tbuckley/cabot-search huggingface dataset:
Overall Survival with Durvalumab after Chemoradiotherapy in Stage III NSCLC
Authors: Scott J Antonia, Augusto Villegas, Davey Daniel, David Vicente, Shuji Murakami, Rina Hui, Takayasu Kurata, Alberto Chiappori, Ki H Lee, Maike de Wit, Byoung C Cho, Maryam Bourhaba, Xavier Quantin, Takaaki Tokito, Tarek Mekhail, David Planchard, Young-Chul Kim, Christos S Karapetis, Sandrine Hiret, Gyula Ostoros, Kaoru Kubota, Jhanelle E Gray, Luis Paz-Ares, Javier de Castro Carpeño, Corinne Faivre-Finn, Martin Reck, Johan Vansteenkiste, David R Spigel, Catherine Wadsworth, Giovanni Melillo, Maria Taboada, Phillip A Dennis, Mustafa Özgüroğlu
Journal: New England Journal of Medicine (2018)

An earlier analysis in this phase 3 trial showed that durvalumab significantly prolonged progression-free survival, as compared with placebo, among patients with stage III, unresectable non-small-cell lung cancer (NSCLC) who did not have disease progression after concurrent chemoradiotherapy. Here we report the results for the second primary end point of overall survival.We randomly assigned patients, in a 2:1 ratio, to receive durvalumab intravenously, at a dose of 10 mg per kilogram of body weight, or matching placebo every 2 weeks for up to 12 months. Randomization occurred 1 to 42 days after the patients had received chemoradiotherapy and was stratified according to age, sex, and smoking history. The primary end points were progression-free survival (as assessed by blinded independent central review) and overall survival. Secondary end points included the time to death or distant metastasis, the time to second progression, and safety.Of the 713 patients who underwent randomization, 709 received the assigned intervention (473 patients received durvalumab and 236 received placebo). As of March 22, 2018, the median follow-up was 25.2 months. The 24-month overall survival rate was 66.3% (95% confidence interval [CI], 61.7 to 70.4) in the durvalumab group, as compared with 55.6% (95% CI, 48.9 to 61.8) in the placebo group (two-sided P=0.005). Durvalumab significantly prolonged overall survival, as compared with placebo (stratified hazard ratio for death, 0.68; 99.73% CI, 0.47 to 0.997; P=0.0025). Updated analyses regarding progression-free survival were similar to those previously reported, with a median duration of 17.2 months in the durvalumab group and 5.6 months in the placebo group (stratified hazard ratio for disease progression or death, 0.51; 95% CI, 0.41 to 0.63). The median time to death or distant metastasis was 28.3 months in the durvalumab group and 16.2 months in the placebo group (stratified hazard ratio, 0.53; 95% CI, 0.41 to 0.68). A total of 30.5% of the patients in the durvalumab group and 26.1% of those in the placebo group had grade 3 or 4 adverse events of any cause; 15.4% and 9.8% of the patients, respectively, discontinued the trial regimen because of adverse events.Durvalumab therapy resulted in significantly longer overall survival than placebo. No new safety signals were identified. (Funded by AstraZeneca; PACIFIC ClinicalTrials.gov number, NCT02125461 .).
Variations in hospitalization and emergency department or observation (ED/OB) stays using the oncology care model (OCM) methodology in Medicare data.
Authors: Shuling Li, Yi Peng, Suying Li, Leon Raskin, Michael Anthony Kelsh, Rebecca Zaha, Prasad L. Gawade, David Henry
Journal: Journal of Clinical Oncology (2018)

