Immunotherapy rechallenge of advanced lung adenocarcinoma with cadonilimab (PD-1/CTLA-4 Bi-specific antibody): a case report.

Lung adenocarcinoma (ADC) is a common pulmonary malignant disease with poor prognosis. Immunotherapeutic strategies are the current cornerstone of first-line therapy in driver-negative advanced lung ADC, but there is no treatment standard once the disease has progressed after the first-line application of immune checkpoint inhibitors (ICIs). Clinically, immunotherapy rechallenges are being attempted. However, it is undeniable that there are still great limitations to rechallenging patients with single- or double-ICI immunotherapy though immunotherapy rechallenges can bring new benefits. Cadonilimab (AK104), a unique bi-specific antibody targeting PD-1/CTLA-4, has similar biological activity but lower toxicity than the combination of CTLA-4 and PD-1 antibodies. Herein, we report a case of advanced lung ADC rechallenged with cadonilimab as a posterior-line therapy. The condition of the patient was maintained at stable disease for 6 months. This might provide a new idea and choice for the challenge of immunotherapy resistance.

Ivonescimab Plus Chemotherapy in Non-Small Cell Lung Cancer With EGFR Variant: A Randomized Clinical Trial.

Importance: For patients with non-small cell lung cancer whose disease progressed while receiving EGFR tyrosine kinase inhibitor (EGFR-TKI) therapy, particularly third-generation TKIs, optimal treatment options remain limited. Objective: To compare the efficacy of ivonescimab plus chemotherapy with chemotherapy alone for patients with relapsed advanced or metastatic non-small cell lung cancer with the epidermal growth factor receptor (EGFR) variant. Design, Setting, and Participants: Double-blind, placebo-controlled, randomized, phase 3 trial at 55 sites in China enrolled participants from January 2022 to November 2022; a total of 322 eligible patients were enrolled. Interventions: Participants received ivonescimab (n = 161) or placebo (n = 161) plus pemetrexed and carboplatin once every 3 weeks for 4 cycles, followed by maintenance therapy of ivonescimab plus pemetrexed or placebo plus pemetrexed. Main Outcomes and Measures: The primary end point was progression-free survival in the intention-to-treat population assessed by an independent radiographic review committee (IRRC) per Response Evaluation Criteria in Solid Tumors version 1.1. The results of the first planned interim analysis are reported. Results: Among 322 enrolled patients in the ivonescimab and placebo groups, the median age was 59.6 vs 59.4 years and 52.2% vs 50.9% of patients were female. As of March 10, 2023, median follow-up time was 7.89 months. Median progression-free survival was 7.1 (95% CI, 5.9-8.7) months in the ivonescimab group vs 4.8 (95% CI, 4.2-5.6) months for placebo (difference, 2.3 months; hazard ratio [HR], 0.46 [95% CI, 0.34-0.62]; P < .001). The prespecified subgroup analysis showed progression-free survival benefit favoring patients receiving ivonescimab over placebo across almost all subgroups, including patients whose disease progressed while receiving third-generation EGFR-TKI therapy (HR, 0.48 [95% CI 0.35-0.66]) and those with brain metastases (HR, 0.40 [95% CI, 0.22-0.73]). The objective response rate was 50.6% (95% CI, 42.6%-58.6%) with ivonescimab and 35.4% (95% CI, 28.0%-43.3%) with placebo (difference, 15.6% [95% CI, 5.3%-26.0%]; P = .006). The median overall survival data were not mature; at data cutoff, 69 patients (21.4%) had died. Grade 3 or higher treatment-emergent adverse events occurred in 99 patients (61.5%) in the ivonescimab group vs 79 patients (49.1%) in the placebo group, the most common of which were chemotherapy-related. Grade 3 or higher immune-related adverse events occurred in 10 patients (6.2%) in the ivonescimab group vs 4 (2.5%) in the placebo group. Grade 3 or higher vascular endothelial growth factor-related adverse events occurred in 5 patients (3.1%) in the ivonescimab group vs 4 (2.5%) in the placebo group. Conclusions: Ivonescimab plus chemotherapy significantly improved progression-free survival with tolerable safety profile in TKI-treated non-small cell lung cancer. Trial Registration: ClinicalTrials.gov Identifier: NCT05184712.

Clinical application of percutaneous kyphoplasty under the guidance of DynaCT in the treatment of compression fractures of thoracolumbar.

OBJECTIVES: This study aims to investigate the clinical application values of percutaneous kyphoplasty (PKP) under the guidance of DynaCT in the treatment of compression fractures of thoracolumbar. METHODS: 57 patients with compression fractures of thoracolumbar who were treated with PKP in The Second People's Hospital of Weifang from December 2014 to August 2016 were selected. Patients were randomly divided into DynaCT+DSA treatment group (27 cases) and DSA treatment group (30 cases) for PKP surgery. There were 19 cases of simple thoracic compression fractures, 28 cases of simple lumbar compression fractures, and 10 cases of thoracic vertebral compression fractures. Bone cement filling and leakage conditions were recorded after surgery. Efficacy of PKP was evaluated at 3 days after operation using visual analogue scale (VAS) and the maximal depth of the affected vertebrae. 71 lesioned vertebrae were treated and all punctures were successful. RESULTS: VAS score and height of the largest depression in vertebrae were significantly improved after surgery (p<0.05), while no significant differences were found between 2 groups. The leakage rate of bone cement in the two groups was 24.3% and 18.4%, respectively. CONCLUSION: DynaCT can be used to guide the development of vertebral puncture program before PKP, guide the accurate puncture during operation, and can be used to evaluate the leakage of bone cement timely and reliably.

