Nivolumab plus cabozantinib for advanced renal cell carcinoma.

Advanced renal cell carcinoma (RCC) remains a challenging oncologic disease to treat despite advancements in therapeutics. Nonetheless, the development of tyrosine kinase inhibitors (TKIs) and immunotherapy has drastically altered the treatment landscape for advanced RCC over the past decade. The current standard-of-care treatment for advanced RCC involves combination TKI and immunotherapy regimens including cabozantinib and nivolumab as studied in the CheckMate 9ER trial. This review summarizes the preclinical and clinical evidence that led to the CheckMate 9ER study, as well as pertinent study aspects such as treatment efficacy, adverse events and patient-related outcomes.

Kidney cancer that has spread to organs and other parts of the body outside of the kidney remains a challenging disease to treat. The treatment of advanced kidney cancer has changed over the past decade with the approval of oral therapies called tyrosine kinase inhibitors and more recently immunotherapy, which utilizes the immune system to treat cancer. A new combination therapy employing cabozantinib and nivolumab has been shown to help patients with advanced kidney cancer live longer and have improvements in quality of life. This new combination therapy is now commonly used to treat advanced kidney cancer.

The Development of Children's Gender-Science Stereotypes: A Meta-analysis of 5 Decades of U.S. Draw-A-Scientist Studies.

This meta-analysis, spanning 5 decades of Draw-A-Scientist studies, examined U.S. children's gender-science stereotypes linking science with men. These stereotypes should have weakened over time because women's representation in science has risen substantially in the United States, and mass media increasingly depict female scientists. Based on 78 studies (N = 20,860; grades K-12), children's drawings of scientists depicted female scientists more often in later decades, but less often among older children. Children's depictions of scientists therefore have become more gender diverse over time, but children still associate science with men as they grow older. These results may reflect that children observe more male than female scientists in their environments, even though women's representation in science has increased over time.

How do generic statements impact performance? Evidence for entity beliefs.

Generic statements about the abilities of children's social groups (e.g. 'Girls/Boys are good at this game') negatively impact children's performance - even if the statements are favorable towards children's own social groups. We explored the mechanism by which generic language impairs children's performance. Across three studies, our findings suggest that generic statements influence children's performance by creating an entity belief (i.e. a belief that a fixed ability determines performance). Children who were exposed to a generic statement about their social group's ability performed worse than children in control conditions. This effect hurt children's performance even when the person who made the generic statement was no longer present and a new person not privy to the statement replaced them. However, when children heard a generic statement paired with an effort explanation (i.e. 'Girls/Boys are good at this game because they try really hard when they draw') they performed better than children who heard the generic statement with no explanation (i.e. just 'Girls/Boys are good at this game') and children who heard the generic statement paired with a trait explanation (i.e. 'Girls/Boys are good at this game because they are smart and really good at drawing'). This work uncovers when and how generic statements that refer to the ability of one's social group hinder performance, informing the development of practices to improve student motivation and learning.

The challenge of using patient reported outcome measures in clinical practice: how do we get there?

BACKGROUND: As patient-reported outcome measures (PROMs) become available to clinicians for routine clinical decision-making, many wonder how to define a meaningful change in a patient's PROM score. Some PROMs have a specific threshold that indicates meaningful change, but since those numbers are based on population averages, they do not necessarily apply to the varying experiences of each individual patient. Rather than viewing this as a weakness of PROMs, it is worth considering how clinicians use other existing measures in clinical decision-making-and whether PROMs can be used similarly. BODY: An informal survey of 43 clinicians reported using measures such as weight, blood pressure, and blood chemistry to inform clinical decision-making. Although clinicians were very consistent with what constituted a meaningful change for some measures (e.g., ECOG performance status), other measures had considerable variability (e.g., weight), often informed by their specialization (for example, differing thresholds for meaningful weight change for adult primary care, pediatrics, and oncology). For interpreting change in measures, they relied on clinical experience (44%), published literature (38%), and established guidelines (35%). In open-response comments, many clarified that the results of any measure had to be taken in the context of each individual patient before making treatment decisions. In short, clinicians already apply individualized clinical judgment when interpreting score changes in existing clinical measures. As clinicians gain familiarity with PROMs, PROMs will likely be utilized in the same way. CONCLUSION: Like other clinical measures from weight to blood chemistry, change in a PROM score is but one piece of a patient's clinical story. Rather than relying on a hard-and-fast number for defining clinically meaningful change in a PROM score, providers should-and many already do-consider the full scope of a patient's experience as they make treatment decisions.

