Cost-effectiveness of neoadjuvant pembrolizumab plus chemotherapy with adjuvant pembrolizumab for early-stage non-small cell lung cancer in the United States

IntroductionPerioperative (neoadjuvant and adjuvant) pembrolizumab has shown favorable efficacy in patients with early-stage non-small cell lung cancer (NSCLC). This study aims to evaluate the cost-effectiveness of this treatment from the perspective of the United States healthcare payers.MethodsWe established a Markov model to compare the cost-effectiveness of perioperative pembrolizumab with that of neoadjuvant chemotherapy in 21-day cycles, utilizing data from the phase 3 KEYNOTE-671 trial. Additional data were extracted from other publications or online sources. Sensitivity analyses were conducted to evaluate the robustness of the findings. A willingness-to-pay threshold of $150,000 per quality-adjusted life-years (QALYs) gained was established. The main outcomes of this study were the measurement of QALYs, overall costs, incremental cost-effectiveness ratio (ICER), and net monetary benefit (NMB).ResultsDuring a 10-year time horizon, the total costs of perioperative pembrolizumab and the control treatment were$224,779.1 and $110,026.3, respectively. The QALYs were 4.19 and 2.97 for the two treatments, respectively, which led to an ICER of$94,222.29 per QALY gained. The NMB at the WTP threshold at $150,000 per QALY gained was$67,931.3. One-way sensitivity analysis identified the cost of pembrolizumab as the primary factor influencing cost-effectiveness. Probabilistic sensitivity analysis indicated a 97.7% probability of perioperative pembrolizumab being cost-effective at the WTP threshold.ConclusionsFrom the perspective of the United States healthcare payers, perioperative pembrolizumab is a cost-effective treatment for patients with early-stage NSCLC

Optimal timing and sequence of combining stereotactic radiosurgery with immune checkpoint inhibitors in treating brain metastases: clinical evidence and mechanistic basis

Abstract Recent evidence has shown that immune checkpoint inhibitors (ICIs) are efficacious for treating brain metastases of various primary tumors. However, the immunosuppressive tumor microenvironment and the blood–brain barrier (BBB) or blood-tumor barrier (BTB) essentially restrict the efficacy of ICIs. Stereotactic radiosurgery (SRS) can be a powerful ally to ICIs due to its trait of disrupting the BBB/BTB and increasing the immunogenicity of brain metastases. The combination of SRS + ICI has shown synergy in brain metastases in several retrospective studies. Nevertheless, the optimal schedule for the combination of SRS and ICI in brain metastases is yet to be determined. In this review, we summarized the current clinical and preclinical evidence on the timing and sequence of SRS + ICI to provide insight into the current state of knowledge about this important area in patient care

Hypervalent Iodine(III)-Mediated Cascade Cyclization of Propargylguanidines and Total Syntheses of Kealiinine B and C

An oxidative cascade cyclization of propargylguanidines promoted by phenyliodonium diacetate (PIDA) was developed. The protocol provides an efficient route for the synthesis of the alkaloids kealiinines B and C as well as homologues. The difference in the electronic nature of the acetylene substituent resulted in two ways of the cyclization. A plausible mechanism is proposed based on the experimental results.status: publishe

Rhodium(III)-catalyzed intermolecular cascade annulation through C-H activation: Concise synthesis of rosettacin

© 2018 Elsevier B.V. An intermolecular annulation of 2-acetylenic aldehydes or ketones with O-substituted N-hydroxybenzamides or N-hydroxyacrylamides through rhodium(III)-catalyzed C–H activation for the synthesis of isoquinolones and indolizinones is developed. This reaction features excellent functional-group tolerance and broad substrate scope, including annulation of various heterocyclic substrates. This approach evaluates the chemoselectivity of the reaction when sterically hindered diaryl-substituted alkynes are incorporated. This method also furnishes an efficient approach for the total synthesis of rosettacin and a topoisomerase I inhibitor.status: publishe

Chemo- and Regioselective Catalyst-Controlled Carbocyclization of Alkynyl Ketones: Rapid Synthesis of 1-Indanones and 1-Naphthols

