Stereotactic radiotherapy vs whole brain radiation therapy in EGFR mutated NSCLC: Results & reflections from the prematurely closed phase III HYBRID trial.

BACKGROUND: All known randomized trials of stereotactic radiotherapy (SRT) versus whole brain radiotherapy (WBRT) for brain metastases (BMs) comprise mixed histologies. The phase III HYBRID trial (NCT02882984) attempted to evaluate the non-inferiority of SRT vs. WBRT specifically for EGFR-mutated non-small cell lung cancer (EGFRm NSCLC) BMs. METHODS: Inclusion criteria were ≤ 5 BMs (any size) from treatment-naïve EGFRm NSCLC. All patients started a first-generation tyrosine kinase inhibitor on the first day of WBRT (37.5 Gy/15 fractions) or SRT (25-40 Gy/5 fractions per tumor volume). The primary endpoint was 18-month intracranial progression-free survival (iPFS; intention-to-treat). RESULTS: The trial commenced in June 2015 and was closed in April 2021 after screening 208 patients but enrolling 85 (n = 41 WBRT, n = 44 SRT; median follow-up 31 and 36 months, respectively). Respectively, 9.5 % vs. 10.2 % of patients experienced intracranial progression at 18 months, and the median iPFS was 21.4 vs. 22.3 months (p > 0.05 for all). The SRT arm experienced higher overall survival and cognitive preservation (p < 0.05 for all). The most notable reason for low enrollment was patients not wishing to risk neurocognitive decline from WBRT. CONCLUSIONS: Although this phase III trial was underpowered, there was no evidence that SRT yielded outcome detriments compared to WBRT for EGFRm NSCLC BMs. Lessons from prematurely closed trials are valuable, as they often provide important experiential perspectives for investigators designing/executing future trials. In the current era, randomized trials involving WBRT without cognitive sparing measures may be at high risk of underaccrual; trial investigators are encouraged to carefully consider our experience when attempting to design such trials. However, trials of molecular-/biologically-stratified patients are highly recommended as the notion of "individualized medicine/oncology" continues to expand.

Discretized butterfly optimization algorithm for variable selection in the rapid determination of cholesterol by near-infrared spectroscopy.

The blood cholesterol level is strongly associated with cardiovascular disease. It is necessary to develop a rapid method to determine the cholesterol concentration of blood. In this study, a discretized butterfly optimization algorithm-partial least squares (BOA-PLS) method combined with near-infrared (NIR) spectroscopy is firstly proposed for rapid determination of the cholesterol concentration in blood. In discretized BOA, the butterfly vector is described by 1 or 0, which represents whether the variable is selected or not, respectively. In the optimization process, four transfer functions, i.e., arctangent, V-shaped, improved arctangent (I-atan) and improved V-shaped (I-V), are introduced and compared for discretization of the butterfly position. The partial least squares (PLS) model is established between the selected NIR variables and cholesterol concentrations. The iteration number, transfer functions and the performance of butterflies are investigated. The proposed method is compared with full-spectrum PLS, multiplicative scatter correction-PLS (MSC-PLS), max-min scaling-PLS (MMS-PLS), MSC-MMS-PLS, uninformative variable elimination-PLS (UVE-PLS), Monte Carlo uninformative variable elimination-PLS (MCUVE-PLS) and randomization test-PLS (RT-PLS). Results show that the I-V function is the best transfer function for discretization. Both preprocessing and variable selection can improve the prediction performance of PLS. Variable selection methods based on BOA are better than those based on statistics. Furthermore, I-V-BOA-PLS has the highest predictive accuracy among the seven variable selection methods. MSC-MMS can further improve the prediction ability of I-V-BOA-PLS. Therefore, BOA-PLS combined with NIR spectroscopy is promising for the rapid determination of cholesterol concentration in blood.

Catalysis of Synergistic Reactions by Host-Guest Assemblies: Reductive Carbonylation of Nitrobenzenes.

Numerous chemical transformations require two or more catalytically active sites that act in a concerted manner; nevertheless, designing heterogeneous catalysts with such multiple functionalities remains an overwhelming challenge. Herein, it is shown that by the integration of acidic flexible polymers and Pd-metallated covalent organic framework (COF) hosts, the merits of both catalytically active sites can be utilized to realize heterogeneous synergistic catalysis that are active in the conversion of nitrobenzenes to carbamates via reductive carbonylation. The concentrated catalytically active species in the nanospace force two catalytic components into proximity, thereby enhancing the cooperativity between the acidic species and Pd species to facilitate synergistic catalysis. The resulting host-guest assemblies constitute more efficient systems than the corresponding physical mixtures and the homogeneous counterparts. Furthermore, this system enables easy access to a family of important derivatives such as herbicides and polyurethane monomers and can be integrated with other COFs, showing promising results. This study utilizes host-guest assembly as a versatile tool for the fabrication of multifunctional catalysts with enhanced cooperativity between different catalytic species.

Variational Mode Decomposition Weighted Multiscale Support Vector Regression for Spectral Determination of Rapeseed Oil and Rhizoma Alpiniae Offcinarum Adulterants.

The accurate prediction of the model is essential for food and herb analysis. In order to exploit the abundance of information embedded in the frequency and time domains, a weighted multiscale support vector regression (SVR) method based on variational mode decomposition (VMD), namely VMD-WMSVR, was proposed for the ultraviolet-visible (UV-Vis) spectral determination of rapeseed oil adulterants and near-infrared (NIR) spectral quantification of rhizoma alpiniae offcinarum adulterants. In this method, each spectrum is decomposed into K discrete mode components by VMD first. The mode matrix Uk is recombined from the decomposed components, and then, the SVR is used to build sub-models between each Uk and target value. The final prediction is obtained by integrating the predictions of the sub-models by weighted average. The performance of the proposed method was tested with two spectral datasets of adulterated vegetable oils and herbs. Compared with the results from partial least squares (PLS) and SVR, VMD-WMSVR shows potential in model accuracy.

Precise localization of small pulmonary nodules using Pre-VATS with Xper-CT in combination with real-time fluoroscopy-guided coil: report of 15 patients.

Purpose: This study aimed to evaluate the value of precise localization of nodules using pre-video-assisted thoracic surgery (VATS) Xper-CT in combination with real-time fluoroscopy-guided coil in the resection of pulmonary nodules using VATS. Materials and Methods: Precise localization of nodules using Xper-CT in combination with real-time fluoroscopy-guided coil and wedge resection using VATS were conducted on 15 patients with 17 small pulmonary nodules (diameter 0.5-1.5 cm) from April 2015 to January 2016. The value of localization was evaluated in terms of procedure time, type of coils, associated complications of localization, and VATS success rate. Results: The success rate of coil localization was found to be 100% in the primary stage (as shown by the CT scan), and the average procedure time was 30-45 min (35.6 ± 3.05 min). No deaths or major complications occurred. Minor complications included five incidents of pneumothorax (the morbidity was 29.4%, 5/17; no patient required chest tube drainage). The dislocation of coil was found in one patient. The results of pathological examination of 17 small pulmonary nodules revealed 11 primary lung cancers, 1 mesenchymal tumor, 3 nonspecific chronic inflammations, 1 hamartoma, and 1 tuberculosis. Two patients with primary lung cancer underwent lobectomy with mediastinal lymph node dissection. Conclusion: The preoperative precise localization of small pulmonary nodules using Xper-CT-guided coil is an effective and safe technique. It helps in the resection of nodules using VATS. It increases the rate of lung wedge resection with few complications and allows for proper diagnosis with a low thoracotomy conversion rate.