uncommon in patients treated with G100, and no unexpected toxicities were observed when combined with pembrolizumab. G100 20 µg (n = 18) resulted in an overall response rate of 33.3% and abscopal tumor regression in 72.2% of patients. This early-phase study provides a foundation for combining an intratumoral TLR4 agonist with agents to produce immune-mediated responses in follicular lymphoma with limited added toxicity.

Treatment Patterns and Outcomes in a Nationwide Cohort of Older and Younger Veterans with Waldenström Macroglobulinemia, 2006-2019.

Little is known about real-world treatment patterns and outcomes in Waldenström macroglobulinemia (WM) following the recent introduction of newer treatments, especially among older adults. We describe patterns of first-line (1 L) WM treatment in early (2006-2012) and modern (2013-2019) eras and report outcomes (overall response rate (ORR), overall survival (OS), progression-free survival (PFS), and adverse event (AE)-related discontinuation) in younger (≤70 years) and older (>70 years) populations. We followed 166 younger and 152 older WM patients who received 1 L treatment between January 2006 and April 2019 in the Veterans Health Administration. Median follow-up was 43.5 months (range: 0.6-147.2 months). Compared to the early era, older patients in the modern era achieved improved ORRs (early: 63.8%, modern: 72.3%) and 41% lower risk of death/progression (hazard ratio (HR) for PFS: 0.59, 95% CI (confidence interval): 0.36-0.95), with little change in AE-related discontinuation between eras (HR: 0.82, 95% CI: 0.4-1.7). In younger patients, the AE-related discontinuation risk increased almost fourfold (HR: 3.9, 95% CI: 1.1-14), whereas treatment effects did not change between eras (HR for OS: 1.4, 95% CI: 0.66-2.8; HR for PFS: 1.1, 95% CI: 0.67-1.7). Marked improvements in survival among older adults accompanied a profound shift in 1 L treatment patterns for WM.

Predicting Survival in Veterans with Follicular Lymphoma Using Structured Electronic Health Record Information and Machine Learning.

The most accurate prognostic approach for follicular lymphoma (FL), progression of disease at 24 months (POD24), requires two years' observation after initiating first-line therapy (L1) to predict outcomes. We applied machine learning to structured electronic health record (EHR) data to predict individual survival at L1 initiation. We grouped 523 observations and 1933 variables from a nationwide cohort of FL patients diagnosed 2006-2014 in the Veterans Health Administration into traditionally used prognostic variables ("curated"), commonly measured labs ("labs"), and International Classification of Diseases diagnostic codes ("ICD") sets. We compared performance of random survival forests (RSF) vs. traditional Cox model using four datasets: curated, curated + labs, curated + ICD, and curated + ICD + labs, also using Cox on curated + POD24. We evaluated variable importance and partial dependence plots with area under the receiver operating characteristic curve (AUC). RSF with curated + labs performed best, with mean AUC 0.73 (95% CI: 0.71-0.75). It approximated, but did not surpass, Cox with POD24 (mean AUC 0.74 [95% CI: 0.71-0.77]). RSF using EHR data achieved better performance than traditional prognostic variables, setting the foundation for the incorporation of our algorithm into the EHR. It also provides for possible future scenarios in which clinicians could be provided an EHR-based tool which approximates the predictive ability of the most accurate known indicator, using information available 24 months earlier.

Real-world practice patterns and outcomes in Veterans with relapsed/refractory diffuse large B-cell lymphoma.

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.

Pharmacist-led collaborative medication management programs for oral antineoplastic therapies: A systematic literature review.

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.

NCCN Guidelines Insights: T-Cell Lymphomas, Version 1.2021.

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.

Atrial Fibrillation and Bleeding in Patients With Chronic Lymphocytic Leukemia Treated with Ibrutinib in the Veterans Health Administration.

BACKGROUND: Chronic lymphocytic leukemia (CLL) is the most common type of leukemia in adults. The introduction of novel oral agents, starting with ibrutinib in 2013, has revolutionized the therapeutic landscape; however, clinical trials have suggested an association between ibrutinib and the risk of bleeding-related adverse events and atrial fibrillation (Afib) in patients with CLL. METHODS: Patients diagnosed and treated for CLL at the Veterans Health Administration (VHA) from 2010 to 2014 were followed until December 31, 2016, death, or lack of utilization of hematology/oncology services for ≥ 18 months; or until incidence of another cancer. Treatments dispensed, evidence of VHA system use, bleeding events, and Afib were determined from the administrative records, laboratory records, pharmacy dispensation records, and clinical notes in the electronic healthcare record. RESULTS: From 2010 to 2014, 2,796 patients were diagnosed and received care for CLL within the VHA, of whom 172 patients received ibrutinib and 291 received bendamustine + rituximab (BR). The use of anticoagulants following induction therapy did not differ between BR and ibrutinib patients (9% vs 8%, respectively), nor did the use of antiplatelets agents (6% vs 2%, respectively). Of the 291 patients that received BR, 12 (4%) developed a bleeding event compared with 20 (12%) who received ibrutinib. Additionally, 13 (8%) ibrutinib patients developed Afib compared with 9 (3%) BR patients. CONCLUSIONS: Real-world evidence from a nationwide cohort of patients with CLL suggests that while ibrutinib is associated with increased bleeding-related adverse events and Afib, the risk is comparable to those reported in previous clinical trials. These findings suggest that patients in real-world clinical care settings with higher levels of comorbidities may be at an increased risk for bleeding events and Afib.

Usability Testing a Potentially Inappropriate Medication Dashboard: A Core Component of the Dashboard Development Process.

BACKGROUND: With the increased usage of dashboard reporting systems to monitor and track patient panels by clinical users, developers must ensure that the information displays they produce are accurate and intuitive. When evaluating usability of a clinical dashboard among potential end users, developers oftentimes rely on methods such as questionnaires as opposed to other, more time-intensive strategies that incorporate direct observation. OBJECTIVES: Prior to release of the potentially inappropriate medication (PIM) clinical dashboard, designed to facilitate completion of a quality improvement project by clinician scholars enrolled in the Veterans Affairs (VA) workforce development Geriatric Scholars Program (GSP), we evaluated the usability of the system. This article describes the process of usability testing a dashboard reporting system with clinicians using direct observation and think-aloud moderating techniques. METHODS: We developed a structured interview protocol that combines virtual observation, think-aloud moderating techniques, and retrospective questioning of the overall user experience, including use of the System Usability Scale (SUS). Thematic analysis was used to analyze field notes from the interviews of three GSP alumni. RESULTS: Our structured approach to usability testing identified specific functional problems with the dashboard reporting system that were missed by results from the SUS. Usability testing lead to overall improvements in the intuitive use of the system, increased data transparency, and clarification of the dashboard's purpose. CONCLUSION: Reliance solely on questionnaires and surveys at the end stages of dashboard development can mask potential functional problems that will impede proper usage and lead to misinterpretation of results. A structured approach to usability testing in the developmental phase is an important tool for developers of clinician friendly systems for displaying easily digested information and tracking outcomes for the purpose of quality improvement.