tbuckley/cabot-search huggingface dataset:
Evaluation of thyroid dysfunction as a candidate surrogate marker for efficacy of sunitinib in patients (pts) with advanced renal cell cancer (RCC)
Authors: P. Wolter, C. Stefan, B. Decallonne, H. Dumez, S. Fieuws, H. Wildiers, P. Clement, D. Debaere, A. Van Oosterom, P. Schöffski
Journal: Journal of Clinical Oncology (2008)

5126 Background: Sunitinib is a multi-target tyrosine kinase inhibitor with anti-angiogenic and anti-proliferative activity mediated by signal blockade of VEGFR1/2, KIT, PDGFR α/β, and FLT-3. Sunitinib has recently been approved for the treatment of RCC. Several studies have identified biochemical thyroid function test (TFT) abnormalities in approximately 2/3 of pts under sunitinib treatment. The possible association of the incidence of sunitinib-induced thyroid dysfunction and progression-free (PFS) and overall survival (OS) has not been analyzed yet. Methods: Thyroid function was evaluated prospectively in pts with advanced RCC on days l and 28 of each treatment cycle. Sunitinib was given at a daily oral dose of 50 mg 4 weeks on, 2 weeks off. For the statistical analysis the Kaplan-Meier method was used to construct curves for PFS and OS. The log-rank test was used to compare between pts with and without biochemical thyroid abnormalities. The analysis has been performed with SAS (version 9.1). The alpha-level has been set at 5%. No corrections have been made for multiple testing. Results: From 11/2005 to 12/2007 53 pts received sunitinib and 40 of them [m: 30, f: 10, median age 59 (42–81) years] were evaluable for thyroid function. In total, 28/40 pts (70%) developed TFT abnormalities: 13 pts (32.5%) developed clinical hypothyroidism requiring hormone substitution. Only in 12 pts (30%) no TFT abnormalities were observed. The median PFS was 3.6 mo (95%CI: 2.3 - 6.0) when there was no biochemical thyroid abnormality and 10.3 months (95%CI: 5.0 - 18.4 mo) in presence of biochemical TFT abnormalities (log rank p = 0,047). The median OS was 6.6 mo (95%CI: 3.3 - 7.9) when there was no biochemical thyroid abnormality and 18.2 mo (95%CI: 7.5 - 22.3) in presence of biochemical abnormalities (log rank p = 0,13). Conclusions: In pts with advanced RCC we observed a positive correlation between sunitinib-induced thyroid dysfunction and clinical outcome that requires further prospective evaluation. Understanding the biology and etiology of sunitinib-induced thyroid dysfunction and assessing its correlation with treatment outcome will help to define the role of thyroid dysfunction as a surrogate marker for efficacy of sunitinib in pts with advanced RCC. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Pfizer Oncology
Standardizing Co-Culture Conditions Between Chronic Lymphocytic Leukemia Cells and Marrow Stromal Cells: Towards a Reliable and Reproducible System to Assess Cell Adhesion-Mediated Drug Resistance
Authors: Antonina Kurtova, Maite P. Quiroga, William G. Wierda, Michael Keating, Jan A. Burger
Journal: Blood (2008)
Cisplatin-based radiochemotherapy in elderly patients with cervical cancer.
Authors: A. Rodica Maricela, L. Minea, X. Bacinschi, I. Isacu, A. Tarlea, M. Nedelcu
Journal: Journal of Clinical Oncology (2010)

e15550 Background: Cervical cancer is a major health problem in Romania because it has advanced stages at diagnose. Older female is a sensible patient category, but their number is in constant increase. We intended to evaluate the efficacy and tolerability of combined conservative treatment for elderly patients with cervical cancer. Methods: Between Jan 2004 and Nov 2007 we treated 63 older patients (median age 75.5 years; range 70 – 86 years) with locally advanced cervical cancer. There were 28 FIGO stage IIB and 35 FIGO stage III patients. All patients had good performance status (ECOG 0-2). 39.7% of patients have concomitant cardiovascular diseases. The treatment consisted in external radiation therapy (total dose 45-50 Gy), HDR brachytherapy (total dose 15-22.5 Gy at point A) and concomitant chemotherapy. The chemotherapy was only platinum salt cisplatin, administered on a weekly schedule (40 mg/sqm on a 30 minutes infusion, weekly during the radiation therapy). The patients received four chemotherapy cycles with 5-FU and cisplatin after irradiation. The response rates were assessed at the end of radiochemotherapy. The follow up period was two years, to determine survival rate and late toxicities. Results: The treatment related acute toxicities were grade 2-3 digestive (55.5%), grade 3-4 hematology (30.1%), and febrile neutropenia (12.7%). Late toxicities were rectitis (14.3%), cystitis (15.9%), grade 2-3 neurological (19%), grade 2 renal function impairment (11.1%), and pelvic fibrosis (14.3%). Some of the complications caused treatment delay but only 3 patients did not finish the intended therapy. Overall treatment was prolonged in 27 cases. No patient died from acute toxicity. Response rates were complete response in 10 patients, partial response in 41 patients, stable disease in 8 patients and progressive disease in 4 patients. Two-year survival rate was 68.25% for stage II and 33.33% for stage III. Conclusions: Elderly patients with locally advanced cervical cancer but good performance status tolerated the curative intended concomitant radiochemotherapy. The toxicities were acceptable and the two-year survival rates were encouraging. This combined therapy may be a good alternative to surgery in elderly patients. No significant financial relationships to disclose.
Regulatory agencies should engage in drug pricing
Authors: Raffaella Ravinetto, Gianluca Gaidano
Journal: BMJ (2016)

