tbuckley/cabot-search huggingface dataset:
Pretreatment Primary Tumor SUVmax on 18F-FDG PET/CT Images Predicts Outcomes in Patients With Salivary Gland Carcinoma Treated With Definitive Intensity-Modulated Radiation Therapy
Authors: Cheng-En Hsieh, Kung-Chu Ho, Chia-Hsun Hsieh, Tzu-Chen Yen, Chun-Ta Liao, Hung-Ming Wang, Chien-Yu Lin
Journal: Clinical Nuclear Medicine (2017)

Purpose The aim of this study was to investigate the prognostic significance of 18F-FDG uptake in salivary gland carcinoma (SGC) patients treated with definitive intensity-modulated radiation therapy (IMRT). Methods We retrospectively examined 46 SGC patients who received pretreatment 18F-FDG PET/CT and definitive IMRT between 2007 and 2014. Most tumors were located in the minor salivary glands (n = 35 [76%]). Forty-six percent (n = 21) of the participants had unresectable disease. The median radiation dose was 72 Gy. Treatment outcomes were examined in relation to clinicopathologic parameters and pretreatment primary tumor SUVmax on 18F-FDG PET/CT. Results After a median follow-up of 54 months, the 5-year locoregional progression-free survival (LRPFS), distant metastasis-free survival, progression-free survival (PFS), and overall survival (OS) rates were 77%, 75%, 63%, and 61%, respectively. The median primary tumor SUVmax was 7.4 (range, 2.3–23.6), and the optimal cutoff value that maximized the prognostic significance for 5-year PFS was 7.4 (P = 0.006). Patients with a high SUVmax (≥7.4) had significantly lower 5-year LRPFS (P = 0.007), distant metastasis-free survival (P = 0.046), and OS (P = 0.013) rates than those with a low SUVmax (<7.4). Multivariate analyses identified SUVmax as the only independent predictor of LRPFS (P = 0.023) and PFS (P = 0.003), whereas both the performance score (P < 0.001) and SUVmax (P = 0.022) were independently associated with OS. Conclusions Pretreatment primary tumor SUVmax on 18F-FDG PET/CT predicts treatment outcomes in SGC patients. Definitive IMRT is an effective treatment strategy when organ function and cosmesis need to be preserved.
Anémie inexpliquée et cirrhose: impact diagnostique et thérapeutique de l 'exploration du grêle par Capsule Vidéo?
Authors: P Jacob, O Favre, J Daudet, MG Lapalus, E Ben Soussan, JC Saurin
Journal: Endoscopy (2005)

La meilleure indication de la Capsule Vidéo (CV) dans l'exploration du grêle est celle de patients présentant une hémorragie digestive d'origine inconnue. Le but de cette étude multicentrique et rétrospective est d'évaluer l'intérêt de la capsule en terme de diagnostic et d'impact thérapeutique pour les patients cirrhotiques porteurs d'une anémie d'étiologie indéterminée.
RespondR signature to predict response in TNBC patients treated with adjuvant taxane based chemotherapy in TCGA dataset.
Authors: Steven Allen Buechler, Yesim Gokmen-Polar, Sunil S. Badve
Journal: Journal of Clinical Oncology (2016)

