tbuckley/cabot-search huggingface dataset:
The outcome of patients with relapsed gestational trophoblastic neoplasm (GTN) after the completion of chemotherapy
Authors: T. Powles, A. Young, D. Short, P. Savage, C. Pappin, P. Schmid, M. Seckl
Journal: Journal of Clinical Oncology (2006)

5033 Background: Women requiring chemotherapy for GTN are stratified into low risk and high risk disease and treated accordingly. The vast majority of patients are cured with chemotherapy. Despite this a small number relapse after completing treatment. The prognostic factors predictive of outcome for these relapsed patients are unclear and are investigated here. Methods: Clinical data at presentation and at the time relapse on patients with relapsed GTN was collected from a prospective data base at the Charing Cross Hospital. This included stage of disease, time to relapse, treatment details and rate of HCG rise. Statistical analysis was performed using the Kaplan Meier method. Univariant and multivariant analysis was performed on the data. Results: Between 1980 and 2004 1708 patients were treated with chemotherapy for GTN. Sixty of these patents have relapsed. The median age of these 60 patients was 29 years (range 30–51) and the median follow up was 10 years. The overall 5 year survival for patients with relapsed GTN was 91% (84–99%). All deaths were tumour related. Patients who initially presented with low risk disease (n = 27) had an overall survival of 100% while those who presented with high risk disease had an overall survival of 91% (66–96%) (p &lt; 0.05). Five patients progressed during treatment for relapsed disease, all of these patients died. Ten patients relapsed for a second time. All of these patients are currently alive and disease free with a median of 11 years of follow up. Significant prognostic factors included stage of disease at presentation, the presence of metastatic disease at relapse and the rate of rise of HCG at relapse. Conclusions: The outcome for patients with relapsed GTN is good especially those who relapse after initially having low risk disease. Failure to obtain a complete remission on 2 nd line chemotherapy is a poor prognostic indicator. No significant financial relationships to disclose.
ALK Protein Analysis by IHC Staining after Recent Regulatory Changes: A Comparison of Two Widely Used Approaches, Revision of the Literature, and a New Testing Algorithm
Authors: Antonio Marchetti, Alessia Di Lorito, Maria Vittoria Pace, Manuela Iezzi, Lara Felicioni, Tommaso D’Antuono, Giampaolo Filice, Luigi Guetti, Felice Mucilli, Fiamma Buttitta
Journal: Journal of Thoracic Oncology (2016)

IntroductionRecent regulatory changes have allowed the diagnostic use of immunohistochemical (IHC) analysis for the identification of patients with non–small cell lung cancer who are eligible for treatment with anaplastic lymphoma receptor tyrosine kinase (ALK) inhibitors. The U.S. Food and Drug Administration has approved the VENTANA ALK (D5F3) CDx Assay (Ventana Medical Systems, Tucson, AZ) as companion diagnostics, and the Italian Medicines Agency has recognized IHC analysis as a diagnostic test indicating an algorithm for patient selection.MethodsOn the basis of the new regulations, we compared two commonly used IHC assays on 1031 lung adenocarcinomas: the VENTANA ALK (D5F3) CDx Assay with the OptiView Amplification Kit (Ventana Medical Systems) and a standard IHC test with the clone 5A4 (Novocastra, Leica Biosystems, Newcastle Upon Tyne, United Kingdom) along with their interpretative algorithms. Fluorescence in situ hybridization (FISH) was performed in all cases. Next-generation sequencing was performed in FISH/IHC analysis–discordant samples.ResultsFISH gave positive results in 33 (3.2%) cases. When FISH was used as a reference, the VENTANA ALK (D5F3) CDx assay had a sensitivity of 90.9% ± 2.6%, a specificity of 99.8% ± 0.6%, and positive and negative predictive values of 93.8% ± 2.1% and 99.7% ± 0.6%, respectively. The clone 5A4–based IHC test showed a sensitivity of 90.9% ± 2.6%, a specificity of 98.3% ± 1.3%, and positive and negative predictive values of 63.8% ± 4.2% and 99.7% ± 0.6%, respectively. Five cases with IHC analysis/FISH-discordant results in our series were analyzed together with those previously reported in the literature. Overall, data from 35 patients indicate a response rate to ALK inhibitors in 100% of FISH-negative/IHC analysis–positive cases (seven of seven) and 46% of FISH-positive/IHC analysis–negative cases (13 of 28), respectively.ConclusionsOur results confirm the difficulty in managing an IHC test without amplification in the absence of confirmatory FISH analysis, as well as the possibility of performing a direct diagnosis in approximately 90% of patients by the VENTANA ALK (D5F3) CDx Assay. On the basis of the recent regulatory changes, the data that have emerged from the literature, and the results of the present study, a new algorithm for ALK assessment in non–small cell lung cancer has been devised.
Abstract P26: Intra-CPR Hypothermia with and Without Volume Loading in an Ischemic Model of Cardiac Arrest
Authors: Demetris Yannopoulos, Menekhem Zviman, Aravindan Kolandaivelu, Ravi Ranjan, Yoav Dori, Valeria Castro, Jon R Resar, Jeffrey A Brinker, Robert F Wilson, Henry R Halperin
Journal: Circulation (2008)

