tbuckley/cabot-search huggingface dataset:
Multidrug-resistant tuberculosis and beyond: an updated analysis of the current evidence on bedaquiline
Authors: Emanuele Pontali, Lia D'Ambrosio, Rosella Centis, Giovanni Sotgiu, Giovanni Battista Migliori
Journal: European Respiratory Journal (2017)

Multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis (TB) continue to be challenging at both the patient and programme level. The World Health Organization (WHO) estimated 480 000 new cases of MDR-TB in 2015 and an additional 100 000 cases diagnosed with rifampicin-resistant TB (RR-TB). India, China and the Russian Federation accounted for almost half (45%) of the total burden [1]. Out of 580 000 patients eligible for MDR-TB treatment, only 125 000 (20%) were enrolled in treatment programmes [1]. Bedaquiline is effective in managing MDR- and XDR-TB. Evidence indicates its tolerability and safety profile are good <http://ow.ly/mWSz308QrVP>
Influence of blood neutrophil to lymphocyte ratio on oncologic outcomes in peritoneal carcinomatosis of appendiceal origin.
Authors: Kamran Idrees, Jason Luciano, Frances Austin, Magesh Sathaiah, Lekshmi Ramalingam, Heather L Jones, James F. Pingpank, Steven Arthur Ahrendt, Amer H Zureikat, Matthew Peter Holtzman, Herbert Zeh, David L. Bartlett, Haroon Choudry
Journal: Journal of Clinical Oncology (2012)

e14184 Background: The Neutrophil to lymphocyte ratio (NLR), a marker of systemic inflammatory response, is associated with prognosis in various cancers. The aim of this study is to evaluate the association of pre-operative NLR with oncologic outcomes in patients with appendiceal carcinomatosis. Methods: Clinico-pathological data were obtained from a prospectively maintained database of patients with appendiceal carcinomatosis who underwent cytoreductive surgery (CRS) and hyperthermic intra-peritoneal chemoperfusion (HIPEC) between 2001 and 2010. Pre-operative absolute neutrophil and lymphocyte counts were used to compute NLR, with elevated NLR defined a priori as &gt;5. Logistic regression modeling and Kaplan-Meier analyses were performed on the available data. Results: 195 patients, with a median age of 54.5 years, underwent CRS and HIPEC. The median follow up time was 1.96 years. There were 41 patients (21%) who had elevated NLR preoperatively. Factors associated with overall survival (OS) were grade (p=0.01), simplified peritoneal cancer index (SPCI) (p=0.013), and age (p=0.02). In patients who did not undergo splenectomy at the time of CRS, elevated NLR, lymph node involvement, SPCI, age and pre-operative albumin were statistically significant predictors of OS on multivariable analysis. None of these factors were significant in patients who underwent splenectomy at the time of CRS. The 5-year overall survival was 57% vs. 31% in patients with NLR&lt;5 compared to NLR&gt;5 respectively (p&lt;0.0001). Time to progression was 30 months compared to 14 months in patients with NLR&lt;5 vs. &gt;5 (p=0.001). Strikingly, the 5-year OS in patients with NLR&lt;5 with or without splenectomy was 63% and 50% compared to patients with NLR&gt;5 with or without splenectomy 37.5% vs. 23%, respectively (p=0.0001). Conclusions: In patients with appendiceal carcinomatosis, pre-operative NLR is a potential systemic inflammatory marker that independently predicts oncologic outcomes. The impact of NLR appears to be influenced by the performance of splenectomy at the time of CRS. Further studies will be required to prospectively validate this systemic inflammatory marker and its interaction with splenectomy.
Next-Generation Global Biomonitoring: Large-scale, Automated Reconstruction of Ecological Networks
Authors: David A. Bohan, Corinne Vacher, Alireza Tamaddoni-Nezhad, Alan Raybould, Alex J. Dumbrell, Guy Woodward
Journal: Trends in Ecology & Evolution (2017)

