Search

Introduction: Geriatric assessment can predict the risk of toxicities of chemotherapy in older adults. Genetic risk categories correlate with survival following intensive chemotherapy in AML. Integrating geriatric assessment for patient profiling and genetic profiling of leukemic cells represents an innovative precision medicine approach to personalize therapy selection in older adults with AML. We report results of a pre-planned interim analysis of a pragmatic phase II trial using such strategy that has an overarching goal to reduce early mortality (NCT03226418). Methods: Patients ≥60 years with a new diagnosis of AML underwent geriatric assessment prior to initiation of treatment. Geriatric assessment of physical function, cognitive function and comorbidity burden were used to determine fitness for intensive chemotherapy (Table 1). Additional assessment included Karnofsky Performance Scale (KPS), Patient Health Questionnaire-9 (PHQ-9), and Mini Nutritional Assessment-Short Form (MNA). Genetic profiling for therapy selection relied on karyotyping and followed the 2017 European LeukemiaNet criteria. While available mutation test results were incorporated to risk stratify, the study did not require to wait for the results prior to therapy initiation given an anticipated turnaround time of 1-2 weeks for mutation test results. Therapy selection followed the algorithm demonstrated in Figure 1. Patients with good or intermediate-risk AML received intensive chemotherapy such as 7+3 +/- gemtuzumab or midostaurin if determined to be fit. Patients with high-risk AML received low-intensity chemotherapy such as a hypomethylating agent with or without novel drugs, or CPX 351 if they were fit and met the FDA-approved indications. Patients with organ dysfunction (e.g. creatinine ≥2 mg/dl) and those requiring chemotherapy for other malignancy received low-intensity chemotherapy. Chemotherapy at diagnosis or follow up could be administered in community oncology settings. Patients were followed for assessment of quality of life, functional and oncologic outcomes. Results: Between July 2017-June 2019, a total of 31 patients (including 1 MDS patient considered screen failure) were enrolled. The pre-planned interim analysis results are based on the first 27 AML patients. Baseline characteristics included a median age of 70 years (range 60-84 years), 56% female, 96% white, and a median KPS of 80% (range 60-100%). As presented in Table 1, over half of the patients had ≥3 comorbidities, impairment in objective physical function (short physical performance battery) and Montreal Cognitive Assessment. Additionally, 67% had poor nutritional status (MNA score of ≤11) and 26% had abnormal depression screen (PHQ-9 score of ≥10). Risk categories included adverse (64%), intermediate (16%), and good-risk AML (20%). Patients had one or more of the following mutations: FLT3 ITD (11%), NPM1 (22%), biallelic CEBPA (4%), IDH1 (15%), IDH2 (8%), RUNX1 (15%), ASXL1 (22%), and TP53 (19%). Three patients received intensive chemotherapy; CPX 351 (n=2) or 7+3+ gemtuzumab (n=1). Other patients received decitabine or azacitidine alone (n=16), azacitidine and venetoclax (n=5) or decitabine and midostaurin (n=3). The median time from diagnosis to therapy initiation was 7 days (0-20 days) whereas the median time from enrollment to therapy initiation was 2 days (range 0-9). Mortality at 30 days from diagnosis was 3.7% (95% confidence interval, CI 0.7-18.3%) and at 90 days was 29.6% (95% CI 15.9-48.5%). Mortality compared favorably to an unmatched historical cohort of patients ≥60 years treated at our center between 2011-2016, where 30-day mortality was 30% (95% CI 22-40%) and 90-day was 41% (95% CI 32-52%) (Future Oncol. 2019;15:1989-95). Conclusions: Our model to personalize AML therapy selection represents an innovative approach to precision medicine that incorporates both geriatric assessment for patient profiling and genetic profiling of leukemia cells. Geriatric assessment demonstrated high frequency of impairment in objective physical and cognitive function. Patients were able to start therapy within a median of 2 days following enrollment. Pragmatic aspects of the trial included broad eligibility criteria and co-management of patients with community oncologists. Our pre-planned interim analysis data appear promising with lower rates of early mortality compared to unmatched historical controls. Disclosures Bhatt: Pfizer: Consultancy; CSL Behring: Consultancy; Agios: Consultancy; Abbvie: Consultancy; Partner therapeutics: Consultancy; Incyte: Consultancy, Research Funding; Tolero Pharmaceuticals: Research Funding; National Marrow Donor Program: Consultancy. Al-Kadhimi:Celldex Biotech: Other: Stocks; Seattle Genetics: Other: Stocks. Armitage:Oncology Analytics: Consultancy; Partner Therapeutics: Consultancy; Samus Therapeutics: Consultancy; Ascentage: Consultancy; Tesaro bio: Membership on an entity's Board of Directors or advisory committees; Union Pacific: Consultancy. Holstein:GSK: Consultancy; Genentech: Membership on an entity's Board of Directors or advisory committees; Sorrento: Consultancy; Celgene: Consultancy; Takeda: Membership on an entity's Board of Directors or advisory committees; Adaptive Biotechnologies: Membership on an entity's Board of Directors or advisory committees. Gundabolu:Samus Therapeutics: Research Funding; Jazz pharmaceuticals: Consultancy; Pfizer: Consultancy; Novartis: Consultancy. OffLabel Disclosure: Single agent azacitidine and decitabine as well as decitabine in combination with midostaurin are not approved by the US FDA for acute myeloid leukemia.

