Skin-Friendly Flexible Ultraviolet Detectors Based on Reversibly Deformable Worm-Like Polymer Nanoparticles.

Flexible ultraviolet (UV) light detection technology has important applications in wearable devices, smart sensors, and other fields and attracts much attention in recent years. However, for most semiconductor-based UV detectors, the elastic modulus between rigid semiconductors and flexible substrates is mismatched, which makes it difficult to fabricate UV detectors that meet the needs of wearable devices. Herein, a fully flexible, large-scale, skin-friendly UV photodetector component centered on photo-responsive worm-like polymer nanoparticles (NPs) is developed, and the resulting device can quantitatively detect UV illumination. Skin-friendly poly(vinyl alcohol) (PVA), amphiphilic azobenzene-containing polymer NPs (AzNPs), and water-soluble ionic liquids (IL) are formed into (AzNPs-IL)/PVA fabrics by electrospinning. There are interactions such as hydrogen bonding among PVA, AzNPs, and IL, which make the material system stable. The UV detector made of the fabric realizes UV sensing through the illuminance-mechanical stress-electrical signal conversion mechanism. It is capable of achieving a response time of 9 s, a detection range of 10-150 mW cm-2, and stability for 1000 cycle tests upon 365 nm UV irradiation. Moreover, it has good skin affinity, and the water contact angle of the fabric is only 23.57°, which holds great promise for wearable smart devices.

Light-Triggered Reversible Swelling of Polymeric Spheres via Surfactant-Free RAFT Emulsion Polymerization-Induced Self-Assembly.

Responsive photonic crystals (RPCs) assembled by monodisperse colloidal particles have attracted enormous interest recently due to their tremendous applications in smart devices. Their structural colors can be determined by particle sizes. However, the lack of a reliable way to tune the sizes in situ limits their development. Herein, we present an efficient route to solve this problem through the fabrication of spherical polymeric particles with light-triggered reversible swelling behavior via surfactant-free reversible addition-fragmentation chain transfer (RAFT) emulsion polymerization-induced self-assembly (PISA). Amphiphilic macro-RAFT agents containing azobenzene groups were synthesized and subsequently employed to mediate the polymerization of methyl methacrylate. Uniform submicron spheres were obtained by modulating solid contents and other parameters. Benefiting from the photoisomerization of azobenzene moieties, the particle sizes expanded and contracted upon alternative ultraviolet/visible-light irradiation accordingly. This strategy will be a supplement to the emulsion PISA and especially give aid to the progress of the RPC materials.

Lymphocyte migration regulation related proteins in urine exosomes may serve as a potential biomarker for lung cancer diagnosis.

BACKGROUND: The migration of lymphocytes shares many similarities in mode and mechanism with the metastasis of lung cancer tumor cells. But changes in the expression of lymphocyte migration regulation related proteins in urine exosomes remain unclear. This study is to investigate the expression changes of lymphocyte migration regulation related proteins in urine exosomes of lung cancer patients, and further verify their correlation with the development and progression of lung cancer. METHODS: Urine exosomes were collected from lung cancer patients and healthy people aged 15-79 years. Mass spectrometry was used to screen and explore the expression changes of lymphocyte migration regulation related proteins in healthy people of different ages. Enzyme-linked immunosorbent assay and western blotting were used to detect the expression changes of lymphocyte migration regulation related proteins in lung cancer patients. RESULTS: Analyzing the data of urine exosome proteomics, a total of 12 lymphocyte related proteins were identified, 5 of which were lymphocyte migration regulation related proteins. Among these proteins, WASL and STK10 proteins showed a gradual decrease in expression with age, and WNK1 protein showed a gradual increase. Lung cancer patients had reduced expression of WASL and increased expression of STK10 and WNK1 proteins in urine exosomes compared to normal people. Urine exosome WASL, STK10, and WNK1 were diagnosed with lung cancer, with a combined AUC of 0.760. CONCLUSIONS: Lymphocyte migration regulation related proteins were differentially expressed in the urine exosome of lung cancer patients, and WASL, STK10 and WNK1 may serve as potential biomarkers for lung cancer diagnosis.