Background: Coronary occlusive ischemic events are responsible for 50 –70% of cardiac arrests in adults. We investigated the effects of intra-CPR mild hypothermia (HTM) (target 32–33°C) with and without volume loading on return to spontaneous circulation (ROSC) and infarction size in a severe, mid-LAD occlusion model of cardiac arrest. Methods: 46 (27±2.3kg) pigs had their mid LAD balloon occluded and were divided in 5 groups. After 15 minutes, ventricular fibrillation (VF) was electrically induced and 5 minutes of untreated VF were followed by 5 minutes of pneumatic vest CPR with a set compression pressure (250mmHg). If ROSC was obtained, animals were followed for another 95 minutes for a total LAD occlusion time of 120 min. Subsequently the balloon was deflated and 90 min of reperfusion were followed by myocardial staining to define area at risk (AAR) and myocardial infarct size. Group A had no additional intervention. Group B received immediately post ROSC surface cooling with cooling blankets and ice. Group C received intra-CPR 680±23ml of 28°C 0.9% NS via a central femoral venous catheter. Group D received during CPR 673±26 of 4°C NS followed by post ROSC surface cooling as in group B. Group E received intra-CPR and post ROSC volume-sparing HTM with an Endovascular Therapeutic Hypothermia System (ETHS) placed into the right atrium and set at a target of 32°C. Results: During CPR, coronary perfusion pressure was significantly decreased in groups C and D compared to groups A, B and E but groups D and E had significantly reduced infarct size. Group E had significantly improved EF compared to all other groups. Table . Conclusions: Intra-CPR HTM significantly reduces myocardial infarction size. Volume loading during CPR is detrimental for ROSC due to reduction of coronary perfusion pressure. ETHS intra-CPR application improves ROSC and post-resuscitation LV function and minimizes infarction in this ischemia-reperfusion cardiac arrest model. Results
Phase II study of SU11248, a multitargeted receptor tyrosine kinase inhibitor (TKI), in patients (pts) with previously treated metastatic breast cancer (MBC)
Authors: K. D. Miller, H. J. Burstein, A. D. Elias, H. S. Rugo, M. A. Cobleigh, M. D. Pegram, P. D. Eisenberg, M. Collier, B. J. Adams, C. M. Baum
Journal: Journal of Clinical Oncology (2005)

563
Physician whistleblower is awarded $59m in Pfizer settlement
Authors: Owen Dyer
Journal: BMJ (2016)

Pfizer has paid $784m (£562m; €710m) to settle claims that its Wyeth Pharmaceuticals unit overcharged the US Medicaid scheme by failing to offer the public payer the same discounts it offered to private hospitals for its drug pantoprazole (which it markets as Protonix), used to treat oesophagitis. Pfizer admitted no wrongdoing and did not own Wyeth when the alleged fraud occurred.

The settlement, while large, broke no records. But it was a bonanza for the two whistleblowers who first sued Pfizer, one a former AstraZeneca sales representative, the other a Louisiana internal medicine specialist, William LaCorte, who received $59m from the US government as his share of the settlement.

LaCorte receives the payout under the “qui …
Minimum reporting standards for clinical research on groin pain in athletes
Authors: Eamonn Delahunt, Kristian Thorborg, Karim M Khan, Philip Robinson, Per Hölmich, Adam Weir
Journal: British Journal of Sports Medicine (2015)

Groin pain in athletes is a priority area for sports physiotherapy and sports medicine research. Heterogeneous studies with low methodological quality dominate research related to groin pain in athletes. Low-quality studies undermine the external validity of research findings and limit the ability to generalise findings to the target patient population. Minimum reporting standards for research on groin pain in athletes are overdue. We propose a set of minimum reporting standards based on best available evidence to be utilised in future research on groin pain in athletes. Minimum reporting standards are provided in relation to: (1) study methodology, (2) study participants and injury history, (3) clinical examination, (4) clinical assessment and (5) radiology. Adherence to these minimum reporting standards will strengthen the quality and transparency of research conducted on groin pain in athletes. This will allow an easier comparison of outcomes across studies in the future.
At the Crossroads of Cancer Stem Cells, Radiation Biology, and Radiation Oncology
Authors: Leo E. Gerweck, Hiroaki Wakimoto
Journal: Cancer Research (2016)