112 Background: The Medicare OCM started in 2016 to improve oncology care and reduce costs. Two metrics for care evaluation are hospitalizations and ED/OB stays. Baseline data (2012−2015) on variations in all-cause hospitalization and ED/OB stays not resulting in hospitalization in the 21 reconciliation-eligible cancer types are not well characterized. Methods: We applied OCM methodology in Medicare fee-for-service 20% sample data to estimate 6-month patient (pt) episodes triggered by chemotherapy, as well as associated cancer type and practice, from 2012 to 2015. Proportions of episodes with hospitalization and ED/OBs stay were summarized overall and by cancer for all episodes and by practice in those with ≥20 pt-episodes. Results: In total, 485,186 pt-episodes at 13,823 practices were identified (mean episodes/practice, 35.1; median, 2; IQR, 1–15). The mean number of episodes/pt was 1.90 overall (from 1.17 in anal cancer to 2.32 in multiple myeloma [MM]). The proportion of episodes with hospitalization was 25% overall (from 14% in breast cancer [BC] to 56% in acute leukemia) and with ED/OB stays was 23% overall (from 18% in BC to 36% in liver cancer). In 2,995 practices with ≥20 total episodes, at practice-level, the proportion of episodes with hospitalization ranged (20 th –80 th percentile) from 14% to 31% and with ED/OB stays from 17% to 29%. For select cancers, the range of proportion of episodes with hospitalization and ED/OB stays were highest for lung cancer (LC) and lowest for BC (Table). Conclusions: The proportion of 6-month OCM episodes of care with hospitalization and ED/OB stays after chemotherapy varied by cancer and was higher for certain solid and hematological malignancies. Variations between practices and cancers are important factors when evaluating OCM performance. [Table: see text]
Another Shock for Sudden Death Prevention after Myocardial Infarction
Authors: Michael E. Field, Richard L. Page
Journal: New England Journal of Medicine (2018)

Sudden cardiac death, typically due to a ventricular tachyarrhythmia, is a devastating complication of myocardial infarction that poses the greatest risk during the first 30 days after the infarct, especially among patients with a reduced left ventricular ejection fraction.1 However, two randomized, controlled trials showed no survival benefit with early implantation of an implantable cardioverter–defibrillator (ICD) after myocardial infarction.2,3 Consequently, clinical practice guidelines recommend waiting for at least 40 days after myocardial infarction and 90 days after coronary revascularization for the implantation of an ICD for primary prevention.4 This paradox of increased risk of sudden cardiac death but lack of . . .
Sodium–Glucose Cotransporter–2 (SGLT-2) Inhibitors and the Treatment of Type 2 Diabetes
Authors: Caroline K. Kramer, Bernard Zinman
Journal: Annual Review of Medicine (2018)

Clinical studies evaluating the cardiovascular safety/impact of sodium-glucose cotransporter-2 (SGLT-2) inhibitors demonstrated a reduction in major adverse cardiovascular events driven primarily by a reduced cardiovascular mortality in individuals with type 2 diabetes and previous cardiovascular disease. These somewhat unexpected results are coupled with SGLT-2 inhibitors' known acute effect of improvement in glycemia, reduction in blood pressure, and weight loss. In this review, we summarize the mechanism of action of SGLT-2 inhibitors, the metabolic effects of this class of medication, and the remarkable results of cardiovascular safety trials. In addition, we discuss adverse effects associated with these medications and the current recommendations for the use of these agents in the management of diabetes.
Feasibility of treatment discontinuation in chronic myeloid leukemia in clinical practice: results from a nationwide series of 236 patients
Authors: Juan Carlos Hernández-Boluda, Arturo Pereira, Irene Pastor-Galán, Alberto Alvarez-Larrán, Alisa Savchuk, José Manuel Puerta, José María Sánchez-Pina, Rosa Collado, Alvaro Díaz-González, Anna Angona, Miguel Sagüés, Valentín García-Gutiérrez, Concepción Boqué, Santiago Osorio, Rolando Vallansot, Luis Palomera, Arantxa Mendizábal, Luis Felipe Casado, Manuel Pérez-Encinas, Raúl Pérez-López, Francisca Ferrer-Marín, Fermín Sánchez-Guijo, Carmen García, Natalia de las Heras, José Luis López-Lorenzo, Francisco Cervantes, Juan Luis Steegmann
Journal: Blood Cancer Journal (2018)

