Awareness and utilization of tumor mutation burden (TMB) as a biomarker for administration of immuno-oncology (I-O) therapeutics by practicing community oncologists in the United States (U.S.).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 2608-2608
Author(s):  
Kristin M. Zimmerman Savill ◽  
Marjorie E. Zettler ◽  
Bruce A. Feinberg ◽  
Yolaine Jeune-Smith ◽  
Ajeet Gajra
Keyword(s):  
Solid Tumors ◽  
Tumor Cells ◽  
Clinical Decision Making ◽  
Objective Response ◽  
Predictive Biomarker ◽  
Clinical Decision ◽  
The United States ◽  
Mutation Burden ◽  
Definition Of ◽  
The U.S

2608 Background: TMB, a measurement of the number of mutations carried by tumor cells, is emerging as a biomarker for the identification of patients who may benefit from certain I-O-based therapies. TMB-high (TMB-H) tumors, defined by the detection of ≥10 mutations/megabase (mut/Mb) in tumor cells using a tissue-based assay such as the FoundationOneCDx (F1CDx) assay (Foundation Medicine, Inc.), may be more likely to respond to some I-O therapies. Higher neoantigen loads of TMB-H tumors have been proposed to contribute to increased responsiveness of TMB-H tumors to certain I-O therapeutics. Pembrolizumab was approved by the FDA on June 16, 2020 for the treatment of adult and pediatric patients with unresectable or metastatic TMB-H tumors, as determined by F1CDx, based on results from the KEYNOTE-158 trial (NCT02628067), which demonstrated that 50% of patients with TMB-H tumors had response durations of ≥24 months, with objective response rates in TMB-H vs. non-TMB-H patients of 29% and 6%, respectively (Marabelle et al, The Lancet Oncology, 2020). This survey-based study aimed to evaluate awareness and utilization of TMB as a biomarker for I-O therapeutics among practicing community oncologists in the U.S. Methods: Questions related to awareness and utilization of TMB as a biomarker for I-O therapeutics were developed by two medical oncologists (AG and BF) and presented to community oncologists in a web-based survey prior to virtual meetings held between October and November 2020. Descriptive statistics were used to analyze the results. Results: Of the 193 participating providers geographically distributed across the U.S., 15% reported being unaware of either the concept of TMB in I-O therapy or how to use the information clinically. 39% of these providers reported testing ≤25% of patients with advanced cancer for TMB, including 8% who do not test for TMB at all. Misconceptions regarding TMB identified among participating providers included the belief that high TMB is considered to be > 5 mut/Mb among 20% of providers, that TMB is essentially the same as MSI-high among 8% of providers, and that there are no therapies with FDA approval based on TMB among 15% of providers. Further, 37% of the participants did not identify pembrolizumab as an agent approved for the treatment of solid tumors based on TMB-H status. Conclusions: These findings demonstrate that there is a knowledge gap regarding the definition of TMB, testing for TMB, as well as implementation of TMB status in clinical decision making. Education directed towards community oncology providers regarding TMB and its use as a predictive biomarker for I-O therapy may improve its utilization and adoption in solid tumors to improve patient outcomes.

scholarly journals Tumor Mutation Burden: A Predictive Biomarker for Gastric Cancer Immunotherapy

2020 ◽  
Author(s):  
Renshen Xiang ◽  
Tao Fu
Keyword(s):  
Gastric Cancer ◽  
T Cells ◽  
Clinical Decision Making ◽  
Immune Cell ◽  
Predictive Biomarker ◽  
Clinical Decision ◽  
Tumor Mutation Burden ◽  
Follicular Helper ◽  
Tumor Purity ◽  
Mutation Burden

Abstract Background: Few studies have focused on the underlying relationship between the prognosis of tumor mutation burden (TMB) and immune cell infiltration in gastric cancer (GC). This study aims to explore the relationship among TMB and various components in tumor microenvironment (TME). Methods: The transcription profiles and somatic mutation data of 375 tumor and 32 normal samples were obtained from TCGA. The specific mutation information was summarized and visualized with waterfall chart, then number of TMB per million bases of each GC sample was calculated. Immune/stromal scores and tumor purity were calculated by the ‘ESTIMATE’ package, and the fractions of 22 immune cells in each sample were evaluated by CIBERSORT algorithm. Finally, Lass regression analysis was utilized to generate a prognostic scoring signature with TCGA cohort as the training set, while GES84437 cohort as the validation set. Results: Higher TMB indicated favorable overall survival (OS, P = 0.043)，better disease specific survival (P = 0.029), and longer progression free interval (P = 0.004). TMB was positively correlated with MSI and tumor purity, while negatively associated with immune/stromal scores. Moreover, TMBhigh group has lower T cells CD4 memory resting (P < 0.001) and T cells regulatory (P < 0.001), and more T cells CD4 memory activated (P < 0.001) and T cells follicular helper (P = 0.009). More importanly, the infiltration of dendritic cells activated predicted a worse OS, while T cells CD4 memory activated and T cells follicular helper meant a better OS. Finally, a nomogram combined TMB-related signature with clinicopathologic variables can successfully predict the OS with high accuracy and efficiency.Conclusion: TMB can effectively reveal the immune infiltration status in TME of GC, and might serve as a prognostic classifier for individualized treatment of clinical decision-making.

