PURPOSE
Donafenib, a novel multikinase inhibitor and a deuterated sorafenib derivative, has shown efficacy in phase Ia and Ib hepatocellular carcinoma (HCC) studies. This study compared the efficacy ...and safety of donafenib versus sorafenib as first-line therapy for advanced HCC.
PATIENTS AND METHODS
This open-label, randomized, parallel-controlled, multicenter phase II-III trial enrolled patients with unresectable or metastatic HCC, a Child-Pugh score ≤ 7, and no prior systemic therapy from 37 sites across China. Patients were randomly assigned (1:1) to receive oral donafenib (0.2 g) or sorafenib (0.4 g) twice daily until intolerable toxicity or disease progression. The primary end point was overall survival (OS), tested for noninferiority and superiority. Efficacy was primarily assessed in the full analysis set (FAS), and safety was assessed in all treated patients.
RESULTS
Between March 21, 2016, and April 16, 2018, 668 patients (intention-to-treat) were randomly assigned to donafenib and sorafenib treatment arms; the FAS included 328 and 331 patients, respectively. Median OS was significantly longer with donafenib than sorafenib treatment (FAS; 12.1 v 10.3 months; hazard ratio, 0.831; 95% CI, 0.699 to 0.988; P = .0245); donafenib also exhibited superior OS outcomes versus sorafenib in the intention-to-treat population. The median progression-free survival was 3.7 v 3.6 months ( P = .0570). The objective response rate was 4.6% v 2.7% ( P = .2448), and the disease control rate was 30.8% v 28.7% (FAS; P = .5532). Drug-related grade ≥ 3 adverse events occurred in significantly fewer patients receiving donafenib than sorafenib (125 38% v 165 50%; P = .0018).
CONCLUSION
Donafenib showed superiority over sorafenib in improving OS and has favorable safety and tolerability in Chinese patients with advanced HCC, showing promise as a potential first-line monotherapy for these patients.
Early and effective surface defect detection in industrial components can avoid the occurrence of serious safety hazards. Since most industrial component surfaces have tiny defects with high ...similarity to the detection background, there are often issues of missed or false detections when defects are detected, leading to low detection accuracy. To deal with the aforementioned issue, this essay suggests a high-precision detection model for surface defects in industrial components based on the YOLOv5 algorithm. First, the original spatial pyramid pooling (SPPF) is innovated by proposing the SPPFKCSPC module, which improves the network's capacity for feature extraction from targets at different scales and fuses multiscale features better. Then, C3 is combined with SPPFKCSPC and replaces the C3 module of the backbone network, which improves feature expression and enhances the receptive field of the network. Finally, the coordinate attention mechanism (CA) has been embedded into the YOLOv5 neck network, and the bounding box regression loss function of the algorithm is improved to EIOU, not only improving the precision of the target localization and recognition model but also enhancing the overall network performance. Based on the public datasets NEU-DET and PV-Multi-Defect, multiple sets of experiments were conducted using innovative algorithms. On the NEU-DET dataset, we got a mean average accuracy (mAP) of 88.3%, which is 7.2% greater than the original approach. On the PV-Multi-Defect dataset, the mAP value reached 97.5%, an improvement of 1.5%. As shown by the experimental data, the detection results significantly improved.
Patients with advanced or metastatic esophageal squamous cell carcinoma (ESCC) have poor prognosis. For these patients, treatment options are limited after first-line systemic therapy.
In this ...open-label phase III clinical study, patients with advanced or metastatic ESCC, whose tumor progressed after first-line systemic treatment, were randomly assigned (1:1) to receive intravenous tislelizumab, an anti-programmed cell death protein 1 antibody, 200 mg every 3 weeks or chemotherapy (investigator's choice of paclitaxel, docetaxel, or irinotecan). The primary end point was overall survival (OS) in all patients. The key secondary end point was OS in patients with programmed death-ligand 1 tumor area positivity (TAP) score ≥ 10%.
In total, 512 patients across 11 countries/regions were randomly assigned. At final analysis, conducted after 410 death events occurred, OS was significantly longer with tislelizumab versus chemotherapy in all patients (median, 8.6
6.3 months; hazard ratio HR, 0.70 95% CI, 0.57 to 0.85; one-sided
= .0001), and in patients with TAP ≥ 10% (median, 10.3 months
6.8 months; HR, 0.54 95% CI, 0.36 to 0.79; one-sided
= .0006). Survival benefit was consistently observed across all predefined subgroups, including those defined by baseline TAP score, region, and race. Treatment with tislelizumab was associated with higher objective response rate (20.3%
9.8%) and a more durable antitumor response (median, 7.1 months
4.0 months) versus chemotherapy in all patients. Fewer patients experienced ≥ grade 3 treatment-related adverse events (18.8%
55.8%) with tislelizumab versus chemotherapy.
