1,875 research outputs found
Sensitive and specific multi-cancer detection and localization using methylation signatures in cell-free DNA
Background:
Early cancer detection could identify tumors at a time when outcomes are superior and treatment is less morbid. This prospective case-control sub-study (from NCT02889978 and NCT03085888) assessed the performance of targeted methylation analysis of circulating cell-free DNA (cfDNA) to detect and localize multiple cancer types across all stages at high specificity.
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Participants and methods:
The 6689 participants [2482 cancer (>50 cancer types), 4207 non-cancer] were divided into training and validation sets. Plasma cfDNA underwent bisulfite sequencing targeting a panel of >100 000 informative methylation regions. A classifier was developed and validated for cancer detection and tissue of origin (TOO) localization.
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Results:
Performance was consistent in training and validation sets. In validation, specificity was 99.3% [95% confidence interval (CI): 98.3% to 99.8%; 0.7% false-positive rate (FPR)]. Stage IâIII sensitivity was 67.3% (CI: 60.7% to 73.3%) in a pre-specified set of 12 cancer types (anus, bladder, colon/rectum, esophagus, head and neck, liver/bile-duct, lung, lymphoma, ovary, pancreas, plasma cell neoplasm, stomach), which account for âŒ63% of US cancer deaths annually, and was 43.9% (CI: 39.4% to 48.5%) in all cancer types. Detection increased with increasing stage: in the pre-specified cancer types sensitivity was 39% (CI: 27% to 52%) in stage I, 69% (CI: 56% to 80%) in stage II, 83% (CI: 75% to 90%) in stage III, and 92% (CI: 86% to 96%) in stage IV. In all cancer types sensitivity was 18% (CI: 13% to 25%) in stage I, 43% (CI: 35% to 51%) in stage II, 81% (CI: 73% to 87%) in stage III, and 93% (CI: 87% to 96%) in stage IV. TOO was predicted in 96% of samples with cancer-like signal; of those, the TOO localization was accurate in 93%.
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Conclusions:
cfDNA sequencing leveraging informative methylation patterns detected more than 50 cancer types across stages. Considering the potential value of early detection in deadly malignancies, further evaluation of this test is justified in prospective population-level studies
Clinical validation of a targeted methylation-based multi-cancer early detection test using an independent validation set
BACKGROUND: A multi-cancer early detection (MCED) test used to complement existing screening could increase the number of cancers detected through population screening, potentially improving clinical outcomes. The Circulating Cell-free Genome Atlas study (CCGA; NCT02889978) was a prospective, case-controlled, observational study and demonstrated that a blood-based MCED test utilizing cell-free DNA (cfDNA) sequencing in combination with machine learning could detect cancer signals across multiple cancer types and predict cancer signal origin (CSO) with high accuracy. The objective of this third and final CCGA substudy was to validate an MCED test version further refined for use as a screening tool. PATIENTS AND METHODS: This pre-specified substudy included 4077 participants in an independent validation set (cancer: n = 2823; non-cancer: n = 1254, non-cancer status confirmed at year-one follow-up). Specificity, sensitivity, and CSO prediction accuracy were measured. RESULTS: Specificity for cancer signal detection was 99.5% [95% confidence interval (CI): 99.0% to 99.8%]. Overall sensitivity for cancer signal detection was 51.5% (49.6% to 53.3%); sensitivity increased with stage [stage I: 16.8% (14.5% to 19.5%), stage II: 40.4% (36.8% to 44.1%), stage III: 77.0% (73.4% to 80.3%), stage IV: 90.1% (87.5% to 92.2%)]. Stage I-III sensitivity was 67.6% (64.4% to 70.6%) in 12 pre-specified cancers that account for approximately two-thirds of annual USA cancer deaths and was 40.7% (38.7% to 42.9%) in all cancers. Cancer signals were detected across >50 cancer types. Overall accuracy of CSO prediction in true positives was 88.7% (87.0% to 90.2%). CONCLUSION: In this pre-specified, large-scale, clinical validation substudy, the MCED test demonstrated high specificity and accuracy of CSO prediction and detected cancer signals across a wide diversity of cancers. These results support the feasibility of this blood-based MCED test as a complement to existing single-cancer screening tests. CLINICAL TRIAL NUMBER: NCT02889978
