tbuckley/cabot-search huggingface dataset:
Agreement between Programmed Cell Death Ligand-1 Diagnostic Assays across Multiple Protein Expression Cutoffs in Non–Small Cell Lung Cancer
Authors: Marianne J. Ratcliffe, Alan Sharpe, Anita Midha, Craig Barker, Marietta Scott, Paul Scorer, Hytham Al-Masri, Marlon C. Rebelatto, Jill Walker
Journal: Clinical Cancer Research (2017)

Purpose: Immunotherapies targeting programmed cell death-1 (PD-1) and programmed cell death ligand-1 (PD-L1) demonstrate encouraging antitumor activity and manageable tolerability in non-small cell lung cancer (NSCLC), especially in patients with high tumor PD-L1 expression, as detected by companion or complementary diagnostic assays developed for individual agents. A laboratory is unlikely to use multiple assay platforms. Furthermore, commercially available diagnostic assays are not standardized, and different assay methods could lead to inappropriate treatment selection. This study establishes the extent of concordance between three validated, commercially available PD-L1 IHC diagnostic assays for NSCLC patients [Ventana SP263 (durvalumab), Dako 22C3 (pembrolizumab), and Dako 28-8 (nivolumab)].Experimental Design: Five hundred formalin-fixed, paraffin-embedded archival NSCLC samples were obtained from commercial sources. Stained slides were read in batches on an assay-by-assay basis by a single pathologist trained in all methods, in a Clinical Laboratory Improvements Amendments program-certified laboratory. An additional pathologist performed an independent review of 200 stained samples for each assay.Results: PD-L1 expression was evaluable with all assays in 493 samples. The three assays showed similar patterns of tumor membrane staining, with high correlation between percent PD-L1 staining. An overall percentage agreement of >90% was achieved between assays at multiple expression cutoffs, including 1%, 10%, 25%, and 50% tumor membrane staining.Conclusions: This study builds optimism that harmonization between assays may be possible, and that the three assays studied could potentially be used interchangeably to identify patients most likely to respond to anti-PD-1/PD-L1 immunotherapies, provided the appropriate clinically defined algorithm and agent are always linked. Clin Cancer Res; 23(14); 3585-91. ©2017 AACR.
Effect of Iron Levels on Women After Premature or Early-Onset Menopause
Authors: Virginia W. Hayes, Ralph George DePalma, Leo R. Zacharski
Journal: JAMA Cardiology (2017)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Cardiology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Cardiology journal
Phase I Study of AR-42 in Relapsed Multiple Myeloma and Lymphoma.
Authors: Craig C. Hofmeister, Zhongfa Liu, Mindy A Bowers, Pierluigi Porcu, Joseph M. Flynn, Beth Christian, Robert A. Baiocchi, Don M. Benson, Leslie A Andritsos, Carli N Greenfield, Megan Sell, Susan Geyer, John C. Byrd, Michael R. Grever
Journal: Blood (2012)
Phase III Randomized Stem Cell Mobilization Trial Comparing Standard Vs Double-Dose G-CSF Vs Standard Doses of G-CSF Plus GM-CSF in Hard to Mobilize Patients Undergoing An Autologous Hematopoietic Stem Cell Transplant (HSCT).
Authors: Elizabeth Berger, Christopher Seet, Mala Parthasarathy, Tulio Rodriguez, Scott E. Smith, Amir Toor, Mary Lee, Cecilia Petrowsky, Mary Fox-Geiman, Patrick Stiff
Journal: Blood (2009)
P2.01-078 Frequent High TIM-3 (HAVCR2) Expression in Resected NSCLC Specimens, Most Notably in Adenocarcinoma Histology
Authors: Aaron Lisberg, Robert Mckenna, Judy Dering, Hsiao-Wang Chen, Dongmei Hou, Naeimeh Kamranpour, Maria Velez, Robert Cameron, Jay Lee, Steven Dubinett, Dennis Slamon
Journal: Journal of Thoracic Oncology (2017)
P2.02-038 Surgical Outcome of Stage III A-cN2/pN2 Non-Small Cell Lung Cancer
Authors: Ryotaro Kamohara, Naoya Yamasaki, Tomoshi Tsuchiya, Keitaro Matsumoto, Takuro Miyazaki, Go Hatachi, Takeshi Nagayasu
Journal: Journal of Thoracic Oncology (2017)
Line-assisted complete closure of duodenal mucosal defects after underwater endoscopic mucosal resection
Authors: Yasushi Yamasaki, Yoji Takeuchi, Noriya Uedo, Noboru Hanaoka, Koji Higashino, Ryu Ishihara, Hiroyasu Iishi
Journal: Endoscopy (2017)

Duodenal endoscopic mucosal resection (EMR) carries a high risk of adverse events, including delayed perforation [1] [2]. Because complete clip closure of mucosal defects can reportedly prevent post-procedural adverse events in the colorectum, we established a line-assisted complete closure (LACC) technique for large mucosal defects after colonic endoscopic submucosal dissection [3]. LACC can be useful in the duodenum, but its feasibility is unknown. Therefore, we investigated the feasibility of LACC of mucosal defects after underwater EMR in the duodenum.
