tbuckley/cabot-search huggingface dataset:
Definition of an imatinib trough concentration threshold in the treatment of advanced gastrointestinal stromal tumors (GIST).
Authors: M. Molimard, S. Bouchet, S. Poulette, E. Chauzit, K. Titier, N. Moore, R. Lassalle, A. Abouelfath, A. Italiano, C. Chevreau, F. Duffaud, M. Rios, D. Cupissol, A. Adenis, I. L. Ray-Coquard, O. Bouche, A. Le Cesne, J. Blay, B. Bui Nguyen
Journal: Journal of Clinical Oncology (2011)

10013 Background: Imatinib (IM) as front-line treatment has dramatically changed the evolution of GIST. Demetri et al. (JCO, 0927. 3141-7) previously showed that patients with trough IM plasma concentrations (Cmin) below 1110 ng/mL (Quartile 1) had shorter time to progression. We prospectively performed routine analysis of I in advanced GIST pts in which we investigated the relationships between Cmin and progression-free survival (PFS). Methods: A clinical database of advanced GIST pts for whom Cmin measurements has been prospectively set. The concentration decile boundary that produced the most statistically significant difference in PFS for patients with Cmin values above and below the value was defined using a log-rank test. Cox regression analysis was performed to evaluate factors associated with longer PFS. Results: We evaluated 102 patients treated by IM 400 mg/day (41 stomach, 34 small bowel and 27 other or unreported primary site localizations) with 253 trough plasma determinations. Median Cmin after steady-state was 784ng/mL (range:154-3321) with 75% inter-individual and 26% intra-patient variabilities. A Cmin threshold of 1030 ng/mL was associated with longer PFS for the whole GIST population (p=0.044). However, a Cmin threshold of 780 ng/mL was found separately for stomach (p=0.043) and small bowel localizations (p=0.049). Cox regression analysis found that Cmin above 780 ng/mL was associated with 71% reduction risk of progression (p=0.008) and that small bowel localization was associated with an increased relative risk of progression of 5.31 versus stomach localization (p=0.007). Conclusions: This analysis of IM in pts treated with 400 mg/d, allowed to define a Cmin threshold of 780 ng/ml associated with 71% reduction of progression risk for stomach and small bowel localizations of advanced GIS.
Superior Efficacy of the Novel Type II, Glycoengineered CD20 Antibody GA101vs. the Type I CD20 Antibodies Rituximab and Ofatumumab
Authors: Sylvia Herter, Inja Waldhauer, Tina Otz, Frank Herting, Sabine Lang, Valeria Nicolini, Michaela Römmele, Thomas Friess, Erwin Van Puijenbroek, Marina Bacac, K. Michael Weidner, Christian Gerdes, Pablo Umana, Christian Klein
Journal: Blood (2010)
Abstract AS12: Integrating genomics, transcriptomics, and proteomics for the discovery of novel biomarkers to complement CA125 in ovarian cancer early detection
Authors: Clayton Boldt, Archana Simmons, Hong Wang, Keith Baggerly, Robert Bast, Samir Hanash
Journal: Clinical Cancer Research (2015)