Bending-Insensitive Intrinsically Flexible Ultraviolet Encoding Devices Based on Piezoelectric Nanogenerator-Supplied Liquid Crystalline Polymer Fabrics.

It is significantly challenging for state-of-the-art wearable electronics to stably monitor physicochemical signals under dynamic motions. Herein, a bending-insensitive, self-powered, and intrinsically flexible UV detector has been realized based on well-designed oriented composite fabrics, consisting of ionic liquid (IL)-containing liquid crystalline polymers (ILCPs) and piezoelectric poly(vinylidene fluoride-trifluoroethylene) [P(VDF-TrFE)] nanogenerators. The novel composite fabrics establish effective UV illuminance-internal stress-electric signal conversion by coupling resistive and piezoelectric effects, with a fast response time of 190 ms. Particularly, benefiting from the intrinsic flexibility of composite fabrics, the ILCP/P(VDF-TrFE) device can maintain stable performance under dynamic bending even if the frequency is up to 2.5 Hz, with a bending insensitivity of less than 1% performance variation under 1.0 mW cm-2 UV light. Combined with the Internet of Things and the American Standard Code for Information Interchange (ASCII), wearable encoding electronics have been successfully implemented with a printing speed of 3.2 s per character under dynamic bending.

Efficacy and safety of anti-PD-1-based therapy in combination with PARP inhibitors for patients with advanced solid tumors in a real-world setting.

BACKGROUND: Rationale exists for combining immune checkpoint inhibitors and PARP inhibitors (PARPi), and results of clinical trials in ovarian cancer are promising, but data in other cancers are limited. METHOD: Efficacy and safety of PARPi/anti-PD-1 in advanced solid tumors were retrospectively analyzed. The efficacy measures included objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS) and overall survival (OS). RESULTS: This retrospective study included data from 40 patients. The ORR was 27.5% (95% CI, 13.0-42.0%), with a DCR of 85.0% (95% CI, 73.4-96.6%). Except four patients in first-line treatment (three with PR and one with SD), the ORR of ≥second-line treatment, non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) was 22.2%, 23.1% and 28.6%, and the DCR was 83.3%, 84.6% and 71.4%, separately. The median PFS of all patients, ≥second-line treatment, NSCLC and SCLC was 4.6 m, 4.2 m, 4.5 m and 3.7 m. The median OS was 9.4 m, 11.4 m, 12.7 m and 5.4 m, respectively. Multivariable analysis revealed that BRCA1/2 mutation was positively correlated with ORR (P = 0.008), and LDH≥250U/L was negatively correlated with lowered DCR (P = 0.018), while lymphocyte number, ECOG and LDH significantly influenced both PFS and OS. We found that the possible resistant mechanisms were sarcomatous degeneration and secondary mutation, including BRCA2 truncation mutation, A2M, JAK1,T790M, KEAP1 and mTOR mutation. 37.5% patients had ≥grade 3 adverse events. CONCLUSION: PARPi/anti-PD-1 is an effective and tolerable method for patients with advanced solid tumors, and BRCA1/2 is a potential biomarker.

Efficacy and safety of apatinib as second-line therapy for advanced gastric cancer: a single-center observational study.

Apatinib has been proven to be effective and safe among patients in the third-line treatment of advanced gastric cancer in phase II and III trials. We aimed to evaluate its efficacy and safety in second-line practice, and to explore the factors associated with efficacy. Between April 2015 and May 2017, a total of 23 patients with advanced gastric adenocarcinoma or adenocarcinoma of gastroesophageal junction were enrolled and followed up retrospectively after failing the first line of systemic therapy. The median progression-free survival was 4.43 months (95% confidence interval: 1.63-7.22) and the median overall survival was 9.11 months (95% confidence interval: 8.22-9.99). Two patients achieved a partial response and 14 patients achieved stable disease. The disease control rate was 69.6% and the objective response rate was 8.7%. The most common adverse events over grade 3 were hypertension (8.7%) and thrombocytopenia (8.7%). No treatment-related death was documented during the drug administration. Apatinib is an effective regimen for the second-line treatment of advanced gastric and gastroesophageal cancer with manageable toxicity.

