tbuckley/cabot-search huggingface dataset:
BK Virus Hemorrhagic Cystitis Is Associated with Graft Versus Host Disease and Increased Health Care Resource Utilization in Patients Undergoing Allogeneic Stem Cell Transplantation
Authors: Wilson Lam, Jan Storek, Nizar J Bahlis, Christopher Brown, Peter Duggan, Michelle Geddes, Mary Lynn Savoie, Mona Shafey, Douglas A. Stewart, Andrew Daly
Journal: Blood (2014)
Comparison of Exhaled Nitric Oxide in Varying Disease States of Allergic Rhinitis in the Pediatric Population
Authors: Pattara Tanticharoenwiwat, Siwaporn Sapsaprung, Prapasri Kulalert, Dhave Setabutr, Orapan Poachanukoon
Journal: Journal of Allergy and Clinical Immunology (2017)
Induction with Combined Modality Therapy Followed by Immunomodulated Post Remission Therapy for Newly Diagnosed Acute Myeloid Leukemia (AML).
Authors: Seema Gupta, Mark A. Weiss, Joseph G. Jurcic, Suzanne Chanel, Bri-Anne Wilson, Emily Biederman, Ellin Berman, David A. Scheinberg, Peter G. Maslak
Journal: Blood (2005)
Tyrosine kinase inhibitors alone as a first-line treatment for patients with non-small-cell lung cancer harboring mutant epidermal growth factor receptor
Authors: T. Iuchi, M. Shingyoji, M. Itakura, Y. Hasegawa, Y. Yoshida, S. Ikegami, T. Setoguchi, H. Ashinuma
Journal: Annals of Oncology (2016)
Systemic therapy and overall survival (OS) in patients (pts) with brain metastases from HER2-positive (HER2+) metastatic breast cancer (MBC).
Authors: R. Bartsch, A. Berghoff, U. Pluschnig, Z. Bago-Horvath, P. C. Dubsky, A. Rottenfusser, C. Wenzel, M. Rudas, F. Fitzal, K. Dieckmann, M. Gnant, C. Zielinski, G. G. Steger
Journal: Journal of Clinical Oncology (2011)

597 Background: Brain metastases (BM) occur frequently in Her2+ MBC. We have previously reported that trastuzumab (T) after diagnosis of BM may improve OS due to prolonged systemic disease control. Based upon those results we investigated whether lapatinib (L) may add additional survival benefit in such patients. Methods: 80 pts treated at the Medical University of Vienna for BM from Her2+ MBC were identified from a BC database. Karnofsky Performance Score (KPS) of at least 70 was required, as low KPS is a known negative predictor of OS. 36 pts were treated before 2002, when routine application of T after diagnosis of BM was started and served as control. The reminders received either T alone or T plus L (either concomitantly or sequentially) with or without chemotherapy after local therapy for BM. Her2 was determined by immunohistochemistry and reanalyzed by FISH if a score of 2+ was gained. OS from diagnosis of BM was defined as primary study endpoint and estimated using the Kaplan-Meier method. A Cox proportional hazards model was applied to correct for other factors associated with OS. Results: Median OS in pts receiving T after diagnosis of BM was 13 m (95%CI 8.85-17.15); corresponding numbers were 9 m (0-20.69) in pts treated with chemotherapy, and 3 m (2.37-3.63) with local therapy alone, respectively. Median OS was not reached in pts receiving L. Addition of L significantly prolonged OS over T alone (p=0.002). After correction for hormone receptor status, visceral metastases, early development of BM (<12 m), KPS, and number of BM (1-3 vs. >3), additional systemic therapy with L (HR 0.29; 95% CI 0.1-0.83; p=0.02) remained an independent predictor of better outcome; pts with >3 BM had significantly shorter OS (HR 6.56; 95%CI 2.44-17.67). Conclusions: Introduction of T improved OS in pts with Her2+ MBC. As our results suggest, addition of L may further improve OS in pts with BM. L and 1-3 BM were significantly associated with longer OS. KPS, on the other hand, had no significant influence, as the study population had a minimum KPS of 70 in order to avoid an inclusion bias. Therefore, pts with BM and higher KPS should receive all available systemic therapy options.
Potential Crosstalk of Interleukin-6-Heme Oxygenase-1 Dependent Mechanism Involved in Resistance to Lenalidomide in Multiple Myeloma Cells
Authors: Jishi Wang, Weibing Wu, Dan Ma, Ping Wang, Lu Cao, Qin Fang, Jiangyuan Zhao, Tangsheng Lu
Journal: Blood (2015)
Non-enrichment-based method for analysis of androgen receptor expression in circulating tumor cells (CTCs) in patients with metastatic castrate-resistant prostate cancer.
Authors: Mitchell E. Gross, Daniel Lazar, Edward H Cho, Madelyn Luttgen, Thomas Metzner, Maria Loressa Uson, Melissa Louise Torrey, Peter Kuhn
Journal: Journal of Clinical Oncology (2012)

