tbuckley/cabot-search huggingface dataset:
A phase 2 study to determine the efficacy and safety of TVB-2640 in combination with bevacizumab in patients with first relapse of high grade astrocytoma.
Authors: Adolfo Enrique Diaz Duque, Henk De Feyter, George Kemble, William McCulloch, Andrew Jacob Brenner
Journal: Journal of Clinical Oncology (2017)

TPS2080 Background: The mainstay of treatment for Glioblastoma Multiforme (GBM) remains surgical removal followed by combined chemotherapy with temozolomide and radiation therapy. Second line Bevacizumab (Bev) is indicated upon progression, but unfortunately the responses are not very long lasting, and there are no therapeutic options available at that point. We have learned that antiangiogenic resistance in GBM is promoted by hypoxia; moreover, metabolomic profile of GBM under such conditions reveals an increased presence of long chain fatty acids. On second hand, tumor cells compared to normal cells depend more on palmitate, and is Fatty Acid Synthase (FASN) the enzyme capable of catalyzing its biosynthesis. Further studies have shown how GBM overexpress FASN and how its inhibition selectively inhibits growth and viability of tumor cells by inducing tumor cell apoptosis. TVB-2640 emerges as a novel agent that selectively inhibits FASN. This study represents a phase 2 clinical investigation of TVB-2640, which is to be conducted in patients with Recurrent High Grade Astrocytoma. Methods: This is a prospective, randomized, phase 2 study of TVB-2640 in combination with Bev or Bev alone in patients with GBM in first relapse. Primary end point is progression free survival (PFS). Patients 18 years or older, with ECOG 0 to 2 and GBM progression following standard combined modality treatment will qualify for the study. Patients will be randomized into 2 separate arms. Patients in arm number one will receive Bev every 2 weeks in combination with TVB-2640 while patients in arm number two will receive Bev alone every 2 weeks. MR-Spectroscopy will be obtained on all patients at day 1 and 28 of first cycle. Starting on cycle 2 day 1, all patients will converge to a single arm and will continue to receive Bev in combination with TVB-2640. A total sample size of 24 patients will provide 90% power to detect a 4 months difference in PFS (3 months for Bev alone (historic controls) versus 7 months for TVB-2640 in combination with Bev, i.e., a hazard ratio of 0.43) using a one-sided log-rank test with alpha = 0.1. The trial is open and enrollment will begin in Feb 2017. Clinical trial information: NCT03032484.
Representation of minorities in oncology clinical trials: Review of the past 14 years.
Authors: Narjust Duma, Jesus Vera Aguilera, Jonas Paludo, Yucai Wang, Konstantinos Leventakos, Aaron Scott Mansfield, Alex A. Adjei
Journal: Journal of Clinical Oncology (2017)

2533 Background: Many cancer clinical trials (CT) lack appropriate representation of specific patients populations, limiting the generalizability of the evidence obtained. Therefore, we determined the representation of ethnic minorities in oncology CT. Methods: Enrollment data from all therapeutic trials reported as completed in clinicaltrial.gov from 2003 to 2016 were analyzed. CT in rare cancers (&lt; 1% incidence) or with recruitment outside of the US were excluded. Enrollment fraction (EF) was defined as the number of enrollees divided by the 2013 SEER database cancer prevalence. Chi-square test was used to estimate differences in categorical data. Results: Out of 1,012 CT, 310 (31%) reported ethnicity with a total of 55689 enrollees. Distribution by race and comparison with data from 1996-2002, US cancer prevalence and US census are described in the Table. Participation in CT varied significantly across ethnic groups, non-Hispanic Whites (NHW) were more likely to be enrolled in CT (EF of 1.2%) than African Americans (EF of 0.7%, p &lt; 0.001) and Hispanics (EF of 0.4%, p&lt;0.001). A decrease in African Americans (AA) and Hispanics (H) enrollment was observed when compared with historical data from 1996 to 2002. Hispanics were less represented in breast and prostate cancer CT contributing only to 3% and 1.5% of the study population; African Americans were less represented in lung (5.4%) and renal cell carcinoma (3%) trials. Asians were well represented and their recruitment doubled over the past 14 years (2% vs 5.3%). Conclusions: African Americans and Hispanics were less likely to be enrolled in CT. Comparing with historical data; we observed a decrease in minorities’ recruitment in the past 14 years. This change could be attributed to the increased complexity of CT and mandatory molecular testing as many minorities lack access to institutions with genetic testing capacity. Future trials should take extra measures to recruit participants that adequately represent the U.S. cancer population. [Table: see text]
Tumor infiltrating lymphocytes (TILs) in breast cancer (BC) patients with progressive disease during neoadjuvant chemotherapy (NAT).
Authors: Jacques Raphael, Sharon Nofech-Mozes, Thivaher Paramsothy, Nim Li, Sonal Gandhi
Journal: Journal of Clinical Oncology (2016)