Over half of chronic myeloid leukemia (CML) patients in deep molecular response do not lose the major molecular response (MMR) after stopping treatment with tyrosine kinase inhibitors (TKI). This strategy is safe in clinical trials, but its applicability in the real-life setting remains unsettled. We describe the outcomes after TKI discontinuation in a nationwide series of 236 CML patients. Median follow-up from treatment discontinuation was 21.5 months and 5 patients died from CML-unrelated causes. TKI therapy was reinitiated due to MMR loss (n = 52), increase ≥ 1 log in BCR-ABL transcript level without losing MMR (n = 12), patient preference (n = 2), and withdrawal syndrome (n = 1). Treatment-free remission rate at 4 years was 64% (95% confidence interval, CI: 55%-72%). Cumulative incidence of molecular recurrence at 3 years was 33% (95% CI: 26%-38%). TKI treatment for < 5 years and MR4.5 duration shorter than 4 years were both associated with higher incidence of molecular recurrence. No patient had disease progression. Response status at last control was: MR4.5 (n = 196), MR4 (n = 15), MMR (n = 14), complete cytogenetic response (n = 10), and other (n = 1). A significant increase in Hb and cholesterol levels was observed after imatinib withdrawal. Our results demonstrate that TKI treatment discontinuation is feasible in real-life clinical practice.
Hyper-N-glycosylated SAMD14 and neurabin-I as driver autoantigens of primary central nervous system lymphoma
Authors: Lorenz Thurner, Klaus-Dieter Preuss, Moritz Bewarder, Maria Kemele, Natalie Fadle, Evi Regitz, Sarah Altmeyer, Claudia Schormann, Viola Poeschel, Marita Ziepert, Silke Walter, Patrick Roth, Michael Weller, Monika Szczepanowski, Wolfram Klapper, Camelia Monoranu, Andreas Rosenwald, Peter Möller, Sylvia Hartmann, Martin-Leo Hansmann, Andreas Mackensen, Henning Schäfer, Elisabeth Schorb, Gerald Illerhaus, Rolf Buslei, Rainer Maria Bohle, Stephan Stilgenbauer, Yoo-Jin Kim, Michael Pfreundschuh
Journal: Blood (2018)
Developing a standardized process for oral chemotherapy management for neuro-oncology.
Authors: Tresa McGranahan, Megan Gershon, Justine Pena, Chamnjot Bains, Margaret Elizabeth McCormick Van Meter, Sarah Salas, Seema Nagpal
Journal: Journal of Clinical Oncology (2018)

258 Background: Oral chemotherapies (OC) have transformed cancer care for millions of patients. While this has improved the patient experience, it presents significant challenges to safety of prescription, administration and side effect monitoring. While there are guidelines for documentation, there is not a best practices system for managing OC. This project identified areas of latent errors and implemented a standardized process for OC management. Methods: After review of the literature, we developed a process map for OC prescriptions at our institution. We then compared processes at three other neuro oncology clinics. We completed a hazard analysis and implemented several changes (see table). We identified binary measures in the medical record for every OC prescription that related to the process changes. Chart review of the 6 months prior to process change was used to create a baseline process mean for each variable. These same variables were monitored every 2 weeks after process change implementation using run charts. Successful process shift was defined as 7 consecutive 2-week averages that were continually on one side of the baseline process mean. Results: 5 months after process change was implemented, we had successfully reduced refills for OC and increased documentation of dose and dose calculation. There is a trend towards improvement in independently verified dose calculation and dedicated chemotherapy teaching visits, however these have not yet reached criteria for process change. Conclusions: This project used published studies, multi-institutional process mapping and hazard analysis to develop and implement a standardize process for OC. This process can be implemented for OC management in other oncology practices. [Table: see text]
The Employers Centers of Excellence in Cancer Care: A collaboration of employers and providers to improve cancer care.
Authors: Manali I. Patel, Rachel V Lee, Neil Smithline, Olivia Ross
Journal: Journal of Clinical Oncology (2018)