194 Background: We have established a fluid phase biopsy approach that identifies CTCs which preserves cytologic features in high-definition (HD) for diagnostic pathology without using immune or surface receptor-based enrichment. HD-CTCs identified with this approach can be used for enumeration and molecular characterization. Methods: Blood was collected from metastatic prostate cancer patients and normal donors in Cyto-Chex tubes (Streck, Omaha, NE) as part of IRB approved protocols at each site. Following erythrocyte lysis, 3 million nucleated cells were deposited on a glass slide. Samples were incubated with a pan-cytokeratin (CK), CD45, and androgen receptor (AR) antibodies and counter-stained with DAPI. LNCaP cells were spiked into normal blood. Images were obtained with a fluorescent scanning microscope and analyzed with a computer algorithm. Candidate HD-CTCs were subsequently verified by expert readers. Slides were re-imaged for quantitative analysis using at a fixed exposure and gain. Results: A total of 227 CTCs from ten patients were compared to 20 LNCaP cells. The median (range) HD-CTCs in this cohort was: 9 (1-62) cells/ml. The mean ± standard deviation measurements in HD-CTCs were observed: CK intensity 60.4±154; total cell area 89.0 ± 53.8 µm 2 ; nuclear area 61.1 ± 36.0 µm 2 . LNCaP cells spiked into normal blood gave the following values: CK intensity 1166+/−306; total cell area 143 ± 48.1 µm 2 ; nuclear area 63.1 ± 18.6 µm 2 . CTCs were additionally classified as either AR positive (AR+) or AR negative (AR−). 37 of the 227 (16.3%) HD-CTCs were AR+. The average CK intensity was significantly higher in AR+ versus AR− cells at 174.23 and 39.86, respectively (p&lt;0.001). The AR expression intensity in AR+ HD-CTCs and LNCaP cells was comparable at 979.4 and 902.2, respectively (p=0.824). Conclusions: We find a positive association between AR and CK expression on a per cell basis. Further, we find AR is expressed at comparable levels in CTCs from patients and human prostate cancer cells in culture. The HD-CTC based approach may be used for enumeration and molecular interrogation of CTCs in patients with prostate cancer.
Preventive dendritic cell vaccination in healthy Lynch syndrome mutation carriers
Authors: H. Westdorp, M.A.J. Gorris, S. Boudewijns, T. Bisseling, A.L. de Goede, M.M. van Rossum, M.J.L. Ligtenberg, G. Schreibelt, I.D. Nagtegaal, C.G. Figdor, W. Gerritsen, N. Hoogerbrugge, I.J.M. de Vries
Journal: Annals of Oncology (2016)
Biopsy-driven study to identify biomarkers of drug resistance in patients with triple-negative breast cancer.
Authors: Adriana Aguilar-Mahecha, Josiane Lafleur, Elaheh Ahmadzadeh, Ewa Przybytkowski, Carole Seguin, Catalin Liviu Dragos Mihalcioiu, Josee-Anne Roy, Christine Desbiens, Andre Robidoux, Elizabeth A. Marcus, Zuanel Diaz, Manuela Pelmus, Gerald Batist, Mark Basik
Journal: Journal of Clinical Oncology (2012)