565 Background: The association between TILs and BC outcomes is still being defined; data suggests that HER-2 positive (HER2) and triple negative (TN) BC that is lymphocyte-predominant (LPBC) has better survival outcomes and higher pathologic complete response (pCR) rates after NAT. The value of TILs in BC progressing versus (vs.) responding to NAT has not been evaluated. Methods: A retrospective review using a NAT database within the Sunnybrook Biomatrix identified BC patients who either progressed during NAT or responded and achieved a pCR. A pathologist with BC expertise semiquantified stromal TILs using HE stained slides. Cases with 60% TILs or more were categorized as LPBC and were compared between the two groups. Overall and Disease Free Survival (OS, DFS) were compared between patients with LPBC vs. low TILs level using the log-rank test. Results: Fifty patients were identified: 21 progressed during NAT and 29 had a pCR. Age, stage and tumor grade were not significantly different between the 2 groups. However, more patients with TN disease progressed during NAT and more HER2+ patients achieved pCR (p= 0.03, p= 0.007 respectively). Only 9% of the patients with progressive disease had high TILs (LPBC) while 31% of the patients with pCR were classified as LPBC. A significant difference in the mean level of TILs was found between the 2 groups (p= 0.01): 32.7% (SD 30.88) vs. 14.2% (SD 16.86). The level of TILs was not associated with any baseline characteristics. Thirty percent and 20% of the HER2+ and TN patients were LPBC respectively (p> 0.1). No difference in the median DFS and OS was detected between patients with low TILs and LPBCs (42.4 (95%CI 29.53-58.87) vs. 38.07 months (95%CI 21.27-44.77), p> 0.1 and 42.4 months (95%CI 30.6-64.4) vs. 43.77 (95%CI 22.1-44.77) p= 0.09 respectively). Conclusions: In this study, BC patients progressing during NAT have low TILs level compared to patients who responded to NAT and achieved a pCR. There was no difference in patient outcomes based on TILs level. Further work is needed to establish the utility of TILs in patients progressing on NAT to help identify novel treatment strategies in this high-risk population.
Performing high-level sport is strongly associated with urinary incontinence in elite athletes: a comparative study of 372 elite female athletes and 372 controls
Authors: Alice Carvalhais, Renato Natal Jorge, Kari Bø
Journal: British Journal of Sports Medicine (2017)

Objective To evaluate the prevalence of urinary incontinence (UI) in female elite athletes compared with controls and to investigate potential risk factors for UI among elite athletes. Methods This cross-sectional study included 372 elite athletes (athletes group, AG) and 372 age-matched controls (control group, CG). The median age was low (19 years) and the vast majority were nulliparous. Potential risk factors, including clinical, demographic and sports practice characteristics, were collected by using a questionnaire. The International Consultation on Urinary Incontinence Questionnaire-Urinary Incontinence-Short Form was applied to estimate the prevalence of UI. OR with 95% CIs were used to estimate the association with UI. The final model was adjusted for constipation, family history of UI and history of urinary infection. Results The prevalence of UI was 29.6% and 13.4% in AG and CG, respectively (p&lt;0.001). The following prevalences were obtained: AG: 19.6% and CG: 3.5% (p&lt;0.001) for stress UI, AG: 3.8% and CG: 5.4% (p=0.292) for urgency UI and AG: 5.9% and CG: 0.8% (p&lt;0.001) for mixed UI. After adjustment, performing high-level sport (adjusted (adj) OR=3.31; 95% CI 2.20 to 4.97), family history of UI (adj OR=1.54; 95% CI 1.04 to 2.29), history of urinary infection (adj OR=1.53; 95% CI 1.05 to 2.23) and constipation (adj OR=1.79; 95% CI 1.07 to 2.98) were associated with UI. Conclusion The prevalence of UI among Portuguese female elite athletes is high and the odds of UI were three times higher than in controls. Also, constipation, family history of UI and history of urinary infections were significantly associated with UI.
Surgical caseload is only one variable that influences outcome
Authors: C. Penfold
Journal: BMJ (1995)