Mazzucato argues that drug pricing policies “must be completely transparent, so that governments can negotiate for better value on behalf of their populations.”1 She also observes that the US government never exercised its right to cap prices of drugs developed through publicly funded research.2 In Europe, the European Medicines …
What is the evidence base for atopic eczema treatments? A summary of published randomized controlled trials
Authors: H. Nankervis, K.S. Thomas, F.M. Delamere, S. Barbarot, S. Smith, N.K. Rogers, H.C. Williams
Journal: British Journal of Dermatology (2016)

Atopic eczema (AE) is a common chronic inflammatory skin condition. While many AE treatment options are available, the evidence to support their efficacy varies in depth and quality. In 2000, a National Institute for Health Research (NIHR) Health Technology Assessment systematic review identified and evaluated existing randomized controlled trials (RCTs) of AE treatments. To ensure continuing utility, the NIHR commissioned an update to the review. Here, we present an overview of the updated report and its key findings. Systematic reviews and RCTs of AE treatments that included participants with AE (criteria based or diagnosed) were identified using Medline, Embase, CENTRAL, Latin American and Caribbean Health Sciences, Allied and Complementary Medicine Database, Cumulative Index to Nursing and Allied Health Literature and Cochrane Skin Group Specialised Register [searched to 31 August 2013 (RCTs) and 31 December 2015 (systematic reviews)]. Outcome measures included symptoms, AE severity, quality of life and adverse effects. Study quality was assessed using the Cochrane Collaboration risk of bias tool. Of the 287 new RCTs identified, only 22 (8%) were judged to have a low risk of bias. When combined with RCTs from the previous review (n = 254), we found 'reasonable evidence of benefit' for corticosteroids, calcineurin inhibitors, Atopiclair® , ciclosporin, azathioprine, ultraviolet radiation and education programmes. Interventions with reasonable evidence of 'no benefit' included some dietary interventions, ion exchange water softeners, multiple daily applications of topical corticosteroids and antibiotic-containing corticosteroids for noninfected AE. Many common treatments lack evidence of efficacy and warrant further evaluation. The evidence base for AE is still hampered by poor trial design and reporting. The trials included in this review were used to establish the Global Resource of EczemA Trials (GREAT) database.
Venetoclax responses of pediatric ALL xenografts reveal sensitivity of MLL-rearranged leukemia
Authors: Seong Lin Khaw, Santi Suryani, Kathryn Evans, Jennifer Richmond, Alissa Robbins, Raushan T. Kurmasheva, Catherine A. Billups, Stephen W. Erickson, Yuelong Guo, Peter J. Houghton, Malcolm A. Smith, Hernan Carol, Andrew W. Roberts, David C. S. Huang, Richard B. Lock
Journal: Blood (2016)
P270 Identifying the optimal D-dimer cut off value for ruling out PEs in an ambulatory care setting: Abstract P270 Table 1
Authors: FA Khan, K Ryanna, E Bailie, Y Vali
Journal: Thorax (2015)