87 Background: Resistance to chemotherapy is the underlying cause of death in most patients dying of breast cancer. Patients with early stages of breast cancer whose tumor is or becomes resistant to chemotherapy have a poor prognosis, while women with advanced breast cancer live as long as their tumors respond to chemotherapy. Because of the great difficulty of obtaining clinical samples from drug resistant tumors in patients, there is scant information about molecular factors from actual drug resistant tumors. This project aims to systematically profile resistant triple negative breast cancers (TNBCs) in order to discover molecular “resistance” genes/proteins as a first step to develop strategies to overcome drug resistance. Methods: Paired biopsies are collected from TNBC patients (NCT01276899). Four needle core biopsies are collected before the initiation of treatment and 2 weeks before surgery or at the time of progression in the neoadjuvant and metastatic settings respectively. Paired biopsies will undergo Next Gen Sequencing, flow sorted aCGH analysis, gene expression and miRNA profiling as well as phosphoproteomic profiling using reverse phase protein arrays. Results: We have currently enrolled 28 patients in the neoadjuvant setting and 3 metastatic patients. We have standardized the methods of collection and processing of tissue and blood specimens to ensure their molecular integrity and compatibility with different genomic and proteomic molecular platforms. Analysis of tumor cellularity has been incorporated into our quality control and we have optimized the extraction of nucleic acids to obtain high yields and optimal quality. In parallel, we have generated acquired resistance to paclitaxel in a panel of TNBC cell lines. These cell lines will also undergo genomic profiling and exome sequencing to identify molecular markers of resistance that will be correlated with the markers found in patient samples. Conclusions: This project will allow us to identify the molecular factors responsible for drug resistance in TNBCs and enable the elaboration of strategies to overcome resistance.
CD26/Dipeptidyl Peptidase IV (DPPIV) Regulates p38 Phosphorylation and Topoisomerase II Alpha Expression in the B-Lymphoma Line Jiyoye, Associated with Enhanced In Vitro and In Vivo Sensitivity to Doxorubicin.
Authors: Toshiko Yamochi, Tadanori Yamochi, Ugur Aytac, Tsutomu Sato, Chikao Morimoto, Nam H. Dang
Journal: Blood (2004)
Preemptive Transfer of GMP-Grade CD8-Depleted Donor Lymphocytes after T-Cell Depleted Reduced-Intensity Transplantation.
Authors: Ralf G. Meyer, Cedrik M. Britten, Abdo Konur, Klaus Bender, Daniela Wehler, Udo Hartwig, Thomas C. Wehler, Chiara Gentilini, Lutz Uharek, Christoph Huber, Karin Kolbe, Wolfgang Herr
Journal: Blood (2005)
Pegylated Interferon-alfa-2a (PEG-IFN-α-2A; PEGASYS™) for Essential Thrombocythemia (ET) and Polycythemia Vera (PV): An Update of an Ongoing Phase II Study.
Authors: Alfonso Quintás-Cardama, Hagop Kantarjian, Guillermo Garcia-Manero, Jorge Cortes, Marie Ann Richie, Gautam Borthakur, Srdan Verstovsek
Journal: Blood (2007)
The trouble with locums
Authors: Richard Murray
Journal: BMJ (2017)

It’s not all about the money

The role of locums—and temporary clinical staff more generally—is in the spotlight. On one side, the release last month of Keith Pearson’s report on medical revalidation pinpoints weaknesses in the oversight of, and support for, doctors working in short term locum positions,1 findings acknowledged by the General Medical Council.2 On the other side, the regular quarterly statements from NHS Improvement on the financial performance of NHS trusts now contain updates on progress in reducing NHS spending on agency staff.3 As at least some of the recent increase in the use of temporary staff has been driven by persistent staff shortages, questions are now also being asked about the quality of NHS workforce planning that has allowed such drastic shortfalls in the workforce to arise in the first place.