Abstract Recent work suggests that a 2-stage strategy incorporating serial measurements of the glycoprotein CA125 in patient serum and the Risk of Ovarian Cancer Algorithm (ROCA), followed by transvaginal ultrasound for women with high-risk scores, may have utility as a screening practice in the general population. However, CA125 only has a sensitivity of 50-60% for early stage disease, and is only present in approximately 80% of all ovarian cancers. Multiple marker panels have shown promise at increasing sensitivity and specificity over CA125 alone, but have not improved lead time for early cancer detection. Therefore, we have taken an unbiased in-depth approach to identify novel plasma biomarkers to complement CA125 in ovarian cancer early detection. Using high-resolution quantitative mass spectrometry, we have profiled the plasma proteome of preclinical patient samples, taken 1 year prior to CA125 elevation and diagnosis, and healthy controls from the Normal Risk Ovarian Screening (NROS) study. With this approach, we have identified over 30 biomarker candidates that are elevated in at least 50% of preclinical samples relative to controls in triplicate experiments, including cancer-specific post-translational modifications. As a means of preliminary validation of promising preclinical biomarkers, we have profiled the plasma proteome of 24 newly diagnosed, early stage ovarian cancer patients and 24 matched healthy controls. Further, half of these patients were selected with uninformative CA125 levels at diagnosis, allowing for the discovery of additional candidate biomarkers that may complement CA125. Correlation of preclinical and newly diagnosed patient plasma data with publicly available genomic and transcriptomic data, as well as proteomic data previously collected from ovarian cancer cell lines resulted in a prioritized list of candidate protein biomarkers and autoantibodies in patient plasma that may improve detection and lead time over CA125. For the most promising candidates, monoclonal antibodies and MagPlex assays are being optimized in order to determine their performance as useful biomarkers in additional patient sera. Multimarker panels will be tested in a training set for the development of a screening algorithm that will be evaluated in preclinical sera to determine the optimized set that improves detection and lead time over CA125. Citation Format: Clayton Boldt, Ph.D., Archana Simmons, Ph.D., Hong Wang, MS, Ph.D., Keith Baggerly, Ph.D., Robert Bast, Jr., M.D., Samir Hanash, M.D., Ph.D.. Integrating genomics, transcriptomics, and proteomics for the discovery of novel biomarkers to complement CA125 in ovarian cancer early detection [abstract]. In: Proceedings of the 10th Biennial Ovarian Cancer Research Symposium; Sep 8-9, 2014; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2015;21(16 Suppl):Abstract nr AS12.
Ongoing complete remissions in phase 1 of ZUMA-1: a phase 1-2 multi-center study evaluating the safety and efficacy of KTE-C19 (anti-CD19 CAR T cells) in patients with refractory aggressive B cell non-Hodgkin lymphoma (NHL)
Authors: F.L. Locke, S.S. Neelapu, N.L. Bartlett, T. Siddiqi, J.C. Chavez, C.M. Hosing, A. Cashen, L.E. Budde, M. Sherman, J.M. Rossi, L. Navale, Y. Jiang, J. Aycock, M. Elias, J. Wiezorek, W.Y. Go
Journal: Annals of Oncology (2016)
Sialylated Fetuin-A as a candidate predictive biomarker for successful grass pollen allergen immunotherapy
Authors: Noémie Caillot, Julien Bouley, Karine Jain, Sandrine Mariano, Sonia Luce, Stéphane Horiot, Sabi Airouche, Chloé Beuraud, Christian Beauvallet, Philippe Devillier, Sylvie Chollet-Martin, Christine Kellenberger, Laurent Mascarell, Henri Chabre, Thierry Batard, Emmanuel Nony, Vincent Lombardi, Véronique Baron-Bodo, Philippe Moingeon
Journal: Journal of Allergy and Clinical Immunology (2016)
Combination of a polyamine-free oral nutritional supplement (ONS) with docetaxel in castrate-resistant prostate cancer (CRPC) patients (pts): A phase II trial.