Undifferentiated spondyloarthritis following allogeneic stem cell transplantation
<p>Abstract</p> <p>Background</p> <p>Stem cell transplant has been utilized in the treatment of malignancies and rheumatic disease. Rheumatic disease may be transferred from the donor with active disease or may be developed in a recipient de novo as a late complication of SCT.</p> <p>Case Presentation</p> <p>We here report the rare case of a 26-year old male patient, who has been diagnosed with undifferentiated spondyloarthropathy after unique circumstance. The patient suffered from intermittent inflammatory back pain and peripheral joint swelling for several years and did not find relief through multiple emergency room visits at different medical facilities. After a thorough history and physical exam, it was noted that our patient had developed signs of axial disease along with dactylitis and overall that he had been insidiously developing an undifferentiated spondyloarthopathy after allogeneic stem cell transplantation.</p> <p>Conclusion</p> <p>Our observation supports the hypothesis that de novo rheumatic disease can develop after stem cell transplant for a variety of reasons. Thus, larger studies and awareness of this association are needed to delineate the exact underlying mechanism(s).</p
A phase I clinical trial of continual alternating etoposide and topotecan in refractory solid tumours
The goal of this phase I study was to develop a novel schedule using oral etoposide and infusional topotecan as a continually alternating schedule with potentially optimal reciprocal induction of the nontarget topoisomerase. The initial etoposide dose was 15âmgâmâ2 b.i.d. days (D)1â5 weeks 1,3,5,7,9 and 11, escalated 5âmg per dose per dose level (DL). Topotecan in weeks 2,4,6,8,10 and 12 was administered by 96âh infusion at an initial dose of 0.2âmgâmâ2âdayâ1 with a dose escalation of 0.1, then at 0.05âmgâmâ2âdayâ1. Eligibility criteria required no organ dysfunction. Two dose reductions or delays were allowed. A total of 36 patients with a median age of 57 (22â78) years, received a median 8 (2â19) weeks of chemotherapy. At DL 6, dose-limiting toxicities consisted of grade 3 nausea, vomiting and intolerable fatigue. Three patients developed a line-related thrombosis or infection and one subsequently developed AML. There was no febrile neutropenia. There were six radiologically confirmed responses (18%) and 56% of patients demonstrated a response or stable disease, typically with only modest toxicity. Oral etoposide 35âmgâmâ2 b.i.d. D1â5 and 1.8âmgâmâ2 96âh (total dose) infusional topotecan D8â11 can be administered on an alternating continual weekly schedule for at least 12 weeks, with promising clinical activity
A search for the decay modes B+/- to h+/- tau l
We present a search for the lepton flavor violating decay modes B+/- to h+/-
tau l (h= K,pi; l= e,mu) using the BaBar data sample, which corresponds to 472
million BBbar pairs. The search uses events where one B meson is fully
reconstructed in one of several hadronic final states. Using the momenta of the
reconstructed B, h, and l candidates, we are able to fully determine the tau
four-momentum. The resulting tau candidate mass is our main discriminant
against combinatorial background. We see no evidence for B+/- to h+/- tau l
decays and set a 90% confidence level upper limit on each branching fraction at
the level of a few times 10^-5.Comment: 15 pages, 7 figures, submitted to Phys. Rev.
