This international, randomized, double-blind phase III study (ONO-4538-52/TASUKI-52) evaluated nivolumab with bevacizumab and cytotoxic chemotherapy as first-line treatment for nonsquamous ...non-small-cell lung cancer (NSCLC).
Between June 2017 and July 2019, this study enrolled treatment-naïve patients with stage IIIB/IV or recurrent nonsquamous NSCLC without sensitizing EGFR, ALK, or ROS1 alterations. They were randomly assigned in a 1 : 1 ratio to receive nivolumab or placebo in combination with carboplatin, paclitaxel, and bevacizumab every 3 weeks for up to six cycles, followed by nivolumab/placebo with bevacizumab until progressive disease or unacceptable toxicity. The primary endpoint was progression-free survival (PFS) assessed by an independent radiology review committee (IRRC).
Overall, 550 patients from Japan, Korea, and Taiwan were randomized; of these patients, 273 and 275 received the nivolumab and placebo combinations, respectively. In the present preplanned interim analysis with a median follow up of 13.7 months, the IRRC-assessed median PFS was significantly longer in the nivolumab arm than in the placebo arm (12.1 versus 8.1 months; hazard ratio 0.56; 96.4% confidence interval 0.43-0.71; P < 0.0001). The PFS benefit was observed across all patients with any programmed death-ligand 1 (PD-L1) expression levels including PD-L1-negative patients. The IRRC-assessed objective response rates were 61.5% and 50.5% in the nivolumab and placebo arms, respectively. The incidence of treatment-related adverse events of grade 3 or 4 was comparable between the two arms; treatment-related adverse events leading to death were observed in five and four patients in the nivolumab and placebo arms, respectively.
The TASUKI-52 regimen should be considered a viable new treatment strategy for treatment-naïve patients with advanced nonsquamous NSCLC.
•Nivolumab with carboplatin, paclitaxel, and bevacizumab was evaluated as first-line therapy for nonsquamous NSCLC.•The nivolumab combination therapy provided superior PFS across all patients with any PD-L1 expression levels.•The median PFS of 12.1 months is the longest among all phase III studies for nonsquamous NSCLC without driver mutations.•No new safety signals were observed.
Background
In the absence of randomized controlled data and even propensity‐matched data, indications for, and outcomes of, laparoscopic repeat liver resection for hepatocellular carcinoma (HCC) ...remain uncertain. This study aimed to clarify the current indications for laparoscopic repeat liver resection for HCC, and to evaluate outcomes.
Methods
Forty‐two liver surgery centres around the world registered patients who underwent repeat liver resection for HCC. Patient characteristics, preoperative liver function, tumour characteristics, surgical method, and short‐ and long‐term outcomes were recorded.
Results
Analyses showed that the laparoscopic procedure was generally used in patients with relatively poor performance status and liver function, but favourable tumour characteristics. Intraoperative blood loss (mean(s.d.) 254(551) versus 748(1128) ml; P < 0·001), duration of operation (248(156) versus 285(167) min; P < 0·001), morbidity (12·7 versus 18·1 per cent; P = 0·006) and duration of postoperative hospital stay (10·1(14·3) versus 11·8(11·8) days; P = 0·013) were significantly reduced for laparoscopic compared with open procedures, whereas survival time was comparable (median 10·04 versus 8·94 years; P = 0·297). Propensity score matching showed that laparoscopic repeat liver resection for HCC resulted in less intraoperative blood loss (268(730) versus 497(784) ml; P = 0·001) and a longer operation time (272(187) versus 232(129); P = 0·007) than the open approach, and similar survival time (12·55 versus 8·94 years; P = 0·086).
Conclusion
Laparoscopic repeat liver resection is feasible in selected patients with recurrent HCC.
Antecedentes
Dado que no existen ensayos clínicos controlados ni estudios de datos emparejados por puntaje de propensión, todavía hay dudas sobre las indicaciones y los resultados de la resección iterativa laparocópica de un carcinoma hepatocelular (hepatocellular carcinoma, HCC). Este estudio tuvo como objetivo esclarecer las indicaciones actuales y los resultados de la resección hepática laparoscópica iterativa del HCC.
Métodos
Se incluyeron los pacientes de 42 centros de cirugía hepática a nivel mundial en los que se había realizado una resección hepática iterativa por HCC. Se analizaron las características del paciente, la función hepática preoperatoria, las características del tumor, el abordaje quirúrgico y los resultados a corto y largo plazo.
Resultados
El análisis demostró que la vía laparoscópica generalmente se utilizaba en pacientes con carácteristicas tumorales favorables, pero con estado funcional y función hepatica relativamente peores. La pérdida de sangre intraoperatoria (254,3 ± 551,2 versus 748,0 ± 1127,7 mL, P < 0,001), la duración de la intervención (247,6 ± 155,8 versus 285,1 ± 167,0 minutos, P < 0,001), la morbilidad (12,7 versus 18,1%, P = 0,005) y la estancia hospitalaria postoperatoria (10,07 ± 14,29 versus 11,80 ± 11,79 días, P = 0,010) fueron significativamente menores para los pacientes tratados por via laparoscópica en comparacion con la vía abierta, mientra que el tiempo de supervivencia fue comparable (mediana 10,04 versus 8,94 años, P = 0,297). El estudio de emparejamiento por puntaje de propensión mostró que la resección hepática iterativa por vía laparoscópica de un HCC (frente a la vía abierta) conllevaba una menor pérdida sanguínea intraoperatoria (268,0 ± 730,2 versus 496,5 ± 784,2 mL, P = 0,01), una mayor duración de la intervención (272,1 ± 187,2 versus 231,8 ± 129,1 minutos , P = 0,07) y un tiempo de supervivencia similar (mediana 12,55 versus 8,94 años, P = 0,0855).