TrendsNext-generation sequencing (NGS) can used to sample nucleic acids in the environment for the presence of species and ecological functions.Machine-learning software can search for 'the ghosts of interactions past' in the raw NGS data to reconstruct the networks of ecological interactions.NGS data and machine-learning in the cloud could be combined in the next generation of global biomonitoring. Autonomous NGS samplers would sequence and upload data for ecological network reconstruction, to detect ecosystem change accurately, cheaply and generically.Reconstruction of highly replicated networks of ecological interaction, using this next generation of biomonitoring, would provide general ecological information for ecosystem comparison and a revolution in the breadth of our understanding of the ecology of ecosystem change.AbstractWe foresee a new global-scale, ecological approach to biomonitoring emerging within the next decade that can detect ecosystem change accurately, cheaply, and generically. Next-generation sequencing of DNA sampled from the Earth's environments would provide data for the relative abundance of operational taxonomic units or ecological functions. Machine-learning methods would then be used to reconstruct the ecological networks of interactions implicit in the raw NGS data. Ultimately, we envision the development of autonomous samplers that would sample nucleic acids and upload NGS sequence data to the cloud for network reconstruction. Large numbers of these samplers, in a global array, would allow sensitive automated biomonitoring of the Earth's major ecosystems at high spatial and temporal resolution, revolutionising our understanding of ecosystem change.
Increased cardiovascular risks associated with primary androgen deprivation therapy versus radical prostatectomy among patients with localized prostate cancer.
Authors: Jinan Liu, Lizheng Shi, A. Oliver Sartor, Richard Culbertson
Journal: Journal of Clinical Oncology (2012)

e15130 Background: We examined whether primary androgen deprivation therapy (PADT), as compared to radical prostatectomy (RP), was associated with cardiovascular disease and death. Methods: Male patients with localized prostate cancer were identified in the SEER-Medicare (01/1998-12/2007). PADT patients were matched to the RP patients via propensity score. Cardiovascular risks ((i.e., ischemic heart disease (IHD), congestive heart failure (CHF), or cerebrovascular disease) were examined by Cox (PH) model; cardiovascular death by Fine &amp; Gray competing risk. Important independent variables were controlled for. Results: The baseline variables were comparable. For the sample without cardiovascular disease (CVD) history, significantly increased risks for IHD, CHF, and aggregate risk of CVD were found in PADT group (all p-values &lt;0.05), and the risks for cerebrovascular disease and cardiovascular death were also increased but not significantly (both p-values&gt;0.05); for the sample with CVD history, all the risks aforementioned were significantly increased in PADT group (all p-values &lt;0.05). Conclusions: In this retrospective study, PADT was associated with increased cardiovascular disease and death when compared with RP, especially in the sample with history of CVD. [Table: see text] [Table: see text]
Docetaxel and curcuminoids (CCM) combination in patients with castration-resistant prostate cancer (CRPC): A phase II study.
Authors: Hakim Mahammedi, Mélanie Pouget, Eloise Planchat, Herve Cure, Xavier Durando, Mathilde Bayet-Robert, Isabelle Van-Praagh, Marc Atger, Laurent Guy, Catherine Abrial, Philippe J. M. Chollet, Jean-Christophe Eymard
Journal: Journal of Clinical Oncology (2013)