<h3>Introduction</h3> Patients attending the ambulatory pulmonary embolism (PE) clinic at the Glenfield Hospital are risk stratified into low, intermediate and high risk based on the BTS scoring.<sup>1</sup> Those with a low or intermediate pre-test probability go on to have a microlatex D-dimer assay and if this is greater than 0.5 ug/mL, imaging in the form of CTPA or VQ scan is carried out. It has been suggested that using a higher cut off value of D-dimer may improve specificity without affecting sensitivity for a PE. <h3>Methods</h3> Data was collected for 2139 consecutive patients who presented to the ambulatory PE clinic between June 2010 and Dec 2014. For each of these patients, age, BTS clinical probability, D-dimer results and final diagnosis was recorded. Receiver operating characteristics (ROC) curve analysis was performed separately for patients with low and intermediate probability, and the optimum cut-off value to exclude PE determined. <h3>Results</h3> Of the 2139 patients, prevalence of PE was 3.2% (50/1535) in the low, 14.2% (63/443) in the intermediate and 26% (42/161) in the high probability group. No patients with a D-dimer of &lt;0.5 ug/mL who were discharged without any radiological investigations have returned with a missed diagnosis of PE. ROC curve analysis showed the optimum D-dimer cut off value in low risk patients was 0.52, and 0.57 in patients with an intermediate risk. <h3>Conclusion</h3> The optimum D-dimer value must be chosen in the context of missed PEs versus scanning fewer people and thus avoiding unnecessary radiation and using resources more efficiently. A higher D-dimer of 1.0 ug/mL would have correctly avoided 161 scans and subsequently saved over £19,000.<sup>2</sup> This must be offset however against patients being incorrectly diagnosed and often ending up in hospital with complications. Using the same cut off of 1.0 ug/mL would have missed a total of 22 PE’s during the study period. Based on this the conventional D-dimer cut off value of 0.5 ug/mL is most appropriate for patients attending the ambulatory PE clinic. <h3>References</h3> 1 Venous Thromboembolic diseases: the management of venous thromboembolic diseases and the role of thrombophilia testing. Costing report. NICE, June 2012 2 British Thoracic Society guidelines for the management of suspected acute pulmonary embolism.<i> Thorax</i> 2003;<b>58</b>:470-484
Neural Predictors of Initiating Alcohol Use During Adolescence
Authors: Lindsay M. Squeglia, Tali M. Ball, Joanna Jacobus, Ty Brumback, Benjamin S. McKenna, Tam T. Nguyen-Louie, Scott F. Sorg, Martin P. Paulus, Susan F. Tapert
Journal: American Journal of Psychiatry (2016)

Underage drinking is widely recognized as a leading public health and social problem for adolescents in the United States. Being able to identify at-risk adolescents before they initiate heavy alcohol use could have important clinical and public health implications; however, few investigations have explored individual-level precursors of adolescent substance use. This prospective investigation used machine learning with demographic, neurocognitive, and neuroimaging data in substance-naive adolescents to identify predictors of alcohol use initiation by age 18.Participants (N=137) were healthy substance-naive adolescents (ages 12-14) who underwent neuropsychological testing and structural and functional magnetic resonance imaging (sMRI and fMRI), and then were followed annually. By age 18, 70 youths (51%) initiated moderate to heavy alcohol use, and 67 remained nonusers. Random forest classification models identified the most important predictors of alcohol use from a large set of demographic, neuropsychological, sMRI, and fMRI variables.Random forest models identified 34 predictors contributing to alcohol use by age 18, including several demographic and behavioral factors (being male, higher socioeconomic status, early dating, more externalizing behaviors, positive alcohol expectancies), worse executive functioning, and thinner cortices and less brain activation in diffusely distributed regions of the brain.Incorporating a mix of demographic, behavioral, neuropsychological, and neuroimaging data may be the best strategy for identifying youths at risk for initiating alcohol use during adolescence. The identified risk factors will be useful for alcohol prevention efforts and in research to address brain mechanisms that may contribute to early drinking.
Specific IgE to Jug r 1 has no additional value compared with extract-based testing in diagnosing walnut allergy in adults
Authors: Mark A. Blankestijn, W. Marty Blom, Henny G. Otten, Joe L. Baumert, Steve L. Taylor, Carla A.F.M. Bruijnzeel-Koomen, Geert F. Houben, André C. Knulst, Rob J.B. Klemans
Journal: Journal of Allergy and Clinical Immunology (2016)
Urokinase Antimetastatic Effects—Letter
Authors: ShahSultan Mirshahi, Eric Pujade-Lauraine, Claudine Soria, Marc Pocard, Massoud Mirshahi, Jeannette Soria
Journal: Cancer Research (2016)

We were surprised by the results of Choi and colleagues showing that urokinase exerts antimetastatic effects by dissociating clusters of circulating tumor cells ([1][1]).