EDITOR,—Recent studies have highlighted deficiencies in the overall standard and organisation of repair of cleft lip and palate in England and Wales, but, contrary to the opinions expressed in these papers, there is no conclusive evidence that surgical caseload is a critical factor in determining outcome.1 2 In a retrospective European multicentre study the number of operations carried out by an operator was just one of several variables that may have influenced the outcome of treatment in patients …
The performance of a comprehensive CTC anti-body capture cocktail in the detection and phenotypic analysis of CTCs.
Authors: Veena M. Singh
Journal: Journal of Clinical Oncology (2016)

e23068 Background: Traditional methods of detecting and classifying circulating tumor cells (CTCs) are complicated by detection limitations and CTC phenotypic heterogeneity. CTCs are generally defined as cytokeratin (CK)-positive, CD45-negative nucleated epithelial cells. However methodologies that rely on single antibody (EPCAM only) capture and detection (CK only) would fail to identify CTCs that are CK-negative. Identification of CK-negative CTCs (cancer stem cells (CSC) or cells undergoing epithelial-mesenchymal transition (EMT)) would be important from a tumor burden perspective and may be more aggressive, drug resistant, prone to metastasis and possibly more clinically relevant. Herein we present a method of both CK+ and CK- CTC capture and identification utilizing a cocktail of antibodies. Methods: Studies were conducted to determine the specificity and sensitivity of an antibody cocktail for detecting CTCs in patient samples. CTCs were captured in our microfluidic device by an antibody cocktail targeting a broad spectrum of CTCs (epithelial, EMT and stem cell). Detection was achieved by either cytokeratin or streptavidin targeting the unbound excess biotin present on the surface of the tumor cell thus captured. Results: Antibodies of the capture cocktail recognize surface antigens on circulating tumor cells with a high degree of specificity and sensitivity and enable the identification both CK-positive and CK-weak or negative CTCs. Our CTC detection rate on clinical samples in patients with metastatic cancer with our enhanced detection technique has improved our CTC detected rate almost three-fold. Conclusions: High specificity and improved sensitivity for isolating and identifying both CK-negative and CK-positive CTCs from patient blood samples was achieved using an antibody cocktail against tumor-specific antigens in combination with our approach. Compared to traditional methods of CTC isolation and detection, the multiplexed anti-body cocktail method improves the capture and characterization of a broader range of CTC phenotypes resulting in a more thorough screen for predictive and prognostic tumor markers, thereby enabling an informed treatment strategy.
A district general hospital experience of the rapid access referral for colorectal cancers
Authors: RK Choudhary, D Debnath, KA Gunning
Journal: Endoscopy (2006)

Aims: Critics doubted the efficacy of the guidelines for referral to 2-week rapid access colorectal cancer (CRC) clinic that was introduced by the Department of Health of England and Wales in August 2000. We aimed to assess the usefulness of the guidelines in a district general hospital over a period of three years.
A phase 1 study of MEDI4736, an anti–PD-L1 antibody, in patients with advanced solid tumors.
Authors: Jose Lutzky, Scott Joseph Antonia, Andy Blake-Haskins, Xia Li, Paul B. Robbins, Aiman M. Shalabi, Jim Vasselli, Ramy A. Ibrahim, Samir Khleif, Neil Howard Segal
Journal: Journal of Clinical Oncology (2014)