e16021 Background: Prostate cancer is a major problem in the aging male population. Docetaxel, the first-line reference treatment in CRPC induces a prostate-specific antigen (PSA) response in 45% of patients and an objective tumor response in 12%. Preclinical studies suggested that curcuminoids inhibit tumor metastasis, invasion and angiogenesis and reverse drug resistance. We wanted to potentiate docetaxel by curcuminoïds in CRPC first line. Our previous phase I study showed the safety and the tolerability of CCM associated to docetaxel for advanced breast cancers. We have conducted in 2009-2010 a phase II study to assess the response of CRPC to this combination. Methods: Patients (n=30) with progressing CRPC and rising PSA were enrolled to receive the experimental treatment. Docetaxel was given in standard conditions (75mg/m², 1h i.v infusion every 3 weeks for 6 cycles + prednisolone) with CCM orally at the dose of 6gr/day (7 days by cycle: d-4 to d+2). The primary endpoint was response rate assessed by biological and paraclinical examinations. The secondary endpoints included safety, time to progression and compliance. Twenty nine patients were evaluable on PSA assessment and 15 on RECIST criteria. Results: 26 patients received the treatment totality and 4 withdrew prematurely. No patient withdrew for toxicity (2 deaths and 2 PSA progressions). A PSA response was observed in 17/29 patients (59%) (4 complete and 13 partial) observed rapidly (before the 3 rd cycle) for 15 patients. The median time to subsequent PSA progression (TTP) was 5.8 months. Six patients (40%) had a partial objective response and 9 (60%) a stable disease. The median TTP on targets was 7.85 months (n=13/15). The regimen was well tolerated, with uncommon grade 3/4 toxicity; no adverse event was attributed to CCM. Of 169 cycles, 150 (89%) were completed with perfect compliance. Overall survival was 19 months (mean) and 24 months (median) with 17 events as of december 2012. Conclusions: These results are promising in improving the response rate to docetaxel in terms of both PSA decrease and objective response, with good tolerability and acceptability of CCM. A randomized trial is necessary to confirm this results. Clinical trial information: NCT01012141.
Use of complementary medicines by patients treated with chemotherapy: Survey in a French day care unit.
Authors: Pauline Fort, Blandine Marsault, Antoine Hertzog, Emilie Dubost, Jean-Marc Tourani, Isabelle Princet
Journal: Journal of Clinical Oncology (2012)

e19555 Background: Nowadays, communication about alternative medicines and biologic therapies is very intense. Anyone can find information, more or less scientific, on internet, television or magazines. Therefore, patients treated with chemotherapy may use many complementary medicines. The purpose of our study is to do a summary of the use of those alternative therapies by our patients in order to evaluate the potential risk of interference with their antitumor treatment. Methods: We carried out a prospective study among patients in the day care unit. During an interview, they were asking for any biological treatment or non-drug alternative medicine used concurrently with the chemotherapy. We found out: antitumor agent, complementary and alternative medicine used, aim of this use (prevention, antitumor action, wellbeing), means of access, person who advised them. Results: 100 patients were interviewed (average = 63 years old, half-and-half men and women). 38% used complementary and alternative medicines: 45% of whom used homeopathy, 39% food supplements, 37% herbal medicine, 29% non-drug alternative medicine (acupuncture, magnetic healer, meditation…). 29% of them associate more than 3 medicines. 61% of patients using herbal medicine, heard about it by word of mouth (friends and family); and 75% buy it by internet or by phone. Most of them are looking for wellbeing. 31% of patients using food supplements, looking for well being too, learnt it by word of mouth; 48% buy it in pharmacy, 40% on internet or by phone. 90% of patients using homeopathy were advised by their pharmacist or attending physician, mostly to prevent chemotherapy side effects. 95% buy it in pharmacy. Conclusions: A lot of patients are concerned by complementary and alternative medicines; and in too many case, they are advised by non-medical people. This survey shows the importance for oncologist to know exactly what kind of treatment their patients are using. Indeed, at least 16 of those patients associate medicines which reduce the antitumor agent’s activity. The survey will continue in other oncologic units.
Glioma patterns of care in Victoria from 1998–2000
Authors: M. Rosenthal, K. Drummond, M. Dally, M. Murphy, L. Cher, D. Ashley, V. Thursfield, G. Giles
Journal: Journal of Clinical Oncology (2006)