It is well known that the role of urokinase (uPA) in cancer is not limited to the vascular compartment, but is also a critical
Global Estimates on the Number of People Blind or Visually Impaired by Diabetic Retinopathy: A Meta-analysis From 1990 to 2010
Authors: Janet L. Leasher, Rupert R.A. Bourne, Seth R. Flaxman, Jost B. Jonas, Jill Keeffe, Kovin Naidoo, Konrad Pesudovs, Holly Price, Richard A. White, Tien Y. Wong, Serge Resnikoff, Hugh R. Taylor
Journal: Diabetes Care (2016)

To estimate global and regional trends from 1990 to 2010 of the prevalence and number of persons visually impaired specifically by diabetic retinopathy (DR), as a complication of the precipitous trends in global diabetes, is fundamental for health planning purposes.The meta-analysis of published population studies from 1990 to 2012 for the Global Burden of Disease Study 2010 (GBD) yielded estimated global regional trends in DR among other causes of moderate and severe vision impairment (MSVI; presenting visual acuity <6/18, ≥3/60) and blindness (presenting visual acuity <3/60).Globally in 2010, out of overall 32.4 million blind and 191 million visually impaired people, 0.8 million were blind and 3.7 million were visually impaired because of DR, with an alarming increase of 27% and 64%, respectively, spanning the two decades from 1990 to 2010. DR accounted for 2.6% of all blindness in 2010 and 1.9% of all MSVI worldwide, increasing from 2.1% and 1.3%, respectively, in 1990. These figures were lower in regions with younger populations (<2% in East and Southeast Asia and Oceania) than in high-income regions (North America, Western Europe, and Australasia) with relatively aging populations (>4%).The number of persons with visual impairment due to DR worldwide is rising and represents an increasing proportion of all blindness/MSVI causes. Age-standardized prevalence of DR-related blindness/MSVI was higher in sub-Saharan Africa and South Asia. One out of 39 blind people had blindness due to DR, and 1 out of 52 visually impaired people had visual impairment due to DR.
Pilot study of intravenous pegylated liposomal doxorubucin (PLD) and intraperitoneal (IP) carboplatin in recurrent ovarian cancer.
Authors: J. Rahaman, V. G. Kolev, L. T. Chuang
Journal: Journal of Clinical Oncology (2010)

e15547 Background: The combination of intravenous carboplatin and PLD is one of the most active regimens in recurrent ovarian cancer. The present pilot study was designed to assess the feasibility, efficacy and safety of the combination of intraperitoneal (IP) carboplatin (AUC = 5) and intravenous PLD (30 mg/m2) given every 21 days in recurrent ovarian cancer. Methods: Patients with recurrent stage I to IIIC epithelial ovarian cancer were evaluated by laparoscopy and if the residual disease was optimal (< 1 cm) were considered candidates for this pilot study. Abdominal port-a-catheters were placed at the time of laparoscopy. Intravenous PLD (30 mg/m2 at a fixed dose) and IP carboplatin (AUC = 5) was given every 21 days. The carboplatin was reduced for toxicities. Patients with catheter issues were converted to intravenous carboplatin. Results: 7 patients were enrolled from January 2008 to August 2009 with a median age of 55 (range 48 to 82 ). 5 of the seven patients required laparoscopic cytoreduction to achieve optimal residual disease. Median # of previous treatments was 1 (range 1 to 3). 3 of 7 were platinum sensitive. 34 cycles were administered (range 2- 7, median = 5). 2/7 patients had catheter related issues and received only 2 and 3 cycles of IP chemotherapy respectively. 2/7 patients required dose reductions of the IP carboplatin for grade 3 and 4 neutropenia and grade 2 thrombocytopenia. There was 2 patients with grade 2 GI toxicities. 4/7 patients had grade 3 and 4 neutropenia and GCSF support was required in 3 patients. 4 patients were evaluable and all had complete clinical responses. 2/4 patients underwent a laparoscopic evaluation post therapy, 1 was completely negative and the other had negative surgical biopsies with isolated positive peritoneal washings. Conclusions: Intravenous PLD (30 mg/m2) and intraperitoneal carboplatin (AUC = 5) is a feasible, well tolerated and promising option in recurrent ovarian cancer. These preliminary results are encouraging and deserve further study in a larger uniform cohort. No significant financial relationships to disclose.
Case 32-1965
Authors: Allan I. Sandler, Benjamin Castleman
Journal: New England Journal of Medicine (1965)

Presentation of CaseAn eighty-five-year-old retired naval architect was admitted to the hospital because of confusion.He had been well except for a "heart attack" twenty years previously, from which there was full recovery. During the three years before admission it was believed that his "mind was slipping." Three months before entry he was treated for pneumonia at another hospital. On several occasions during the week before admission he failed to recognize his wife and family. Two days before entry he fell down several steps and became incontinent of urine. On the day of admission twitching of one side of . . .
Incidence of thyroid dysfunction in renal cell carcinoma (RCC) patients treated with pazopanib in prospective clinical trials.
Authors: P. Wolter, L. McCann, C. N. Sternberg, T. E. Hutson, F. Mehmud, L. N. Pandite, P. Schoffski
Journal: Journal of Clinical Oncology (2011)