1079 Background: Patients with triple-negative breast cancer (TNBC), who achieve pathological complete response (pCR) following neoadjuvant taxane-anthracycline (AT) based chemotherapy have improved survival. However, in current practice a priori identification of these patients is not possible. We have previously documented that the 19-gene RespondR score significantly stratifies TNBC patients by likelihood of response to neo-adjuvant AT therapy (ASCO 2015). In this study, we further analyzed patients treated with adjuvant taxanes in the TCGA dataset and a microarray dataset to document the broader utility of the signature. Methods: The microarray based 19-gene signature was first adapted to next generation RNA-seq data. Following normalization, the RespondR score was calculated for TNBC patients in The Cancer Genome Atlas (TCGA) treated with a taxane. RespondR was also studied in the Affymetrix microarray dataset GSE58812 from TNBC patients (n = 107) treated with adjuvant therapy. The primary endpoint was recurrence-free survival at 5 years. Results: RespondR score was normalized to TNBC samples in TCGA using RNA-seq data, and also using Agilent microarray data on the same samples with a high degree of concordance (p < 10-16). Eighty-four patients in the TCGA cohort were treated with taxanes (45 clearly identified as adjuvant) and had 5-year follow-up data. Taxane-treated TNBC patients in TCGA with high RespondR score (46%) have significantly better 5-year relapse-free survival (0.92, 95%CI 0.82-1.0) than patients with low RespondR score (0.68, 95%CI 0.52-0.89). In GSE58812, the high RespondR group (37%) has significantly better 5-year event-free survival (0.80, 95%CI 0.68 – 0.93) than in the low RespondR group (0.67 95%CI 0.56 – 0.79). Conclusions: The RespondR signature can be successfully adapted to analyze RNA-seq data. RespondR accurately predicts those TNBC patients likely to achieve improved 5-year recurrence free survival using adjuvant AT chemotherapy. RespondR can provide critical predictive information to TNBC patients and physicians.
Pleasing both authors and readers
Authors: G. Eysenbach, T. Delamothe, M. Mullner, R. Smith
Journal: BMJ (1999)

Trust wants help in formulating system to recognise performance of salaried GPsEditor-General practitioners (academic and non-academic) are still excluded from the merit award arrangements for consultants.We are therefore asking readers to help us formulate a system to recognise progress and performance for salaried general practitioners in our trust.We currently employ several general practitioners on the NHS consultant salary scale.They take part in the discretionary points system, but we would like now to develop detailed proposals by which they could progress through enhanced payments-wholly funded by the trustagainst meritorious criteria, which would be widely recognised and acknowledged.This would give them similar opportunities for recognition to those
The long noncoding RNA<i>Wisper</i>controls cardiac fibrosis and remodeling
Authors: Rudi Micheletti, Isabelle Plaisance, Brian J. Abraham, Alexandre Sarre, Ching-Chia Ting, Michael Alexanian, Daniel Maric, Damien Maison, Mohamed Nemir, Richard A. Young, Blanche Schroen, Arantxa González, Samir Ounzain, Thierry Pedrazzini
Journal: Science Translational Medicine (2017)

A super-enhancer–associated long noncoding RNA, Wisper , controls cardiac fibrosis and pathological remodeling in the damaged heart.
Preexisting endothelial cells mediate cardiac neovascularization after injury
Authors: Lingjuan He, Xiuzhen Huang, Onur Kanisicak, Yi Li, Yue Wang, Yan Li, Wenjuan Pu, Qiaozhen Liu, Hui Zhang, Xueying Tian, Huan Zhao, Xiuxiu Liu, Shaohua Zhang, Yu Nie, Shengshou Hu, Xiang Miao, Qing-Dong Wang, Fengchao Wang, Ting Chen, Qingbo Xu, Kathy O. Lui, Jeffery D. Molkentin, Bin Zhou
Journal: Journal of Clinical Investigation (2017)

