Citations

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Neuroendocrine and Adrenal Gland Tumors focus on the diagnosis, treatment, and management of patients with neuroendocrine tumors (NETs), adrenal tumors, pheochromocytomas, paragangliomas, and multiple endocrine neoplasia. NETs are generally subclassified by site of origin, stage, and histologic characteristics. Appropriate diagnosis and treatment of NETs often involves collaboration between specialists in multiple disciplines, using specific biochemical, radiologic, and surgical methods. Specialists include pathologists, endocrinologists, radiologists (including nuclear medicine specialists), and medical, radiation, and surgical oncologists. These guidelines discuss the diagnosis and management of both sporadic and hereditary neuroendocrine and adrenal tumors and are intended to assist with clinical decision-making. This article is focused on the 2021 NCCN Guidelines principles of genetic risk assessment and counseling and recommendations for well-differentiated grade 3 NETs, poorly differentiated neuroendocrine carcinomas, adrenal tumors, pheochromocytomas, and paragangliomas.

AbstractBackgroundPositron emission tomography (PET)‐based measures of baseline total‐body tumor burden may improve risk stratification in intermediate‐risk Hodgkin lymphoma (HL).Materials and methodsEvaluable patients were identified from a cohort treated homogeneously with the same combined modality regimen on the Children's Oncology Group AHOD0031 study. Eligible patients had high‐quality baseline PET scans. Metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were each measured based on 15 thresholds for every patient. Univariate and multivariable Cox regression and Kaplan–Meier survival analyses assessed for an association of MTV and TLG with event‐free survival (EFS).ResultsFrom the AHOD0031 cohort (n = 1712), 86 patients were identified who (i) were treated with four cycles of doxorubicin, bleomycin, vincristine, etoposide, prednisone, cyclophosphamide (ABVE‐PC) chemotherapy followed by involved field radiotherapy, and (ii) had a baseline PET scan that was amenable to quantitative analysis. Based on univariate Cox regression analysis, six PET‐derived parameters were significantly associated with EFS. For each of these, Kaplan–Meier analyses and the log‐rank test were used to compare patients with highest tumor burden (i.e., highest 15%) to the remainder of the cohort. EFS was significantly associated with all six PET parameters (all p < .029). In a multivariable model controlling for important covariates including disease bulk and response to chemotherapy, MTV2BP was significantly associated with EFS (p = .012).ConclusionMultiple baseline PET‐derived volumetric parameters were associated with EFS. MTV2BP was highly associated with EFS when controlling for disease bulk and response to chemotherapy. Incorporation of baseline MTV into risk‐based treatment algorithms may improve outcomes in intermediate‐risk HL.

Aim The objective was to examine the prevalence of atherosclerotic cardiovascular disease (ASCVD) and its risk factors among patients with RA with diabetes mellitus (RA-DM) and patients with RA without diabetes mellitus (RAwoDM), and to evaluate lipid and blood pressure (BP) goal attainment in RA-DM and RAwoDM in primary and secondary prevention. Methods The cohort was derived from the Survey of Cardiovascular Disease Risk Factors in Patients with Rheumatoid Arthritis from 53 centres/19 countries/3 continents during 2014–2019. We evaluated the prevalence of cardiovascular disease (CVD) among RA-DM and RAwoDM. The study population was divided into those with and without ASCVD, and within these groups we compared risk factors and CVD preventive treatment between RA-DM and RAwoDM. Results The study population comprised of 10 543 patients with RA, of whom 1381 (13%) had DM. ASCVD was present in 26.7% in RA-DM compared with 11.6% RAwoDM (p<0.001). The proportion of patients with a diagnosis of hypertension, hyperlipidaemia and use of lipid-lowering or antihypertensive agents was higher among RA-DM than RAwoDM (p<0.001 for all). The majority of patients with ASCVD did not reach the lipid goal of low-density lipoprotein cholesterol <1.8 mmol/L. The lipid goal attainment was statistically and clinically significantly higher in RA-DM compared with RAwoDM both for patients with and without ASCVD. The systolic BP target of <140 mm Hg was reached by the majority of patients, and there were no statistically nor clinically significant differences in attainment of BP targets between RA-DM and RAwoDM. Conclusion CVD preventive medication use and prevalence of ASCVD were higher in RA-DM than in RAwoDM, and lipid goals were also more frequently obtained in RA-DM. Lessons may be learnt from CVD prevention programmes in DM to clinically benefit patients with RA .