scholarly journals ACADEMIA’S ROLE TO DRIVE CHANGE IN THE ORTHOTICS AND PROSTHETICS PROFESSION

2021 ◽  
Vol 4 (2) ◽  
Author(s):  
Géza Kogler ◽  
Christopher Hovorka
Keyword(s):  
Technology Use ◽  
Clinical Training ◽  
Clinical Decision Making ◽  
New Technologies ◽  
Clinical Care ◽  
Clinical Decision ◽  
The United States ◽  
Academic Program ◽  
Number Of Patients ◽  
Curricular Emphasis

This position paper outlines the important role of academia in shaping the orthotics and prosthetics (O&P) profession and preparing for its future. In the United States, most healthcare professions including O&P are under intense pressure to provide cost effective treatments and quantifiable health outcomes. Pivotal changes are needed in the way O&P services are provided to remain competitive. This will require the integration of new technologies and data driven processes that have the potential to streamline workflows, reduce errors and inform new methods of clinical care and device manufacturing. Academia can lead this change, starting with a restructuring in academic program curricula that will enable the next generation of professionals to cope with multiple demands such as the provision of services for an increasing number of patients by a relatively small workforce of certified practitioners delivering these services at a reduced cost, with the expectation of significant, meaningful, and measurable value. Key curricular changes will require replacing traditional labor-intensive and inefficient fabrication methods with the integration of newer technologies (i.e., digital shape capture, digital modeling/rectification and additive manufacturing). Improving manufacturing efficiencies will allow greater curricular emphasis on clinical training and education – an area that has traditionally been underemphasized. Providing more curricular emphasis on holistic patient care approaches that utilize systematic and evidence-based methods in patient assessment, treatment planning, dosage of O&P technology use, and measurement of patient outcomes is imminent. Strengthening O&P professionals’ clinical decision-making skills and decreasing labor-intensive technical fabrication aspects of the curriculum will be critical in moving toward a digital and technology-centric practice model that will enable future practitioners to adapt and survive. Article PDF Link: https://jps.library.utoronto.ca/index.php/cpoj/article/view/36673/28349 How To Cite: Kogler GF, Hovorka CF. Academia’s role to drive change in the orthotics and prosthetics profession. Canadian Prosthetics & Orthotics Journal. 2021; Volume 4, Issue 2, No.21. https://doi.org/10.33137/cpoj.v4i2.36673 Corresponding Author: Géza F. KoglerOrthotics and Prosthetics Unit, Kennesaw State University.E-Mail: [email protected] ID: https://orcid.org/0000-0003-0212-5520

Implementation of Semantic Search to Support Clinical Decision-Making

2015 ◽  
pp. 270-286
Author(s):  
Andrew Tawfik ◽  
Karl Kochendorfer
Keyword(s):  
Human Performance ◽  
Clinical Decision Making ◽  
Information Overload ◽  
Clinical Decision ◽  
Human Performance Technology ◽  
The United States ◽  
Semantic Search ◽  
Current Case ◽  
Performance Technology

The current case study is situated within a large, land grant hospital located in the Midwestern region of the United States. Although the physicians had seen an increase in medical related human performance technology (HPTs) within the organization (e.g. computer physician ordered entry) some challenges remained as the hospital sought to improve the productivity of the electronic health record (EHRs). Specifically, physicians had difficulty finding information embedded within the chart due to usability problems and information overload. To overcome the challenges, a semantic search within the chart was implemented as a solution for physicians to retrieve relevant results given the conceptual semantic pattern. The case study will discuss many elements of the implementation based on our experience and feedback from clinicians. The case will specifically highlight the importance of training and change agents within an organization.

scholarly journals Direct oral anticoagulant monitoring: what laboratory tests are available to guide us?

