Oncologist Perceptions of Racial Disparity, Racial Anxiety, and Unconscious Bias in Clinical Interactions, Treatment, and Outcomes.

BACKGROUND: Cancer spares no demographic or socioeconomic group; it is indeed the great equalizer. But its distribution is not equal; when structural discrimination concentrates poverty and race, zip code surpasses genetic code in predicting outcomes. Compared with White patients in the United States, Black patients are less likely to receive appropriate treatment and referral to clinical trials, genetic testing, or palliative care/hospice. METHODS: In 2021, we administered a survey to 369 oncologists measuring differences in perceptions surrounding racial disparity, racial anxiety, and unconscious bias and adverse influence on clinical interactions, treatment, and outcomes for non-White patients. We analyzed responses by generational age group, sex/gender, race/ethnicity, US region, and selection of "decline to respond." RESULTS: The most significant differences occurred by age group followed by race/ethnicity. Racial disparity was perceived as moderate to very high by 84% of millennial, 69% of Generation X, and 57% of baby boomer oncologists, who were also 86% more likely than millennials and 63% more likely than Generation Xers to perceive low/nonexistent levels of racial anxiety/unconscious bias. CONCLUSIONS: Most oncologists rarely or never perceived racial anxiety/unconscious bias as adversely influencing clinical treatment or survival outcomes in non-White patients, and White oncologists were 85% more likely than non-White oncologists to perceive rare/nonexistent influence on referral of non-White patients to palliative care/hospice. The discrepancy between 62% of oncologists perceiving moderate to very high levels of racial anxiety/unconscious bias and 37% associating them with adverse influence on non-White patients shows a disconnect, especially among older oncologists (baby boomers), who were also least likely to select the decline option. Together, these factors hinder effective patient-provider communication and result in differential care and outcomes. Oncologists should uncover their own perceptions surrounding racial disparity, racial anxiety, and unconscious bias and modify their behaviors accordingly. It is this simple-and this complicated. Cancer does not discriminate, and neither should cancer care.

In vivo and in silico pharmacokinetics and biodistribution of a melanocortin receptor 1 targeted agent in preclinical models of melanoma.

The melanocortin 1 receptor (MC1R) is overexpressed in most melanoma metastases, making it a promising target for imaging of melanomas. In this study, the expression of MC1R in a large fraction of patients with melanoma was confirmed using mRNA and tissue microarray. Here, we have characterized the in vivo tumor and tissue distribution and pharmacokinetics (PK) of uptake and clearance of a MC1R specific peptidomimetic ligand conjugated to a near-infrared fluorescent dye. We propose an interdisciplinary framework to bridge the different time and space scales of ligand-tumor-host interactions: intravital fluorescence microscopy to quantify probe internalization at the cellular level, a xenograft tumor model for whole body pharmacokinetics, and a computational pharmacokinetic model for integration and interpretation of experimental data. Administration of the probe into mice bearing tumors with high and low MC1R expression demonstrated normalized image intensities that correlated with expression levels (p < 0.05). The biodistribution study showed high kidney uptake as early as 30 min postinjection. The PK computational model predicted the presence of receptors in the kidneys with a lower affinity, but at higher numbers than in the tumors. As the mouse kidney is known to express the MC5R, this hypothesis was confirmed by both coinjection of a ligand with higher MC5R affinity compared to MC1R and by injection of lower probe concentrations (e.g., 1 nmol/kg), both leading to decreased kidney accumulation of the MC1R ligand. In addition, through this interdisciplinary approach we could predict the rates of ligand accumulation and clearance into and from organs and tumors, and the amount of injected ligand required to have maximum specific retention in tumors. These predictions have potential to aid in the translation of a targeted agent from lab to the clinic. In conclusion, the characterized MC1R-specific probe has excellent potential for in vivo detection of melanoma metastases. The process of cell-surface marker validation, targeted imaging probe development, and in vitro, in vivo, and in silico characterization described in this study can be generally applied to preclinical development of targeted agents.

Reducing Avoidable Emergency Visits and Hospitalizations With Patient Risk-Based Prescriptive Analytics: A Quality Improvement Project at an Oncology Care Model Practice.