Introduction: At-work stress is rapidly becoming a significant contributory cause of occupational disease, while sedentary work and dietary indiscretion, taken together, have contributed to cardiovascular disease, known to be associated with substantial morbidity and mortality. The aim of the CV-Ecosystem Model is to provide an individual approach by systematic environmental modification of the work site. Methods and Results: Our model which we term the CV-Ecosystem Model includes two basic tenets: 1) Workstation technologic design 2) Flexible physiologic activity. Workstation technologic design utilizes the services of a certified Ergonomist to engineer a comfortable, safe, and effective work environment. It is tailored to the unique physiologic needs of the worker while enhancing productivity within different environments. Computer aided design software would evaluate ergonomics to maximally mitigate the risk and incidence of eye strain, musculoskeletal disorders, repetitive movement disorders such as Carpal Tunnel Syndrome, etc unique to that work activity. Flexible physiologic activity would permit a worker to actively focus on basic needs during work time, on site; this would include exercise activity and food intake, channeled into healthy options. Exercise time would provide a sense of calm during stressful projects and enhance emotional well-being. In this regard, a three hour period of time, weekly, could be allocated to fitness or meditation. Conveniently located food stations could provide a variety of healthy, plant-based, fresh food options. Both would come with flexible, relative control and scheduling of these activities, within a social environment and context. Conclusions: The CV Ecosystem Model, due to its simple technology and relative low cost, could be successfully implemented in a number of enterprises, including all healthcare facilities, with benefit to employee health, wellbeing, and favorable to the business bottom line.

Abstract Cytotoxic T lymphocytes (CTL's) are capable of killing tumor cells throughout the body, and can be stimulated to do so by a form of immunotherapy known as PD-1 checkpoint blockade. However, the majority of patients given anti-PD-1 therapeutics do not respond to treatment. Thus, we sought to identify key factors associated with failure of PD-1 blockade in order to develop strategies that could significantly improve response rates. We performed single-cell RNA-seq analysis of peripheral CD8+ T cells from responding and non-responding patients and found that the non-responders had less NKG7 expression. Functional assays revealed that knock-down of NKG7 compromised cytolytic granule localization and trafficking within CTL's. Since decreasing NKG7 reduced the cytolytic efficiency of CD8+ T cells, we next hypothesized that by increasing expression of NKG7 we could promote better T cell killing of tumor and enhance the effects of immune checkpoint inhibitors. To test this, we utilized peripheral blood samples from melanoma patients who failed to respond to anti-PD-1 treatment and transfected the PBMC's with NKG7 mRNA. The addition of NKG7 mRNA significantly increased T cell killing of melanoma tumor cells in an in vitro cytotoxicity assay, and this effect was even more robust in combination with anti-PD-1 or anti-PD-L1 pre-treatment. To confirm that over-expression of NKG7 could improve CD8+ T cell killing in an antigen-specific manner, we transfected OT-1 transgenic T cells with murine sequence of NKG7 mRNA or control mRNA. OT-1 CD8+ T cells with increased NKG7 expression exhibited enhanced cytolytic ability when challenged with either EL4 cells pulsed with OVA peptide or B16-OVA tumor cells in vitro. In addition, NKG7 mRNA-transfected OT-1 CD8+ T cells suppressed the aggressive growth of B16-OVA cells in vivo significantly better than control OT-1 CD8+ T cells. These results indicate that deficits in a T cell-intrinsic cytolytic factor can lead to failure of PD-1/L1 blockade and establish NKG7 as a new therapeutic target for enhancing response to cancer immunotherapy. Citation Format: Whitney J. Barham, Ti Wen, Ying Li, Henan Zhang, Cindy Liu, Jacob Hirdler, Joanina Gicobi, Fabrice Lucien-Matteoni, Yiyi Yan, Haidong Dong. NKG7 mRNA therapy increases the anti-tumor cytotoxicity of CD8 T cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 504.