Authors: Bernard G Cipolla, Xavier Artignan, Laurent Miglianico, Dominique Bligny, Christine Abraham, Jacques Philippe Moulinoux
Journal: Journal of Clinical Oncology (2012)

e15131 Background: Polyamines (PA) are essential for cancer cell growth. Reducing exogenous PA (foods + gut flora) and blocking PA synthesis, reduces tumour growth and potentializes chemotherapy in rodent tumour models. We have developed a PA “free” ONS, which inhibits tumour growth by 40% in pre-clinical models and assessed its tolerance with docetaxel in CRPC pts. Methods: 30 pts, 71 ± 7 years, with metastatic CRPC, median PSA: 95 ng/ml, were assessed for tolerance, quality of life (QOL) (QLQ C-30 questionnaire), W.H.O. performance status (P.S.), pain scores and prostate specific antigen (PSA) response. 90% pts were painful. 75% pts had opiate or morphinic analgesics at day 0 (D0). Median pain score is 5 (0 to 10 scale). The PA free ONS was given as sole diet (6 cans a day) for 14 days then progressively reduced and given with low PA containing foods. Docetaxel administration started on day 21 for 6, 75 mg/m 2 injections, every three weeks with prednisone. Nutrialys Medical Nutrition, France, provided the PA free ONS. Results: 27 pts were evaluated for the PA ONS free phase. 18 pts completed the trial at scheduled dates and docetaxel doses. 9 pts did not complete the trial: disease progression (n=4), initial thrombocytemia (n=2), 2 deaths and 1 GI intolerance PA free ONS stage: No specific toxicity. QOL (p=0,04), pain (p=0,03) and anorexia (p=0,01) are improved at day 14. 1 pt had a &gt; 50 % PSA decrease. PA free ONS + docetaxel stage: grade 1 or 2 nausea, vomiting or diarrhoea in &lt; 35 % pts, 12% grade 1 neuropathy, no onycholysis or skin toxicity. Body weight and biological parameters are preserved except for two grade 4 neutropenias. P.S., Q.O.L. and pain scores and anorexia are improved. 55% pts cut their analgesics by ≥ 30% WITH stable or improved pain score. 13 pts (70% pts who completed the trial) had an &gt; 50% PSA decrease with an 8 weeks median response time. Conclusions: A PA free ONS exclusive diet is well tolerated with significant QOL and pain improvements. The docetaxel PA free ONS combination tolerance is excellent with improved P.S., pain score and analgesic reduction. AE during chemotherapy are minimal. PSA responses are observed in a significant proportion of treated patients.
Prevalence and impact of correlative science in breast cancer phase II trials.
Authors: T. Zhang, E. P. Hamilton, A. Schneider, K. Patel, A. Kamal, J. M. Peppercorn
Journal: Journal of Clinical Oncology (2011)

1046 Background: Correlative science (CS) can augment clinical trial results by identifying biomarkers of response and resistance to a novel intervention. There is little data on how frequently CS is included in breast cancer phase II trials (BP2T). We evaluated recently published BP2T to identify prevalence, characteristics, and outcomes of CS. Methods: Using search terms “breast cancer” and “phase II trials” in Pubmed, we identified BP2T of systemic therapy published between June 2005 and June 2010. Reports were abstracted by 2 independent reviewers for trial characteristics, report of CS, CS features including endpoints, material, nature of sample (clinical, optional or mandatory biopsy), adequacy of samples, biopsy safety, and CS outcomes. Descriptive statistics, Fisher’s exact test, and Chi-square analysis were performed. Results: 298 eligible trials enrolling a total of 18,782 patients were abstracted. 81 trials (27.2%) enrolling 5807 patients (30.9%) involved CS. Of these, 57 (70.4%) included tissue, 16 (28%) used optional research biopsy and 17 (30%) required mandatory biopsy. No trial reported biopsy safety. 55 (68%) of trials with CS specified the CS endpoint. For 44 trials (54%) the authors reported that CS was successful, while for 17 trials (21%) they specifically reported insufficient material. CS predicted response, toxicity or further characterized the tumor in 50 trials (62%). BP2T sponsored by pharmaceutical industry were more likely to involve CS (33.7% vs. 17.1%, p=0.0017). Neoadjuvant trials vs. metastatic trials and U.S.-based vs. non-U.S. trials were more likely to include CS (47% vs. 21.2%, p=0.0001; 37% vs. 21%, p=0.005). Single arm BP2T were less likely to include CS vs. randomized BP2T and phase I/II trials (22.5% vs. 42.3%, p=0.0011). There was no statistical difference between likelihood of reporting success or insufficient material for mandatory vs. optional research biopsy trials. Conclusions: A minority of recently published BP2T trials included CS. When CS is included, results frequently add to trial information. Reporting of CS endpoints, adequacy of samples, and biopsy safety is inconsistent or absent, and should be considered in all trials to inform policy debates over optimal and ethical CS design.
Gene Frequencies of the HNA-4a and -5a Neutrophil Antigens in Brazilians and a New Polymerase Chain Reaction-Restriction Fragment Length Polymorfism Method for HNA-5a Genotyping.