PURPOSE: Cancer-related emergency department (ED) visits and hospitalizations that would have been appropriately managed in the outpatient setting are avoidable and detrimental to patients and health systems. This quality improvement (QI) project aimed to leverage patient risk-based prescriptive analytics at a community oncology practice to reduce avoidable acute care use (ACU). METHODS: Using the Plan-Do-Study-Act (PDSA) methodology, we implemented the Jvion Care Optimization and Recommendation Enhancement augmented intelligence (AI) tool at an Oncology Care Model (OCM) practice, the Center for Cancer and Blood Disorders practice. We applied continuous machine learning to predict risk of preventable harm (avoidable ACU) and generated patient-specific recommendations that nurses implemented to avert it. RESULTS: Patient-centric interventions included medication/dosage changes, laboratory tests/imaging, physical/occupational/psychologic therapy referral, palliative care/hospice referral, and surveillance/observation. Nurses contacted patients every 1-2 weeks after initial outreach to assess and maintain adherence to recommended interventions. Per 100 unique OCM patients, monthly ED visits dropped from 13.7 to 11.5 (18%), a sustained month-over-month improvement. Quarterly admissions dropped from 19.5 to 17.1 (13%), a sustained quarter-over-quarter improvement. Overall, the practice realized potential annual savings of $2.8 million US dollars (USD) on avoidable ACU. CONCLUSION: The AI tool has enabled nurse case managers to identify and resolve critical clinical issues and reduce avoidable ACU. Effects on outcomes can be inferred from the reduction; targeting short-term interventions toward patients most at-risk translates to better long-term care and outcomes. QI projects involving predictive modeling of patient risk, prescriptive analytics, and nurse outreach may reduce ACU.

Modeling negative cooperativity in streptavidin adsorption onto biotinylated microtubules.

The nanoscale architecture of binding sites can result in complex binding kinetics. Here, the adsorption of streptavidin and neutravidin to biotinylated microtubules is found to exhibit negative cooperativity due to electrostatic interactions and steric hindrance. This behavior is modeled by a newly developed kinetic analogue of the Fowler-Guggenheim adsorption model. The complex adsorption kinetics of streptavidin to biotinylated structures needs to be considered when these intermolecular bonds are employed in self-assembly and nanobiotechnology.

The Use and Knowledge of Validated Geriatric Assessment Instruments Among US Community Oncologists.

PURPOSE: The use of a standardized geriatric assessment (GA) to inform treatment decisions in older adults with cancer improves quality of life, reduces treatment-related toxicity, and is guideline-recommended. This study aimed to assess community oncologists' knowledge and utilization of GAs. METHODS: Between September 2019 and February 2020, practicing US-based oncologists were invited to attend live meetings and complete web-based surveys designed to collect information on treatment decision making and various practice-based challenges in oncology care. RESULTS: Among the 349 oncologists surveyed, 74% practiced in a community setting. Sixty percent did not use a formal GA to inform treatment decisions for any of their older patients; the most common reasons for not using a GA were "Too cumbersome to incorporate into routine practice" (44%) and "Adds no value beyond the comprehensive history and physical exam" (36%). Validated GA instruments used in routine clinical practice included: Mini-Mental State Exam (54%), Comprehensive Geriatric Assessment (23%), Cancer and Aging Research Group toxicity tool (12%), and Chemotherapy Risk Assessment Scale for High-Age Patients tool (9%). Nineteen percent of oncologists were not aware of any validated GA instruments. Eastern Cooperative Oncology Group performance status and comorbidities were the most frequently used assessment factors to inform treatment decisions (88% and 73%, respectively). CONCLUSION: Many oncologists have not incorporated GA tools because of perceptions that GAs are difficult to implement or do not add any value. Increasing education of the benefits of GA-directed therapy could help to increase GA utilization among community oncologists.

Barriers to Chimeric Antigen Receptor T-Cell (CAR-T) Therapies in Clinical Practice.

