Anlotinib in patients with relapsed or refractory thymic epithelial tumors: a study of 50 cases.

The optimal pharmaceutical regimen for advanced thymic epithelial tumors (TETs) remains controversial when first-line chemotherapy fails. This retrospective study aims to evaluate the efficacy and safety of anlotinib treatment for patients with relapsed and refractory TETs. Patients with progressive disease after failure of platinum-based chemotherapy were enrolled in this study. Anlotinib was orally taken once a day at an initial dose of 12 mg (10 mg when body weight <60 kg). The cycle was repeated every 3 weeks (2 weeks of treatment followed by 1-week rest). Objective response rate (ORR) and progression-free survival (PFS) were recorded as primary endpoints. There were 50 patients enrolled in this study from October 2018 to June 2021 at a median age of 50 (range 23-79) years old. Patients with thymoma and thymic carcinoma were 33 (66%) and 17 (34%), respectively. The ORR in thymoma and thymic carcinoma patients were 33% (11/33) and 41% (7/17), respectively. The median PFS (mPFS) was 7 (95% CI, 5.9-10.2) months in thymoma patients and 6 (95% CI, 4.6-9.3) months in the thymic carcinoma group. Eleven patients experienced dose reduction due to toxicities, among whom, eight patients discontinued treatment even after dose reduction. Six patients with thymoma showed myasthenia gravis deterioration during treatment, and two of them died of myasthenia gravis crisis. Anlotinib is active in patients with advanced TETs refractory to routine chemotherapy. Prescription of anlotinib to patients with myasthenia gravis should be made cautiously.

Hexamethyldisilazane-Mediated Amidination of Sulfonamides and Amines with Formamides.

Hexamethyldisilazane was reacted with formamides to generate N,N-disubstituent formimidamide, after which a reaction with sulfonamides was induced to form sulfonylformamidines. This protocol can be applied for arylformamidine formation in which anilines are used as substrates under optimized conditions. The advantages of this method are high efficiency, structural diversity in products with good yields, and applicability in large-scale operations.

Postoperative Radiotherapy for Resected Stage IIIA-N2 Non-small-cell Lung Cancer: A Population-Based Time-Trend Study.

INTRODUCTION: The value of postoperative radiotherapy (PORT) for resected stage IIIA-N2 non-small-cell lung cancer (NSCLC) is controversial with few studies focusing on whether PORT always plays a part in clinical practice and generates benefits to patients across different time periods. We investigated this issue using the Surveillance, Epidemiology, and End Results Database (SEER) and assessed the temporal trends spanning 27 years. METHODS: Within SEER, we selected stage IIIA-N2 NSCLC patients who underwent a lobectomy or pneumonectomy and coded as receiving PORT or never receiving radiotherapy over three time periods: 1988 to 1996, 1997 to 2005, 2006 to 2014. For each period, survival analyses were performed and propensity score matching (PSM) was used in the potentially beneficial subgroup. RESULTS: 45.4% of 5568 eligible patients received PORT. The yearly PORT use rates varied largely from 27.8% to 74.4%. Overall survival (OS) was distinctly improved over the period. The application of PORT had a significant impact on survival only in period 1 and 3. In subgroup analysis, the OS benefit of PORT was significant in each period in patients with 50% or more lymph node ratio (LNR) both before (hazard ratios, and P values of 0.647, P = .002; 0.804, P = .008; 0.721, P < .001 for period 1, 2, 3, respectively) and after PSM (0.642, P = .006; 0.785, P = .004; 0.748, P = .003 for period 1, 2, 3, respectively). CONCLUSIONS: The benefits of PORT are lasting and stable throughout the years in patients with LNR of 50% or more. This might provide a clue on proper patient selection for PORT application.

Manipulating the Rate and Overpotential for Electrochemical Water Oxidation: Mechanistic Insights for Cobalt Catalysts Bearing Noninnocent Bis(benzimidazole)pyrazolide Ligands.

Electrochemical water oxidation is known as the anodic reaction of water splitting. Efficient design and earth-abundant electrocatalysts are crucial to this process. Herein, we report a family of catalysts (1-3) bearing bis(benzimidazole)pyrazolide ligands (H 2 L1-H 2 L3). H 2 L3 contains electron-donating substituents and noninnocent components, resulting in catalyst 3 exhibiting unique performance. Kinetic studies show first-order kinetic dependence on [3] and [H2O] under neutral and alkaline conditions. In contrast to previously reported catalyst 1, catalyst 3 exhibits an insignificant kinetic isotope effect of 1.25 and zero-order dependence on [NaOH]. Based on various spectroscopic methods and computational findings, the L3Co2 III(µ-OH) species is proposed to be the catalyst resting state and the nucleophilic attack of water on this species is identified as the turnover-limiting step of the catalytic reaction. Computational studies provided insights into how the interplay between the electronic effect and ligand noninnocence results in catalyst 3 acting via a different reaction mechanism. The variation in the turnover-limiting step and catalytic potentials of species 1-3 leads to their catalytic rates being independent of the overpotential, as evidenced by Eyring analysis. Overall, we demonstrate how ligand design may be utilized to retain good water oxidation activity at low overpotentials.