There are two related concerns about the use, or overuse, of temporary staff in the health service. The first is the effect that such staff may have on the quality of care. Staff moving rapidly between …
Cancer-related anemia: Correlation analysis among serum levels of hemoglobin, IL-6, hepcidin, albumin, and erythropoietin
Authors: S. Takahashi, T. Kosaka, M. Hattori, K. Fujimoto-Ouchi, Y. Shimonaka, H. Yasuno, M. Noguchi, K. Mori, E. Ogata
Journal: Journal of Clinical Oncology (2009)

e20655 Background: Hepcidin is a peptide hormone that regulates iron re-utilization and has been implicated as causing anemia by restricting the delivery of iron to erythrocyte progenitors. A potent inducer of hepcidin in hepatocytes is IL-6, an inflammatory cytokine. In the present study, we investigated the relationship between cancer-related anemia and inflammatory activity, including the cytokines. Methods: Anemia in newly diagnosed patients (pts) with solid tumors or malignant lymphoma was studied excluding pts showing evidence of myelosuppression and hepatic and renal failure. The characteristics of anemia in cancer pts were compared with those in mice bearing human lung large cell cancer LC-6-JCK. Hematological assessment was conducted using clinical practice methods. Serum levels of cytokines were determined by ELISA. Hepcidin was measured by LC/MS/MS. Results: Thirty parameters were analyzed in 11 pts. Clustering analysis of the 30 parameters resulted in 3 clusters including hemoglobin (Hb)/albumin (Alb), IL-6/hepcidin/ferritin, and erythropoietin (EPO). Hb levels showed weak negative correlation with IL-6 and hepcidin and a positive correlation with Alb levels (R=0.763, P=0.006). In addition, IL-6 levels weakly correlated with hepcidin and Alb. Hepcidin correlated with ferritin (R=0.729, P=0.011). Correlations were observed between quality of life in cancer pts and anemia parameters including Hb and IL-6. Mice bearing LC-6-JCK tumors developed anemia with characteristic parameters similar to cancer pts with anemia ( Table ). A rat anti-mouse IL-6 receptor monoclonal antibody prevented the development of anemia in the LC-6-JCK model. Conclusions: Present results suggest that cancer-related anemia associates with IL-6, Alb and inflammatory acute phase reaction including hepcidin and ferritin. Further analysis of anemia in cancer pts and murine models would be useful for investigating the mechanisms of cancer anemia. [Table: see text] No significant financial relationships to disclose.
In Reply
Authors: Steven R. Alberts, Daniel J. Sargent, Sharlene Gill, Charles L. Loprinzi
Journal: Journal of Clinical Oncology (2005)

noted a survival benefit from adjuvant chemotherapy in the MSI-negative, or microsatellite-stable, patient group.We therefore hypothesized that a more common phenotype that was nevertheless closely related to the MSI-positive phenotype may be responsible for survival benefit achieved with fluorouracil-based chemotherapy in population-based colorectal cancer trials.At the time, we speculated that this might be the cytosine-phosphate-guanine island methylator phenotype because of known sex and site differences in its frequency; we recently published direct evidence in support of this hypothesis. 3We urge workers in this field to give careful consideration to the site of tumor origin when comparing their results with our earlier observations.It is also important to bear in mind that results obtained with the highly selected and generally younger patients who enter clinical trials may be different than those seen in population-based studies.This is an essential consideration if age-, sex-and tumor-site-related phenomena such as aberrant folate metabolism and DNA methylation are involved in the response to fluorouracil-based therapies.
A preliminary study of attitudes toward the assessment and management of cancer cachexia among medical oncologists and nurses.
Authors: Egidio Del Fabbro, Antonio A.L. Vigano
Journal: Journal of Clinical Oncology (2014)