A catalyst-controlled intramolecular carbocyclization of 2-alkynyl aryl ketones is presented. Under rhodium(III) catalysis, 1-indanones are formed through 5-exo-dig carbocyclizations with exclusive chemo-, regio- and stereoselectivity. When catalyzed by copper(I), 1-naphthols are obtained through 6-endo-dig carbocyclizations with exclusive chemo- and regioselectivity.status: publishe

Fabrication of Oil-Water Separation Filter Paper by Simple Impregnation with Fluorinated Poly-Acrylate Emulsion

A fluorinated poly-acrylate emulsion with various fluorine contents was prepared by a seeded semi-continuous emulsion polymerization method and applied to filter paper for oil-water separation applications. The effects of surface wetting behavior on the oil-water separation efficiency of the prepared filter paper were studied. The results show that the prepared highly hydrophobic and superoleophilic filter paper presented 94.45 wt% water separation efficiency and strong mechanical strength. In addition, the oil-water separation stability and durability of the filter paper were also tested and shown to be suitable for use in real oil-water separation applications. These properties indicate that the filter paper has great potential applications in the oil-water separation industry

Rhodium(III)-catalyzed intramolecular annulation through C-H activation: concise synthesis of rosettacin and oxypalmatime

A flexible and efficient rhodium(iii)-catalyzed intramolecular annulation of benzamides bearing tethered alkynes for the synthesis of indolizinones and quinolizinones is reported. This reaction shows a broad substrate scope and excellent functional-group tolerance, including different kinds of heterocyclic substrates, such as furan, thiophene, pyrrole, benzofuran, benzothiophene, indole and isonicotinamide substrates. This method also provides a practical and efficient approach for the synthesis of rosettacin and oxypalmatime.status: publishe

Synthesis of Pyrrolo[1,2-b]isoquinolines via Gold(I)-Catalyzed Cyclization/Enyne Cycloisomerization/1,2-Migration Cascade

A gold(I)-catalyzed cascade transformation of N-alkynic 2-ynamides for the rapid and efficient synthesis of the indolizidine scaffold is developed. Through a sequential nucleophilic cyclization/enyne cycloisomerization/1,2-migration process, diverse pyrrolo[1,2-b]isoquinolines are obtained under mild conditions in a regiospecific and convergent manner. Various alkyl and aryl migrating groups are tolerated in this process. The electronic effect of the migrating group is comprehensively investigated. The study of the mechanism indicates that the pathway involving a gold carbenoid species is the main pathway and that the 1,2-migration of alkyl and aryl groups to the gold carbenoid occurs in an intramolecular fashion. This cascade reaction is also employed as the key step for the synthesis of a decumbenine B analogue.status: publishe

A rapid identification method for soft tissue markers of dentofacial deformities based on heatmap regression

Abstract Objective The purpose of this study was to construct a facial deformity dataset and a network model based on heatmap regression for the recognition of facial soft tissue landmarks to provide a basis for clinicians to perform cephalometric analysis of soft tissue. Materials and methods A 34-point face marker detection model, the Back High-Resolution Network (BHR-Net), was constructed based on the heatmap regression algorithm, and a custom dataset of 1780 facial detection images for orthognathic surgery was collected. The mean normalized error (MNE) and 10% failure rate (FR10%) were used to evaluate the performance of BHR-Net, and a test set of 50 patients was used to verify the accuracy of the landmarks and their measurement indicators. The test results were subsequently validated in 30 patients. Results Both the MNE and FR10% of BHR-Net were optimal compared with other models. In the test set (50 patients), the accuracy of the markers excluding the nose root was 86%, and the accuracy of the remaining markers reached 94%. In the model validation (30 patients), using the markers detected by BHR-Net, the diagnostic accuracy of doctors was 100% for Class II and III deformities, 100% for the oral angle plane, and 70% for maxillofacial asymmetric deformities. Conclusions BHR-Net, a network model based on heatmap regression, can be used to effectively identify landmarks in maxillofacial multipose images, providing a reliable way for clinicians to perform cephalometric measurements of soft tissue objectively and quickly