This phase II study investigated the efficacy and safety of everolimus, an inhibitor of mammalian target of rapamycin (mTOR), in locally advanced or metastatic thyroid cancer.
Patients with thyroid ...cancer of any histology that was resistant or not appropriate for 131I received everolimus 10 mg daily orally until unacceptable toxicity or disease progression. The primary end point was disease control rate partial response (PR) + stable response ≥12 weeks. Secondary end points included response rates, clinical benefit (PD + durable stable disease (SD), progression-free survival (PFS), overall survival, duration of response, and safety.
Thirty-eight of 40 enrolled patients were evaluable for efficacy. The disease control rate was 81% and two (5%) patients achieved objective response; their duration of response was 21+ and 24+ weeks. Stable disease (SD) and progressive disease was reported in 76% and 17% of patients, respectively. Seventeen (45%) patients showed durable SD (≥24 weeks) and clinical benefit was reported in 19 (50%) patients. Median PFS was 47 weeks 95% confidence interval (CI) 14.9–78.5. Calcitonin, CEA, and thyroglobulin concentrations were ≥50% lower than baseline in three (30%) and four (44%) patients with medullary thyroid cancer and five (33%) patients with PTC, respectively. The most common treatment-related adverse events were mucositis (84%), anorexia (44%), and aspartate transaminase/alanine transaminase elevation (26%).
Everolimus had a limited activity with low response rate in locally advanced or metastatic thyroid cancer. Reasonable clinical benefit rate and safety profile may warrant further investigation.
NCT01164176.
Objective
To compare the efficacy of two types of progestogen therapy for preventing preterm birth (PTB) and to review the relevant literature.
Design
A multicentre, randomised, open‐label, ...equivalence trial and a meta‐analysis.
Setting
Tertiary referral hospitals in South Korea.
Population
Pregnant women with a history of spontaneous PTB or short cervical length (<25 mm).
Methods
Eligible women were screened and randomised at 16‒22 weeks of gestation to receive either 200 mg of vaginal micronised progesterone daily (vaginal group) or an intramuscular injection of 250 mg 17α‐hydroxyprogesterone caproate weekly (IM group). Stratified randomisation was carried out according to participating centres and indications for progestogen therapy. This trial was registered at ClinicalTrials.gov (NCT02304237).
Main outcome measure
Preterm birth (PTB) before 37 weeks of gestation.
Results
A total of 266 women were randomly assigned and a total of 247 women (119 and 128 women in the vaginal and IM groups, respectively) were available for the intention‐to‐treat analysis. Risks of PTB before 37 weeks of gestation did not significantly differ between the two groups (22.7 versus 25.8%, P = 0.571). The difference in PTB risk between the two groups was 3.1% (95% CI −7.6 to 13.8%), which was within the equivalence margin of 15%. The meta‐analysis results showed no significant differences in the risk of PTB between the vaginal and IM progestogen treatments.
Conclusion
Compared with vaginal progesterone, treatment with intramuscular progestin might increase the risk of PTB before 37 weeks of gestation by as much as 13.8%, or reduce the risk by as much as 7.6%, in women with a history of spontaneous PTB or with short cervical length.
Tweetable
Vaginal and intramuscular progestogen showed equivalent efficacy for preventing preterm birth before 37 weeks of gestation.
Tweetable
Vaginal and intramuscular progestogen showed equivalent efficacy for preventing preterm birth before 37 weeks of gestation.
A
bstract
The Reactor Experiment for Neutrino Oscillation (RENO) experiment has been taking data using two identical liquid scintillator detectors since August 2011. The experiment has observed the ...disappearance of reactor neutrinos in their interactions with free protons, followed by neutron capture on hydrogen (n-H). Based on 1500 live days of data taken with 16.8 GW
th
reactors at the Hanbit Nuclear Power Plant in Korea, the near (far) detector observes 567690 (90747) electron antineutrino candidate events with the n-H data. This provides an independent measurement of neutrino mixing angle
θ
13
and a consistency check on the validity of the result obtained from the data with neutron capture on Gadolinium (n-Gd). Furthermore, it provides an important cross-check on the systematic uncertainties of the n-Gd measurement. Based on a rate-only analysis, we obtain sin
2
2
θ
13
= 0
.
086 ± 0
.
008(stat
.
) ± 0
.
014(syst
.
). The combination of this result with that of n-Gd is also reported.
Design of the RAON accelerator systems Jeon, D.; Hong, I. S.; Kim, H. J. ...
Journal of the Korean Physical Society,
10/2014, Letnik:
65, Številka:
7
Journal Article
Recenzirano
The RAON is the name of the heavy ion accelerator facility under construction in Korea that includes the In-flight Fragment (IF) and Isotope Separation On-Line (ISOL) facilities to support ...cutting-edge research in various science fields. The superconducting linac is the driver for the IF facility that can accelerate beams from proton to uranium with 200 MeV/u, 400 kW (for uranium beam). A 70-MeV, 1-mA H
−
cyclotron is the driver for the ISOL facility and is followed by a post-accelerator consisting of s superconducting linac that can accelerate rare-isotope (RI) beams and deliver them to experimental halls. These facilities provide high-intensity stable ion and rare isotope (RI) beams for domestic and international users. In this paper, design and prototyping efforts for the RAON accelerator systems are presented.
We conducted co-clinical trials in patient-derived xenograft (PDX) models to identify predictive biomarkers for the multikinase inhibitor dovitinib in lung squamous cell carcinoma (LSCC).
The ...PDX01-02 were established from LSCC patients enrolled in the phase II trial of dovitinib (NCT01861197) and PDX03-05 were established from LSCC patients receiving surgery. These five PDX tumors were subjected toin vivo test of dovitinib efficacy, whole exome sequencing and gene expression profiling.
The PDX tumors recapitulate histopathological properties and maintain genomic characteristics of originating tumors. Concordant with clinical outcomes of the trial enrolled-LSCC patients, dovitinib produced substantial tumor regression in PDX-01 and PDX-05, whereas it resulted in tumor progression in PDX-02. PDX-03 and -04 also displayed poor antitumor efficacy to dovitinib. Mutational and genome-wide copy number profiles revealed no correlation between genomic alterations ofFGFR1-3 and sensitivity to dovitinib. Of note, gene expression profiles revealed differentially expressed genes including FGF3 and FGF19 between PDX-01 and 05 and PDX-02-04. Pathway analysis identified two FGFR signaling-related gene sets, FGFR ligand binding/activation and SHC-mediated cascade pathway were substantially up-regulated in PDX-01 and 05, compared with PDX-02-04. The comparison of gene expression profiles between dovitinib-sensitive versus -resistant lung cancer cell lines in the Cancer Cell Line Encyclopedia database also found that transcriptional activation of 18 key signaling components in FGFR pathways can predict the sensitivity to dovitinib both in cell lines and PDX tumors. These results highlight FGFR pathway activation as a key molecular determinant for sensitivity to dovitinib.
FGFR gene expression signatures are predictors for the response to dovitinib in LSCC.
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