141 Background: Rising costs demand collaborations that lower expenditures and improve patients’ experiences and outcomes. We created a novel employer-provider collaboration to enhance value-based cancer care. Methods: We created an Employers Center of Excellence Network (ECEN) for the Pacific Business Group on Health (PBGH) employee groups. The ECEN provides competitive bundled rates that include travel for in-person patient consultation, advanced assessment and treatment by multidisciplinary case reviews, and ongoing specialized treatment care coordination and follow-up on a routine basis with the local care team.The ECEN development process included: focus groups, expert panel development, and a rigorous selection process. A Request for Proposal was publicized to all west coast NCI-designated comprehensive cancer centers. After interviews, selected sites were invited to submit a full proposal and a few were selected for a site visit.. In addition to overall cancer care excellence, a key criterion for acceptance was the demonstrated willingness and ability of the center to provide long-term support for the patient and home oncologist in the patient’s home market, so that the center’s expertise and support would be ongoing for the duration of the cancer treatment. Results: Of 8 sites that participated in team-assessment interviews, 4 were selected to submit a full proposal, 3 selected for in-person visits, and 1 selected to participate. In January 2019, we plan to implement a 6-month pilot with a PBGH employer group and the provider site to evaluate the ECEN's feasibility and effects on quality, patient-reported outcomes, and costs. Conclusions: Our novel employer-provider collaboration aims to improve cancer care delivery by providing planned and supported NCI-designated cancer care in close collaboration with the home oncologist. We plan to expand the ECEN development process across the US to develop a network of collaborating providers and employers to improve patient-centered, value-based cancer care.
A process for improving patient survey scores in the oncology care model (OCM).
Authors: Manuel Perry, Katie Rudy-Tomczak, Scott Hines
Journal: Journal of Clinical Oncology (2018)

222 Background: The Oncology Care Model is an alternative payment model created by The Center for Medicare and Medicaid Services. Our goal was to improve patient education and to improve the patient experience. We hired nurse practitioners to achieve this. Methods: Crystal Run Healthcare is a multi-specialty group practice with nine oncologists. A total of 4 nurse practitioners have been hired since implementation of the OCM Program in July 1, 2016. All oncology patients and their family who are scheduled to initiate a new treatment program or a change in an existing treatment are scheduled to meet with a nurse practitioner for 60-75 minutes in order to review details of their treatment including a 13-point treatment summary recommended by the Institute of Medicine. Results: CMS administered anonymous patient surveys at baseline and in rolling 6 month episodes reported every 3 months. Data is represented from January-September 2016 (baseline)and is compared to July 2016-March 2017. Since implementation of our nurse practitioner access program, patient survey scores improved dramatically. Average overall rating improved from the 11 th -20 th percentile to 71 st -80 th percentile. The most dramatic improvement occurred in shared decision making which improved from 11 th -20 th percentile to the 91 st -99 th percentile. Conclusions: The addition of nurse practitioners who are tasked with educating patients regarding their treatment offers an opportunity for patients to have a comprehensive visit to review treatment details. The most striking improvement was seen in shared decision making which likely reflects the benefits of a prolonged discussion between the nurse practitioner, the patient and their family.[Table: see text]
Incidental Orbital Neuroendocrine Metastases on 111In-OctreoScan and MRI
Authors: Yin Jie Chen, Michael D. Farwell
Journal: Clinical Nuclear Medicine (2018)

Neuroendocrine tumors have a propensity to metastasize, but rarely to the orbits. A 69-year-old woman with history of neuroendocrine tumor of pancreatic primary underwent routine follow-up In-pentetreotide (OctreoScan) imaging, with 24-hour whole-body planar images showing subtle right periorbital tracer uptake that localized to extraocular muscles on subsequent SPECT/CT. Orbital MRI further defined the location of these highly suspicious orbital metastases, which were treated with external radiation, with follow-up MRI showing decreased size of the orbital metastases. Early identification and treatment of orbital metastases is critical to help preserve vision and quality of life.
Abstract 18905: Novel Oral Anticoagulant Availability Increases Appropriate Use of Anticoagulants for Nonvalvular Atrial Fibrillation in the Elderly Aged >= 75 Years Old in Clinical Practice
Authors: Qi Zheng, Chino Aneke-Nash, Jonathan L Halperin, David A Vorchheimer
Journal: Circulation (2016)

