678 research outputs found
Best practice considerations on the assessment of robotic assisted surgical systems:results from an international consensus expert panel
Background Health technology assessments (HTAs) of robotic assisted surgery (RAS) face several challenges in assessing the value of robotic surgical platforms. As a result of using different assessment methods, previous HTAs have reached different conclusions when evaluating RAS. While the number of available systems and surgical procedures is rapidly growing, existing frameworks for assessing MedTech provide a starting point, but specific considerations are needed for HTAs of RAS to ensure consistent results. This work aimed to discuss different approaches and produce guidance on evaluating RAS. Methods A consensus conference research methodology was adopted. A panel of 14 experts was assembled with international experience and representing relevant stakeholders: clinicians, health economists, HTA practitioners, policy makers, and industry. A review of previous HTAs was performed and seven key themes were extracted from the literature for consideration. Over five meetings, the panel discussed the key themes and formulated consensus statements. Results A total of ninety-eight previous HTAs were identified from twenty-five total countries. The seven key themes were evidence inclusion and exclusion, patient- and clinician-reported outcomes, the learning curve, allocation of costs, appropriate time horizons, economic analysis methods, and robotic ecosystem/wider benefits. Conclusions Robotic surgical platforms are tools, not therapies. Their value varies according to context and should be considered across therapeutic areas and stakeholders. The principles set out in this paper should help HTA bodies at all levels to evaluate RAS. This work may serve as a case study for rapidly developing areas in MedTech that require particular consideration for HTAs.</p
A phase II study of S-1 monotherapy administered for 2 weeks of a 3-week cycle in advanced gastric cancer patients with poor performance status
Systemic chemotherapy for gastric cancer is often associated with treatment-related toxicity, which is particularly severe in patients with a poor performance status. In this paper, we describe the first study to evaluate S-1 monotherapy as an option for advanced gastric cancer patients who are not candidates for combination chemotherapy due to poor clinical condition. Fifty-two patients with Eastern Cooperative Oncology Group (ECOG) performance scale 2ā3, whose general condition had made use of combination chemotherapy impossible, were enrolled. S-1 was administered to 30 patients as second- or third-line therapy. The initial dose of S-1 was 35āmgāmā2, administered b.i.d for 14 days every 3 weeks. With a median follow-up period of 33 weeks, the median progression-free survival, and overall survival were 11 weeks (95% CI, 8ā14) and 33 weeks (95% CI, 19ā47), respectively. The overall 1-year survival rate was 29% by intent-to-treat analysis. The overall response rate was 12% (95% CI, 3ā21), and the percentage of stable disease was 35%, resulting in the disease control rate of 47% (95% CI, 32ā60). Significant drug-related toxicity included grade 3 diarrhoea (14%), anorexia (14%), fatigue (10%), neutropenia (10%), and leucopenia (6%). In conclusion, this study indicated the modest activity of S-1 in gastric cancer patients with poor performance status
Search for Electroweak Production of Single Top Quarks in ppbar Collisions
We present a search for electroweak production of single top quarks in the
electron+jets and muon+jets decay channels. The measurements use ~90 pb^-1 of
data from Run 1 of the Fermilab Tevatron collider, collected at 1.8 TeV with
the DZero detector between 1992 and 1995. We use events that include a tagging
muon, implying the presence of a b jet, to set an upper limit at the 95%
confidence level on the cross section for the s-channel process ppbar->tb+X of
39 pb. The upper limit for the t-channel process ppbar->tqb+X is 58 pb.Comment: 11 pages, 2 figures. This is the published versio
A Quasi-Model-Independent Search for New Physics at Large Transverse Momentum
We apply a quasi-model-independent strategy ("Sleuth") to search for new high
p_T physics in approximately 100 pb^-1 of ppbar collisions at sqrt(s) = 1.8 TeV
collected by the DZero experiment during 1992-1996 at the Fermilab Tevatron.