Chimeric antigen receptor T-cell (CAR-T) therapy is a revolutionary cancer treatment modality where a patient's own T cells are collected and engineered ex vivo to express a chimeric antigen receptor (CAR). These reprogrammed CAR-T cells, when reinfused into the same patient, stimulate a T-cell mediated immune response against the antigen-expressing malignant cells leading to cell death. The initial results from pivotal clinical trials of CAR-T agents have been promising, leading to multiple approvals in various hematologic malignancies in the relapsed setting, including acute lymphoblastic leukemia (ALL), diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma, follicular lymphoma, and, more recently, multiple myeloma. However, since the initial trials and US Food and Drug Administration approvals, there have been significant barriers to the widespread use of this therapy. The barriers to the use of CAR-T therapy include complex logistics, manufacturing limitations, toxicity concerns, and financial burden. This review discusses potential solutions to overcome these barriers in order to make this life-changing therapy widely accessible.

Impact of social determinants of health on cancer care: a survey of community oncologists.

OBJECTIVE: Cancer survival rates have improved over the past few decades, yet socioeconomic disparities persist. Social determinants of health (SDOH) have consistently been shown to correlate with health outcomes. The objective of this study was to characterise oncologists' perceptions of the impact of SDOH on their patients, and their opinions on how these effects could be remediated. DESIGN: Cross-sectional survey of physicians. SETTING: Web-based survey completed prior to live meetings held between February and April 2020. PARTICIPANTS: Oncologists/haematologists from across the USA. EXPOSURE: Clinical practice in a community-based or hospital-based setting. MAIN OUTCOME AND MEASURE: Physician responses regarding how SDOH affected their patients, which factors represented the most significant barriers to optimal health outcomes and how the impact of SDOH could be mitigated through assistance programmes. RESULTS: Of the 165 physicians who completed the survey, 93% agreed that SDOH had a significant impact on their patients' health outcomes. Financial security/lack of insurance and access to transportation were identified most often as the greatest barriers for their patients (83% and 58%, respectively). Eighty-one per cent of physicians indicated that they and their staff had limited time to spend assisting patients with social needs, and 76% reported that assistance programmes were not readily accessible. Government organisations, hospitals, non-profit organisations and commercial payers were selected by 50% or more of oncologists surveyed as who should be responsible for delivering assistance programmes to patients with social needs; 42% indicated that pharmaceutical manufacturers should also be responsible. CONCLUSION: Our survey found that most oncologists were aware of the impact of SDOH on their patients but were constrained in their time to assist patients with social needs. The physicians in our study identified a need for more accessible assistance programmes and greater involvement from all stakeholders in addressing SDOH to improve health outcomes.

Expanded Access and Right To Try Requests: The Community Oncologist's Experience.

PURPOSE: For patients with cancer who have exhausted approved treatment options and for whom appropriate clinical trials are not available, access to investigational drugs through the US Food and Drug Administration's Expanded Access (EA) program has been an alternative since the program's inception more than 30 years ago. In 2018, federal Right To Try legislation was passed in the United States, creating a second pathway-one that bypasses the US Food and Drug Administration-to obtain unapproved drugs outside of clinical trials. The use of the two programs by community medical oncologists and hematologist-oncologists has not been studied. METHODS: Between October 2019 and February 2020, community oncologists-hematologists from across the United States completed web-based surveys about EA and Right To Try pathways for accessing unapproved drugs for their patients. Physicians were asked about their utilization of, and perceptions of, the two programs. RESULTS: Of the 238 physicians who completed the survey, 46% indicated that they had attempted to gain access to an investigational drug for a patient using the EA program, whereas 14% reported attempting to use Right To Try pathway to obtain an unapproved drug for a patient. Eighty-nine percent of those who tried to use the EA program reported success in obtaining the investigational drug versus 73% of those who attempted to use the Right To Try pathway. CONCLUSION: Our survey found that most community oncologists-hematologists were aware of both the EA and Right To Try pathways, but there is room for improvement in understanding and utilization of the programs.

Perceptions of community hematologists/oncologists on barriers to chimeric antigen receptor T-cell therapy for the treatment of diffuse large B-cell lymphoma.

Objective: To determine the perceptions of US community-based hematologists/oncologists regarding approved CAR-T therapies in relapsed/refractory large B-cell lymphoma and barriers to their adoption in practice. Materials & methods: In February and November 2019, US physicians with diverse geographic representation submitted responses via a web-based survey prior to or via an audience response system at the live meetings. Results: In February and November, 46 and 29% of physicians indicated that they had not referred any patients for CAR-T therapy, respectively. Cumbersome logistics, high cost and toxicity were defined as major barriers to prescribing CAR-T therapy. Conclusions: These findings highlight a need to improve processes, and address costs, to ensure timely access to this potentially curative therapy for relapsed/refractory large B-cell lymphoma patients.