The mechanisms that promote the generation of new coronary vasculature during cardiac homeostasis and after injury remain a fundamental and clinically important area of study in the cardiovascular field. Recently, it was reported that mesenchymal-to-endothelial transition (MEndoT) contributes to substantial numbers of coronary endothelial cells after myocardial infarction. Therefore, the MEndoT has been proposed as a paradigm mediating neovascularization and is considered a promising therapeutic target in cardiac regeneration. Here, we show that preexisting endothelial cells mainly beget new coronary vessels in the adult mouse heart, with essentially no contribution from other cell sources through cell-lineage transdifferentiation. Genetic-lineage tracing revealed that cardiac fibroblasts expand substantially after injury, but do not contribute to the formation of new coronary blood vessels, indicating no contribution of MEndoT to neovascularization. Moreover, genetic-lineage tracing with a pulse-chase labeling strategy also showed that essentially all new coronary vessels in the injured heart are derived from preexisting endothelial cells, but not from other cell lineages. These data indicate that therapeutic strategies for inducing neovascularization should not be based on targeting presumptive lineage transdifferentiation such as MEndoT. Instead, preexisting endothelial cells appear more likely to be the therapeutic target for promoting neovascularization and driving heart regeneration after injury.
SF3B1-initiating mutations in MDS-RSs target lymphomyeloid hematopoietic stem cells
Authors: Teresa Mortera-Blanco, Marios Dimitriou, Petter S. Woll, Mohsen Karimi, Edda Elvarsdottir, Simona Conte, Magnus Tobiasson, Monika Jansson, Iyadh Douagi, Matahi Moarii, Leonie Saft, Elli Papaemmanuil, Sten Eirik W. Jacobsen, Eva Hellström-Lindberg
Journal: Blood (2017)
Optimal weight control strategies in cancer patients: A systematic review.
Authors: Nathalie LeVasseur, Mark J. Clemons, Sasha Mazzarello, Lisa Vandermeer, Lee Jones, Anil Abraham Joy, Anil Abraham Joy, Stephanie Smith, Brian Hutton, John Frederick Hilton
Journal: Journal of Clinical Oncology (2016)

10109 Background: Obesity remains an underestimated contributor to global cancer incidence and cancer-related mortality. Accumulating evidence suggests excessive energy intake and suboptimal levels of physical activity may be important after the diagnosis of cancer, and may influence recurrence and overall survival (OS). Objective: Conduct a systematic review to evaluate data from randomized trials of weight control strategies used in cancer patients. Methods: A systematic search of Medline, Embase and the Cochrane Register of Controlled Trials through April 2015 was performed. Randomized trials of weight management strategies in cancer patients were sought. Outcomes studied included; change in weight, BMI and waist circumference, disease-free survival, recurrence-free survival and OS survival. Random effects meta-analyses were planned provided that included studies were considered to be clinically and methodologically homogenous. Results: Of 2941 abstracts, 312 were retained for review of the full texts. Sixty-four publications describing 47 studies met the inclusion criteria, including 10,411 enrolled patients. Overall, 13 studies consisted of dietary interventions, 21 consisted of exercise interventions and 13 consisted of both dietary and exercise interventions. Endpoints included changes in weight (39 studies, 9,947 pts), BMI (30 studies, 5,784 pts), waist circumference (20 studies, 1,546 pts), recurrence-free survival (3 studies, 5,767 pts) and overall survival (3 studies, 5,767 pts). Network meta-analyses of available data are in progress. Study results suggest that weight control strategies including dietary and exercise interventions may be effective at reducing weight, BMI and waist circumference. Two large studies showed statistically significant recurrence-free survival benefits with weight control strategies and one showed OS benefit with an exercise intervention. Conclusions: Data from included trials suggest benefits of weight control strategies to decrease weight, BMI and waist circumference. Few trials have been designed to detect PFS or OS benefits. Larger trials are warranted to better define the role of weight control strategies in the management of cancer patients and cancer survivors.
Effect of distress and personality factors on the preference-sensitive decision making of <i>BRCA1/2</i> mutation carriers on preventive options.
Authors: Kerstin Rhiem, Kirsten Wassermann, Jutta Giesecke, Natalie Herold, Monika Maringa, Simone Reichstein-Gnielinski, Verena Zarghooni, Rita K. Schmutzler
Journal: Journal of Clinical Oncology (2016)