Background Diagnosis of non-esophageal eosinophilic gastrointestinal disorders requires quantification of tissue eosinophils. Our objective was to evaluate eosinophil peroxidase (EPX) immunohistochemistry (IHC) as a method for histologic diagnosis of eosinophilic gastritis (EG) and eosinophilic duodenitis (EoD). Methods We performed a retrospective analysis of biopsies from pediatric EG/EoD cases and controls. Subjects with EG or EoD had ≥30 eosinophils per high power field (eos/hpf) in ≥5 hpf in the stomach and/or ≥3 hpf in the duodenum, respectively. Controls had no histopathologic diagnosis recorded. Tissue eosinophil counts were assessed by hematoxylin & eosin stains. EPX stains were assessed using a unique histopathologic scoring system. Slides were digitized and EPX+ staining area/mm 2 was quantified by image analysis. Results Twenty-six EG/EoD cases and 40 controls were analyzed. EPX scores and EPX/mm 2 levels were markedly elevated in EG/EoD (p ≤ 0.0001). Eosinophil density (eos/mm 2 ) correlated strongly with EPX scores and EPX/mm 2 levels in the stomach (r ≥ 0.77) and moderately with EPX scores and EPX/mm 2 levels in the duodenum (r ≥ 0.52); (p < 0.0001). EPX quantification identified EG/EoD subjects with high diagnostic accuracy (EPX score: AUC = 1 for EG and EoD; EPX/mm 2 : AUC = 0.98 (95%CI 0.96-1) for EG, AUC = 0.91 (95%CI 0.81-1) for EoD). Conclusion EPX-based assessment of eosinophilic inflammation may facilitate automated histologic diagnosis.

8020 Background: MM patients (pts) often receive several lines of therapy with multiple drug combinations and, as lenalidomide (R)-containing regimens are commonly used as first-line therapy, R-free options for subsequent lines are necessary. Additionally, as pts age and become less tolerant to treatment, more convenient regimens, such as all-oral options, with less toxicity are needed. Dexamethasone (dex)-based doublets are effective and tolerable in this setting. Methods: Proteasome inhibitor (PI)-exposed and/or intolerant and R-refractory pts who had ≥2 prior therapies (N = 122) were randomized 3:2 to receive: ixazomib (ixa) 4 mg (5.5 mg from cycle 2 if tolerated) on day (d) 1, 8, 15, and dex 20 mg (≥75 years [yrs], 10 mg) on d 1, 2, 8, 9, 15, 16, 22, 23; or pomalidomide (pom) 4 mg on d 1–21, and dex 40 mg (≥75 yrs, 20 mg) on d 1, 8, 15, 22, in 28-d cycles until progressive disease (PD) or unacceptable toxicity. Pts were stratified by age ( < 65 vs ≥65 yrs), International Staging System (ISS) disease stage at study entry (I/II vs III), and prior lines of therapy (2 vs ≥3). The study was powered to test the primary endpoint of progression-free survival (PFS). Results: In the ixa-dex (n = 73) vs pom-dex (n = 49) arms, median age was 72 vs 68 yrs (36% vs 18% ≥75 yrs), 25% vs 22% of pts had ISS stage III MM, and 52% vs 53% had received ≥3 prior therapies (per stratification). At data cutoff (5/31/2020), 19% vs 20% of pts were ongoing on treatment with ixa-dex vs pom-dex; primary reasons for discontinuation were PD (47% vs 57%) and adverse events (AEs; 23% vs 12%). With median follow-up of 15.3 vs 17.3 months (mos), median PFS (mPFS) was 7.1 vs 4.8 mos with ixa-dex vs pom-dex (hazard ratio [HR] 0.847; 95% confidence interval [CI] 0.535–1.341; p = 0.477); the Table shows mPFS by prior lines, and secondary endpoints. Pts received a median of 6 cycles with both ixa-dex (range 1–25) and pom-dex (range 1–27); 64% of ixa-dex pts were able to escalate to a 5.5 mg dose of ixa. 69% vs 81% of ixa-dex vs pom-dex pts had grade (G) ≥3 AEs, 51% vs 53% had serious AEs, 39% vs 36% had an AE leading to drug discontinuation, 44% vs 32% had an AE leading to dose reduction, and 13% vs 13% died on study. Health-related quality of life (HRQoL; EORTC QLQ-C30/MY20, and EQ-5D-5L) was maintained, and similar between arms. Conclusions: Ixa-dex prolonged PFS vs pom-dex in these heavily pretreated, PI-exposed and/or intolerant, R-refractory pts, but the difference was not statistically significant. Ixa-dex was well tolerated, with lower G≥3 AE rates vs pom-dex, and comparable HRQoL. Clinical trial information: NCT03170882.