e23179 Background: Engaging patients in shared decision-making can help select an appropriate treatment for an individual and enhance patients’ experience and satisfaction with their care. This requires an in-depth understanding of patients’ values and preferences of various aspects of cancer treatment. A questionnaire to assess patient preferences is currently lacking. The purpose of our study was to develop a questionnaire that would fill this gap. Methods: We reviewed published literature to develop a theoretical framework to explain how cancer patients chose a specific therapy for themselves, and to identify key aspects of treatment that determine patients’ decisions about treatment. Three key domains (efficacy, safety and other characteristics of treatment such as need for hospital stay) were identified (Bhatt VR, J Geriatr Oncol. 2018 Nov 27 [Epub ahead of print]) and a mutli-dimensional self-report questionnaire with 49 items was developed. Each item was rated for relevance by 10 experts (oncologists, oncology nurses, advanced practice providers, social workers and pharmacists) to assess content validity (Lawshe formula) (Meas Eval Couns Dev, 47: 79–86). Ratings of ‘very relevant’ or ‘relevant’ were used to identify an essential question. Experts also suggested refinement of items. Three community members and 9 patients evaluated the instrument for face validity. Results: A content validity index for the questionnaire was 0.82. Face validity was confirmed. Based on input from the various stakeholders, the number of items, content, and format of the questionnaire was revised. The revised questionnaire includes a total of 36 items under four sections: safety (14 items), efficacy (4 items), treatment characteristics (8 items) and global items (10 items). Conclusions: We have developed a novel tool and established content and face validity. This self-report questionnaire can be used to understand patients’ preferences of cancer treatment. Further psychometric studies are planned to evaluate reliability and validity. Our ultimate goal is to use this tool to enhance communication between physicians and patients and facilitate shared decision-making.

Background: The role of B-type natriuretic peptide (BNP) is less understood in the risk stratification of patients with an acute exacerbation of chronic obstructive pulmonary disease (AECOPD), especially in patients with normal left ventricular ejection fraction (LVEF). Methods: This retrospective study from 2008 to 2012 evaluated all adult patients with AECOPD having BNP levels and available echocardiographic data demonstrating LVEF ≥40%. The patients were divided into groups 1, 2, and 3 with BNP ≤ 100, 101 to 500, and ≥501 pg/mL, respectively. A subgroup analysis was performed for patients without renal dysfunction. Outcomes included need for and duration of noninvasive ventilation (NIV) and mechanical ventilation (MV), NIV failure, reintubation at 48 hours, intensive care unit (ICU) and total length of stay (LOS), and in-hospital mortality. Two-tailed P < .05 was considered statistically significant. Results: Of the total 1145 patients, 550 (48.0%) met our inclusion criteria (age 65.1 ± 12.2 years; 271 [49.3%] males). Groups 1, 2, and 3 had 214, 216, and 120 patients each, respectively, with higher comorbidities and worse biventricular function in higher categories. Higher BNP values were associated with higher MV use, NIV failure, MV duration, and ICU and total LOS. On multivariate analysis, BNP was an independent predictor of higher NIV and MV use, NIV failure, NIV and MV duration, and total LOS in groups 2 and 3 compared to group 1. B-type natriuretic peptide continued to demonstrate positive correlation with NIV and MV duration and ICU and total LOS independent of renal function in a subgroup analysis. Conclusion: Elevated admission BNP in patients with AECOPD and normal LVEF is associated with worse in-hospital outcomes and can be used to risk-stratify these patients.