Impact of Lymphocyte Subsets on Chemotherapy Efficacy and Long-term Survival of Patients with Advanced Non-small-cell Lung Cancer.

Objective To analyze the impact of lymphocyte subsets on chemotherapy efficacy and long-term survival of patients with advanced non-small cell lung cancer(NSCLC).Methods Totally 125 NSCLC patients who had received first-line chemotherapy including paclitaxel and pemetrexed with/without platinum were enrolled in this study.Lymphocytes from peripheral blood were collected before and after two cycles of first-line chemotherapy.Flow cytometry was performed to determine the expressions of 21 fluorescence-labeled lymphocyte subsets.Based on the imaging findings,chemotherapy efficacy was evaluated,and impact of the lymphocyte subsets on progression-free survival(PFS)and overall survival(OS)were analyzed.Results The baseline peripheral lymphocyte subsets showed no significant difference among groups receiving different treatment protocols(all P>0.05).After 2 cycles of chemotherapy,the percentage of CD4+CD29+lymphocytes was(16.87±5.28)% in progressive disease group,which was significantly lower than those in complete remission+partial remission group [(22.42±7.88)%,P=0.013] and stable disease group [(21.88±6.81)%,P=0.009].The median PFS was 7.07 months and median OS was 23.00 months.Cox multivariable regression analysis showed that the percentages of HLA-DR+(HR:1.03,95%CI:1.01-1.05,P<0.001) and CD3+HLA-DR+lymphocytes (HR:1.05,95%CI:1.01-1.08,P<0.001)were positively correlated with OS.Conclusions The rise of CD4+CD29+T lymphocytes in patients after chemotherapy indicates good chemotherapy efficacy.Higher percentage of HLA-DR+and CD3+HLA-DR+lymphocytes in peripheral blood before chemotherapy predicts favorable prognosis.

Overexpression of MicroRNA-221 is associated with poor prognosis in non-small cell lung cancer patients.

The abnormal expression of microRNA-221 was detected in several cancers and some studies had indicated that microRNA-221 was associated with cancer prognosis. This study was aimed to evaluate the prognostic significance of microRNA-221 in non-small cell lung cancer (NSCLC). Quantitative real-time polymerase chain reaction (qRT-PCR) was used for detecting the relative expression levels of microRNA-221 in the pathological tissues and corresponding normal tissues of 104 NSCLC patients. The relationship between the expression levels and the clinical features was estimated by Chi-square method and the overall survival of patients at different expression levels was demonstrated by Kaplan-Meier method. Cox regression analysis was used to evaluate the prognostic significance of microRNA-221. The relative expression levels of microRNA-221 in the pathological tissues were remarkably higher than that in the corresponding normal tissues (1.71 vs 1.07, P = 0.000). The expression level was associated with lymph node metastasis (P = 0.001). The results of Kaplan-Meier method indicated that patients with high expression level of microRNA-221 had shorter overall survival time than those with low expression level (36.8 vs 45.2 months, P = 0.001). Moreover, Cox regression analysis suggested that microRNA-221 was a useful independent biomarker for NSCLC prognosis (HR = 1.873, 95 % CI = 1.267-2.768, P = 0.002). The aberrant expression of microRNA-221 is associated with NSCLC progression and it might be a potential biomarker for NSCLC prognosis.

Comparative efficacy of six programmed cell death Protein-1 inhibitors as first-line treatment for advanced non-small cell lung cancer: a multicenter retrospective cohort study.

The purpose of this study was to assess the comparative efficacy of six programmed cell death-1 inhibitors (nivolumab, pembrolizumab, sintilimab, tislelizumab, toripalimab, and camrelizumab) that have been used as first-line therapy for Chinese patients with advanced non-small cell lung cancer (NSCLC), which remains unclear. We determined the differences in efficacy by observing patient survival data, with the goal of informing future treatment options. Retrospective data analysis from June 2015 to April 2023 included 913 patients across six groups: nivolumab (123%, 13.5%), pembrolizumab (421%, 46.1%), sintilimab (239%, 26.1%), tislelizumab (64%, 7.0%), toripalimab (39%, 4.3%), and camrelizumab (27%, 3.0%). The median progression-free survival (PFS) for each group was 16.0, 16.1, 18.4, 16.9, 23.7, and 12.8 months, and the median overall survival (OS) was 33.7, 36.1, 32.5, not reached, 30.9 and 46.0 months for the nivolumab, sintilimab, pembrolizumab, tislelizumab, toripalimab, and camrelizumab groups, respectively. While differences existed in the objective response rates among groups (p < 0.05), there were no significant differences (all p > 0.05) in PFS or OS. The findings suggest comparable efficacy among these PD-1 inhibitors for NSCLC treatment, underscoring their collective suitability and aiding treatment decisions.