Hematology ◽  
2019 ◽  
Vol 2019 (1) ◽  
pp. 194-197 ◽  
Author(s):  
Ravi Sarode
Keyword(s):  
Clinical Decision Making ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Rapid Assessment ◽  
Clinical Decision ◽  
The United States ◽  
Thrombin Inhibitor ◽  
Thrombin Time ◽  
Clinical Scenarios

Abstract Direct oral anticoagulants (DOACs) are increasingly used in the treatment and prophylaxis of thromboembolism because of several advantages over vitamin K antagonists, including no need for laboratory monitoring. However, it has become increasingly important in certain clinical scenarios to know either actual DOAC concentration (quantitative) or presence of DOAC (qualitative). These clinical conditions include patients presenting with major bleeding or requiring urgent surgery who may need a reversal or hemostatic agent, extremes of body weight, failed therapy, etc. Prothrombin time and activated partial thromboplastin time are variably affected by factor Xa inhibitors (FXaIs) and direct thrombin inhibitor (DTI), respectively, depending on reagents’ sensitivity, and hence, they cannot be relied on confidently. Thrombin time is highly sensitive to very low amounts of DTI; thus, normal value rules out a clinically significant amount. Liquid chromatography mass spectrometry accurately measures DOAC levels but is clinically impractical. Dilute thrombin time and ecarin-based assays using appropriate calibrators/controls provide an accurate DTI level. Anti-Xa assay using corresponding FXaI calibrators/controls provides accurate drug levels. However, these assays are not readily available in the United States compared with some other parts of the world. Heparin assays using anti-Xa activity often have a linear relationship with calibrated FXaI assays, especially at the lower end of on-therapy levels, and they may provide rapid assessment of drug activity for clinical decision making. Currently, there is very limited knowledge of DOAC effect on viscoelastic measurements. Although there is uniformity in expression of DOAC concentrations in nanograms per milliliter, a universal FXaI DOAC assay is urgently needed.

Complete Count of U.S. Transportation Workforce

2000 ◽  
Vol 1719 (1) ◽  
pp. 259-266
Author(s):  
Basav Sen ◽  
Michael A. Rossetti
Keyword(s):  
The United States ◽  
Double Counting ◽  
Transportation Industry ◽  
Industry Data ◽  
Definition Of ◽  
Nonfarm Employment ◽  
Employment Data ◽  
Transportation Activity ◽  
The U.S ◽  
Complete Count

Described are the development and application of an original methodology for a comprehensive and consistent count of transportation-related employment in the United States. In addition, the study represents a general example of how transportation analysts can effectively use and combine classification-based data to answer specific crosscutting questions. The method involved computing the union of two different sets of transportation employment data: transportation industry data, counting all workers in industries that provide or support transportation, and transportation occupational data, counting all workers performing transportation functions. A union, instead of a straightforward sum, was used to avoid double counting of workers employed in the defined transportation and transportation-related industries. A broad definition of transportation-related industries and occupations was used, allowing a complete accounting of employment generated by transportation in the economy. It was concluded that transportation industries account for 13 million workers, or about 10 percent of total nonfarm employment of 128.4 million, and transportation occupations outside of transportation industries accounted for another 3.5 million workers, or about an additional 3 percent of nonfarm employment. Thus, about 16.5 million workers either work directly in or support transportation activity in the U.S. economy; this constitutes about 13 percent—approximately 1 in 8 jobs—of the nonfarm workforce.

The History of Mitigation in Death Penalty Cases

2020 ◽  
pp. 34-45
Author(s):  
Russell Stetler
Keyword(s):  
Death Penalty ◽  
The United States ◽  
Theory And Practice ◽  
Death Sentences ◽  
Eighth Amendment ◽  
Mitigating Factors ◽  
History Of ◽  
Definition Of ◽  
Effective Representation ◽  
The U.S

This chapter discusses how the theory and practice of mitigation have evolved over more than four decades, thereby helping to define the modern death penalty era in the United States. Prior to 1976, juries generally made death penalty decisions in a unitary proceeding. Juries then had unfettered discretion to impose death sentences, and the results were so arbitrary that in 1972 the U.S. Supreme Court struck down all the existing death penalty statutes. In 1976, the Court approved new statutes that guided jurors’ discretion. The Court required individualized sentencing in which jurors could consider mitigating factors based on the diverse frailties of humankind. This broad definition of what might inspire juries to reject death was elaborated in succeeding decades in a series of decisions relying on the Eighth Amendment. Social workers and other nonlawyers became critical members of multidisciplinary capital defense teams providing effective representation under the Sixth Amendment.

Reassessment of the definition of castrate levels of testosterone: implications for clinical decision making

Urology ◽  
2000 ◽  
Vol 56 (6) ◽  
pp. 1021-1024 ◽  
Author(s):  
Michael G Oefelein ◽  
Adrian Feng ◽  
Michael J Scolieri ◽  
Daniel Ricchiutti ◽  
Martin I Resnick
Keyword(s):  
Decision Making ◽  
Clinical Decision Making ◽  
Clinical Decision ◽  
Definition Of

scholarly journals Public views regarding the responsibility of patients, clinicians, and institutions to participate in research in the United States