3001^ Background: Immune-suppressing molecules such as PD-L1 can be co-opted by cancer cells to suppress the natural immune response to cancer. Upregulation of PD-L1 and inhibition of antitumor T-cell activation is observed in several tumor types. MEDI4736 is a human IgG1 antibody which binds specifically to PD-L1, preventing binding to PD-1 and CD80. Methods: An ongoing phase 1 multicenter, open-label study (NCT01693562) is evaluating safety, pharmacokinetics (PK), and antitumor activity of MEDI4736 given IV every 2 (q2w) or 3 wks (q3w) in a 3+3 dose escalation with a 28-day (q2w) or 42-day (q3w) dose-limiting toxicity (DLT) window, followed by expansion in 8 solid tumors. Response was assessed by immune-related response criteria in escalation. Results: As of Jan 17, 2014, 26 patients (pts) (13 NSCLC, 8 melanoma, 5 other) in dose escalation (median age 59 yrs; 35-77), all PS 0-1, with a median of 4 prior treatments, received a median of 5 (1-25) q2w and 4.5 (1-7) q3w doses of MEDI4736 across 6 cohorts (0.1 – 10 mg/kg q2w; 15 mg/kg q3w). MEDI4736 showed dose-dependent PK. Evidence of ADA impacted PK exposure in only 1 patient. No DLTs or maximum tolerated dose were identified for q2w or q3w dosing. Treatment-related AEs occurred in 34% of pts, all Grade 1-2; none led to discontinuation of study drug. The most frequent treatment-related AEs were diarrhea, fatigue, rash, and vomiting (12% each). No pneumonitis, colitis, or hyperglycemia occurred. Of 26 pts, 4 PRs (3 NSCLC, 1 melanoma) and 5 additional pts with tumor shrinkage not meeting PR were observed. Disease control rate (PR + SD ≥ 12 wks) was 46%. Tumor shrinkage, as early as 6 wks, was seen at all dose levels, and benefit was durable; 11 pts remain on study as of the data cutoff (2+ to 14.9+ mos). Expansion cohorts opened Sep 2013 using a 10 mg/kg q2w dose; 151 pts have been dosed, with the opportunity to enroll > 600 pts. Preliminary clinical activity has been observed with acceptable safety across a range of tumors including SCCHN, pancreatic, gastric, NSCLC, and melanoma. Conclusions: MEDI4736 has demonstrated an acceptable safety profile and durable clinical activity in this dose-escalation study. Expansion in multiple cancers and development of MEDI4736 as monotherapy and in combination is ongoing. Clinical trial information: NCT01693562.
Clinical Characteristics and Outcome of Infective EndocarditisInvolving Implantable Cardiac Devices
Authors: Eugene Athan, Vivian H Chu, Pierre Tattevin, Christine Selton-Suty, Phillip Jones, Christoph Naber, Jose M Miro, Salvador Ninot, Nuria Fernandez-Hidalgo, Emanuele Durante-Mangoni, Denis Spelman, Bruno Hoen, Tatjana Lejko-Zupanc, Enrico Cecchi, Franck Thuny, Margaret M Hannan, Paul Pappas, Margaret Henry, Vance G Fowler, Anna Lisa Crowley, Andrew Wang, Tomáš Freiberger, Jiří Pol, Barbora Mališová
Journal: JAMA (2012)

Context Infection of implantable cardiac devices is an emerging
disease with significant morbidity, mortality, and health care
costs. Objectives To describe the clinical characteristics and
outcome of cardiac device infective endocarditis (CDIE) with
attention to its health care association and to evaluate the
association between device removal during index hospitalization
and outcome. Design, Setting, and Patients Prospective cohort
study using data from the International Collaboration on
Endocarditis-Prospective Cohort Study (ICE-PCS), conducted June
2000 through August 2006 in 61 centers in 28 countries.
Patients were hospitalized adults with definite endocarditis as
defined by modified Duke endocarditis criteria. Main Outcome
Measures In-hospital and 1-year mortality. Results CDIE was
diagnosed in 177 (6.4% [95% CI, 5.5%-7.4%]) of a total cohort
of 2760 patients with definite infective endocarditis. The
clinical profile of CDIE included advanced patient age (median,
71.2 years [interquartile range, 59.8-77.6]); causation by
staphylococci (62 [35.0% {95% CI, 28.0%-42.5%}] Staphylococcus
aureus and 56 [31.6% {95% CI, 24.9%-39.0%}] coagulase-negative
staphylococci); and a high prevalence of health care-associated
infection (81 [45.8% {95% CI, 38.3%-53.4%}]). There was
coexisting valve involvement in 66 (37.3% [95% CI,
30.2%-44.9%]) patients, predominantly tricuspid valve infection
(43/177 [24.3%]), with associated higher mortality. In-hospital
and 1-year mortality rates were 14.7% (26/177 [95% CI,
9.8%-20.8%]) and 23.2% (41/177 [95% CI, 17.2%-30.1%]),
respectively. Proportional hazards regression analysis showed a
survival benefit at 1 year for device removal during the
initial hospitalization (28/141 patients [19.9%] who underwent
device removal during the index hospitalization had died at 1
year, vs 13/34 [38.2%] who did not undergo device removal;
hazard ratio, 0.42 [95% CI, 0.22-0.82]). Conclusions Among
patients with CDIE, the rate of concomitant valve infection is
high, as is mortality, particularly if there is valve
involvement. Early device removal is associated with improved
survival at 1 year. JAMA. 2012;307(16):1727-1735
Thérapie Photodynamique avec le Foscan à 514nm des dysplasies de haut grade ef des Carcinomes intramuqueux sur oesophage de Barrett et sur muqueuse malphigienne: résultats comparatifs à long terme
Authors: J Etienne, N Dorme, G Bourg-Heckly, B Gayet, F Mal, JF Flejou, P Validire, JP Flejou
Journal: Endoscopy (2005)