Identification of Novel Germline Variants in Early-Onset Familial Classical Hodgkin Lymphoma with Exome Sequencing
Authors: Outi Kilpivaara, Heikki Ristolainen, Peter Kamper, Minna Taskinen, Silva Saarinen, Sirpa Leppä, Francesco d'Amore, Aaltonen A. Lauri
Journal: Blood (2014)
P40 Development of 18f and 68ga-labelled cyclic peptides for positron emission tomography imaging of αvβ6 in idiopathic pulmonary fibrosis
Authors: JA Thompson, J Domarkas, C Cawthorne, SJ Archibald, S Hart
Journal: Thorax (2016)

<h3></h3> Biomarkers, capable of identifying the stage and aggressiveness of idiopathic pulmonary fibrosis (IPF) at the time of diagnosis, would improve the accuracy of prognostication and facilitate targeting anti-fibrotic drug therapy to patients who are most likely to benefit. The integrin α<sub>v</sub>β<sub>6</sub> is highly expressed in injured lung epithelium and is a key activator of transforming growth factor β (TGF-β), which plays a crucial role in the initiation and maintenance of fibrosis. Positron emission tomography (PET) imaging tracers that permit visualisation of lung α<sub>v</sub>β<sub>6</sub> expression have potential as novel therapeutic and prognostic biomarkers in IPF. Several α<sub>v</sub>β<sub>6</sub> integrin-binding cyclic peptides were synthesised using solid phase supported peptide synthesis and functionalised via their N-terminus or side chain amino group with a 6-amino- or a 6-azidohexanoic acid spacer to provide a convenient attachment site for either 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) or an 2-ethynyl-6-[18F]-fluoropyridine prosthetic group for radiolabelling with <sup>68</sup>Ga or <sup>18</sup>F, respectively. The α<sub>v</sub>β<sub>6</sub>-binding capability of these peptide derivatives was assessed by competitive binding enzyme-linked immunosorbent assay (ELISA) and flow cytometry. Peptide derivatives that displayed strong affinity for α<sub>v</sub>β<sub>6</sub> were taken forward to “hot” cell surface binding experiments to evaluate their selectivity for the target. Stability of radiolabelled peptides was measured in human serum. Competitive binding ELISA experiments (Figure 1) and flow cytometry experiments, showed that cRGD1 and cRGD4 were able to inhibit the binding of α<sub>v</sub>β<sub>6</sub>-specific 10D5 mAb to α<sub>v</sub>β<sub>6 </sub>with IC<sub>50</sub> values of 6.6 nM and 1.6 nM, respectively. Labelling cRGD1 and cRGD4 with fluorine and gallium resulted in IC<sub>50</sub> values of 12.2 nM and 1.2 nM for <sup>19</sup>F-Pyr-cRGD1 and <sup>68</sup>Ga-DOTA-cRGD4, respectively. Serum stability studies of <sup>68</sup>Ga-DOTA-cRGD4 have shown that this tracer is &gt;90% stable after 2 half-lives of <sup>68</sup>Ga (136 min). Radiolabelled cyclic RGD peptides have showed favourable binding and stability characteristics to warrant their investigation by PET imaging <i>in vivo</i>. A xenograft murine model using α<sub>v</sub>β<sub>6</sub><sup>+</sup> and α<sub>v</sub>β<sub>6</sub><sup>-</sup> tumours is currently under development to validate tracer uptake and biodistribution <i>in vivo</i>.