Prognosis of immune checkpoint inhibitor-related myocarditis: Retrospective experience of a single institution.

BACKGROUND: Myocarditis related to immune checkpoint inhibitors (ICIs) treatment is a rare but potentially life-threatening adverse event. To gain insight into this condition, we analyzed the clinical characteristics and prognosis of patients with ICI-related myocarditis. METHODS: Data on the clinical characteristics, management, and outcomes of patients diagnosed with ICI-related myocarditis between August 2018 and August 2023 in our institution were gathered retrospectively from medical records. Outcomes included the occurrence of major adverse cardiac events (MACE). RESULTS: Among 8875 patients who received ICI therapy, 31 patients experienced ICI-related myocarditis. These 31 patients had a mean age of 62 ± 12 years and included 24 (77.4 %) males and 19 patients (61.3 %) with at least one risk factor for cardiovascular disease. The median duration from ICI initiation to the onset of myocarditis symptoms was 6.3 weeks (interquartile range, 4.3-8.1 weeks). Twenty-one patients (67.7 %) developed grade 3-4 myocarditis. Thirteen patients (42 %) experienced MACE after myocarditis onset, and 15 patients (48.4 %) showed a troponin rise > 4 times the maximum limit of the standard range. On receiver operating characteristic curve analysis, troponin level could predict MACE in patients with ICI-related myocarditis with an area under the curve of 0.82 (95 % confidence interval [CI]: 0.66-0.98, p = 0.003). From Kaplan-Meier analysis, the occurrence of MACE (p = 0.002) was an independent influencing factor on patients' overall survival. CONCLUSIONS: ICI-related myocarditis frequently leads to MACE, which is associated with poor prognosis. Elevated troponin levels and electrocardiogram abnormalities in these patients may help predict the occurrence of MACE.

Prognosis of immune checkpoint inhibitor-induced myasthenia gravis: a single center experience and systematic review.

Background: Immune checkpoint inhibitors (ICI)-induced myasthenia gravis (MG) is an uncommon but potentially fatal neurotoxicity. We aim to help physicians familiarize themselves with the clinical characteristics of ICI-induced MG, facilitating early diagnosis and prompt intervention. Methods: We searched the Chinese People's Liberation Army General Hospital medical record system from January 2017 to August 2023 for patients diagnosed with ICI-induced MG. We systematically reviewed the literature until August 2023 to identify all similar patients. We collected clinical information on these patients. Results: 110 patients were identified, 9 from our institution and 101 from case reports. In our institution, Median age was 66 years (range: 49-79 years). 6 were males. The most common was lung cancer (n = 4). All patients had no previous history of MG and received PD-1 or PD-L1 inhibitors. The median time from ICI initiation to first MG symptoms was 4 weeks (range: 2-15 weeks). ICIs were discontinued in all patients. Most patients initially received high-dose corticosteroids, and their symptoms improved. Some patients are discharged with corticosteroids maintenance therapy. In addition, 55 patients (50%) with concomitant myositis and/or myocarditis and MG-induced mortality were more common in the myositis and/or myocarditis group (10.9% vs. 34.5%, p = 0.016). Overlap of myositis with MG (OR = 3.148, p = 0.009) and anti-AChR antibody positivity (OR = 3.364, p = 0.005) were both significantly associated with poor outcomes. Conclusion: Our study reveals the prognosis of ICI-induced MG and suggests that myositis and/or myocarditis are severe comorbidities of ICI-induced MG, emphasizing the importance of early diagnosis and clinical intervention.

Rechallenge of immune checkpoint inhibitors in advanced non-small cell lung cancer.