Seamless Integration of Computer-Adaptive Patient Reported Outcomes into an Electronic Health Record.

BACKGROUND: Patient-reported outcome (PRO) measures have become an essential component of quality measurement, quality improvement, and capturing the voice of the patient in clinical care. In 2004, the National Institutes of Health endorsed the importance of PROs by initiating the Patient-Reported Outcomes Measurement Information System (PROMIS), which leverages computer-adaptive tests (CATs) to reduce patient burden while maintaining measurement precision. Historically, PROMIS CATs have been used in a large number of research studies outside the electronic health record (EHR), but growing demand for clinical use of PROs requires creative information technology solutions for integration into the EHR. OBJECTIVES: This paper describes the introduction of PROMIS CATs into the Epic Systems EHR at a large academic medical center using a tight integration; we describe the process of creating a secure, automatic connection between the application programming interface (API) which scores and selects CAT items and Epic. METHODS: The overarching strategy was to make CATs appear indistinguishable from conventional measures to clinical users, patients, and the EHR software itself. We implemented CATs in Epic without compromising patient data security by creating custom middleware software within the organization's existing middleware framework. This software communicated between the Assessment Center API for item selection and scoring and Epic for item presentation and results. The middleware software seamlessly administered CATs alongside fixed-length, conventional PROs while maintaining the display characteristics and functions of other Epic measures, including automatic display of PROMIS scores in the patient's chart. Pilot implementation revealed differing workflows for clinicians using the software. RESULTS: The middleware software was adopted in 27 clinics across the hospital system. In the first 2 years of hospital-wide implementation, 793 providers collected 70,446 PROs from patients using this system. CONCLUSION: This project demonstrated the importance of regular communication across interdisciplinary teams in the design and development of clinical software. It also demonstrated that implementation relies on buy-in from clinical partners as they integrate new tools into their existing clinical workflow.

Patient-reported outcomes in metastatic renal cell carcinoma trials using combinations versus sunitinib as first-line treatment.

Over the past 5 years, several new immunotherapy treatments have been tested for metastatic renal cell carcinoma (mRCC). Clinical trials assessing combinations of different immunotherapies, or of an immunotherapy with a tyrosine kinase inhibitor (TKI), have reported improved clinical outcomes compared with the standard of care - that is, treatments using TKIs alone. However, to understand the holistic impact of new treatments on patients, physicians must also consider effects on health-related quality of life (HRQoL). As patient-reported outcome measures (PROMs) on HRQoL are often treated as a secondary outcome in clinical trials, their collection and reporting are non-standardized and, therefore, difficult to compare and interpret. However, results from six clinical trials indicate that two immunotherapy treatments overwhelmingly outperform sunitinib in HRQoL measurements: nivolumab plus cabozantinib (CheckMate 9ER) and atezolizumab plus bevacizumab (IMmotion151). An additional two treatments generally outperform sunitinib: nivolumab plus ipilimumab (CheckMate 214) and lenvatinib plus pembrolizumab (CLEAR). Of three studies that reported no difference from sunitinib, two suffered design flaws that might have obscured HRQoL benefits (JAVELIN Renal 101 and KEYNOTE-426). To ensure future HRQoL data are of the highest quality and comparable across trials, future studies should adopt best practices for the design, analysis and reporting of PROMs.