1589 Background: Rates of prophylactic mastectomy (PM) have increased since the 1990ies and particularly after the outing of Angelina Jolie. Sensitive diagnostic tests such as magnetic resonance imaging and genetic testing have been cited as justification for the surgical procedure. However, psychosocial factors influencing patients´ preferences concerning preventive options are still unknown. Methods: From June 2013 to December 2014 BRCA1/2-mutation carriers (n = 159) were investigated in terms of distress (HADS), personality factors (FPI), calculated breast cancer risk and sociodemographic factors concerning their decision about preventive options (intensified breast cancer surveillance and PM) (funded: German Federal Ministry of Health, grant no. IIA5-2512 FSB 002). Results: We identified a significantly increased percentage of healthy and diseased BRCA1/2-mutation carriers with pathologic anxiety levels (HADS-A > 10) (27%) compared to the general population (7%). Moreover, we found a clear association between pathologic anxiety levels and patients´ decisions in favor of (PM), while the majority of mutation carriers with normal anxiety levels (HADS-A < 8) decided to participate in the intensified surveillance program (p < .001). Somatic complains (p = .12), emotionality (p = < .001) and social orientation (p = .12) are significantly associated with the decision for PM while mutation carriers with increased life satisfaction participated mainly in the ISP (p = .001). Calculated breast cancer risk, age, level of education and family history do not correlate with the decision making process. Conclusions: Calculated breast cancer risks and experiences of breast cancer disease are not essential influencing factors within the decision making process, while pathologic anxiety levels and personality factors drive the use of PM. Psychosocial screening before and after genetic counselling and testing should be mandatory to identify individuals with pathologic anxiety levels. Furthermore, prospective studies need to investigate the influence of psychosocial intervention on anxiety levels and the preference-sensitive decision making.
Relationship of RAS and <i>TP53</i> predictive value for cetuximab (C) benefit: Results of the EXPERT-C trial.
Authors: Francesco Sclafani, David Gonzalez, David Cunningham, Sanna Hullki Wilson, Clare Peckitt, Josep Tabernero, Bengt Glimelius, Andres Cervantes, Andrew Wotherspoon, Alice Dewdney, Gina Brown, Diana M. Tait, Jacqueline Rose Oates, Ian Chau
Journal: Journal of Clinical Oncology (2014)

447 Background: We previously reported that TP53 status may predict C benefit in patients with locally advanced rectal cancer treated with neoadjuvant chemotherapy and chemoradiotherapy (CRT) and this effect appeared to be independent of KRAS. Recent studies indicate that NRAS mutations and KRAS mutations beyond exons 2-3 may also preclude benefit from anti-EGFRs. We analyzed whether the predictive value of TP53 in EXPERT-C was independent of RAS. Methods: 164 patients received 4 cycles of CAPOX followed by CRT, surgery, and 4 cycles of adjuvant CAPOX (n=81) or the same regimen plus C (CAPOX-C, n=83) and were analyzed for KRAS (exons 2-3) and NRAS (exon 3). TP53 mutations (exons 4-9) were screened for by CE-SSCA. KRAS (exon 4) and NRAS (exons 2 and 4) mutations were screened for by bi-directional Sanger sequencing. Progression-free survival (PFS) and overall survival (OS) were estimated with Kaplan-Meier methods and log-rank analysis was used to compare the treatment arms. The interaction between treatment and TP53 was adjusted for prognostic variables and RAS in a multivariate model. Results: 75/144 (52%) eligible patients had a TP53 mutation. 81/86 patients with known KRAS (exons 2-3) and NRAS (exon 3) wild-type (WT) status were analyzed for the remaining RAS mutations. Of these, 11 (13%) had tumours with mutation in KRAS exon 4 (11%) or NRAS exons 2/4 (2%). Overall, 75/144 (52%) patients were RAS WT (CAPOX, n=39; CAPOX-C, n=36). After a median follow-up of 65 months, no difference in PFS (HR 1.21, p=0.59) and OS (HR 0.97, p=0.94) was observed between TP53 mutant patients treated with CAPOX or CAPOX-C. In TP53 WT patients, the addition of C was associated with a statistically significant improvement in PFS (HR 0.23, p=0.02) and OS (HR 0.16, p=0.02). A significant interaction between TP53 status and C effect was found (PFS, p=0.029; OS, p=0.036). In multivariate analyses, this interaction remained significant even after adjusting for RAS status (PFS, p=0.026; OS, p=0.033). Conclusions: In EXPERT-C, the value of TP53 as predictive biomarker for C benefit was independent of RAS. The value of monoallelic vs. biallelic TP53 inactivation will be presented at the meeting.
Leveraging Six Sigma instruments to optimize cancer screening in an urban community hospital.
Authors: Uri Goldberg, Madhumati R. Kalavar, Hendy Jean, Neil Gupta, Rajat Mukherji, Kurt Kodroff, Neil Pasco
Journal: Journal of Clinical Oncology (2016)