Bronchial artery chemoembolization with drug-eluting beads versus bronchial artery infusion followed by polyvinyl alcohol particles embolization for advanced squamous cell lung cancer: A retrospective study.

PURPOSE: To analyze the efficacy and safety of bronchial arterial embolization (BACE) with drug-eluting beads (DEB) versus bronchial artery infusion (BAI) followed by polyvinyl alcohol (PVA) particle embolization for the treatment of advanced squamous cell lung cancer after the failure of systemic therapy. METHOD: Thirty-six patients with advanced squamous cell lung cancer who underwent bronchial arterial interventional therapy were included in this retrospective study. The DEB group (n = 20) was treated with nedaplatin and DEB loaded with gemcitabine, and the PVA group (n = 16) BAI with nedaplatin and gemcitabine followed by embolization with PVA particles. The treatment efficacy and complications were analyzed. RESULTS: The technical success rate was 100 %. The two groups were followed up for a median period of 8.9 months. The mean overall survival (OS) in the DEB group was 12.6 months (95 % CI:9.99-15.21), which was significantly longer than 8.14 months (95 % CI:6.07-10.2) in the PVA group (p = 0.007). The median progression-free survival (PFS) in the DEB group was 4.3 months (95 % CI:2.33-6.27), significantly longer than 3.2 months (95 % CI:2.55-3.85) in the PVA group (p = 0.030). The objective response rate (ORR) six months after the procedure was 50 % in the DEB group and 12.5 % in the PVA group. In the univariate and multivariate analyses, DEB-BACE was an independent prognostic factor for survival. Only grade 1 adverse events like fever, chest pain, and cough were seen. CONCLUSIONS: DEB-BACE may be a good choice for patients with advanced lung squamous cell carcinoma, as it could prolong OS and PFS without increasing adverse events.

The role of the canonical nf-κb signaling pathway in the development of acute liver failure.

As a clinical emergency with a high mortality rate, the treatment of acute liver failure has been paid attention to by society. At present, liver transplantation is the most effective treatment for acute liver failure, but there is still an insufficient supply of liver sources and a poor prognosis. In view of the current therapeutic development of this disease, more researchers have turned their attention to the research of drugs related to the NF-κB pathway. The NF-κB canonical pathway has been proven to play a role in a variety of diseases, regulating inflammation, apoptosis, and other physiological processes. More and more evidence shows that the NF-κB canonical pathway regulates the pathogenesis of acute liver failure. In this review, we will summarize the regulation process of the NF-κB canonical pathway on acute liver failure, and develop a new way to treat acute liver failure by targeting the components of the pathway.

XPC Protein Improves Lung Adenocarcinoma Prognosis by Inhibiting Lung Cancer Cell Stemness.

Objective: Xeroderma Pigmentosum Complementation Group C (XPC) is a protein involving in nucleotide excision repair (NER). XPC also plays an important role in the lung cancer occurrence with the mechanism remian unclear up to date. Studies showed that the increased stemness of lung cancer cells is related to the recurrence and metastasis of lung cancer. This study aimed to study and analyze the correlation of XPC with lung cancer stem cell biomarkers expression and the overall survival (OS) of lung adenocarcinoma patients. Methods: 140 cases of clinical lung adenocarcinoma tissue samples and 48 cases of paired paracancerous tissue samples were made into tissue microarray. Immunohistochemistry (IHC) was used to detect the expression of XPC and CD133 in cancer and paracancerous tissues. Semi-quantitative analysis and statistics were performed by Pannoramic Digital Slide Scanner. The expression of XPC and CD133 in fresh tissues was verified by Western blotting assay. siXPC was used to knock down XPC in lung cancer cell lines to study the effect of XPC on the expression of lung cancer stem cell biomarkers and the ability of cell invasion. And shXPC was used to knockdown XPC in A549 and H1650 to study the effect of XPC on the expression of lung cancer stem cell biomarkers. Results: IHC and Western blotting results showed that XPC expression significantly decreased, while CD133 expression significantly increased in cancer tissues comparing to paracancerous tissues (P XPC < 0.0001, P CD133 = 0.0395). The high level of XPC in cancer was associated with a better prognosis (Log-rank p = 0.0577) in lung adenocarcinoma patients. Downregulation of XPC in lung cancer cells showed increased expression of cancer stem cell biomarkers and the increased cell invasion abilities. Conclusion: It is suggested that XPC can exert the ability of anti-tumor formation, tumor invasion and metastasis inhibition, and prognostic survival improvement in lung adenocarcinoma patients by regulating the stemness of lung cancer cells.