44 Background: A recent international consensus on the definition and classification of the cancer anorexia / cachexia syndrome (CACS) will facilitate clinical trial design, development of practice guidelines, and routine clinical management. Non-pharmacological interventions such as dietary counseling and promising new drugs have demonstrated improved outcomes in preliminary trials. Management of nutritional impact symptoms such as severe pain, depression, early satiety and chronic nausea also produce weight gain. These important advances contrast with the apparent low priority given to this condition by oncological societies worldwide. Our objective was to evaluate the attitudes of medical oncologists and nurses in the assessment and management of CACS in non-small cell lung cancer. Methods: Surveys were administered electronically to US-based, community medical oncologists (n=76 respondents) and oncology nurses (n=25), members of the Sermo research database which includes over 275,000 active healthcare providers, pre-qualified through telephone or online screening. A proprietary MedPulse tool achieved random geographic distribution of respondents through a staged query–response process. Results: 67% of medical oncologists selected weight loss as the most important criterion for diagnosing CACS in their daily practice, consistent with the consensus definition. However, only 4% of respondents described CACS as inevitable or very likely to develop in patients maintaining good performance status through first-line therapy. Community providers identified the management of symptoms that affect appetite as very important (58.8%), important (31.4%) or somewhat important (7.8%), but only 9.8% indicated they currently use a formal tool to evaluate these symptoms. 72% would consider using a brief assessment tool in clinical practice. Conclusions: Our surveys suggest community oncologists recognize the core criteria for the diagnosis of CACS, although there may be under-recognition of the condition’s prevalence. There is considerable interest in adopting a brief symptom assessment tool for screening, management and referral of affected or at-risk patients.
Standardized criteria for required palliative care consultation on the solid tumor oncology service.
Authors: Kerin Adelson, Julia Paris, Cardinale B. Smith, Jay Horton, R. Sean Morrison
Journal: Journal of Clinical Oncology (2013)

37 Background: Studies have shown that routine integration of Palliative Care (PC) for patients with advanced cancer is associated with improved symptom control, clearer understanding of prognosis, lower utilization of health care resources, and increased hospice use. The 2012 ASCO guidelines call for incorporation of PC for any patient with metastatic cancer and/or high symptom burden. Despite a top-rated PC division at Mount Sinai, our Solid Tumor (ST) Division utilized PC and hospice less than other medical centers. Our inpatient ST service consistently demonstrated poor quality metrics. Our 2011-2012 UHC statistics were: mortality index, 1.35 (target &lt;1), 30-day readmission rate, 21.7%, (target &lt; 10.3%) and length of stay (LOS) index, 1.23 (target &lt;1). We hypothesized that implementing standardized criteria for PC consultation would improve these metrics. Methods: During this 3-month pilot, criteria for PC consultation included patients with one or more of the following: stage IV disease, Stage III lung or pancreatic cancer, hospitalization within prior 30 days, &gt;7 day hospitalization, uncontrolled symptoms (pain, nausea, dyspnea, delirium, distress). We looked at two baseline groups for comparison: 1) patients who met eligibility in a six week period prior to the intervention 2) For UHC index data, we used the hospital dashboard average over a 1-year period prior to the intervention. This included all ST patients who were eligible for the intervention (60%) and those who were not (40%). Primary outcomes were: hospice utilization, ST mortality index, 30-day readmission rate and LOS. Results: Comparing Group 1 to the Pilot Group, palliative care consultation doubled from 41% to 82%, 30-day readmission decreased from 36% to 17% (p= .022), and hospice utilization increased from 14% to 25% (p=.146). UHC data (Group 2 vs. Pilot) showed: mortality index improved (1.35 to .59) and 30-day readmission rates decreased (21.7% to 13.5%, p=.026). LOS was unchanged (1.23 to 1.25). Conclusions: Mandating palliative care consults for patients at the highest risk for in hospital death and readmission improved hospice utilization, 30-day readmission, oncology service mortality and adherence with ASCO guidelines.
150O Clinical safety and activity from a phase 1 study of LOXO-101, a selective TRKA/B/C inhibitor, in solid-tumor patients with NTRK gene fusions
Authors: D.S. Hong, A. Dowlati, H.A. Burris, J.J. Lee, M.S. Brose, A.F. Farago, T.M. Bauer, M. Taylor, A.T. Shaw, S. Smith, N. Nanda, S. Cruickshank, M.C. Cox, R. Doebele
Journal: Annals of Oncology (2016)
Exposure–Response Analysis of Alvocidib (Flavopiridol) Treatment by Bolus or Hybrid Administration in Newly Diagnosed or Relapsed/Refractory Acute Leukemia Patients
Authors: Carl LaCerte, Vijay Ivaturi, Joga Gobburu, Jacqueline M. Greer, L. Austin Doyle, John J. Wright, Judith E. Karp, Michelle A. Rudek
Journal: Clinical Cancer Research (2017)