e13046 Background: In 2010, the U.S. Department of Health and Human Services implemented a quality improvement initiative known as “Healthy People 2020” designed to improve outcomes across a broad array of illnesses by 2020. Within the category of cancer, the initiative’s goals include improving screening rates. As poor socioeconomic status has long been associated with lower screening and higher mortality rates, and given the low socioeconomic status of much of our patient population, our institution has implemented Six Sigma techniques designed to decrease variability in cancer screening measures, reduce healthcare disparities, and improve screening outcomes. Methods: Beginning in the 4th quarter of 2013, our hospital’s Ambulatory Care department implemented a bimonthly rapid cycle evaluation of physicians designed to analyze a variety of patient care metrics including breast and colorectal cancer screening rates within each physician’s respective patient panel. Data for each quarter was systematically distributed to each physician and a care navigation team was assembled to ensure screening compliance via patient outreach in the form of phone calls and certified mail. Results: Data from the 1st quarter of 2014 until the 2nd quarter of 2015 were collected from two sites affiliated with our institution’s outpatient service. During that timeframe, the rate of colorectal screening—which includes colonoscopy and serial fecal occult blood testing—increased at Site 1 from 79.1% to 84.4% and at Site 2 from 70.8% and 75%. With respect to breast cancer screening, the rate at Site 1 remained virtually unchanged (90.4% and 90.1%) while the rate at Site 2 increased from 80.7% to 86.0%. Conclusions: As our intervention has demonstrated, cancer screening may be optimized by the use of a low-cost, easily implementable, and easily replicable intervention leveraging Six Sigma instruments. In light of the challenges affecting our institution’s predominately African-American and Latino populations—particularly as they relate to access to care and timely cancer diagnoses—our intervention may go a long way toward reducing disparities and improving outcomes in these increasingly disadvantaged populations.
Perceptions of the relative harm of electronic cigarettes compared to conventional cigarettes among smokers and non-smokers in the US.
Authors: Leo Chen, Jinjin Shan, Yi Min Ng, Aydan Kesici, Thanh Thien Phan, Winson Y. Cheung
Journal: Journal of Clinical Oncology (2016)

e13047 Background: Electronic cigarettes (e-cigs) are a novel nicotine delivery system introduced in 2003 as a harm-reducing substitute for conventional cigarettes. E-cigs have been described by experts as the most feasible policy option to reduce tobacco-attributable illness and death, but public opinion regarding e-cigs remain mixed. Methods: We used data from Health Information National Trends Survey (HINTS), which is a nationally representative survey collected by National Cancer Institute to investigate use of cancer-related information by the public. By merging HINTS data, we analyzed 10,492 total responses to assess demographic characteristics associated with the belief that e-cigs are less harmful than conventional cigarettes. Logistic regression was used to test all associations. Results: In this cohort, 40% were men, 60% were White, and 42% were current/former smokers. Among them, only a minority (34%) perceived e-cigs to be less harmful. On multivariate analyses, history of smoking, younger age, men, and extremes of household incomes were associated with beliefs that e-cigs are less harmful. For instance, current and former smokers had 2.51 and 1.39 higher odds, respectively, of holding this perception (p < 0.001) (see Table). Conclusions: Our findings support the feasibility of substituting conventional cigarettes with e-cigs as a harm reduction strategy among current smokers. Specific subgroups may require additional interventions for effective smoking cessation. Variable Level Multivariate Model OR P-Value Believe e-cig less harmful No NA NA Yes NA NA Smoker Status Never REF REF Current 2.51 < 0.001 Former 1.39 < 0.001 Age 18-34 REF REF 35-49 0.72 < 0.001 50-64 0.61 < 0.001 65-74 0.41 < 0.001 75+ 0.25 < 0.001 Gender M REF REF F 0.69 < 0.001 Ethnicity White REF REF Hispanic 0.49 < 0.001 Black 0.49 < 0.001 Other 0.66 < 0.001 Marital Status Single REF REF Married 0.84 0.014 Divorced, Widowed, Separated 1.05 0.566 Employed No REF REF Yes 0.84 0.824 Education < High School REF REF High School Grad 0.98 0.880 Some College 1.06 0.586 Bachelor 1.20 0.119 Post-Bacc. Degree 1.39 0.008 Household Income ($ in 1000s) < 20 REF REF 20-35 1.36 < 0.001 35-50 1.15 0.131 50-75 1.27 0.008 75+ 1.44 < 0.001
Real-life effectiveness of T-DM1 in heavily pretreated HER2-positive advanced breast cancer patients: An Italian observational study.
Authors: Alessandra Fabi, Katia Cannita, Gianluigi Ferretti, Mariangela Ciccarese, Grazia Arpino, Filippo Montemurro, Nicla Maria La Verde, Daniele Giulio Generali, Giuseppina Scandurra, Gianfranco Filippelli, Michelangelo Russillo, Ida Paris, Simonetta Stani, Agnese Fabbri, Mauro Minelli, Francesco Cognetti, Diana Giannarelli
Journal: Journal of Clinical Oncology (2016)