11521 Background: The management of Gliomas is complex and requires a multidisciplinary approach. The care of such patients (pts) may be variable. The State of Victoria has a population of approximately 4 million people and over 300 new glioma cases diagnosed annually. Methods: This was a retrospective cohort study conducted by surveying doctors involved in managing incident adult glioma cases identified from the population based Victorian Cancer Registry during 1998–2000. The survey was conducted in 2004–5 obtaining at least four years follow-up data on all pts. Results: 828 pts were considered eligible for this study. 264 pts (32%) were aged over 70 years and 92 (11%) were aged over 80 years. 105 (13%) did not have a histologic diagnosis and 473 (57%) had glioblastoma multiforme (GBM). Complete macroscopic resection was performed in 209 pts (25%). Of all pts with a glioma, 612 (74%) and 326 (54%) were referred at initial diagnosis for consideration of radiotherapy and chemotherapy respectively. In 473 pts with GBM, 406 (86%) and 147 (31%) pts were initially referred for consideration of radiotherapy and chemotherapy respectively. Only 39 pts(5%) were enrolled on a clinical trial. The median survival for pts with a GBM was 7.4 months with a 3% five-year survival. Conclusions: This is one of the largest ever-reported glioma management surveys. Much of the patient demographics and approach to treatment were expected and represent a reasonable “standard of care”. Importantly, this study emphasises the elderly nature of this patient population and identifies areas of concern including: absence of histologic diagnosis, lack of multi-disciplinary care and low clinical trial enrolment. No significant financial relationships to disclose.
Profiling the Genomic Landscape at the Early Stages of CLL: Low Genomic Complexity and Paucity of Driver Mutations in MBL and Indolent CLL
Authors: Andreas Agathangelidis, Viktor Ljungström, Lydia Scarfò, Claudia Fazi, Maria Gounari, Tatiana Pandzic, Lesley-Ann Sutton, Kostas Stamatopoulos, Giovanni Tonon, Richard Rosenquist, Paolo Ghia
Journal: Blood (2016)
Evaluating collagen neoepitopes as pharmacodynamic biomarkers of GS-5745, an MMP9 inhibitor, in advanced gastric cancer.
Authors: Carrie Baker Brachmann, Yafeng Zhang, Marianna Zavodovskaya, Jing Hu, Julia D. Maltzman, Victoria Smith, Yuanyuan Xiao, Scott D Patterson
Journal: Journal of Clinical Oncology (2017)

58 Background: Cancer is characterized by continuous remodeling of the extracellular matrix (ECM) through a process of degradation and replacement of ECM components, such as collagens. Matrix-metalloproteinase 9 (MMP9) is involved in this remodeling and its inhibition is hypothesized to reduce ECM turnover. MMP9 expression is limited in healthy tissues, but high in tumor epithelia, infiltrating inflammatory cells and fibroblasts. Collagen I and III fragments (neoepitopes C1M and C3M) in blood may provide a measure of tumor MMP activity (BMC Cancer 13:554. 2013). GS-5745 is a monoclonal antibody that specifically inhibits MMP9 and has shown efficacy in combination with chemotherapy in advanced gastric cancer in an ongoing ph I study of multiple cancer types (NCT01803282). Exploratory analyses of collagen neoepitopes from patients in the gastric cancer cohort are reported here. Methods: C1M and C3M were measured by ELISA in serum samples (Nordic Bioscience). Healthy volunteer (HV) samples were age-matched. Pharmacodynamic evaluation and association with clinical outcomes were assessed by non-parametric tests; nominal p-values are reported. Results: Pharmacodynamic Evaluation (Table):Baseline (BL) levels of C1M and C3M were higher in gastric cancer patients than HVs. C1M and C3M displayed a pharmacodynamic response after 1 treatment cycle. Inhibition of C1M continued to decline with treatment. Association with Best Overall Response:There was no association of BL C1M or C3M level with best overall response. 13 of 20 responders had decreased C1M at C2D1; however, of the 3 patients with progressive disease, none had an on-treatment decrease in C1M. Conclusions: These data suggest an association between circulating C1M as a pharmacodynamic biomarker of GS-5745 in combination with chemotherapy in gastric cancer patients. Circulating neoepitope biomarkers will continue to be explored in all ongoing and future oncology GS-5745 studies. Clinical trial information: NCT01803282. [Table: see text]
Efficacy and safety of bevacizumab combined with chemotherapy in the treatment of patients with metastatic well-differentiated duodeno-pancreatic endocrine tumors (BETTER study).
Authors: Michel Ducreux, Jean-François Seitz, Denis Smith, Dermot O'Toole, Céline Lepère, Laurence Bitoun, Emmanuel Mitry
Journal: Journal of Clinical Oncology (2012)