Reports that a small subset of tumor cells initiate and sustain tumor growth, are resistant to radiation and drugs, and bear specific markers have led to an explosion of cancer stem cell research. These reports imply that the evaluation of therapeutic response by changes in tumor volume is misleading, as volume changes reflect the response of the sensitive rather than the resistant tumorigenic cell population. The reports further suggest that the marker-based selection of the tumor cell population will facilitate the development of radiation treatment schedules, sensitizers, and drugs that specifically target the resistant tumorigenic cells that give rise to treatment failure. This review presents evidence that contests the observations that cancer stem cell markers reliably identify the subset of tumor cells that sustain tumor growth and that the marker-identified population is radioresistant relative to the marker-negative cells. Experimental studies show that cells and tumors that survive large radiation doses are not more radioresistant than unirradiated cells and tumors, and also show that the intrinsic radiosensitivity of unsorted colony-forming tumor cells, in combination with the fraction of unsorted tumor cells that are tumor initiating, predicts tumor radiocurability.
Genomic landscape of high-grade T1 micropapillary bladder tumors.
Authors: Joaquim Bellmunt, Guangwu Guo, Stephanie A. Mullane, Anna Orsola, Lillian Werner, Paul Van Hummelen, Aaron Thorner, Massimo Loda, Toni K. Choueiri, Justine A. Barletta, David J. Kwiatkowski, Matthew Meyerson, Eliezer Mendel Van Allen
Journal: Journal of Clinical Oncology (2015)

299 Background: The genomic landscape of high-grade T1 micropapillary bladder tumors (HGT1micropap) is unknown. Clinically, micropapillary bladder cancer is an aggressive and possibly lethal disease. Our main objective was to assess the genomic landscape of HGT1micropap through identifying mutations, insertions/deletions (indels), translocations, and copy number variations (CNVs). Methods: We prospectively identified nine HGT1micropap with 45.4 months of median follow up. Patients were treated in a uniform manner using TUR, BCG, and appropriate follow up. We performed whole exome sequencing using Ilumina Exome _v5 plus translocation. Mutations and indels were called using the Firehose pipeline. CNVs were called using ExomeCNV. We examined the mutational landscape and compared the genomic alterations to TCGA (&gt;T2, n=131) 2 and publicly available data on non-muscle invasive bladder tumors (Ta/T1, n=37) 1 . Results: Within the HGT1micropap, mutations on TP53, KMT2D, TSC1, and ATM were suggested to occur more frequently compared to the NMIBC control group 1 . FGFR3 was seen at the expected frequency for NMIBC. The mutations of interest are presented in Table 1 with the percentage seen in the other cohorts. Of interest, TSC1 was seen in higher frequency in micropapillary than in the NMIBC or the TCGA cohort 2 . We did not see any patterns between CNVs and mutations. We also saw two patients with severe chromothripsis. 3 patients had loss of chromosome 9 or 9q without any other severe chromosome alterations. CNV alterations will be presented and compared to MIBC. Conclusions: In this preliminary analysis, our HGT1micropap, showed a mutational landscape more similar to MIBC compared to NMIBC bladder landscape. We did not find any clear driver of the micropapillary histology at the exome level in this limited sample of patient, which may indicate that tumor heterogeneity or epigentic changes may be driving this aggressive phenotype. [Table: see text]
Drp1-Dependent Mitochondrial Autophagy Plays a Protective Role Against Pressure Overload–Induced Mitochondrial Dysfunction and Heart Failure
Authors: Akihiro Shirakabe, Peiyong Zhai, Yoshiyuki Ikeda, Toshiro Saito, Yasuhiro Maejima, Chiao-Po Hsu, Masatoshi Nomura, Kensuke Egashira, Beth Levine, Junichi Sadoshima
Journal: Circulation (2016)

