tbuckley/cabot-search huggingface dataset:
L-BLP25 treatment for advanced non-small cell lung cancer (NSCLC): Safety data from a phase IIb trial compared with an integrated safety analysis (ISA).
Authors: C. A. Butts, N. Murray, A. W. Maksymiuk, A. Price, G. D. Goss, D. Soulieres, I. Joerg, K. Tyroller, M. H. Falk, F. A. Shepherd
Journal: Journal of Clinical Oncology (2010)

e13058 Background: Safety data are not yet available for the potential long-term treatment of NSCLC with vaccines. In a phase IIB open-label, randomized trial, treatment with the therapeutic cancer vaccine L-BLP25 plus best supportive care (BSC) for stage IIIB and IV NSCLC improved median survival time over BSC alone (17.4 vs. 13.0 months, respectively). We report safety data for this trial and for an ISA of 5 completed trials for NSCLC (4 phase II, including the phase IIB trial, and 1 phase I) in which 153 patients (pts) received L-BLP25. Methods: In the phase IIB trial, pts were randomized to receive once-weekly doses of L-BLP25 (1000 μg sc) for 8 weeks, then L-BLP25 (1000 μg sc) at 6-week intervals plus BSC or BSC alone. Cyclophosphamide (CP) (300 mg/m2, iv single dose) was given 3 days before first L-BLP25 dose. All phase II trials used 1000 μg L-BLP25 primary doses, and either 1000 or 250 μg maintenance doses. The phase I trial compared 20 and 200 μg L- BLP25 primary and maintenance doses. Results: The frequencies of most adverse events (AEs) were comparable for the two treatment arms of the phase IIB trial (Table). However, ≥10% differences were observed between the treatment arms for AEs representing injection-site reactions (ISRs), flu-like symptoms, and rash. The most frequent AEs in both arms of the phase IIB trial and the ISA were those typical of underlying NSCLC or attributable to flu-like symptoms. Gastrointestinal AEs were common, with nausea for L-BLP25-treated pts primarily CP-related. The frequency of ISRs was similar for L-BLP25-treated pts in the phase IIB trial and the ISA. Serious AEs were reported for fewer pts in the L-BLP25 arm (33%) than the BSC arm (41%) in the phase IIB trial, and for 33% of pts in the ISA. Conclusions: Safety data from the phase IIB trial were comparable with the ISA data and confirmed a favorable safety profile for L-BLP25 in NSCLC. AEs with ≥25% incidence in either the phase IIB trial or the ISA AE (%) Phase IIB trial ISA BSC(n = 83) L-BLP25 + BSC(n = 88) L-BLP25(n = 153) Any 96 100 100 Cough 35 52 47 Fatigue 43 51 44 Nausea 41 50 54 Dyspnea 39 39 36 Anorexia 30 34 25 Back pain 19 31 25 Chest pain 19 31 25 Injection site erythema - 25 25 Headache 25 24 33 Arthralgia 19 20 25 Nodule - 16 25 Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Merck KGaA Merck Serono Merck KGaA Merck, Merck Serono EMD Serono
Stage I testicular tumor: How frequently to scan?
Authors: Sindhu Ramamurthy, Najibah Mahtab, Helen Showler, John A. Frew, Ian D. Pedley, Ashraf Azzabi, Jolene Brown, Rhona Margaret McMenemin
Journal: Journal of Clinical Oncology (2014)

380 Background: Testicular malignancy is the most common cancer affecting men aged between 15 and 44 years. In our centre, almost all low-risk seminoma (LRS) stage-I and non-seminomatous germ cell tumours (NSGCT) stage I (high and low-risk) tumours are followed-up on a surveillance program (SP) for a minimum of 5 years. LRS patients are scanned at 4, 6, and 12 monthly intervals during years 1, 2, and 3 to 5 years respectively. NSGCT undergo computer tomography (CT) scan at 3 monthly intervals in years 1 and 2, 4 monthly in year 3 and 6 monthly thereafter. Clinical examination, Chest X-ray (CXR) and tumour markers (TM) are performed at each visit. This retrospective audit examined if relapses were first detected by raised TM or radiologically, and if there was any difference in detection rate between these investigations to recommend reducing the frequency of CT scans, especially in lower risk groups, and therefore cumulative radiation exposure. Methods: The patient population was obtained from hospital electronic database. Metastatic patients, clinical trials patients and those who received adjuvant treatment upfront were excluded. Results: 396 patients were enrolled from 1999 to September 2013. 153 patients were followed-up in SP. 33 relapses (mean age 37 years, range 17-56) detected in SP. The mean relapse free survival period was 55.3 months (range 9.6-43.3) from date of diagnosis. No relapses were first detected on CXR. 4 patients had only TM elevated and 6 had CT abnormality found post TM elevation. 11 had simultaneous CT and TM abnormalities. For 12 patients, CT abnormality was detected with no TM raise. Of these, 8 were high risk (7 NSGCT and 1 pure seminoma) and 4 were low risk NSGCT. Patients were treated with standard BEP/EP chemotherapy regimen on relapse. All patients are alive to date and continue to be followed-up regularly. Conclusions: 12 patients in our study had relapses detected radiologically with no TM rise. 25% of these patients had low risk NSGCT. Without the CT scan, these patients would have faced potential delay in diagnosis and treatment. Results of prospective randomised trials are awaited to produce evidence to place confidence in less number of CT-scans for these patients during follow- up. Until then we recommend the current standard protocol be followed.
Human Papillomavirus–Associated Oropharyngeal Squamous-Cell Carcinoma
Authors: Adam L Holtzman, Kathryn Hitchcock
Journal: New England Journal of Medicine (2016)