Evidence for an excess of B -> D(*) Tau Nu decays
Based on the full BaBar data sample, we report improved measurements of the
ratios R(D(*)) = B(B -> D(*) Tau Nu)/B(B -> D(*) l Nu), where l is either e or
mu. These ratios are sensitive to new physics contributions in the form of a
charged Higgs boson. We measure R(D) = 0.440 +- 0.058 +- 0.042 and R(D*) =
0.332 +- 0.024 +- 0.018, which exceed the Standard Model expectations by 2.0
sigma and 2.7 sigma, respectively. Taken together, our results disagree with
these expectations at the 3.4 sigma level. This excess cannot be explained by a
charged Higgs boson in the type II two-Higgs-doublet model. We also report the
observation of the decay B -> D Tau Nu, with a significance of 6.8 sigma.Comment: Expanded section on systematics, text corrections, improved the
format of Figure 2 and included the effect of the change of the Tau
polarization due to the charged Higg
Search for the decay modes D^0 â e^+e^-, D^0 â ÎŒ^+ÎŒ^-, and D^0 â e^±Όâ
We present searches for the rare decay modes D^0âe^+e^-, D^0âÎŒ^+ÎŒ^-, and D^0âe^±Ό^â in continuum e^+e^-âcc events recorded by the BABAR detector in a data sample that corresponds to an integrated luminosity of 468ââfb^(-1). These decays are highly GlashowâIliopoulosâMaiani suppressed but may be enhanced in several extensions of the standard model. Our observed event yields are consistent with the expected backgrounds. An excess is seen in the D^0âÎŒ^+ÎŒ^- channel, although the observed yield is consistent with an upward background fluctuation at the 5% level. Using the FeldmanâCousins method, we set the following 90% confidence level intervals on the branching fractions: B(D^0âe^+e^-)<1.7Ă10^(-7), B(D^0âÎŒ^+ÎŒ^-) within [0.6,8.1]Ă10^(-7), and B(D^0âe^±Ό^â)<3.3Ă10^(-7)
Measurement of the branching fraction and CP content for the decay B(0) -> D(*+)D(*-)
This is the pre-print version of the Article. The official published version can be accessed from the links below. Copyright @ 2002 APS.We report a measurement of the branching fraction of the decay B0âD*+D*- and of the CP-odd component of its final state using the BABAR detector. With data corresponding to an integrated luminosity of 20.4ââfb-1 collected at the ΄(4S) resonance during 1999â2000, we have reconstructed 38 candidate signal events in the mode B0âD*+D*- with an estimated background of 6.2±0.5 events. From these events, we determine the branching fraction to be B(B0âD*+D*-)=[8.3±1.6(stat)±1.2(syst)]Ă10-4. The measured CP-odd fraction of the final state is 0.22±0.18(stat)±0.03(syst).This work is supported by DOE and NSF (USA), NSERC (Canada), IHEP (China), CEA and CNRS-IN2P3 (France), BMBF (Germany), INFN (Italy), NFR (Norway), MIST (Russia), and PPARC (United Kingdom). Individuals have received support from the A.P. Sloan Foundation, Research Corporation, and Alexander von Humboldt Foundation
Study of the reaction e^{+}e^{-} -->J/psi\pi^{+}\pi^{-} via initial-state radiation at BaBar
We study the process with
initial-state-radiation events produced at the PEP-II asymmetric-energy
collider. The data were recorded with the BaBar detector at center-of-mass
energies 10.58 and 10.54 GeV, and correspond to an integrated luminosity of 454
. We investigate the mass
distribution in the region from 3.5 to 5.5 . Below 3.7
the signal dominates, and above 4
there is a significant peak due to the Y(4260). A fit to
the data in the range 3.74 -- 5.50 yields a mass value
(stat) (syst) and a width value (stat)(syst) for this state. We do not
confirm the report from the Belle collaboration of a broad structure at 4.01
. In addition, we investigate the system
which results from Y(4260) decay
Evidence for the h_b(1P) meson in the decay Upsilon(3S) --> pi0 h_b(1P)
Using a sample of 122 million Upsilon(3S) events recorded with the BaBar
detector at the PEP-II asymmetric-energy e+e- collider at SLAC, we search for
the spin-singlet partner of the P-wave chi_{bJ}(1P) states in the
sequential decay Upsilon(3S) --> pi0 h_b(1P), h_b(1P) --> gamma eta_b(1S). We
observe an excess of events above background in the distribution of the recoil
mass against the pi0 at mass 9902 +/- 4(stat.) +/- 2(syst.) MeV/c^2. The width
of the observed signal is consistent with experimental resolution, and its
significance is 3.1sigma, including systematic uncertainties. We obtain the
value (4.3 +/- 1.1(stat.) +/- 0.9(syst.)) x 10^{-4} for the product branching
fraction BF(Upsilon(3S)-->pi0 h_b) x BF(h_b-->gamma eta_b).Comment: 8 pages, 4 postscript figures, submitted to Phys. Rev. D (Rapid
Communications
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