4147 Background: Retrospective studies of phosphorylated STAT3 (pSTAT3, a regulator of gene expression) in cancer-lineage cells have suggested it is a biomarker of poor prognosis. We analyzed data from 3 phase 3 RCTs (BRIGHTER [T1; NCT02178956], CO.23 [T2; NCT01830621], CanStem111P [T3; NCT02993731]) to evaluate the prognostic impact of pSTAT3 on OS in GI cancer patients (pts). Methods: pSTAT3 was evaluated in archival tumor tissue from pts with gastric or gastroesophageal junction adenocarcinoma (T1), colorectal cancer (T2), or pancreatic cancer (T3) who received standard of care in the control arms (CTL) of their respective trials. pSTAT3 positive (+) or negative (−) status was determined by detecting pSTAT3 in both tumor and tumor microenvironment (TME) cells in a laboratory-developed immunohistochemistry (IHC) assay (T1; T2), later developed into the investigational pSTAT3 IHC D3A7 assay (Agilent Technologies, Inc.) (T3). The positivity cutoff requires a sample have both a TME score of 2 and ≥5% of tumor cells staining positively for pSTAT3. Pre-analytical variables (eg, specimen collection, handling, and processing), tumor indication, and slight differences in the assays used for each study may contribute to relative differences in evaluable rates between studies. In an exploratory analysis, OS was compared in pSTAT3+ vs pSTAT3− pts via an unstratified log-rank test. Results: In each study, intent-to-treat pts with evaluable pSTAT3 results were considered pSTAT3-evaluable. This abstract includes pSTAT3-evaluable pts randomized to the CTL arms (T1: n/N=248/357, 69.5%; T2: n/N=110/144, 76.4%; T3: n/N=243/569, 42.7%). Baseline characteristics are presented in the table. Median (m) OS was shorter in pts with pSTAT3+ tumors across all studies (T1 hazard ratio [HR]=1.32 [95% confidence interval (CI): 1.00, 1.74]; T2 HR=2.40 [1.50, 3.83]; T3 HR=1.08 [0.77, 1.50]). Conclusions: In pSTAT3-evaluable populations from 3 RCTs across GI cancers, CTL pts with pSTAT3+ (vs pSTAT3−) tumors had shorter mOS. These results suggest that pSTAT3 positivity may be a biomarker of poor clinical outcome. Clinical trial information: NCT02178956; NCT01830621; NCT02993731. [Table: see text]

AbstractAims and ObjectivesThe purpose of this paper is to describe a model to guide nursing science in a clinical practice‐based setting. Exemplars are provided to highlight the application of this nursing research model, which can be applied to other clinical settings that aim to fill evidence gaps in the literature.BackgroundNurse scientists are well positioned to develop new knowledge aimed at identifying global health solutions to multiple disparities. The generation and application of this knowledge are essential to inform and guide professional nursing practice. While a number of evidence‐based practice models exist to guide the integration of literature findings and other sources of evidence into practice, there is a need for additional models that serve as a guide and focus for the conduct of research in distinct scientific areas in practice‐based settings.DesignModel development and description.MethodsMayo Clinic is a large, comprehensive healthcare system with a mission to address unmet patient needs through practice, research and education. PhD‐prepared nurse scientists engage in practice‐based research as an integral component of Mayo Clinic's mission. A practice‐based nursing research model was developed with the intent to advance nursing research in a clinical setting.ResultsThe components of the Mayo Clinic Nursing Research model include symptom science, self‐management science and caregiving science. The generation of nursing science is focused on addressing needs of patients with complex health conditions, inclusive of caregivers.ConclusionsWhile clinical settings provide rich opportunities for the conduct of research, priorities need to be established in which to focus scientific endeavours. The Mayo Clinic Nursing Research model may be applicable to nurses around the globe who are engaged in the generation of knowledge to guide practice.Relevance to Clinical PracticeThe Mayo Clinic Nursing Research model can be used by nurse scientists embedded in healthcare settings to address clinically relevant questions, advance the generation of new nursing knowledge and ultimately improve the health and well‐being of patients and caregivers.