A 68-year-old man presented with a mass on the left side of his neck. A biopsy was performed, and histopathological examination revealed squamous-cell carcinoma that was positive for HPV and overexpressed p16, a tumor-suppressor gene product.
Bivalirudin or unfractionated heparin in patients with acute coronary syndromes managed invasively with and without ST elevation (MATRIX): randomised controlled trial
Authors: Sergio Leonardi, Enrico Frigoli, Martina Rothenbühler, Eliano Navarese, Paolo Calabró, Paolo Bellotti, Carlo Briguori, Marco Ferlini, Bernardo Cortese, Alessandro Lupi, Salvatore Lerna, Dennis Zavallonito-Parenti, Giovanni Esposito, Simone Tresoldi, Antonio Zingarelli, Stefano Rigattieri, Cataldo Palmieri, Armando Liso, Fabio Abate, Marco Zimarino, Marco Comeglio, Gabriele Gabrielli, Alaide Chieffo, Salvatore Brugaletta, Ciro Mauro, Nicolas M Van Mieghem, Dik Heg, Peter Jüni, Stephan Windecker, Marco Valgimigli
Journal: BMJ (2016)

To test the optimal antithrombotic regimen in patients with acute coronary syndrome. Randomised controlled trial. Patients with acute coronary syndrome with and without ST segment elevation in 78 centres in Italy, the Netherlands, Spain, and Sweden. 7213 patients with acute coronary syndrome and planned percutaneous coronary intervention: 4010 with ST segment elevation and 3203 without ST segment elevation. The primary study results in the overall population have been reported previously. Patients were randomly assigned, in an open label fashion, to one of two regimens: bivalirudin with glycoprotein IIb/IIIa inhibitors restricted to procedural complications or heparin with or without glycoprotein IIb/IIIa inhibitors. Primary endpoints were the occurrence of major adverse cardiovascular events, defined as death, myocardial infarction or stroke; and net adverse clinical events, defined as major bleeding or major adverse cardiovascular events, both assessed at 30 days. Analyses were performed by the principle of intention to treat. Use of a glycoprotein IIb/IIIa inhibitor in patients assigned to heparin was planned at baseline in 30.7% of patients with ST segment elevation, in 10.9% without ST segment elevation, and in no patients assigned to bivalirudin. In patients with ST segment elevation, major adverse cardiovascular events occurred in 118 (5.9%) assigned to bivalirudin and 129 (6.5%) assigned to heparin (rate ratio 0.90, 95% confidence interval 0.70 to 1.16; P=0.43), whereas net adverse clinical events occurred in 139 (7.0%) patients assigned to bivalirudin and 163 (8.2%) assigned to heparin (0.84, 0.67 to 1.05; P=0.13). In patients without ST segment elevation, major adverse cardiovascular events occurred in 253 (15.9%) assigned to bivalirudin and 262 (16.4%) assigned to heparin (0.97, 0.80 to 1.17; P=0.74), whereas net adverse clinical events occurred in 262 (16.5%) patients assigned to bivalirudin and 281 (17.6%) assigned to heparin (0.93, 0.77 to 1.12; P=0.43). A bivalirudin monotherapy strategy compared with heparin with or without glycoprotein IIb/IIIa inhibitors, did not result in reduced major adverse cardiovascular events or net adverse clinical events in patients with or without ST segment elevation.Trial Registration ClinicalTrials.gov NCT01433627.
A persistent cough
Authors: H L Adams, D C Howlett
Journal: BMJ (2016)

A 60 year old woman presented with a hoarse voice and persistent dry cough. Flexible nasendoscopy showed a smooth, round swelling on the posterior third of the tongue.