P3.02b-077 Osimertinib Expanded Access Program for Previously Treated Patients With Advanced EGFR T790M Mutation-Positive NSCLC
Authors: Edgardo Santos, Barry Kaplan, Eli Kirshner, Elisabeth Croft, Lecia Sequist, Lea Burke, Jiefen Munley, Geoffrey Oxnard
Journal: Journal of Thoracic Oncology (2017)
Long-term outcome of patients with steroid-refractory acute severe UC treated with ciclosporin or infliximab
Authors: D Laharie, A Bourreille, J Branche, M Allez, Y Bouhnik, J Filippi, F Zerbib, G Savoye, L Vuitton, J Moreau, A Amiot, J Cosnes, E Ricart, O Dewit, A Lopez-Sanroman, M Fumery, F Carbonnel, G Bommelaer, B Coffin, X Roblin, G van Assche, M Esteve, M Farkkila, JP Gisbert, P Marteau, S Nahon, M de Vos, J Lambert, JY Mary, E Louis
Journal: Gut (2017)

Objective Ciclosporin and infliximab have demonstrated short-term similar efficacy as second-line therapies in patients with acute severe UC (ASUC) refractory to intravenous steroids. The aim of this study was to assess long-term outcome of patients included in a randomised trial comparing ciclosporin and infliximab. Design Between 2007 and 2010, 115 patients with steroid-refractory ASUC were randomised in 29 European centres to receive ciclosporin or infliximab in association with azathioprine. Patients were followed until death or last news up to January 2015. Colectomy-free survival rates at 1 and 5 years and changes in therapy were estimated through Kaplan-Meier method and compared between initial treatment groups through log-rank test. Results After a median follow-up of 5.4 years, colectomy-free survival rates (95% CI) at 1 and 5 years were, respectively, 70.9% (59.2% to 82.6%) and 61.5% (48.7% to 74.2%) in patients who received ciclosporin and 69.1% (56.9% to 81.3%) and 65.1% (52.4% to 77.8%) in those who received infliximab (p=0.97). Cumulative incidence of first infliximab use at 1 and 5 years in patients initially treated with ciclosporin was, respectively, 45.7% (32.6% to 57.9%) and 57.1% (43.0% to 69.0%). Only four patients from the infliximab group were subsequently switched to ciclosporin. Three patients died during the follow-up, none directly related to UC or its treatment. Conclusions In this cohort of patients with steroid-refractory ASUC initially treated by ciclosporin or infliximab, long-term colectomy-free survival was independent from initial treatment. These long-term results further confirm a similar efficacy and good safety profiles of both drugs and do not favour one drug over the other. Trial registration number EudraCT: 2006-005299-42; ClinicalTrials.gouv number: NCT00542152 ; post-results.
P1.08-064 Surgery for Malignant Pulmonary Tumor Invading Proximal Left Main Pulmonary Artery
Authors: Fumihiro Tanaka, Yusuke Nabe, Akihiro Taira, Taiji Kuwata, Soichi Oka, Yasuhiro Chikaishi, Ayako Hirai, Kazue Yoneda, Yuko Tashima, Koji Kuoroda, Naoko Imanishi
Journal: Journal of Thoracic Oncology (2017)
A Patient-Reported Outcome Measure for Symptoms and Symptom Burden of Acute Myeloid Leukemia (AML) and Myelodysplastic Syndrome (MDS)
Authors: Loretta A. Williams, Araceli Garcia-Gonzalez, Hycienth O. Ahaneku, Jorge E. Cortes, Guillermo Garcia-Manero, Hagop M. Kantarjian, Tito R. Mendoza, Qiuling Shi, Gautam Borthakur, Jan A. Burger, Elias J. Jabbour, Koichi Takahashi, Huei K. Lin, Achala Limaye, Charles S. Cleeland
Journal: Blood (2015)
S56 Neural respiratory drive and cardiac function in patients with obesity-hypoventilation-syndrome following setup of non-invasive ventilation for hypercapnic respiratory failure
Authors: A Onofri, M Patout, G Arbane, M Pengo, P Marino, J Steier
Journal: Thorax (2016)