Frequency and Causes of Burnout in US Community Oncologists in the Era of Electronic Health Records.

BACKGROUND: Physician burnout, characterized by exhaustion of physical or emotional strength, cynicism, and lack of achievement, has become a worsening phenomenon in medicine, contributing to higher health care costs and patient/physician dissatisfaction. How burnout has affected hematologists and oncologists is not well studied. METHODS: US community oncologists/hematologists were queried via a Web-based survey from September-November 2018. Physicians were asked about frequency of burnout symptoms, drivers of work-related stress, and their perceptions on management of workload. RESULTS: Among the 163 physicians surveyed, 46% felt a substantial amount of stress at work. Most physicians felt emotionally (85%) and physically (87%) exhausted. A majority of physicians felt lethargic (67%), ineffective (64%), and/or detached (63%). In a typical workweek, 93% needed time beyond time allocated to clinical care to complete work responsibilities. Electronic health record (EHR) responsibilities caused moderate to excessive stress at work for 67% of physicians; 79% of physicians worked on EHRs outside of clinic hours. Other sources of excessive stress were changing reimbursement models (33%), interactions with payers (31%), and increasing patient and caregiver demands (31%). A third of physicians have considered retiring early or changing their career path to cope. To combat burnout, physicians' practices have used advanced practice providers, invested in information technology, and/or hired additional administrative staff. However, the majority of physicians stated they had optimal or good control over their workload. CONCLUSION: Most oncologists experience burnout symptoms and require additional time beyond that allocated to clinical care to complete their workload. The discordance between oncologists' admission of stress and exhaustion while claiming good control over those same burdens warrants exploration in future research.

Real-time ultrasound-guided needle injection of the mouse jugular vein.

This unit describes a novel method for direct venous injection into mice that offers potentially significant advantages over commonly used mouse vein injection techniques. This is achieved via percutaneous needle placement into the mouse jugular vein under real-time B-mode ultrasound (US) imaging. Real-time US imaging of the injection process allows for immediate determination of the overall success of injection. Unique, and potentially significant, advantages of this technique over others include: (1) direct visual confirmation of needle tip placement in the lumen of the vein, (2) immediate visual detection of extravascular extravasation of injectate, when compared to blinded techniques, such as tail vein injections, and (3) reduced morbidity and mortality compared to surgical vascular access techniques (i.e., jugular vein cannulation). This technique may lead to more accurate determination of the success of the injection procedure for each mouse, thus improving the quality of acquired data in dependent mouse experiments.

Cargo loading onto kinesin powered molecular shuttles.

Cells have evolved sophisticated molecular machinery, such as kinesin motor proteins and microtubule filaments, to support active intracellular transport of cargo. While kinesins tail domain binds to a variety of cargoes, kinesins head domains utilize the chemical energy stored in ATP molecules to step along the microtubule lattice. The long, stiff microtubules serve as tracks for long-distance intracellular transport. These motors and filaments can also be employed in microfabricated synthetic environments as components of molecular shuttles. In a frequently used design, kinesin motors are anchored to the track surface through their tails, and functionalized microtubules serve as cargo carrying elements, which are propelled by these motors. These shuttles can be loaded with cargo by utilizing the strong and selective binding between biotin and streptavidin. The key components (biotinylated tubulin, streptavidin, and biotinylated cargo) are commercially available. Building on the classic inverted motility assay, the construction of molecular shuttles is detailed here. Kinesin motor proteins are adsorbed to a surface precoated with casein; microtubules are polymerized from biotinylated tubulin, adhered to the kinesin and subsequently coated with rhodamine-labeled streptavidin. The ATP concentration is maintained at subsaturating concentration to achieve a microtubule gliding velocity optimal for loading cargo. Finally, biotinylated fluorescein-labeled nanospheres are added as cargo. Nanospheres attach to microtubules as a result of collisions between gliding microtubules and nanospheres adhering to the surface. The protocol can be readily modified to load a variety of cargoes such as biotinylated DNA, quantum dots or a wide variety of antigens via biotinylated antibodies.