Authors: José D.B. Cardone, Akemi K. Chiba, Angela M.M.I. Norcia, João P.B. Vieira-Filho, José O. Bordin
Journal: Blood (2005)
Prostate cancer incidence and disease-specific survival in men participating in the ERSPC with an initial PSA less than 3.0 ng/mL.
Authors: M. Bul, P. J. van Leeuwen, X. Zhu, F. H. Schröder, M. J. Roobol
Journal: Journal of Clinical Oncology (2011)

7 Background: The European Randomized Study of Screening for Prostate Cancer (ERSPC) applies a prostate- specific antigen (PSA) cut-off &gt;3.0 ng/mL as an indication for biopsy. We analyzed the incidence and disease-specific mortality for prostate cancer (PC) within ERSPC Rotterdam for men with an initial PSA &lt;3.0 ng/ml in a 15-year follow-up period. Methods: From 1993-1999, a total of 42,376 men identified from population registries in the Rotterdam region (55-74 yrs) were randomized to a screening or control arm. During the first screening round 19,950 men were screened, with biopsies being initially recommended in case of abnormal DRE or PSA &gt;4.0 ng/mL. From 1997 on, solely PSA &gt;3.0 ng/mL was used. The screening interval was 4 yrs. A total of 15,758 men (79%) had an initial PSA &lt;3.0 ng/mL. Follow-up was complete until January 2009. Results: From 1993-2008, 915 PC cases were diagnosed in 15,758 men (5.8%, median age 62.3 yrs) with an initial PSA &lt;3.0 ng/mL (733 screen detected and 182 interval detected). Median follow-up was 11 yrs. PC incidence increased significantly with higher initial PSA levels (Table). Aggressive PC (clinical stage &gt;T2c, Gleason score &gt;8, PSA &gt;20 ng/mL, positive lymph nodes or metastases at diagnosis) was detected in 65/733 screen detected PC (8.9%) and 102/182 interval detected PC (56.0%). PC death occurred in 23 cases (5 screen detected and 18 interval detected) in the total population (0.15%), with increasing risk in men with higher initial PSA values. Conclusions: The risk of (aggressive) PC and PC mortality in a screening population with initial PSA &lt;3.0 ng/mL increases significantly with higher PSA levels. The risk of dying of PC is minor in men with initial PSA &lt;1.0 ng/mL. Interval detected PC is more aggressive and has a substantial influence on PC specific mortality. [Table: see text] [Table: see text]
Efficacy of sitagliptin for the hospital management of general medicine and surgery patients with type 2 diabetes (Sita-Hospital): a multicentre, prospective, open-label, non-inferiority randomised trial
Authors: Francisco J Pasquel, Roma Gianchandani, Daniel J Rubin, Kathleen M Dungan, Isabel Anzola, Patricia C Gomez, Limin Peng, Israel Hodish, Tim Bodnar, David Wesorick, Vijay Balakrishnan, Kwame Osei, Guillermo E Umpierrez
Journal: The Lancet Diabetes & Endocrinology (2016)
Pediatric Hospital Volume and Induction Mortality in Pediatric Acute Lymphoblastic Leukemia (ALL)
Authors: Jennifer J. Wilkes, Sean Hennessy, Rui Xiao, Susan R. Rheingold, Alix E. Seif, Yuan-Shung Huang, Neika Vendetti, Yimei Li, Rochelle Bagatell, Richard Aplenc, Brian T. Fisher
Journal: Blood (2014)
A cleaner burning biomass-fuelled cookstove intervention to prevent pneumonia in children under 5 years old in rural Malawi (the Cooking and Pneumonia Study): a cluster randomised controlled trial