Tislelizumab significantly improved OS compared with chemotherapy as second-line therapy in patients with advanced or metastatic ESCC, with a tolerable safety profile. Patients with programmed death-ligand 1 TAP ≥ 10% also demonstrated statistically significant survival benefit with tislelizumab versus chemotherapy.
Objectives
To distinguish squamous cell carcinoma (SCC) from lung adenocarcinoma (ADC) based on a radiomic signature
Methods
This study involved 129 patients with non-small cell lung cancer (NSCLC) ...(81 in the training cohort and 48 in the independent validation cohort). Approximately 485 features were extracted from a manually outlined tumor region. The LASSO logistic regression model selected the key features of a radiomic signature. Receiver operating characteristic curve and area under the curve (AUC) were used to evaluate the performance of the radiomic signature in the training and validation cohorts.
Results
Five features were selected to construct the radiomic signature for histologic subtype classification. The performance of the radiomic signature to distinguish between lung ADC and SCC in both training and validation cohorts was good, with an AUC of 0.905 (95% confidence interval CI: 0.838 to 0.971), sensitivity of 0.830, and specificity of 0.929. In the validation cohort, the radiomic signature showed an AUC of 0.893 (95% CI: 0.789 to 0.996), sensitivity of 0.828, and specificity of 0.900.
Conclusions
A unique radiomic signature was constructed for use as a diagnostic factor for discriminating lung ADC from SCC. Patients with NSCLC will benefit from the proposed radiomic signature.
Key points
• Machine learning can be used for auxiliary distinguish in lung cancer.
• Radiomic signature can discriminate lung ADC from SCC.
• Radiomics can help to achieve precision medical treatment.
Background The aim of this study was to investigate the influence of serum iron levels in advanced gastric cancer (GC) patients treated with programmed cell death protein-1 (PD-1) inhibitors. Methods ...We retrospectively reviewed 149 GC patients who were treated with PD-1 inhibitors at our center. Clinicopathological characteristics, laboratory data, and clinical outcomes were analyzed. Results Multivariate analysis showed that Eastern Cooperative Oncology Group performance status (ECOG PS), histological subtype, and baseline serum iron levels were independent prognostic factors for overall survival (OS), while ECOG PS, multiple metastatic sites, and baseline serum iron levels were independent prognostic factors for progression-free survival (PFS). Patients with baseline low serum iron levels (LSI) had a significantly shorter median OS and PFS compared to patients with normal serum iron levels (NSI) (Median OS: 7 vs. 14 months, p = 0.001; median PFS: 3 vs. 5 months, p = 0.005). Patients with baseline LSI had a disease control rate (DCR) of 58.3% at 2 months after PD-1 inhibitor initiation (M2), compared to 81.1% in patients with NSI (p = 0.005). Patients with baseline LSI had a DCR of 43.8% at 4 months, compared to 64.2% in patients with NSI (p = 0.017). Conclusions LSI was associated with worse OS, PFS, and DCR in GC patients treated with PD-1 inhibitors and might be a quick and efficient biomarker to predict the efficacy of PD-1 inhibitors. Keywords: Gastric cancer, Serum iron, Immune checkpoint inhibitor, Biomarker
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Dirac cone, one of the main characters of topological materials, provides us an approach to explore topological phase transitions and topological states. Single-element 2D-Xenes are prominent ...candidates for hosting Dirac cones. Till now, the multiple Dirac cones, Dirac-like cones, and semi-metal Dirac point have been discovered in them. However, it is still difficult to realize the tunable Dirac cones due to the lack of appropriate materials. Using first-principles calculations, this paper proposes that monolayer selenium with square lattice could achieve tunable Dirac cones and a topological phase transition. Double structural phases of the monolayer selenium can be distinguished according to strain applied, i.e., buckled square and buckled rectangular phases, which have rich Dirac physics. There exist four anisotropic Dirac cones in the buckled square phase, owing to fourfold symmetry. The buckled rectangular phase hosts a topological phase transition from a 2D topological insulator with double Dirac cones to a simple insulator, with a Dirac semi-metal having single Dirac point as the phase transition point. Moreover, the topological insulator has a global band gap of 0.16 eV, suggesting its potential utilizations in room-temperature devices. These studies will greatly promote the development of the Dirac physics and widen the application ranges of 2D-Xenes.
Association of immune-related adverse events with tumor response has been reported. Reactive cutaneous capillary endothelial proliferation (RCCEP) is the most common adverse event related to ...camrelizumab, an immune checkpoint inhibitor, but lack of comprehensive analyses. In this study, we conducted comprehensive analyses on RCCEP in advanced hepatocellular carcinoma (HCC) patients treated with camrelizumab monotherapy.