2019 ◽  
Vol 16 (6) ◽  
pp. 574-579 ◽  
Author(s):  
Kevin P Weinfurt ◽  
Li Lin ◽  
Jeremy Sugarman
Keyword(s):  
Health System ◽  
Online Survey ◽  
Clinical Decision Making ◽  
Clinical Decision ◽  
The United States ◽  
Robust Learning ◽  
Learning Health System ◽  
English Speaking ◽  
Nationally Representative ◽  
Public Views

Background The need for more and better evidence to inform clinical decision making among all stakeholders has fueled calls for creating learning healthcare systems. The successful realization of a learning healthcare system seems to assume that various parties have a responsibility to participate in learning activities, including research. The objective of this study was to determine whether members of the general public perceive an ethical responsibility to participate in pragmatic clinical research that would be inherent to a learning health system. Methods A total of 2994 English-speaking adults completed a nationally representative online survey. Results About two-thirds of respondents were relatively neutral regarding a responsibility for themselves and others to participate in research; the remainder felt that they and others did not have a responsibility to participate in research. Conclusions Efforts to justify and develop a robust learning health system in an ethically acceptable fashion need to take these findings into account.

scholarly journals A “Lymphocyte MicroRNA Signature” as Predictive Biomarker of Immunotherapy Response and Plasma PD-1/PD-L1 Expression Levels in Patients with Metastatic Renal Cell Carcinoma: Pointing towards Epigenetic Reprogramming

Cancers ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3396
Author(s):  
Lorena Incorvaia ◽  
Daniele Fanale ◽  
Giuseppe Badalamenti ◽  
Chiara Brando ◽  
Marco Bono ◽  
...  
Keyword(s):  
Clinical Decision Making ◽  
Checkpoint Inhibitors ◽  
Predictive Biomarkers ◽  
Predictive Biomarker ◽  
Clinical Decision ◽  
Mirna Expression Profile ◽  
Immune Checkpoints ◽  
Cancer Evolution ◽  
Specific Subset ◽  
Number Of Patients

Introduction of checkpoint inhibitors resulted in durable responses and improvements in overall survival in advanced RCC patients, but the treatment efficacy is widely variable, and a considerable number of patients are resistant to PD-1/PD-L1 inhibition. This variability of clinical response makes necessary the discovery of predictive biomarkers for patient selection. Previous findings showed that the epigenetic modifications, including an extensive microRNA-mediated regulation of tumor suppressor genes, are key features of RCC. Based on this biological background, we hypothesized that a miRNA expression profile directly identified in the peripheral lymphocytes of the patients before and after the nivolumab administration could represent a step toward a real-time monitoring of the dynamic changes during cancer evolution and treatment. Interestingly, we found a specific subset of miRNAs, called “lymphocyte miRNA signature”, specifically induced in long-responder patients (CR, PR, or SD to nivolumab >18 months). Focusing on the clinical translational potential of miRNAs in controlling the expression of immune checkpoints, we identified the association between the plasma levels of soluble PD-1/PD-L1 and expression of some lymphocyte miRNAs. These findings could help the development of novel dynamic predictive biomarkers urgently needed to predict the potential response to immunotherapy and to guide clinical decision-making in RCC patients.

When Immigrants Are Not Migrants: Counting Arrivals of the Foreign Born Using the U.S. Census

1998 ◽  
Vol 32 (1) ◽  
pp. 127-144 ◽  
Author(s):  
Mark Ellis ◽  
Richard Wright
Keyword(s):  
United States ◽  
The United States ◽  
Foreign Born ◽  
Skill Levels ◽  
Migration Status ◽  
Recent Immigrant ◽  
Two Measures ◽  
Definition Of ◽  
The U.S ◽  
The Way

This paper compares characteristics of recent immigrant arrivals in the United States using two measures from the decennial U.S. census: the came-to-stay question and the migration question. We show that a little under 30 percent of immigrants who reported they came to stay between 1985–1990 on the 1990 U.S. Census Public Use Micro Sample were resident in the United States on April 1, 1985. A similar analysis of the 1980 censue reveals that 22 percent of immigrants who reported they came to stay between 1975–1980 lived in the United States on April 1, 1975. Thus among recent arrivals, defined as those who reported they came to stay in the quinquennium preceding the census, a large number were resident in the United States five years before the census date. Furthermore, the proportion of recent arrivals present in the United States five years before the census increased between 1975–1980 and 1985–1990. We show that the profile of recent arrivals is sensitive to their migration status. Generally, in both the 1975–1980 and 1985–1990 cohorts, those resident in the United States five years before the census have significantly less schooling and lower incomes than those who were abroad. Accordingly, we argue that estimates of the skill levels and hourly wages of recent arrivals to the United States vary with the way arrival is measured. Researchers who rely on Public Use samples of the U.S. census for their data should be aware that the year of entry question implies a broader definition of arrival than the migration question. We caution that immigration researchers should consider the idea of arrival more carefully to help distinguish newcomers from the resident foreign born.

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