4633 Background: Pazopanib is a small molecule, selective, multi tyrosine kinase inhibitor (TKI), targeting vascular endothelial growth factor receptors (VEGFR)-1, -2 and -3, c-kit and platelet derived growth factor receptor (PDGF-R). Pazopanib is approved for the treatment of advanced RCC and is given by oral daily dosing. Other TKIs for this indication induce thyroid dysfunction in up to 85% of patients (pts) (Rini, B 2007). The incidence and severity of thyroid dysfunction were explored in pazopanib-treated pts participating in 3 trials, where thyroid function tests were systematically assessed. Methods: Thyroid function data from 578 RCC pts participating in trials VEG102616 (phase II), VEG105192 (phase III), and VEG107769 (phase III extension) were analyzed. Serum TSH values were collected at baseline and every 12 weeks. Free T3 and T4 were assessed at baseline and when TSH was abnormal during treatment. Results: In 578 pts, the incidence of elevated TSH at baseline (>5 MU/L) was 37 (6%).167 (29%) pts had a TSH value of >5 MU/L during treatment; 97 (17%) pts had TSH values of >5-10 MU/L during treatment; 45 (8%) pts had TSH values of >10-20 MU/L, and 25 (4%) pts had TSH values of >20 MU/L. Hypothyroidism (TSH >5-10 MU/L and T4 <LLN) was observed in 19 (3%) pts. Hypothyroidism with TSH >10 MU/L and T4<LLN was diagnosed in 15 (3%) pts. Hyperthyroidism, defined as TSH <0.3 MU/L and T4>ULN, was seen in 8 (1%) pts. Thyroid replacement therapy was received by 20 (3%) pts with a TSH elevation. Hypothyroidism was reported as an AE in 26 (4%) pts (15 Grade 1, 10 Grade 2 and 1 unknown grade) by the investigators. Thyroid dysfunction was never reported as a severe adverse event in any pt. Conclusions: In clinical trials, pazopanib, the most recently approved treatment for advanced RCC, lead to a very low incidence of thyroid dysfunction. The low rate of hypothyroidism may partly explain the low incidence of fatigue (19%) and asthenia (14%) with pazopanib (Sternberg 2010), given these conditions can result from hypothyroidism. As fatigue has a profound detrimental effect on HRQoL in RCC pts (Larkin 2010), this data should be considered when making clinical treatment decisions in pts with advanced RCC.
VEGF Potentiates GD3-Mediated Immunosuppression by Human Ovarian Cancer Cells
Authors: Irina V. Tiper, Sarah M. Temkin, Sarah Spiegel, Simeon E. Goldblum, Robert L. Giuntoli, Mathias Oelke, Jonathan P. Schneck, Tonya J. Webb
Journal: Clinical Cancer Research (2016)

Abstract Purpose: Natural killer T (NKT) cells are important mediators of antitumor immune responses. We have previously shown that ovarian cancers shed the ganglioside GD3, which inhibits NKT-cell activation. Ovarian cancers also secrete high levels of VEGF. In this study, we sought to test the hypothesis that VEGF production by ovarian cancers suppresses NKT-cell–mediated antitumor responses. Experimental Design: To investigate the effects of VEGF on CD1d-mediated NKT-cell activation, a conditioned media model was established, wherein the supernatants from ovarian cancer cell lines (OV-CAR-3 and SK-OV-3) were used to treat CD1d-expressing antigen-presenting cells (APC) and cocultured with NKT hybridomas. Ovarian cancer–associated VEGF was inhibited by treatment with bevacizumab and genistein; conditioned medium was collected, and CD1d-mediated NKT-cell responses were assayed by ELISA. Results: Ovarian cancer tissue and ascites contain lymphocytic infiltrates, suggesting that immune cells traffic to tumors, but are then inhibited by immunosuppressive molecules within the tumor microenvironment. OV-CAR-3 and SK-OV-3 cell lines produce high levels of VEGF and GD3. Pretreatment of APCs with ascites or conditioned medium from OV-CAR-3 and SK-OV-3 blocked CD1d-mediated NKT-cell activation. Inhibition of VEGF resulted in a concomitant reduction in GD3 levels and restoration of NKT-cell responses. Conclusions: We found that VEGF inhibition restores NKT-cell function in an in vitro ovarian cancer model. These studies suggest that the combination of immune modulation with antiangiogenic treatment has therapeutic potential in ovarian cancer. Clin Cancer Res; 22(16); 4249–58. ©2016 AACR.