Purpose: To elucidate any differences in the exposure-response of alvocidib (flavopiridol) given by 1-hour bolus or a hybrid schedule (30-minute bolus followed by a 4-hour infusion) using a flavopiridol/cytosine arabinoside/mitoxantrone sequential protocol (FLAM) in patients with acute leukemia. The hybrid schedule was devised to be pharmacologically superior in chronic leukemia based on unbound exposure.Experimental Design: Data from 129 patients in three FLAM studies were used for pharmacokinetic/pharmacodynamic modeling. Newly diagnosed (62%) or relapsed/refractory (38%) patients were treated by bolus (43%) or hybrid schedule (57%). Total and unbound flavopiridol concentrations were fit using nonlinear mixed-effect population pharmacokinetic methodologies. Exposure-response relationships using unbound flavopiridol AUC were explored using recursive partitioning.Results: Flavopiridol pharmacokinetic parameters were estimated using a two-compartment model. No pharmacokinetic covariates were identified. Flavopiridol fraction unbound was 10.9% and not different between schedules. Partitioning found no association between dosing schedule and clinical response. Clinical response was associated with AUC ≥ 780 h*ng/mL for newly diagnosed patients and AUC ≥ 1,690 h*ng/mL for relapsed/refractory patients. Higher exposures were not associated with increases in severe adverse events (≥ grade 3).Conclusions: Pharmacokinetic modeling showed no difference in flavopiridol plasma protein binding for bolus versus hybrid dosing. Further trials in newly diagnosed patients with acute leukemia should utilize the bolus FLAM regimen at the MTD of 50 mg/m2/day. Trials in relapsed/refractory patients should use the hybrid dosing schedule at the MTD (30/60 mg/m2/day) to achieve the higher exposures required for maximal efficacy in this population. Clin Cancer Res; 23(14); 3592-600. ©2017 AACR.
Money in the Bank: Distortive Effects of Accumulated Earnings on Risky Choice
Authors: Arkady Konovalov, Ian Krajbich
Journal: Neuron (2017)

A new study by Juechems et al. (2017) demonstrates that individuals take fewer risks as they accumulate monetary reward. The ventromedial prefrontal cortex plays a key role in the decision process, encoding both momentary reward and the context of the accumulated wealth.
Patient-reported outcomes (PROs) and impact of lactate dehydrogenase (LDH) levels on outcomes in a phase 3 trial (NGR015) with best investigator choice (BIC) plus or minus NGR-hTNF in previously treated patients with malignant pleural mesothelioma (MPM)
Authors: V. Gregorc, A. Bulotta, M.G. Viganò, G. Citterio, G. Petrella, E. Brioschi, M. Ducceschi, L. Gianni, S. Colombi, G. Rossoni, G. Salini, V. Savia, A. Lambiase, C. Bordignon
Journal: Annals of Oncology (2016)