4036 Background: Gastrointestinal neuroendocrine tumors (NET) overexpress vascular endothelial growth factor (VEGF), thus we hypothesized that Bevacizumab (Bv), a monoclonal antibody targeting VEGF in combination with chemotherapy may show an activity in duodeno-pancreatic NET. Methods: This multicenter, open-label, non-randomized, two- group phase II trial assessed in one group the efficacy and safety of Bv (7.5 mg/kg IV on day 1, every 3 weeks), combined with 5-FU/streptozotocin (stz): 5-FU 400 mg/m²/d; Stz 500 mg/m²/d IV, d1-5/ every 42 days, during a minimum of 6 months in patients (pts) with progressive, metastatic, well-differentiated duodeno-pancreatic NET (WHO 2000), not previously treated with chemotherapy, ECOG PS ≤2 and Ki 67 index &lt; 15%. Primary endpoint was progression-free survival (PFS). Secondary endpoints were overall survival (OS), response rate, safety and quality of life. Study duration was 24 months. Results: In the ITT population, 34 pts were enrolled, 22 (64.7%) were men, median age 55.3 years (37.0-77.6), 33 (97.1%) pts had ECOG-PS 0/1. Most metastases were in the liver 33 (97.1%) pts or lymph nodes 14 (41.2%) pts. Ki-67 proliferative index was 0-2% in 8 (25%) pts, 3-4% in 5 (15.6%), 5-9% in 6 (18.8%), 10-14% in 12 (37.5%) and 15% in 1(3.1%) pt. Median treatment duration was 14.0 months; median number of cycles was 10. At 24 months, median PFS was 23.7 months [95%CI: 14.5; not reached] based on 18 events. PFS rate at 18 months was 62%. Tumor control rate was 100% (n= 34) including partial response in 19 (55.9%) pts and stable disease in 15 (44.1%) pts. Survival rate at 24 months was 88%. Median OS was not reached, 5 patients died. CTC grade 3/4 Adverse Events (AEs) occurred in 23 (67.6%) of pts, mainly digestive 5 (14.7%) pts. G3/4 Bv targeted AEs were hypertension in 7 (20.6%) pts and thromboembolism in 4 (11.8%). Conclusions: Efficacy data in this phase II trial assessing a novel approach with Bv and 5-FU/stz in duodeno-pancreatic NET is encouraging and the toxicity profile is acceptable. Results suggest that Bv may have a place in the treatment of pancreatic NET and warrant further investigation in a phase III trial.
Efficacy and safety results from CurrentS, a double-blind, randomized, phase III study of second-line erlotinib (150 mg versus 300 mg) in current smokers with advanced non-small cell lung cancer (NSCLC).
Authors: Egbert F. Smit, Radj Gervais, Caicun Zhou, Enriqueta Felip, Ji Feng Feng, Salih Zeki Guclu, Mathias Hoiczyk, Elena Dorokhova, Ulrich Freudensprung, Pablo Diego Perez-Moreno, Martin Reck
Journal: Journal of Clinical Oncology (2014)