Authors: Kevin Mortimer, Chifundo B Ndamala, Andrew W Naunje, Jullita Malava, Cynthia Katundu, William Weston, Deborah Havens, Daniel Pope, Nigel G Bruce, Moffat Nyirenda, Duolao Wang, Amelia Crampin, Jonathan Grigg, John Balmes, Stephen B Gordon
Journal: The Lancet (2016)

BackgroundWHO estimates exposure to air pollution from cooking with solid fuels is associated with over 4 million premature deaths worldwide every year including half a million children under the age of 5 years from pneumonia. We hypothesised that replacing open fires with cleaner burning biomass-fuelled cookstoves would reduce pneumonia incidence in young children.MethodsWe did a community-level open cluster randomised controlled trial to compare the effects of a cleaner burning biomass-fuelled cookstove intervention to continuation of open fire cooking on pneumonia in children living in two rural districts, Chikhwawa and Karonga, of Malawi. Clusters were randomly allocated to intervention and control groups using a computer-generated randomisation schedule with stratification by site, distance from health centre, and size of cluster. Within clusters, households with a child under the age of 4·5 years were eligible. Intervention households received two biomass-fuelled cookstoves and a solar panel. The primary outcome was WHO Integrated Management of Childhood Illness (IMCI)-defined pneumonia episodes in children under 5 years of age. Efficacy and safety analyses were by intention to treat. The trial is registered with ISRCTN, number ISRCTN59448623.FindingsWe enrolled 10 750 children from 8626 households across 150 clusters between Dec 9, 2013, and Feb 28, 2016. 10 543 children from 8470 households contributed 15 991 child-years of follow-up data to the intention-to-treat analysis. The IMCI pneumonia incidence rate in the intervention group was 15·76 (95% CI 14·89–16·63) per 100 child-years and in the control group 15·58 (95% CI 14·72–16·45) per 100 child-years, with an intervention versus control incidence rate ratio (IRR) of 1·01 (95% CI 0·91–1·13; p=0·80). Cooking-related serious adverse events (burns) were seen in 19 children; nine in the intervention and ten (one death) in the control group (IRR 0·91 [95% CI 0·37–2·23]; p=0·83).InterpretationWe found no evidence that an intervention comprising cleaner burning biomass-fuelled cookstoves reduced the risk of pneumonia in young children in rural Malawi. Effective strategies to reduce the adverse health effects of household air pollution are needed.FundingMedical Research Council, UK Department for International Development, and Wellcome Trust.
Epidemiology and Characteristics of Pain in Patients Suffering from Advanced Haematological Malignancies in the Home Care (HC) Setting: An Italian Survey.
Authors: Pasquale Niscola, Claudio Cartoni, Claudio Romani, Marco Giovannini, Gregorio Brunetti, Gianna Maria D’Elia, Luca Cupelli, Paolo De Fabritiis, Robin Foà, Franco Mandelli
Journal: Blood (2006)
Prevention of Tumor Formation after Allogeneic In Utero Transplantation of Cynomolgus Monkey Embryonic Stem Cell-Derived Hematopoietic Precursors.
Authors: Yutaka Hanazono, Hiroaki Shibata, Naohide Ageyama, Yujiro Tanaka, Yukiko Kishi, Shinichiro Nakamura, Kyoko Sasaki, Satoshi Hayashi, Yoshihiro Kitano, Keiji Terao
Journal: Blood (2005)
Primary androgen deprivation (PAD) followed by active surveillance for newly diagnosed prostate cancer (PC).