What abnormality is shown in the midline at the posterior tongue base on this axial T2 weighted magnetic resonance image (fig 1⇓)?



Fig 1  Axial section, T2 weighted magnetic resonance image at the level of the tongue base.



A cystic remnant of the thyroglossal duct (thyroglossal cyst).

### Discussion

The magnetic resonance image shows a thin walled, cystic lesion in the …
Circulating tumour DNA carrying patient-specific mutations in TP53 as an early response biomarker in relapsed high grade serous ovarian cancer.
Authors: Christine A. Parkinson, Davina Gale, Anna Piskorz, Charlotte Hodgkin, Heather Biggs, Helen Addley, Penny Moyle, Sue Freeman, Evis Sala, Karen Hosking, Ioannis Gounaris, Mercedes Jimenez-Linan, Helena Margaret Earl, Wendi Qian, Nitzan Rosenfeld, James D. Brenton
Journal: Journal of Clinical Oncology (2016)

e23040 Background: Novel biomarkers are required to accurately assess tumour burden and response in cancer. In patients with relapsed high-grade serous ovarian carcinoma (HGSOC) we tested (i)if TP53 mutations in circulating tumour DNA (ctDNA) could be used as a personalised biomarker and (ii) if changes after 1 cycle of chemotherapy could predict progression free survival (PFS). Methods: Formalin-fixed paraffin-embedded tumour tissue and serial plasma samples were collected from 31 patients with relapsed HGSOC during a total of 51 lines of chemotherapy. Patient-specific assays were developed to quantify TP53 ctDNA allele fraction (AF) using microfluidic digital PCR and were compared with CA125 as the gold standard. Patients were considered assessable for ctDNA response if they had a baseline ctDNA sample within 14 days of cycle 1 of chemotherapy, a matched sample prior to cycle 2 of chemotherapy, and evaluable ctDNA ( > 40 mutant TP53 allele counts/ml). Results: TP53 ctDNA was detectable at baseline in 43/51 (84%) of chemotherapy lines compared with 49/51 (95%) for CA125. Median TP53 ctDNA AF at baseline was 0.08 (IQR: 0.012-0.22) and median CA125 was 422 (IQR: 205-1108). Median time to nadir was 37 days for TP53 ctDNA AF compared with 70 days for CA125. 32 lines of chemotherapy were assessable for ctDNA response. Median fall after 1 cycle of chemotherapy was 74% for TP53 ctDNA AF, and 17% for CA125. On univariate analysis, fall in TP53 ctDNA AF and volume of disease were significantly associated with PFS. On multivariate analysis only a fall in TP53 ctDNA AF was an independent predictor of PFS (HR of 0.26, CI 0.078-0.929, p = 0.038). A fall of less than 60% TP53 ctDNA AF after 1 cycle defined poor responders and predicted progression within 6 months (and progression on CT by the end of treatment) with 71% sensitivity and 88% specificity. When only patients without recent ascitic or pleural drains were analysed (n = 24), sensitivity increased to 75% and specificity to 100%. Conclusions: Quantitation of TP53 ctDNA is a promising biomarker for response in patients with relapsed HGSOC. A reduction of < 60% of TP53 ctDNA AF by cycle 2 of chemotherapy treatment may predict poor outcome.
Prognostic factors for response and survival of second-line chemotherapy in patients with relapsed small cell lung cancer (SCLC)
Authors: Y. Kim, K. Goto, K. Yoh, S. Niho, H. Ohmatsu, K. Kubota, N. Saijo, Y. Nishiwaki
Journal: Journal of Clinical Oncology (2007)