<h3>Background</h3> Chronic hypercapnic respiratory failure in obesity hypoventilation syndrome (OHS) is commonly treated with non-invasive ventilation (NIV). We hypothesised that treatment of OHS would improve neural respiratory drive (NRD) and improve cardiac function. <h3>Patients and methods</h3> A prospective, observational single-centre study was conducted. OHS patients were assessed recording NRD, as measured by the electromyogram of the parasternal intercostals (EMGpara) before, during and after NIV set-up and cardiac function with trans-thoracic echocardiography (TTE) before and after NIV set-up. Follow up appointments were planned at 6-weeks (6W-FU) and 3 Months (3M-FU). The tricuspid annular plane systolic excursion (TAPSE) score was used to assess the right ventricular (RV) function and EMGpara%max and neural respiratory drive index (NRDI) were recorded to assess NRD. The Wilcoxon test was used to compare baseline with follow-up results. <h3>Results</h3> 10 patients (age 55.9 (7.6) years, females 50%, weight 126.6 (29.1) kg, BMI 48.1 (7.5) kg/m<sup>2</sup>) were studied. 3 patients were non-compliant with NIV. NRDI and EMGpara%maxsignificantly improved following NIV set-up, and this effect was maintained at 3M-FU (EMGpara%max 24.4 (12.9)%, 16.9 (5.4)% and 18.6 (6.5)%, p = 0.028 and p = 0.035; NRDI 480.4 (256.0)/min, 314.7 (125.6)/min and 379.5 (138.0)/min, p = 0.22 and p = 0.012; Figure 1). There were no significant differences in cardiac function between baseline and 3M-FU (TAPSE: 2.6 (0.6) mm vs. 2.4 (0.4) mm, p = 1.00) or systolic pulmonary artery pressures (sPAP 36.7 (15.2) mmHg vs 35.8 (16.2) mmHg, p: 0.50). The TAPSE score in compliant patients seemed to improve (n = 3; 2.3 (0.6) mm vs. 2.7 (0.3) mm) while non compliant patients experienced a deterioration (n = 3; 2.7 (0.5) mm vs. 2.2 (0.4) mm). <h3>Conclusions</h3> NIV improves NRD and respiratory parameters in patients with OHS. However, cardiac function does not improve over a three-month period despite the significant improvements in ventilation. These results are influenced by treatment adherence.
S101 Single centre experience of switching patients with idiopathic pulmonary fibrosis from pirfenidone to nintedanib
Authors: A Rathnapala, A Fries, C Ruggiero, LP Ho, RK Hoyles
Journal: Thorax (2016)

<h3>Background</h3> Idiopathic Pulmonary Fibrosis (IPF) is a progressive disease with an average life expectancy of 2–4 years. The anti-fibrotic agents Nintedanib and Pirfenidone slow disease progression, and are routinely prescribed by specialist ILD centres. Choice of agent is guided by patient and physician preference, and potential tolerance of side effects. Our centre has prescribed Nintedanib since March 2015, and Pirfenidone since 2013. <h3>Objectives</h3> To identify the reasons driving a change of anti-fibrotic from Pirfenidone to Nintedanib, and the frequency of reported side effects and specialist nursing input before and after the switch. <h3>Methods</h3> This retrospective study examined patients who had been switched from Pirfenidone to Nintedanib (March 2015–July 2016), including patients with &gt;1 month duration of each agent. Data was taken from patient records including nursing advice via the ILD nurse-led helpline. <h3>Results</h3> We identified 16 patients, with a mean duration of Pirfenidone 9 (1–30) months prior to the switch, and 8 (2–15) months Nintedanib use. Average age 73 (65–84) years, male:female 14:2, definite: probable IPF 11:5, median duration since IPF diagnosis 27 (8–65) months, median %FVC 75 (62–90) at initiation of Pirfenidone, and 68 (53–85) %FVC at initiation of Nintedanib. Rationale for switch. Disease progression (n = 5): decline in FVC ≥ 10% over one year (n = 3), acute exacerbation (n = 2). Intolerable side effects (n = 11): fatigue (3), diarrhoea (2), nausea(2),appetite or weight loss (2), skin rash (1), mood disturbance (1). Impact of switch on side effects and nursing contact. In 9 months before the switch, 13 patients made 1.5 (mean) calls (range 1–3) to the ILD helpline for advice on Pirfenidone side effect management. After the switch, over 8 months, 3 patients made 2 (mean) contacts (range 1–3) for Nintedanib related side effects (diarrhoea). Of 5 patients switched to Nintedanib for disease progression, 3 had follow up for six months, showing &gt;10% improvement in the%FVC (n = 1), stability (n = 1), persistent mild decline ( &lt; 5%) %FVC (n = 1). <h3>Conclusions</h3> This study illustrates the potential of Nintedanib as an alternative for those who have disease progression despite Pirfenidone; there is good tolerance to Nintedanib with none of this cohort having to stop treatment due to side effects.