Data were derived from a Chinese nationwide, multicenter phase 2 trial of camrelizumab in pre-treated advanced HCC. The occurrence, clinicopathological characteristics, and prognostic value of RCCEP were analyzed.
With a median follow-up of 12.5 months, 145 of the 217 camrelizumab-treated patients (66.8%) experienced RCCEP (all grade 1 or 2). RCCEP occurred on the skin surface, mainly on the skin surface of head, face, and trunk. RCCEP could be divided into 5 types including "red-nevus-like," "pearl-like," "mulberry-like," "patch-like," and "tumor-like," according to the morphological features. RCCEP biopsy and pathology showed capillary endothelial hyperplasia and capillary hyperplasia in dermis. Significant association between RCCEP occurrence with higher objective response rate was observed (19.3% vs. 5.6%; one-sided p = 0.0044). Compared with those without RCCEP, patients with RCCEP had prolonged progression-free survival (median PFS; 3.2 months vs. 1.9 months; one-sided p < 0.0001) and overall survival (median OS; 17.0 months vs. 5.8 months; one-sided p < 0.0001). In multivariable analyses, the development of RCCEP was significantly associated with prolonged PFS and OS after adjusting for baseline covariates. In addition, the landmark analyses of PFS and OS were consistent with the unadjusted analysis.
RCCEP occurred on the skin surface and was an immune response of skin capillary endothelial cells. RCCEP occurrence positively associated with outcomes of camrelizumab in advanced HCC.
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•Activated carbon layer covered graphene (ACG) with the adjustable thickness has been fabricated.•The electrochemical performance of ACG is related to the thickness of the active ...layer on the surface of the ACG.•The ACG with a suitable thickness of 1–2nm exhibits a high specific capacitance of 248.4Fg−1 at 1Ag−1.•An outstanding rate capability has been obtained with a capacitance of 187.5Fg−1 at 100Ag−1.
Carbon-based nanostructures have drawn special attention for use in supercapacitive applications due to their high specific surface area and stability. Balancing the conflict between activity and the conductivity of carbon based electrode materials would contribute to comprehensive energy storage performance for practical application. In this work, an activated carbon layer covered graphene (ACG) with adjustable thickness has been fabricated by hydrothermal treatment of graphene oxide with glucose and further activation with a KOH agent. The electrochemical performance of ACG is related to the thickness of the active layer on the surface of the ACG. The ACG with a suitable thickness of 1–2nm exhibits a high specific capacitance of 248.4Fg−1 at 1Ag−1 and perfect rate performance with a high capacitance of 187.5Fg−1 at a large current density of 100Ag−1 owing to both high activity and conductivity. Particularly, the synergetic effect of the active porous carbon and conductive graphene results in considerable energy properties of the ACG based symmetric devices.
Metabolite identification plays a critical role in the phases during drug development. Drug metabolites can contribute to efficacy, toxicity, and drug-drug interaction. Thus, the correct ...identification of metabolites is essential to understand the behavior of drugs in humans. Drug administration authorities (e.g., FDA, EMA, and NMPA) emphasize evaluating the safety of human metabolites with exposure higher than 10% of the total drugrelated components. Many previous reviews have summarized the various methods, tools, and strategies for the appropriate and comprehensive identification of metabolites. In this review, we focus on summarizing the importance of identifying metabolites in the preclinical and clinical phases of drug development. Summarized scenarios include the role of metabolites in pharmacokinetics/pharmacodynamics (PK/PD) analysis, disproportional exposure of metabolites that contribute to drug toxicity, changes in metabolite exposure in renal-impaired patients, covalent tyrosine kinase inhibitors (anticancer drugs), and metabolite identification of drug candidates from natural medicines. This review is aimed to provide meaningful insight into the significant role of metabolite identification in drug development.
Chromatographic method has long been recognized as the most widely used separation method in bioanalytical research. However, the relatively low sensitivity of existing chromatographic methods ...remains a significant challenge, as the requirements for experimental procedures become more demanding. This review discusses the main causes for the low sensitivity of chromatographic methods and aims to introduce different technologies for enhancing their sensitivity in the following aspects: (i) different pretreatment methods for improving clean‐up efficiency and recovery; (ii) derivatization step for altering the chromatographic behavior of analytes and enhancing MS ionization efficiency; (iii) optimal LC–MS conditions and appropriate separation mechanism; and (iv) applications of other chromatographic methods, including miniaturized LC, 2D‐LC, 2D‐GC, and supercritical fluid chromatography. Altogether, this review is devoted to summarizing the recent technologies reported in the literature and providing new strategies for the detection of bioanalytes.
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