The primary aim of this study was to determine the characteristics that current chairpersons in restorative dentistry, general dentistry, prosthodontics, and operative dentistry departments in U.S. dental schools feel are most relevant in contributing to their success. The secondary aim was to determine these individuals' rankings of the importance of a listed set of characteristics for them to be successful in their position. All 82 current chairs of the specified departments were invited to respond to an electronic survey. The survey first asked respondents to list the five most essential characteristics to serve as chair of a department and to rank those characteristics based on importance. Participants were next given a list of ten characteristics in the categories of management and leadership and, without being aware of the category of each individual item, asked to rank them in terms of importance for their success. A total of 39 chairpersons completed the survey (47.6% response rate; 83.3% male and 16.2% female). In section one, the respondents reported that leadership, vision, work ethic, integrity, communication, and organization were the most essential characteristics for their success. In section two, the respondents ranked the leadership characteristics as statistically more important than the management characteristics (p0.0001) for being successful in their positions.

We compared current Centers for Disease Control and Prevention surveillance criteria with the newer adult screening criteria (ASC) for identifying pediatric ventilator-associated pneumonia (VAP). Possible cases of VAP identified by ASC (n = 17) and cases of VAP identified by the older current surveillance criteria (n = 15) are comparable, but only 9 were identified by both. Positive end expiratory pressure was inferior to fraction of inspired oxygen in identifying ventilator-associated conditions by ASC.

Palliative care competencies at the pediatric resident training level expand learned knowledge into behavior. The objective of this study was to investigate mode of palliative care education delivery preferred by pediatric residents and to report on participatory approach to resident palliative care curriculum design. A one-hour monthly palliative care curriculum was designed and implemented in a participatory manner with 20 pediatric residents at a free-standing Midwestern children’s hospital. Outcome measures included pediatric residents’ personal attitude and perceived training environment receptivity before and after implementation of a palliative care competency-based curriculum. An 18-item survey utilizing Social Cognitive Theory Constructs was administered at baseline and after palliative care curriculum implementation (2017⁻2018 curricular year). Pediatric residents prioritized real case discussions in group format (16/20) over other learning formats. Topics of highest interest at baseline were: discussing prognosis and delivering bad news (weighted average 12.9), pain control (12.3), goals of care to include code status (11.1), and integrative therapies (10.7). Summary of ordinal responses revealed improvement in self-assessment of personal attitude toward palliative care and training environment receptivity to palliative care domains after year-long curriculum implementation. Curricular approach which is attentive to pediatric residents’ preferred learning format and self-assessment of their behaviors within their care setting environment may be beneficial in competency-based primary palliative training.