Background— Mitochondrial autophagy is an important mediator of mitochondrial quality control in cardiomyocytes. The occurrence of mitochondrial autophagy and its significance during cardiac hypertrophy are not well understood. Methods and Results— Mice were subjected to transverse aortic constriction (TAC) and observed at multiple time points up to 30 days. Cardiac hypertrophy developed after 5 days, the ejection fraction was reduced after 14 days, and heart failure was observed 30 days after TAC. General autophagy was upregulated between 1 and 12 hours after TAC but was downregulated below physiological levels 5 days after TAC. Mitochondrial autophagy, evaluated by electron microscopy, mitochondrial content, and Keima with mitochondrial localization signal, was transiently activated at ≈3 to 7 days post-TAC, coinciding with mitochondrial translocation of Drp1. However, it was downregulated thereafter, followed by mitochondrial dysfunction. Haploinsufficiency of Drp1 abolished mitochondrial autophagy and exacerbated the development of both mitochondrial dysfunction and heart failure after TAC. Injection of Tat-Beclin 1, a potent inducer of autophagy, but not control peptide, on day 7 after TAC, partially rescued mitochondrial autophagy and attenuated mitochondrial dysfunction and heart failure induced by overload. Haploinsufficiency of either drp1 or beclin 1 prevented the rescue by Tat-Beclin 1, suggesting that its effect is mediated in part through autophagy, including mitochondrial autophagy. Conclusions— Mitochondrial autophagy is transiently activated and then downregulated in the mouse heart in response to pressure overload. Downregulation of mitochondrial autophagy plays an important role in mediating the development of mitochondrial dysfunction and heart failure, whereas restoration of mitochondrial autophagy attenuates dysfunction in the heart during pressure overload.
Feasibility of outpatient palliative care for oncology patients within the safety net.
Authors: Heather A. Harris, Anne Kinderman, Kathleen Kerr
Journal: Journal of Clinical Oncology (2014)

38 Background: Palliative care (PC) combined with standard oncology care has been shown to improve patient outcomes and reduce health care costs. In safety-net systems, where limited resources mandate containing costs across settings, outpatient PC (OP PC) could be an important tool for improving quality while lowering costs. Multiple studies have shown that oncology patients cared for in safety net systems often present very late in the course of illness, raising concerns about the proportion of patients who could be referred to an OP PC clinic. To address this question we analyzed utilization patterns among cancer patients cared for at our facility to examine the need for and expected net costs of an OP PC service. Methods: Retrospective cohort study of oncology patients cared for at an urban, safety-net hospital who died between July 2010 and June 2013. We used cancer registry data to identify decedents and claims data to evaluate utilization patterns and cost of care in the final 6 months of life. Results: Among the 403 cancer patients who died in the study period we found heavy, late utilization of inpatient (IP) services: 307 (76%) were admitted to the hospital in the 6 months preceding death, 45% in the final month of life. One third of patients died in the hospital and another 4% died within 3 days of hospital discharge. Direct costs per admission averaged $22,275. While late presentation was common, 133 (33%) patients had multiple health system encounters 91-180 days prior to death: early enough to be referred to an OP PC clinic. We modeled clinic costs assuming an annual volume of 50 patients, to be followed monthly for the last 4 months of life by a physician-nurse-social worker team. Annual staffing costs were estimated at $88,290. Prior research has shown that utilization of IP services in the final month of life is 40% lower amongst patients who receive early OP PC. Using that value, we estimated that providing OP PC to 50 patients annually would avoid 38 hospitalizations, with resulting avoided direct costs of $846,450. Conclusions: This feasibility study reveals that OP PC in the safety net can provide substantial return on investment, even if such services are only used by a subset of oncology patients who present earlier in their disease course.
Abstract 13238: Aortic Annulus in Severe Bicuspid Aortic Valve Stenosis: Implications for Transcatheter Aortic Valve Therapies
Authors: Femi Philip, Mobolaji Ige, Nadeen Faza, Menon Venugopal, Paul Schoenhagen, Milind Desai, Patrick Whitlow, Samir Kapadia
Journal: Circulation (2013)

Background: Transcatheter aortic valve replacement (TAVR) is used to treat severe aortic stenosis (AS) but contraindicated in bicuspid aortic valves (BCV). We sought to characterize the aortic annulus in BCV and tricuspid aortic valves (TCV). Methods: We identified patients with severe AS who underwent multi-detector computed tomographic (MDCT) imaging prior to surgical aortic valve replacement (SAVR, n=200) for BCV and TAVR (n=200) for TCV from 2006-2013. Annulus measurements of the basal ring (short- and long-axis, area-derived diameter), coronary ostia height, sinus area (SA), sino-tubular junction area (STJ), calcification and eccentricity index (EI, 1-short axis/long axis) were made. Results: Patients undergoing TAVR were older (58.7 years versus 78.8 years, p=0.02) with a high prevalence of atherosclerosis (70% vs. 20%, p=0.04) than those undergoing SAVR. There were no differences in the severity of AS or aortic insufficiency in both groups (p=0.8). Aortic annulus area were similar (49.2 ± 17.2 mm2 ...
Distinct Glycosylation of Serum Proteins in Patients With Cancer: Brief Communication 2
Authors: Israel Rostenberg, Jesús Guízar-Vázquez, Pablo Suárez, Rafael Rico, Lourdes Nungaray, César Domínguez
Journal: JNCI Journal of the National Cancer Institute (1978)