Authors: Mark Creamer Scholz, Meg Groom, Andrew Kaddis, Richard Y. Lam, Robert Jennrich
Journal: Journal of Clinical Oncology (2012)

244 Background: Men undergoing local therapy (LT) with radiation or surgery incur substantial risk of permanent sexual, urinary and rectal toxicity. Active surveillance is only recommended for men with Low-Risk PC who have &lt; 34% biopsy cores positive. Studies of PAD as an alternative to LT are sparse. Methods: Retrospective analysis of 102 men with localized PC administered 12 months of an LHRH agonist and antiandrogen (PAD) followed by immediate biopsy (BX1). Outcome assessed: The incidence of implementing further treatment with either LT or androgen deprivation (AD) if there was subsequent progression on active surveillance (PAS) or if BX1 was positive. Post PAD monitoring included quarterly PSA testing, follow-up biopsy and imaging with color doppler ultrasound and endorectal MRI. Participants were screened for heart disease and osteoporosis and monitored for changes in body weight, BP, liver enzymes, anemia, blood sugar and cholesterol. All received empiric bisphosphonates and 5-alpha reductase inhibitors and were instructed to eat a low fat diet and perform resistance exercise. Results: Patient characteristics: D’Amico risk category (DRC) Low: n=22; Intermediate: n=30; High: n= 50. Baseline factors assessed as potential predictors of PAS: Age, PSA, PSA velocity, PSA nadir, Gleason, % core biopsies, stage, prostate volume, DRC. Baseline medians for the 102 men: Age 67.3, PSA 7.8, Gleason 3+4, Cores &gt; 50%, stage T1c, prostate volume 45cc. 55 men had PAS and required LT and/or AD over a median of 7.3 years follow up. Type of treatment administered after PAS by DRC: Low: AD 1, LT 3. Intermediate: AD 5, LT 10. High: AD 15, LT 21. Two men developed clinical progression. There were no PC deaths. Four men died of other causes: lung CA, melanoma, emphysema and MI. Only DRC (p&lt;0.01) and PSA nadir (p&lt;0.04) predicted PAS (3 men had PSA nadir &gt; 0.1 and all were positive at BX1). Conclusions: PAD frequently induces durable remissions in men with Low and Intermediate risk PC despite a high prevalence of &gt; 50% core biopsies positive at baseline in this population. 38% of the 55 men with PAD elected additional AD rather than undergoing LT suggesting that for some men enduring the toxicity profile of AD was preferable to the perceived risks of LT.
Getting back from the basics: What is the role for attention and fronto-parietal circuits in consciousness?
Authors: Paul E Dux
Journal: Behavioral and Brain Sciences (2016)

Morsella et al. present a novel theory of consciousness which is more "low-level, circumscribed, counterintuitive, and passive" than previous accounts. There is much to like about this approach. However, what are the explanatory costs associated with these characteristics? In particular, how does this low-level and passive theory accommodate evidence for top-down attention being necessary (but not sufficient) for visual consciousness?
Neoadjuvant endocrine therapy with exemestane in locally advanced breast cancer: The initial results from a Brazilian breast cancer center.
Authors: F. Marziona, A. Mattar, R. Hegg, S. J. Belloni, S. B. Rocha, E. G. Tavares, W. M. Monteiro, A. Q. Carneiro, S. M. Kuwamoto, L. H. Gebrim
Journal: Journal of Clinical Oncology (2011)

135 Background: Endocrine therapy is a well-established treatment for hormone-positive breast cancer, both in the adjuvant and the metastatic setting. Neoadjuvant chemotherapy has been used to increase the number of patients who are eligible for breast-conservation therapy (BCT) by inducing tumor downstaging. Neoadjuvant endocrine therapy (NET) is mostly used in patients who are not eligible for chemotherapy (almost reserved to postmenopausal patients). The clinical response with NET in postmenopausal patients with locally advanced breast cancer (LABC) and positive hormonal receptors is almost 75% with aromatase inhibitors (AI). The comparison among tamoxifen and the three AI (anastrozole, letrozole, and exemestane) shows a superiority to AI regarding BCT. There are few data in premenopausal women and NET. Methods: 29 women with rich positive hormone receptor were enrolled in the study between January to September of 2010. Patients received exemestane 25mg/day (EXE) and as we included both pre (12 patients) and postmenopausal (17 patients) women, the premenopausal ones were submitted to ooforectomy. Results: All patients were clinical stage III. In the premenopausal group 6 patients were submitted to surgery and 5 are still taking EXE. Between the two groups 9 patients were submitted to surgery, 4 showed response and are scheduling to surgery, 10 are still taking exemestane. Five patients had serious comorbidities and were submitted to radiotherapy after 9 months of EXE (one without clinical tumor) and are asymptomatic for at least 4 months. Just one patient (premenopausal) had tumor progression after 5 months of EXE and was switched to chemotherapy. Most common side effects were arthralgia/myalgia grade 1/2. Conclusions: In Brazil LABC is frequent and neoadjuvant chemotherapy is the standard treatment. We offered a treatment with a lower cost and especially lower side effects. Because of the initial stage, BCS was not possible, but we had clinical response in about 75% of the patients. This approach was good for patients with comorbidities, and despite the NET is not established for premenopausal patients our initial results encourage us to recommend it.