Introduction: Registry data indicate that anticoagulation (AC) is underprescribed in patients (pts) with nonvalvular atrial fibrillation (NVAF), especially in the elderly. Novel oral anticoagulants...
Abstract 17616: Notch Signaling Modulates the Electrical Behavior of Cardiomyocytes
Authors: Keerat Kaur, Carol Eisenberg, Alejandro Andrade, Kevin Agostinucci, Jason T Jacobson, Khaled Qanud, Giulia Borghetti, Leonard Eisenberg, Thomas H Hintze, Marcello Rota
Journal: Circulation (2017)

The Notch receptor signaling is active during cardiac development, silenced postnatally, and reactivated under pathological conditions, raising the possibility that this transduction system contrib...
Hypercalcemia and cancer: Differential diagnosis and treatment
Authors: Jonathan Zagzag, Mimi I. Hu, Sarah B. Fisher, Nancy D. Perrier
Journal: CA A Cancer Journal for Clinicians (2018)

Abstract Incidentally detected hypercalcemia usually presents in an indolent manner and is most likely caused by primary hyperparathyroidism. In contrast, hypercalcemia in the patient with a history of cancer presents in a wide range of clinical settings and may be severe enough to warrant hospitalization. This form of hypercalcemia is usually secondary to hypercalcemia of malignancy and can be fatal. Hypercalcemia of malignancy is most commonly mediated by tumoral production of parathyroid hormone–related protein or by cytokines activating osteoclast degradation of bone. The initial workup, differential diagnoses, confirmatory laboratory testing, imaging, and medical and surgical management of hypercalcemia are described in the patient with cancer.
Hepatocellular malignancy in ABCB11/BSEP disease (progressive familial intrahepatic cholestasis, type 2): Four patients.
Authors: Y Meier, B Stieger, L Moore, J Raftos, H Arnell, B Fischler, A Nemeth, N Papadogiannakis, I Jankowska, J Pawlowska, J Cielecka-Kuszyk, P Kluge, J Byrne, S Strautnieks, R Thompson, A Knisely
Journal: Hepatology (2004)
Abstract 18898: Abnormal Conduction and Arrhythmias Precede the Development of Dilated Cardiomyopathy in D1275n Mutant Mice
Authors: Dina M Stroud, Kevin R Bersell, Jessica Delaney, Lynn Hall, Esperanza Agullo-Pascual, Hyun S Hwang, Tao Yang, Bjorn Knollmann, Mario Delmar, Franz Baudenbacher, Dan M Roden
Journal: Circulation (2016)