Conclusión
La resección hepática iterativa por vía laparoscópica es factible en pacientes seleccionados con HCC recidivado.
This report describes a propensity score matching analysis of open versus laparoscopic repeat liver resection. The laparoscopic procedure is generally used in patients with relatively low performance status and relatively poor liver function but favourable tumour characteristics. The present data indicate that laparoscopic repeat liver resection is feasible, yielding acceptable short‐ and long‐term outcomes, for treatment of recurrent hepatocellular carcinoma in selected patients. ORLR‐PSM, propensity score‐matched open repeat liver resection group; LRLR‐PSM, propensity score‐matched laparoscopic repeat liver resection group.
Selection is key
In Vivo Gold Complex Catalysis within Live Mice Tsubokura, Kazuki; Vong, Kenward K. H.; Pradipta, Ambara R. ...
Angewandte Chemie International Edition,
March 20, 2017, Letnik:
56, Številka:
13
Journal Article
Recenzirano
Metal complex catalysis within biological systems is largely limited to cell and bacterial systems. In this work, a glycoalbumin–AuIII complex was designed and developed that enables organ‐specific, ...localized propargyl ester amidation with nearby proteins within live mice. The targeted reactivity can be imaged through the use of Cy7.5‐ and TAMRA‐linked propargyl ester based fluorescent probes. This targeting system could enable the exploitation of other metal catalysis strategies for biomedical and clinical applications.
The first metal‐catalyzed reaction that proceeds within live mice is based on a targeting approach with glycans. Glycoalbumin–AuIII complexes can be accumulated in specific organs where they catalyze amide bond formation between a propargyl ester probe and amine groups on nearby proteins. The selective targeting was confirmed by whole body fluorescence imaging and analysis of dissected tissues.
The fluxgate magnetometer MGF on board the Mio spacecraft of the BepiColombo mission is introduced with its science targets, instrument design, calibration report, and scientific expectations. The ...MGF instrument consists of two tri-axial fluxgate magnetometers. Both sensors are mounted on a 4.8-m long mast to measure the magnetic field around Mercury at distances from near surface (initial peri-center altitude is 590 km) to 6 planetary radii (11640 km). The two sensors of MGF are operated in a fully redundant way, each with its own electronics, data processing and power supply units. The MGF instrument samples the magnetic field at a rate of up to 128 Hz to reveal rapidly-evolving magnetospheric dynamics, among them magnetic reconnection causing substorm-like disturbances, field-aligned currents, and ultra-low-frequency waves. The high time resolution of MGF is also helpful to study solar wind processes (through measurements of the interplanetary magnetic field) in the inner heliosphere. The MGF instrument firmly corroborates measurements of its companion, the MPO magnetometer, by performing multi-point observations to determine the planetary internal field at higher multi-pole orders and to separate temporal fluctuations from spatial variations.
Perovskite‐type structures (ABO3) have received significant attention because of their crystallographic aspects and physical properties, but there has been no clear evidence of a superconductor with ...a double‐perovskite‐type structure, whose different elements occupy A and/or B sites in ordered ways. In this report, hydrothermal synthesis at 220 °C produced a new superconductor with an A‐site‐ordered double perovskite structure, (Na0.25K0.45)(Ba1.00)3(Bi1.00)4O12, with a maximum Tc of about 27 K.
A double helping: The title compound was prepared by hydrothermal reaction of NaBiO3⋅n H2O, Ba(OH)2⋅8 H2O, and KOH at 220 °C. The structure of the double perovskite was determined to be (Na0.25K0.45)(Ba1.00)3(Bi1.00)4O12, and thermally decomposed to a simple perovskite structure above 400 °C. The synthesized compounds exhibit superconductive diamagnetism, and zero resistivity below 8 K.
Abstract
Despite the latent and unique benefits of imaging uranium and thorium's distribution in the earth's interior, previously proposed experimental techniques used to identify the incoming ...geo-neutrino's direction are not applicable to practical imaging due to the high miss-identification in a neutrino's track reconstruction. After performing experimental studies and Monte-Carlo simulations, we confirmed that a significant improvement is possible in neutrino tracking identification with a
6
Li-loaded neutrino detector. For possible imaging applications, we also explore the feasibility of producing geo-neutrinographic images of gigantic magmatic reservoirs and deep structure in the mantle. We anticipate and plan to apply these newly designed detectors to radiographic imaging of the Earth's interior, monitoring of nuclear reactors and tracking astrophysical sources of neutrinos.
PDF