Over thirty-two e mu X, W+jets-like, Z+jets-like, and 3(lepton/photon)X
exclusive final states are systematically analyzed for hints of physics beyond
the standard model. Simultaneous sensitivity to a variety of models predicting
new phenomena at the electroweak scale is demonstrated by testing the method on
a particular signature in each set of final states. No evidence of new high p_T
physics is observed in the course of this search, and we find that 89% of an
ensemble of hypothetical similar experimental runs would have produced a final
state with a candidate signal more interesting than the most interesting
observed in these data.Comment: 28 pages, 17 figures. Submitted to Physical Review
Search for Large Extra Dimensions in Dielectron and Diphoton Production
We report a search for effects of large extra spatial dimensions in ppbar
collisions at a center-of-mass energy of 1.8 TeV with the DZero detector, using
events containing a pair of electrons or photons. The data are in good
agreement with the expected background and do not exhibit evidence for large
extra dimensions. We set the most restrictive lower limits to date, at the 95%
confidence level, on the effective Planck scale between 1.0 TeV and 1.4 TeV for
several formalisms and numbers of extra dimensions.Comment: 6 pages, 2 figures, submitted to Phys. Rev. Let
DLEC1 is a functional 3p22.3 tumour suppressor silenced by promoter CpG methylation in colon and gastric cancers
Promoter CpG methylation of tumour suppressor genes (TSGs) is an epigenetic biomarker for TSG identification and molecular diagnosis. We screened genome wide for novel methylated genes through methylation subtraction of a genetic demethylation model of colon cancer (double knockout of DNMT1 and DNMT3B in HCT116) and identified DLEC1 (Deleted in lung and oesophageal cancer 1), a major 3p22.3 TSG, as one of the methylated targets. We further found that DLEC1 was downregulated or silenced in most colorectal and gastric cell lines due to promoter methylation, whereas broadly expressed in normal tissues including colon and stomach, and unmethylated in expressing cell lines and immortalised normal colon epithelial cells. DLEC1 expression was reactivated through pharmacologic or genetic demethylation, indicating a DNMT1/DNMT3B-mediated methylation silencing. Aberrant methylation was further detected in primary colorectal (10 out of 34, 29%) and gastric tumours (30 out of 89, 34%), but seldom in paired normal colon (0 out of 17) and gastric (1 out of 20, 5%) samples. No correlation between DLEC1 methylation and clinical parameters of gastric cancers was found. Ectopic expression of DLEC1 in silenced HCT116 and MKN45 cells strongly inhibited their clonogenicity. Thus, DLEC1 is a functional tumour suppressor, being frequently silenced by epigenetic mechanism in gastrointestinal tumours
Prognostic significance of T-cellāinflamed gene expression profile and PD-L1 expression in patients with esophageal cancer
PURPOSE: The ability of the Tācellāinflamed gene expression profile (GEP) to predict clinical outcome in esophageal cancer (EC) is unknown. This retrospective observational study assessed the prognostic value of GEP and programmed death ligand 1 (PDāL1) expression in patients with EC treated in routine clinical practice. METHODS: Tumor samples of 294 patients from three centers in Denmark, South Korea, and the United States, collected between 2005 and 2017, were included. Tācellāinflamed GEP score was defined as nonālow or low using a cutoff of ā1.54. A combined positive score (CPS) ā„10 was defined as PDāL1 expression positivity. Associations between overall survival (OS) and GEP status and PDāL1 expression were explored by Cox proportional hazards models adjusting for age, sex, histology, stage, and performance status. RESULTS: Median age was 65 years; 63% of patients had adenocarcinoma (AC) and 37% had squamous cell carcinoma (SCC). Thirtyāsix percent of tumors were GEP nonālow, with higher prevalence in AC (46%) than SCC (18%). Twentyāone percent were PDāL1āpositive: 32% in South Korean samples versus 16% in nonāAsian samples and 26% in SCC versus 18% in AC. GEP scores and PDāL1 CPS were weakly correlated (Spearmanās RĀ =Ā 0.363). OS was not significantly associated with GEP status (nonālow vs low; adjusted hazard ratio, 0.91 [95% CI, 0.69ā1.19]) or PDāL1 expression status. CONCLUSION: Neither GEP nor PDāL1 expression was a prognostic marker in Asian and nonāAsian patients with EC
Direct Search for Charged Higgs Bosons in Decays of Top Quarks
We present a search for charged Higgs bosons in decays of pair-produced top
quarks in pbar p collisions at sqrt(s) = 1.8 TeV using 62.2 pb^-1 of data
recorded by the D0 detector at the Fermilab Tevatron collider. No evidence is
found for signal, and we exclude at 95% confidence most regions of the (M
higgs, tan beta) parameter space where the decay t->H b has a branching
fraction greater than 0.36 and B(H -> tau nu) is large.Comment: 11 pages, 4 figures, submitted to Phys. Rev. Let
A comprehensive survey of genomic alterations in gastric cancer reveals systematic patterns of molecular exclusivity and co-occurrence among distinct therapeutic targets
Objective: Gastric cancer is a major gastrointestinal malignancy for which targeted therapies are emerging as treatment options. This study sought to identify the most prevalent molecular targets in gastric cancer and to elucidate systematic patterns of exclusivity and co-occurrence among these targets, through comprehensive genomic analysis of a large panel of gastric cancers. Design: Using high-resolution single nucleotide polymorphism arrays, copy number alterations were profiled in a panel of 233 gastric cancers (193 primary tumours, 40 cell lines) and 98 primary matched gastric non-malignant samples. For selected alterations, their impact on gene expression and clinical outcome were evaluated. Results: 22 recurrent focal alterations (13 amplifications and nine deletions) were identified. These included both known targets (FGFR2, ERBB2) and also novel genes in gastric cancer (KLF5, GATA6). Receptor tyrosine kinase (RTK)/RAS alterations were found to be frequent in gastric cancer. This study also demonstrates, for the first time, that these alterations occur in a mutually exclusive fashion, with KRAS gene amplifications highlighting a clinically relevant but previously underappreciated gastric cancer subgroup. FGFR2-amplified gastric cancers were also shown to be sensitive to dovitinib, an orally bioavailable FGFR/VEGFR targeting agent, potentially representing a subtype-specific therapy for FGFR2-amplified gastric cancers. Conclusion: The study demonstrates the existence of five distinct gastric cancer patient subgroups, defined by the signature genomic alterations FGFR2 (9% of tumours), KRAS (9%), EGFR (8%), ERBB2 (7%) and MET (4%). Collectively, these subgroups suggest that at least 37% of gastric cancer patients may be potentially treatable by RTK/RAS directed therapies
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