Background: The D1275N SCN5A mutation is associated with dilated cardiomyopathy (DCM) in humans. We have previously reported that in 12 week old mice carrying humanized SCN5A alleles, DCM is evident by echo in those homozygous for D1275N (DN/DN) compared to those homozygous for the wild-type allele (H/H), with striking conduction slowing and disorganization by ECG. The present experiments were designed establish the time course of these defects to further understand the pathophysiology of D1275N-related DCM. Methods and Results: By 3 weeks, QRS duration was markedly prolonged and disorganized in DN/DN mice (HH, n=11, 9.8 ± 0.2; DN/DN, n=9, 22.3 ± 2.2 P<0.05) and optical mapping at 3 and 10 weeks showed slow, dyssynchronous conduction in DN/DN mice. However, at 3 weeks, there was no significant difference in ejection fraction or heart rate. Indices of calcium handling were also near-identical in DN/DN and H/H mice, and there were no differences in alpha-actinin, ryanodine receptor, dystrophin, and syntroph...
Re: Dipen J. Parekh, Isidinha M. Reis, Erik P. Castle, et al. Robot-assisted Radical Cystectomy Versus Open Radical Cystectomy in Patients with Bladder Cancer (RAZOR): An Open-label, Randomised, Phase 3, Non-inferiority Trial. Lancet 2018;391:2525–36
Authors: Sandaruwani Abeysiri, Toby Richards
Journal: European Urology (2018)
RB1 Heterogeneity in Advanced Metastatic Castration-Resistant Prostate Cancer
Authors: Daniel Nava Rodrigues, Nicola Casiraghi, Alessandro Romanel, Mateus Crespo, Susana Miranda, Pasquale Rescigno, Ines Figueiredo, Ruth Riisnaes, Suzanne Carreira, Semini Sumanasuriya, Paola Gasperini, Adam Sharp, Joaquin Mateo, Alan Makay, Christopher McNair, Matthew Schiewer, Karen Knudsen, Gunther Boysen, Francesca Demichelis, Johann S. de Bono
Journal: Clinical Cancer Research (2018)

Metastatic castration-resistant prostate cancer (mCRPC) is a lethal but clinically heterogeneous disease, with patients having variable benefit from endocrine and cytotoxic treatments. Intrapatient genomic heterogeneity could be a contributing factor to this clinical heterogeneity. Here, we used whole-genome sequencing (WGS) to investigate genomic heterogeneity in 21 previously treated CRPC metastases from 10 patients to investigate intrapatient molecular heterogeneity (IPMH).Experimental Design: WGS was performed on topographically separate metastases from patients with advanced metastatic prostate cancer. IPMH of the RB1 gene was identified and further evaluated by FISH and IHC assays.WGS identified limited IPMH for putative driver events. However, heterogeneous genomic aberrations of RB1 were detected. We confirmed the presence of these RB1 somatic copy-number aberrations, initially identified by WGS, with FISH, and identified novel structural variants involving RB1 in 6 samples from 3 of these 10 patients (30%; 3/10). WGS uncovered a novel deleterious RB1 structural lesion constituted of an intragenic tandem duplication involving multiple exons and associating with protein loss. Using RB1 IHC in a large series of mCRPC biopsies, we identified heterogeneous expression in approximately 28% of mCRPCs.mCRPCs have a high prevalence of RB1 genomic aberrations, with structural variants, including rearrangements, being common. Intrapatient genomic and expression heterogeneity favors RB1 aberrations as late, subclonal events that increase in prevalence due to treatment-selective pressures.
Abstract 14073: Trajectory of Congestion Metrics by Ejection Fraction in Acute Heart Failure - Findings From the Heart Failure Network
Authors: Andrew P Ambrosy, Ankeet Bhatt, Dianne Gallup, Kevin Anstrom, Javed Butler, Adam D DeVore, G. M Felker, Stephen J Greene, Adrian F Hernandez, Jacob P Kelly, Robert J Mentz
Journal: Circulation (2016)

Background: Differences in the clinical course of congestion by underlying ejection fraction (EF) have not been well-characterized in acute heart failure (AHF). Methods: A post-hoc analysis was performed using pooled data from the DOSE, CARRESS, and ROSE trials. All patients were admitted for primary diagnosis of AHF defined by the presence of one symptom and one sign of HF. Patients were grouped as reduced EF ≤40%, borderline EF = 41-49%, or preserved EF ≥50%. Pearson χ2 and Kruskal-Wallis tests were used to compare clinical characteristics. Multivariable regression analysis was used to assess the association between measures of congestion and the composite of death, rehospitalization, or unscheduled outpatient visits at 60 days. Results: Overall, 732 (86%) patients had EF documentation within the prior year. Mean age was 68±13 years and 74% were male. Patients with preserved EF were older, more likely to be female, less likely to have an ischemic HF etiology, and had a higher prevalence of atrial fibril...