e12019 Background: T-DM1 showed remarkable activity in metastatic (m) HER-2 positive breast cancer (BC) and it recently was approved for clinical use in patients (pts) who previously failed trastuzumab and taxanes. The impact of drug prescription in real life compared with the findings reported in clinical trials exerting a strict accrual criteria has been rarely assessed. We investigated use and effectiveness of T-DM1 in daily practice. Methods: We included all pts with HER2-positive mBC, diagnosed in 12 Italian oncology hospitals between 2013 and 2015. Our aim was to assess the actual use of T-DM1 in HER2 positive mBC pts and its efficacy in clinical practice. Results: The data of 119 pts were retrospectively collected. The median age was 49 years (28-78), visceral metastases were present in 91 pts (77%) and brain metastases in 44 (37%). It is noteworthy that 29 pts (24%) received T-DM1 as second-line, 42 (35%) as third-line, and 43 (36%) as fourth- or further-line option. Moreover, 4 pts had TDM-1 as first-line therapy because < 6 months between adjuvant therapy and recurrence. The overall response rate (ORr) was 38%, disease control rate (DCR) 68%, median progression-free survival (mPFS) 6.3 months (95% C.I.: 4.7-7.8), overall survival (OS) 14.4 months (95% C.I.: 12.7-16.1). Considering the only 12 (10%) pts progressing after pertuzumab, the ORr by T-DM1 was 27%, CB 64%, mPFS 5.4 months. T-DM1 given as second-line showed an activity of 36%, as third and fourth line of 31%. The ≥ grade 3 toxicities were alopecia (3.4%), piastrinopenia (2.5%), neutropenia (2.5%), high transaminases levels (3.3%). Conclusions: To our knowledge this is the first real life multicenter retrospective study evaluating efficacy and safety of TDM-1 in heavily pretreated HER2-positive mBC pts. There was no evidence of unexpected adverse events with a very manageable toxicity overall and we observed a remarkable efficacy in this setting of pts. These findings need to be taken with caution due to the number of pts studied and because of the different lines of previous treatments considered. We confirm the therapeutic potential T-DM1 across a heterogeneous population of HER2-positive pts who failed to trastuzumab and taxanes.
Underreporting of End-of-Life Decisions in Critical Care Trials: A Call to Modify the Consolidated Standards of Reporting Trials Statement
Authors: Jonathan Messika, Stéphane Gaudry, Florence Tubach, Sylvie Guillo, Didier Dreyfuss, David Hajage, Jean-Damien Ricard
Journal: American Journal of Respiratory and Critical Care Medicine (2017)