18023 Background: Despite high response rates to initial chemotherapy, the majority of patients with SCLC experience tumor progression. Previous studies showed that both the response to initial chemotherapy and the response duration are important for predicting the efficacy of second-line chemotherapy. Therefore, relapsed SCLC is commonly classified into two groups: sensitive relapse (respond to initial chemotherapy and relapse more than 3 months after the completion of initial chemotherapy) and refractory relapse (not respond to initial chemotherapy or respond but relapse within 3 months). However, prognostic factors of the second-line chemotherapy have not been fully understood. Methods: From July 1992 to December 2003, four hundred and seventy-four patients with SCLC received chemotherapy as initial treatment, subsequently 229 patients received second-line chemotherapy (144 sensitive relapse and 85 refractory relapse) in our hospital. We analyzed the association of patients’ clinical factors with response and survival of second-line chemotherapy in sensitive relapsed patients and refractory relapsed patients, separately. For sensitive relapsed patients, analyzed clinical factors were as follows: age (&lt;70/=70), gender (M/F), response to initial chemotherapy (CR/PR), PS at relapse (&lt;2/=2) and the extent of disease at relapse (LD/ED). For refractory relapsed patients, analyzed clinical factors were as follows: age (&lt;70/=70), gender (M/F), response to initial chemotherapy (responder/non-responder), PS at relapse (&lt;2/=2) and the extent of disease at relapse (LD/ED). Results: Response to second-line chemotherapy was significantly correlated with PS in sensitive relapsed patients, however, no significant factor was detected in refractory relapsed patients. For survival, PS was the only significant prognostic factor in both sensitive and refractory relapsed patients. The median survival time was 328 days (PS&lt;2) and 128 days (PS=2) in sensitive relapsed patients (p&lt;0.0001), while 195 days (PS&lt;2) and 113 days (PS=2) in refractory relapsed patients (p=0.0001), respectively. Conclusions: PS was the only significant prognostic factor for survival both in sensitive and refractory relapsed SCLC. No significant financial relationships to disclose.
Pooled Safety Analysis From Phase (Ph) 1 and 2 Studies of Carfilzomib (CFZ) In Patients with Relapsed and/or Refractory Multiple Myeloma (MM)
Authors: Seema B. Singhal, David Samuel diCapua Siegel, Thomas Martin, Ravi Vij, Michael Wang, Andrzej J Jakubowiak, Sagar Lonial, Vishal Kukreti, Jeffrey A. Zonder, Alvin F. Wong, Leanne McCulloch, Michael Kauffman, Ashraf Z. Badros, Ruben Niesvizky, Robert Z. Orlowski, A. Keith Stewart, Sundar Jagannath
Journal: Blood (2010)
Right ventricular dysfunction in heart failure with preserved ejection fraction: a systematic review and meta‐analysis
Authors: Thomas M. Gorter, Elke S. Hoendermis, Dirk J. van Veldhuisen, Adriaan A. Voors, Carolyn S.P. Lam, Bastiaan Geelhoed, Tineke P. Willems, Joost P. van Melle
Journal: European Journal of Heart Failure (2016)
P1052 : An imbalance between Th17 and Treg key to pathogenesis of non-alcoholic fatty liver disease in morbidly obese patients
Authors: P. Iruzubieta, M.T. Arias-Loste, A. Domínguez, A. López-Useros, C. Santa Cruz, Á. Estébanez, D. San Segundo, D. Ramos, A. Azueta, S. Llerena, C. Alonso, J. Cabezas, M. López Hoyos, J. Crespo
Journal: Journal of Hepatology (2015)
Abstract 11821: An International Perspective of Current Patterns of Antiplatelet Drug Use in Acute Coronary Syndrome Patients. Results from the EPICOR Study
Authors: Hector Bueno, Robert F Storey, Nicolas Danchin, Joaquin Sanchez-Coviza, Muriel Licours, Lieven Annemans, J. W Jukema, Uwe Zeymers, Frans Van de Werf
Journal: Circulation (2012)

Purpose. To describe the current patterns of utilization of antiplatelet therapies (AT) before and during hospitalization for acute coronary syndromes (ACS). Methods. EPICOR (NCT01171404) is a prospective international observational study (10,568 patients enrolled in 555 primary, secondary and tertiary care hospitals in 20 countries across Europe and Latin America between September 1, 2010, and March 31, 2011, prior to availability of ticagrelor) designed to describe current use of AT before, during and after hospitalization in a broad ACS population. This is the descriptive analysis of the patterns of AT use in the acute phase of ACS care (before hospital discharge). Results. Of all possible combinations, most patients were treated with aspirin (A) and clopidogrel (C) (n=7369, 69.7%), followed by triple AT (TAT) (n=1706, 16.1%) with either A+C+GPIIb/IIIa inhibitors (GPI), or A+prasugrel (P)+GPI. Other ATs included P±A (572, 5.4%), A alone±GPI (559, 5.3%), and C alone±GPI (292, 2.8%). Overall, patients tr...
Pharmacogenomic Markers of Clinical Efficacy in a Dose-Dense Therapy Regimen (R-CHOP14) in Diffuse Large B Cell Lymphoma
Authors: Cristina Napoli, Stefania Nobili, Ida Landini, Gabriele Perrone, Angela Valenti, Marco Brugia, Benedetta Puccini, Gemma Benelli, Morena Doria, Maurizio Martelli, Erica Finolezzi, Alice Di Rocco, Simonetta di Lollo, Luigi Rigacci, Alberto Bosi, Enrico Mini
Journal: Blood (2011)
The role of adjuvant radiotherapy after marginal excision for local control of extremity and truncal soft tissue sarcoma
Authors: Y. B. Kim, K. H. Shin, G. E. Kim, S. B. Han, J. K. Roh, C. O. Suh
Journal: Journal of Clinical Oncology (2006)