But La thérapie photodynamique (PDT) avec le Foscan à 514nm avait été jugée efficace sur les dysplasies de haut grade (DHG) et les carcinomes intramuqueux (CIM) sur oesophage de Barrett et sur muqueuse malphigienne. Le but de l'étude a été de comparer les résultats à long terme.
Сучасні можливості застосування препаратів вісмуту у хворих із гастродуоденальною патологією
Authors: N.V. Kharchenko, I.Ya. Lopukh, I.A. Korulya, K.V. Barannikov
Journal: GASTROENTEROLOGY (2013)

Подані сучасні дані про механізми впливу колоїдного субцитрату вісмуту на слизову гастродуоденальної зони й місце препаратів вісмуту у схемах лікування інфекції Helicobacter pylori з урахуванням показників антибіотикорезистентності.
Traitement de la douleur de la pancréatite chronique par endoprothèse „définitive“ du wirsung: résultats à long terme
Authors: F Gadroy, R Roda, F Hedelius, N Claudel, R Bory, B Napoléon, C Lefort, T Ponchon
Journal: Endoscopy (2006)

Pour de nombreuses équipes, le traitement endoscopique par mise en place de prothèse plastique est devenu le traitement de première intention chez les patients porteurs de pancréatite chronique douloureuse, présentant une dilatation du canal principal. Les résultats à court terme sont satisfaisants mais l'efficacité à long terme est mal connue et pourrait diminuer. Laisser les prothèses en place de façon définitive pourrait permettre de contrôler la douleur de façon durable. Les résultats à long terme de cette modalité thérapeutique ont été analysés à partir d'une série de 40 patients.
Urgent chemotherapy for hospitalized cancer patients in the United States: Analysis of inpatient mortality by tumor type from the 2012 National Inpatient Sample.
Authors: Joseph James Shatzel, Elizabeth Hutchinson, Molly M Daughety, Jonathan Edmiston, Jeremy Paul Cetnar
Journal: Journal of Clinical Oncology (2016)

e13079 Background: Chemotherapy is potentially curative for many and offers palliation for others. Almost all studies that guide chemotherapy use occur in ambulatory settings. The practice of giving urgent chemotherapy to hospitalized patients to improve survival has not been studied in multiple tumor types, but occurs routinely in practice. The purpose of this study is to determine the incidence, epidemiology and mortality of urgent chemotherapy in hospitalized cancer patients. Methods: Using the 2012 National Inpatient Sample (NIS), admissions with the ICD-9-CM code for chemotherapy administration (99.25) were evaluated. We stratified admissions as elective vs. urgent, and stratified by cancer type, length of stay, cost, comorbidity, and mortality. p-valves were calculated using student t-test. Results: Of the 7,296,968 admissions in the 2012 NIS, 40,500 involved chemotherapy administration. 20,497 admissions were elective (50.6%) and 19,553 were urgent (50.4%). 51% of urgent chemotherapy admissions involved hematologic malignancies (lymphoma [n = 4919], leukemia [n = 4071], myeloma [n = 1006]). 49% involved solid tumors, most commonly lung (n = 2283), breast (n = 1106), and colon (n = 830). Of the solid tumor admissions who received urgent chemotherapy, the most likely to die while inpatient were lung cancer (8.15%), other respiratory tract cancers (7.41%), and prostate cancer (6.88%). Urgent chemotherapy was more likely to be given to patients with higher comorbidities and portended higher rates of dialysis, mechanical ventilation, longer length of stay, higher discharge rates to skilled nursing, and increased inpatient mortality (all with p-values < 0.001). Conclusions: The practice of giving urgent inpatient chemotherapy was as prevalent as elective chemotherapy in the U.S., despite the lack of data supporting this practice in certain tumor types. Among specific malignancies, there were higher costs, worse outcomes, and significant inpatient mortality. Future studies are needed to determine if there is a role for urgent chemotherapy in hospitalized patients with certain tumor types or if this practice should continue.