Immune checkpoint inhibitor (ICI) rechallenge in non-small cell lung cancer (NSCLC) is a promising therapeutic strategy. The situation for ICI rechallenge can be divided into three categories: adverse events (AEs); resistance to ICIs, and rechallenge becomes compulsive because of tumor relapse while the patients had completed a 2 year course of immunotherapy. However, these categories are still controversial and should be explored further. Through voting at the 6th Straits Summit Forum on Lung Cancer, in this study we summarize the consensus of 147 experts in ICI rechallenges. A total of 97.74% experts agreed to rechallenge; 48.87% experts rechallenge with the original drug, and the others rechallenge with a different drug; 40.3% agreed to rechallenge directly after progression; 88.06% experts agreed to ICI rechallenge with a combination regimen; and factors such as previous performance status score, PD-1 expression, and age should also be considered. Understanding the the clinical studies in ICI rechallenge could bring us one step closer to understanding the consensus. In patients with advanced NSCLC who have suffered recurrent or distant metastasis after immunotherapy, the option of rechallenge with ICIs is a promising treatment option.

Central nervous system efficacy of rezivertinib (BPI-7711) in advanced NSCLC patients with EGFR T790M mutation: A pooled analysis of two clinical studies.

BACKGROUND: Rezivertinib (BPI-7711) is a novel third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) which revealed the systematic and central nervous system (CNS) antitumor activities for EGFR T790M-mutated advanced NSCLC in previous clinical studies and is further analyzed here. METHODS: Eligible patients from the previous phase I and phase IIb studies of rezivertinib were included for pooled analysis. Post-progressive patients who received a prescribed dosage (≥180 mg) of rezivertinib orally once daily were included in full analysis set (FAS), while those with stable, asymptomatic CNS lesions, including measurable and non-measurable ones at baseline were included in CNS full analysis set (cFAS). Patients with measurable CNS lesions were included in CNS evaluable for response set (cEFR). BICR-assessed CNS objective response rate (CNS-ORR), CNS disease control rate (CNS-DCR), CNS duration of response (CNS-DoR), CNS progression-free survival (CNS-PFS), and CNS depth of response (CNS-DepOR) were evaluated. RESULTS: 355 patients were included in FAS, among whom 150 and 45 patients were included in cFAS and cEFR. This pooled analysis showed the CNS-ORR was 32.0% (48/150; 95% CI: 24.6-40.1%) and the CNS-DCR was 42.0% (63/150; 95% CI: 34.0-50.3%) in cFAS, while that in cEFR were 68.9% (31/45; 95% CI: 53.4-81.8%) and 100% (45/45; 95% CI: 92.1-100.0%). In cEFR, the median CNS-DepOR and the mean of CNS-DepOR were -52.0% (range: -100.0 to 16.1%) and -46.8% (95% CI: -55.5 to -38.1%). In cFAS, the median CNS-DoR and CNS-PFS were 13.8 (95% CI: 9.6-not calculable [NC]) and 16.5 (95% CI: 13.7-NC) months. CONCLUSIONS: Rezivertinib demonstrated encouraging clinical CNS efficacy among advanced NSCLC patients with EGFR T790M mutation and CNS metastases.

Clinical definition of secondary resistance to immunotherapy in non-small cell lung cancer.

Immune checkpoint inhibitors (PD-1/PD-L1 and CTLA-4 blockade) have revolutionized the treatment landscape in non-small cell lung cancer (NSCLC). Secondary resistance to immunotherapy (IO), which poses a substantial challenge in clinical settings, occurs in several initial responders. Currently, new treatment approaches have been extensively evaluated in investigational studies for these patients to tackle this difficult problem; however, the lack of consistency in clinical definition, uniform criteria for enrollment in clinical trials, and interpretation of results remain significant hurdles to progress. Thus, our expert panel comprehensively synthesized data from current studies to propose a practical clinical definition of secondary resistance to immunotherapy in NSCLC in metastatic and neoadjuvant settings. In addition to patients who received IO alone (including IO-IO combinations), we also generated a definition for patients treated with chemotherapy plus IO. This consensus aimed to provide guidance for clinical trial design and facilitate future discussions with investigators. It should be noted that additional updates in this consensus are required when new data is available.