9573 Background: Adjuvant radiotherapy (RT) has been shown to improve local control (LC) in patients with extremity and truncal soft tissue sarcoma (STS). The purpose of this study was to analyze how much RT promoted LC in patients with marginally excised STS compared with patients with widely excised STS. Methods: Two hundred and thirty-two patients with STS (173 extremity cases and 59 trunk cases) who had received conserving surgery were divided into 3 groups according to marginal status and the addition of RT; (1) wide excision alone (n = 56, Group A), (2) wide excision plus RT (n = 64, Group B) and (3) marginal excision plus RT (n = 112, Group C). LC, overall survival, and morbidity rates were retrospectively compared among 3 groups. Results: There were no differences in age, gender, pathologic type, and tumor site among three groups, but Group A had the higher incidence of small-sized tumor and low grade tumor than other groups. Thirty-eight patients experienced local failures (LF) after completion of treatment. Group C had similar incidence of LF compared with Group B (Group A; 4%, Group B; 21%, and Group C; 19%). Overall 5-year and 10-year LC rates were 80% and 70%, and there were no significant differences between Group B and Group C in 10-year LC rate (Group A; 84%, Group B; 65%, and Group C; 68%). Tumor grade and tumor site were found to be significant predictors of LF. Group C had lower 10-year overall actuarial survival rate compared with Group B (Group A; 85%, Group B; 78%, and Group C; 69%). This was associated with significantly different incidence of distant failure (Group A; 11%, Group B; 16%, and Group C; 29%, p=0.008). Seven patients suffered from wound dehiscence, and 1 patient from bone necrosis. The incidence of Grade 3–4 late complication was higher in Group B than Group A and Group C (Group A; 0%, Group B; 9.3%, and Group C; 1.7%, p=0.03). Conclusions: Our data indicate that RT seems to promote LC in patients with positive or close margin up to that of patients with wide margin in extremity and truncal STS. We suggest that conserving surgery and RT for patients with marginal STS should be the alternative choice rather than aggressive surgery for better LC without deteriorating limb-function or causing serious complication. No significant financial relationships to disclose.
Effect of Empagliflozin on Left Ventricular Mass and Diastolic Function in Individuals With Diabetes: An Important Clue to the EMPA-REG OUTCOME Trial?
Authors: Subodh Verma, Ankit Garg, Andrew T. Yan, Anup K. Gupta, Mohammed Al-Omran, Andre Sabongui, Hwee Teoh, C. David Mazer, Kim A. Connelly
Journal: Diabetes Care (2016)

Amid the excitement over the results of the BI 10773 (Empagliflozin) Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients (EMPA-REG OUTCOME) trial (1), the potential mechanisms through which empagliflozin produced a rapid and profound reduction in hospitalization for heart failure and cardiovascular (CV) death in subjects with type 2 diabetes remain entirely unexplained. Importantly, the effects of empagliflozin on objective measures of cardiac structure and function are unknown (2). We report the first systematic analysis of echocardiograms of 10 patients with type 2 diabetes and established CV disease in whom empagliflozin 10 mg/day was initiated as per approved clinical indication, without any other concurrent changes in medications. Transthoracic echocardiograms, performed before and 3 months after initiation of empagliflozin, were analyzed by an experienced cardiac echocardiographer not involved in the clinical care of the patients and blinded to identity of the patients and the study order (pre vs. post). Informed patient consent and ethics approval were obtained.

Baseline patient characteristics were as follows: 80% were men, age was mean (SD) 67.6 (6.6) years, 40% had a previous myocardial infarction, 90% had undergone vascularization, and estimated glomerular filtration rate was 77.5 (21.3) mL/min/1.73 m2. Background medications included the following: eight patients on metformin, five patients on dipeptidyl peptidase-4 inhibitors, one …
EARLY PREDICTION OF DELIRIUM IN ICU PATIENTS (E-PRE-DELIRIC): MULTINATIONAL DEVELOPMENT ANT) VALIDATION OF AN EARLY DELIRIUM PREDICTION MODEL FOR INTENSIVE CARE PATIENTS
Authors: A Wassenaar, M van den Boogaard, Theo van Achterberg, A Slooter, M Kuiper, M Hoogendoorn, K Simons, E Maseda, N Pinto, C Jones, A Luetz, A Schandl, W Verbrugghe, L Aitken, F van Haren, R Donders, L Schoonhoven
Journal: Intensive Care Medicine (2014)