8046 Background: Pts with NSCLC who are active smokers may have increased erlotinib metabolism v non-smokers, which reduces exposure. Methods: Pts with stage IIIB/IV NSCLC (failed first-line platinum-based chemotherapy, current smokers) were randomized to receive standard dose erlotinib (150 mg/day; E150) or an experimental dose (300 mg/day; E300) until progression/death/unacceptable toxicity. Pts were assessed every 6 wks. Primary endpoint: progression-free survival (PFS). Secondary endpoints included: overall survival (OS), disease control rate (DCR), and safety. Planned sample size: 300 randomized pts; 277 PFS events needed to show a HR of 0.714 (median PFS improvement from 10 to 14 wks; E300 was expected to provide a longer median PFS v E150) with 80% power (5% 2-sided α). Results: Baseline characteristics were balanced (Table). Efficacy and safety results are reported (Table). Conclusions: CurrentS, the first and largest trial in active smokers with NSCLC to date, did not show a statistically significant increase in PFS (primary endpoint) when erlotinib was given at 300 mg v 150 mg. OS (secondary endpoint) was not different between the arms. There was a numerical increase in AESIs with the higher dose. PK data will be presented. Clinical trial information: NCT01183858. E150 E300 ITT population N=154 N=159 Ethnicity, n (%) Caucasian 97 (63.0) 99 (62.3) Asian 46 (29.9) 49 (30.8) Other/not reported 11 (7.1) 11 (6.9) Histology, n (%) Adenocarcinoma 100 (64.9) 96 (60.4) Squamous cell carcinoma 42 (27.3) 48 (30.2) Large cell carcinoma 6 (3.9) 7 (4.4) Other 6 (3.9) 8 (5.0) ECOG PS, n (%) 0–1 145 (94.2) 148 (93.1) 2 9 (5.8) 11 (6.9) Smoking status Median pack yrs 31.3 30.0 PFS Events, n (%) 143 (92.9) 140 (88.1) Median, wks 6.9 7.0 *HR (95% CI) 1.05 (0.83–1.33) *Log-rank p 0.671 OS Events, n (%) 122 (79.2) 123 (77.4) Median, mo 6.8 6.8 *HR (95% CI) 1.03 (0.80–1.32) *Log-rank p 0.846 DCR, % (95% CI) 40.3 (32.4–48.5) 36.5 (29.0–44.5) Safety population n=154 n=158 Relative dose intensity (% of planned), mean (SD) 98.6 (5.9) 97.1 (8.4) AEs of special interest (AESI; all grades), n (%) Rash 63 (40.9) 97 (61.4) Diarrhea 30 (19.5) 47 (29.7) Interstitial lung disease 0 (0.0) 2 (1.3) * Unstratified.
Adjuvant androgen deprivation (ADT) versus mitoxantrone plus prednisone (MP) plus ADT in high-risk prostate cancer (PCa) patients following radical prostatectomy: A phase III intergroup trial (SWOG S9921) NCT00004124.
Authors: L. Michael Glode, Catherine M. Tangen, Maha Hussain, Gregory P. Swanson, David Peter Wood, Wael Sakr, Nancy Ann Dawson, Naomi B. Haas, Thomas W. Flaig, Tanya B. Dorff, Daniel W. Lin, E. David Crawford, David I. Quinn, Nicholas J. Vogelzang, Ian Murchie Thompson
Journal: Journal of Clinical Oncology (2017)

2 Background: High risk localized Pca patients are more likely to relapse and suffer morbidity/mortality from metastatic disease after prostatectomy. Adjuvant ADT can reduce this risk. We hypothesized that MP in addition to two years of ADT could further reduce mortality from PCa. Methods: Participants with clinically localized (T1-T3, N0, M0) PCa received radical prostatectomy. Eligibility required ≥ 1 high risk criteria defined as Gleason sum ≥8; pT3b or pT4 or N1; Gleason 7 with positive margin; any one of these preoperative findings: PSA&gt;15ng/ml, biopsy Gleason &gt;7, biopsy Gleason &gt;6 with PSA&gt;10. ADT arm consisted of bicalutamide and goserelin for 2 years. ADT+MP arm received ADT plus 6 cycles of M 12mg/m 2 + P 5mg BID. Primary endpoint was survival (OS). Median OS was anticipated to be 10 years in ADT arm requiring 680 patients/arm to detect a hazard ratio of 1.30 with 92% power and one-sided α=0.05. Results: S9921 enrolled patients from 10/99 to 1/07 when the DSMC recommended stopping due to increased incidence of leukemia in the ADT+MP arm. Of 983 patients randomized, 22 ineligible. 481 eligible on ADT and 480 on ADT+MP. Patients were stratified by stage (≤pT2, ≥pT3, N0 or N+), Gleason score, and intent to receive adjuvant radiation (RT) (Y/N). Median age was 60 years, 84% were white, presurgical PSA was 7.6 ng/ml, 16% had positive nodes, 26% intended to receive RT, 63% had positive margins. 11 ADT and 20 ADT+ MP received no protocol treatment. Median follow-up is 11.2 years. Conclusions: Survival was greater than anticipated in both arms. MP increases the risk of leukemia. There is no evidence that MP improves PCa specific survival when added to 2 years of adjuvant ADT. Clinical trial information: NCT00004124. [Table: see text]