Concanavalin A and wheat germ agglutinin, lectins that interact with serum glycoprotein in a manner similar to the antigen--antibody reaction, were used as "antibodies" in a single radial immunodiffusion technique to test a coded serum panel (from the National Cancer Institute, Bethesda, Md., and the Mayo Clinic, Rochester, Minn.) containing a) 99 serum samples from patients with different types of malignant neoplasms of the gastrointestinal tract, prostate gland, and lung, b) 50 samples from patients with benign diseases of the same organs as those affected in the cancer patients, and c) 50 samples from apparently healthy smokers. The resulting precipitation rings were not correlated to serum protein concentration, and the differences (demonstrated by Student's t-test and with a generalization of the one-sided two-sample Kolmogorov-Smirnov statistic for evaluating diagnostic tests) established that serum glycoproteins are glycosylated differently in cancer patients than in people without cancer.
Meta-Analyses of Published Results Are Unreliable
Authors: Marc Buyse, Robert W. Carlson, Pascal Piedbois, R. Fossati, C. Confalonieri, V. Torri, A. Liberati
Journal: Journal of Clinical Oncology (1999)

Limburgs Univ Ctr, Diepenbeek, Belgium. Stanford Univ, Med Ctr, Palo Alto, CA USA. Hop Henri Mondor, F-94010 Creteil, France.Buyse, M, Limburgs Univ Ctr, Diepenbeek, Belgium.
Interleukin-15 deficiency promotes the development of T-cell acute lymphoblastic leukemia in non-obese diabetes mice with severe combined immunodeficiency
Authors: D Bobbala, R Kandhi, X Chen, M Mayhue, E Bouchard, J Yan, H Knecht, F Barabé, S Ramanathan, S Ilangumaran
Journal: Leukemia (2016)
Is hormone-replacement therapy (HRT) a plausible explanation for the recent increase in large breast tumor incidence?
Authors: W. C. Mertens, V. Hilbert, D. Katz, R. B. Arenas, G. Makari-Judson
Journal: Journal of Clinical Oncology (2004)

9659 Background:HRT and inadequate screening are proposed explanations for a recent increased incidence of tumors > 5 cm (CA Cancer J Clin 2003;53:342). Methods: Data from a large hospital tumor registry of women diagnosed 1980–2002 with unilateral tumors were evaluated for size, stage, histology, age and (2000–2) detection method. Univariate associations were explored and stepwise linear/logistic multivariate models constructed. Results: Of 4652 cases; 76% had adequate size data; missing data were associated with diagnosis before 1986 and stage IV disease. While women with more recent diagnoses were younger (p<.0001), the proportion < 40 years did not change (1980–89: 7.0%; 2000–2: 8.8%; p=.12). In the 1980's, later year of diagnosis correlated with decreasing tumor size (p=.012) and proportion > 5 cm (p=.036); after 1989, increasing patterns were seen (p=.027 and p=.0004). Tumor size for women age < 40 increased (mean 2.67 [1980–89] to 3.48 [2000–2] cm, p<.0001) while those 40–50 (2.38 to 2.37 cm, p<.0001) and > 50 (2.43 to 2.09 cm, p<.0001) exhibited decreases. Since 1980 increasing proportions > 5 cm were seen for women age < 40 (p = .0053) and 40–50 (p = .028) but not > 50 (p = .79); the proportion of tumors stage ≥ IIIA did not change for patients age < 40 (despite fewer stage IV cases), while decreases were seen for those 40–50 (p=.001) and > 50 (p<.0001). Continuous variables were positively (year, age2, year2) or negatively (age, age/year interaction) correlated with increasing proportions > 5cm/ ≥ stage IIIA in univariate/multivariate models. Since 2000, patient-detected tumors in those age < 40 were larger compared to self-detected tumors in older women (p=.01), but mammographically-detected tumors were of similar size in both age groups. Conclusions: After decreasing during the 1980's, tumor size/tumors > 5 cm have increased; this seems to be limited to premenopausal women, particularly age < 40. HRT is an unlikely explanation; others possibilities include earlier age at detection combined with less effective screening for younger women, and more diligent primary tumor measurements coinciding with fewer stage IV presentations. No significant financial relationships to disclose.