Despite the fact there are currently a dozen treatment options for esophageal adenocarcinoma (EAC), durable patient responses to anticancer therapies are hard to achieve in EAC patients. The rate of incidence of EAC is increasing faster than any cancer in our country, and the survival rates have remained very low for decades, even in the current era of molecular medicine. Therefore, our group designed an ambitious, large scale mass spectrometric experiment to cast a molecular dragnet across our patient samples to detect overexpression and downregulation patterns that contribute to the aggressiveness of EAC. We used FFPE tissue samples from esophagectomy surgery before any chemotherapy or radiation had been administered, analyzing unadulterated EAC tissue, Barrett's esophagus (BE) tissue, and normal esophageal squamous epithelium from 50 patients. Our platform consisted of pathologist-guided microdissection, a Liquid Tissue® process turning FFPE tissue into a digested lysate, discovery mass spectrometry (TripleTOF 6600) and extensive biostatistics. We discovered a perfect storm of pathogenic processes which explains from several perspectives the aggressiveness of this disease as well as EAC's proclivity to resist chemotherapeutic agents. We found 20 relevant proteomic events in which tumor suppressors are turned off, growth factors are overexpressed, chemoresistance markers are upregulated, chemosensitivity markers are downregulated as well as revealing eight new potential drug targets in which therapeutic antagonism could slow tumorigenesis in EAC. Of these 20 proteins we robustly investigated four markers (DAD1, ISG15, S100P and UBE2N) which all have mutual intersections with prognostic, diagnostic and therapeutic aspects of esophageal pathogenesis. Overexpression of DAD1 (9 out of 10), ISG15 (10/10), S100P (10/10) and UBE2N (10/10) was discovered in BE tissue. In the adjacent EAC tissue, we found significant overexpression of DAD1 (20 out of 20), ISG15 (20/20), S100P (20/20) and UBE2N (19/20) proteins. These expression levels spiked when transitioning from normal squamous epithelium to highly dysplastic BE tissue demonstrating that BE starts to act like cancer by using more glucose for energy (Warburg effect), increasing proliferative measures, and suppressing apoptosis. Also, overexpressed DAD1 protein levels contributes to cisplatin resistance which is striking since 95% of the 123 patients treated at CUMC for EAC received cisplatin in the first-line setting. S100P expression has been found to increase resistance to 5-FU in colorectal cancer. 5-FU was prescribed to 72% of the patients in our cohort (n=123), so if there is innate resistance to the two most prescribed drugs for EAC patients then alternative patient management strategies are needed. Here we've discovered four new prognostic and therapeutic biomarkers with potential clinical utility for EAC. Citation Format: Joe Abdo, Chris Wichman, Nick E. Dietz, John Fleegel, Pawel Ciborowski, Sumeet K. Mittal, Devendra K. Agrawal. Discovery of novel markers in Barrett's-related esophageal adenocarcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2691.

This study evaluated learning outcomes and student perceptions of collaborative learning in an undergraduate nursing program. Participants in this 3-phase action research study included students enrolled in a traditional and an accelerated nursing program. The number of students who passed the unit examination was not significantly different between the 3 phases. Students had positive and negative perceptions about the use of collaborative learning.

The diagnostic value of tumor markers, carcinoembryonic antigen (CEA), cancer antigen (CA) 15-3, CA 19-9, CA 125, cytokeratin fragment (CYFRA), and neuron-specific enolase (NSE) in pleural fluid to differentiate between benign and malignant pleural effusion (MPE) has not yet been clearly established. A review of English language studies using human subjects was performed. Sensitivity and specificity values of the chosen tumor markers were pooled using a random effects model to generate hierarchical summary receiver operator curves to determine the diagnostic performance of each tumor marker. A total of 49 studies were included in the final analysis. Pooled sensitivity and specificity values for chosen tumor markers for diagnosing MPE are as follows: CEA, 0.549 and 0.962; CA 15-3, 0.507 and 0.983; CA 19-9, 0.376 and 0.980; CA 125, 0.575 and 0.928; CYFRA, 0.625 and 0.932; NSE, 0.613 and 0.884. The use of individual tumor markers in diagnosing MPE has many benefits (cost, invasiveness, and so forth). Although these tumor markers exhibit high specificity, the low sensitivity of each marker limits the diagnostic value. We conclude that tumor markers used individually are of insufficient diagnostic accuracy for clinical use. Tumor markers used in various combinations or from serum may have some potential worth further investigation.

Student evaluations of teaching (SETs) are important because in most academic settings, they serve as the primary basis for assessing faculty teaching, one of two key inputs into promotion and tenu...

We studied radiation exposure (RE) in trauma patients [1]. To adjust for injury severity the New Injury Severity Score (NISS) or the Injury Severity Score (ISS) can be used to group patients. We sought to determine whether there is a difference in the calculated RE per group when the patients are grouped using either the NISS or ISS.

Trauma patients are subjected to higher radiation exposure (RE) as a function of Injury Severity Score (ISS) [1]. Analysis of this dataset was done to ascertain if RE varied with patient age.