P2.02-035 The Advantage of Induction Chemoradiotherapy in Bronchoplastic Procedure for Non-Small Cell Lung Cancer Accompanied with Central Disease Region
Authors: Hiroki Sato, Shinichi Toyooka, Takeshi Kurosaki, Kazuhiko Shien, Kentaro Miyoshi, Shinji Ohtani, Hiromasa Yamamoto, Seiichiro Sugimoto, Junichi Soh, Masaomi Yamane, Takahiro Oto, Shinichiro Miyoshi
Journal: Journal of Thoracic Oncology (2017)
P249 Comparison of physiological versus mathematical methods for quality control in mbw normalised phase iii analysis
Authors: M Arigliani, N Verger, E Raywood, J Duncan, A Bush, P Aurora
Journal: Thorax (2016)

<h3>Background</h3> Breathing pattern cannot be controlled in small children, so multiple breath washout SnIII analysis has to exclude inadequate volume breaths. <h3>Aim</h3> To compare an existing mathematical breath exclusion algorithm with a physiological method. <h3>Methods</h3> School age children with CF (30) and controls (30) performed SF6MBW with mass spectrometer, with uncontrolled tidal breathing. Two different breath exclusion methods were compared, with exclusion based on: 1) Expired tidal volume (VT) deviating by &gt;25% of the median VT<sup>1</sup> 2) VT &lt;3 Langley dead space<sup>2</sup> volume or 90% bigger than the median VT Runs with &gt;33% excluded breaths were removed. Volume corrected Scond was calculated from subjects with 3 valid runs. <h3>Results</h3> Far fewer subjects were excluded by the physiological Langley method, than by the mathematical method (Table). The mean and SD for Scond was identical by both methods, implying that the mathematical algorithm excludes valid data. <h3>Conclusion</h3> A physiological approach to data cleaning prior to SnIII analysis allows retention of data that would be inappropriately excluded mathematically. <h3>References</h3> Bigler A, <i>et al</i>. <i>Paediatric Pulmonol</i> 2015;<b>50</b>(8):805–13. Langley FE, <i>et al</i>. <i>Colloques INSERM</i> 1975;<b>51</b>:209–212.
The Large Pharmaceutical Company Perspective
Authors: Michael Rosenblatt
Journal: New England Journal of Medicine (2017)

Large pharmaceutical companies conduct clinical trials to evaluate efficacy and identify safety issues for candidate drugs as effectively, efficiently, and expeditiously as possible, while addressing simultaneously the requirements of regulatory authorities across the globe.To put the fewest people at risk and to learn the most, these trials often are configured to provide evidence for health care providers, regulatory approval, and reimbursement from health agencies.Because there are so many unknowns, pharmaceutical research and development is a high-risk business with the highest failure rate for new product candidates of any industry. High-Or der Comple x it y in Ou t comes Tr i a l s Conduc ted by L a rge Compa niesThe American libertarian L.K. Samuels wrote, "Complexity in a system tends to increase that system's inefficiency; the greater the number of variables, the greater the probability of those variables clashing, and in turn, the greater the potential for conflict and disarray.Because more can go wrong, more will." 1 Phase 3 outcomes trials conducted by large pharmaceutical companies are among the most complex experiments performed in medicine.In my opinion, it is this complexity that represents the single greatest challenge facing large pharmaceutical companies. 2,3lthough the hypothesis being tested may seem straightforward, the actual trial has many variables, is fraught with risk (both the scientific risk of experiment and the operational risk of implementation), and is often shaped by unexpected events that may be related not to the investigational drug but rather to the play of chance (Fig. 1, and see the interactive graphic, available with the full text of this article at NEJM.org).Success in this context requires broad expertise in the sciences fundamental to the therapeutic area being tested, talent in managing large and diverse teams, and a large, complex administrative apparatus.The activities of clinical investigators, protocol designers, statisticians, independent experts, project managers, institutional review boards, data and safety monitoring committees, manufacturers, quality controllers, suppliers, compliance officers, and others need to be orchestrated at multiple (sometimes hundreds) of trial sites in many countries.Many of these entities function under their own unique goals and rules.Outcomes trials of treatments for chronic diseases must be conducted over several years in order to accrue clinically meaningful information.These longer study cycle times are an additional source of complexity, with challenges in recruitment and retention. 3Failure to retain participants in a trial leads to the problem of "missing data" -which then becomes an issue in interpreting results on trial completion.Furthermore, "drop ins" (e.g., the patient's personal physician pre-
P2.03a-062 Characterization and Targeting of the DNA Repair Gene, XRCC6BP1, in Cisplatin Resistant NSCLC
Authors: Martin Barr, Saravjeet Singh, Emma Foley, Yuexi He, Vincent Young, Ronan Ryan, Siobhan Nicholson, Niamh Leonard, Sinead Cuffe, Kenneth O’Byrne, Stephen Finn
Journal: Journal of Thoracic Oncology (2017)