Dinuclear Cobalt Complexes for Homogeneous Water Oxidation: Tuning Rate and Overpotential through the Non-Innocent Ligand.

In this study, dinuclear cobalt complexes (1 and 2) featuring bis(benzimidazole)pyrazolide-type ligands (H2 L and Me2 L) were prepared and evaluated as molecular electrocatalysts for water oxidation. Notably, 1 bearing a non-innocent ligand (H2 L) displayed faster catalytic turnover than 2 under alkaline conditions, and the base dependence of water oxidation and kinetic isotope effect analysis indicated that the reaction mediated by 1 proceeded by a different mechanism relative to 2. Spectroelectrochemical, cold-spray ionization mass spectrometric and computational studies found that double deprotonation of 1 under alkaline conditions cathodically shifted the catalysis-initiating potential and further altered the turnover-limiting step from nucleophilic water attack on (H2 L)CoIII 2 (superoxo) to deprotonation of (L)CoIII 2 (OH)2 . The rate-overpotential analysis and catalytic Tafel plots showed that 1 exhibited a significantly higher rate than previously reported Ru-based dinuclear electrocatalysts at similar overpotentials. These observations suggest that using non-innocent ligands is a valuable strategy for designing effective metal-based molecular water oxidation catalysts.

Bevacizumab in combination with paclitaxel and platinum for previously treated advanced thymic epithelial tumors.

There are no optimal regimens for advanced thymic epithelial tumors (TETs) when frontline chemotherapy fails. In this study, we aimed to assess the activity of Bevacizumab in combination with a routine chemotherapeutic regimen. Patients with advanced TETs who had failed after previous chemotherapy were enrolled in this study. Paclitaxel (160 mg/m2) and cisplatin (70 mg/m2) or carboplatin (area under the curve, 6) plus Bevacizumab (7.5 mg/kg) were intravenously injected on day 1.The treatment was repeated every 3 weeks until the disease progressed or intolerable toxicities occurred. Between March 2018 and August 2020, a total of 49 patients (21 thymoma and 28 thymic carcinoma) received the new treatment. There were 28 men and 21 women with a median age of 50 years (range: 21-73 years). The median number of cycles was 3 (range: 1-6) per patient. The objective response rate (ORR) for all patients was 43% (21/49). The ORRs for thymoma and thymic carcinoma were 24% and 57%, respectively. The median progression-free survival for thymoma and thymic carcinoma was 6 and 8 months, respectively. Hematological toxicities were the main side effects. Paclitaxel and platinum plus Bevacizumab showed promising effects in refractory or relapsed advanced TETs without severe toxicity. Even when applied as salvage therapy, this regimen resulted in a better ORR than frontline chemotherapy.

Prognostic index for estimating the survival benefit of postoperative radiotherapy in pathologic N2 non-small cell lung cancer: A real-world validation study.

OBJECTIVES: This study aimed to evaluate the effect of postoperative radiotherapy (PORT) in patients with resected pathologic N2 (pN2) non-small cell lung cancer (NSCLC) with different locoregional recurrence (LRR) risks. MATERIALS AND METHODS: The primary cohort and validation cohort were retrieved from two independent medical centres. Data for all consecutive patients with completely resected pathologic stage T1-3N2M0 NSCLC were analysed. Patients without PORT in the primary cohort were identified as a training set. Significant prognostic factors for LRR were identified by the Fine-Gray model to develop a prognostic index (PI) in the training set. RESULTS: The primary cohort consisted of 357 patients who met the eligibility criteria (training set, 287 patients without PORT). The external validation cohort consisted of 1044 patients who met the eligibility criteria (validation set, 711 patients without PORT). Heavy cigarette smoking history, clinical N2 status (cN2), and the number of positive lymph nodes >4 were identified as independent risk factors. The PI was computed as follows: PI＝0.8*smoking history＋0.5*cN2＋0.7*the number of involved lymph nodes (reference level was assigned the value 1 and risk level the value 2). In the low-risk group (PI score< = 3), PORT showed a trend towards decreased LRR rates but not significantly improved overall survival (OS). In the high-risk group (PI score>3), PORT significantly reduced the risk of LRR and improved OS. CONCLUSIONS: We constructed and validated a PI to predict individually the effect of PORT in patients with completely resected pN2 NSCLC. Patients with a higher PI score can benefit from PORT in terms of OS.