International expert consensus on diagnosis and treatment of lung cancer complicated by chronic obstructive pulmonary disease.

Background: Lung cancer combined by chronic obstructive pulmonary disease (LC-COPD) is a common comorbidity and their interaction with each other poses significant clinical challenges. However, there is a lack of well-established consensus on the diagnosis and treatment of LC-COPD. Methods: A panel of experts, comprising specialists in oncology, respiratory medicine, radiology, interventional medicine, and thoracic surgery, was convened. The panel was presented with a comprehensive review of the current evidence pertaining to LC-COPD. After thorough discussions, the panel reached a consensus on 17 recommendations with over 70% agreement in voting to enhance the management of LC-COPD and optimize the care of these patients. Results: The 17 statements focused on pathogenic mechanisms (n=2), general strategies (n=4), and clinical application in COPD (n=2) and lung cancer (n=9) were developed and modified. These statements provide guidance on early screening and treatment selection of LC-COPD, the interplay of lung cancer and COPD on treatment, and considerations during treatment. This consensus also emphasizes patient-centered and personalized treatment in the management of LC-COPD. Conclusions: The consensus highlights the need for concurrent treatment for both lung cancer and COPD in LC-COPD patients, while being mindful of the mutual influence of the two conditions on treatment and monitoring for adverse reactions.

[Clinical characteristics and prognostic factors of malignancy-associated hypercalcemia in squamous cell carcinoma].

OBJECTIVE: To explore the clinical characteristics and prognostic factors of patients diagnosed with squamous cell carcinoma (SCC) and presented malignancy-associated hypercalcemia (MAH). METHODS: We retrospectively analyzed the clinical data of 36 patients with biopsy-proven SCC and presented MAH who were treated at the our department from January 2001 to December 2010. The survival were analyzed using the Kaplan-Meier method and Cox analysis. RESULTS: Among these 36 patients, the median blood calcium level was 2.94 mmol/L (2.77-4.87 mmol/L), and the median survival time was only 45 days (1-839 d). Log-rank test showed that central nervous system symptoms, bone metastasis, and hypercalcemia occurring over 160 days after cancer diagnosis were predictors for poor survival(p=0.003, P=0.049, P=0.005). In the COX proportional hazard model analysis, central nervous system symptoms and hypercalcemia occurring over 160 days after cancer diagnosis were independent prognostic factors for survival time (RR=5.721, P=0.000; RR=4.624, P=0.001). CONCLUSIONS: Patients with squamous cell carcinoma (SCC) and presented MAH have poor prognosis. Central nervous system symptoms and hypercalcemia occurring over 160 days after cancer diagnosis are independent predictors of the prognosis.

Seismic design of rectangular/square columns in SDOF systems based on their damage performance.

The quantitative relationship between the energy dissipation capacity of RC members and displacement deformation, cumulative energy dissipation and structural design parameters were established by the research group in the early stage, and then the damage index based on energy dissipation capacity and performance index limits were proposed. Based on the existing research, the seismic design method of RC square/rectangular column members for SDOF systems based on damage performance is proposed, and the method is introduced by an example. It is found that the seismic design method establishes a quantitative relationship between the structural design parameters and seismic parameters, which is convenient to guide the structural design. The increase in the ratio of transverse reinforcement can reduce the damage to RC column members, but when the ratio of transverse reinforcement exceeds a certain threshold value, the damage reduction effect is not obvious. The increase of the earthquake duration can aggravate the development of the damage to the RC column members, and the increasing effect is first fast and then slow. This seismic design method can make up for the deficiency that the duration effect is not considered in the current seismic code.

Characterizing HDAC Pathway Copy Number Variation in Pan-Cancer.

Background: Histone deacetylase (HDAC) plays a crucial role in regulating the expression and activity of a variety of genes associated with tumor progression and immunotherapeutic processes. The aim of this study was to characterize HDAC pathway copy number variation (CNV) in pan-cancer. Methods: A total of 10,678 tumor samples involving 33 types of tumors from The Cancer Genome Atlas (TCGA) were included in the study. Results: HDAC pathway CNV and CNV gain were identified as prognostic risk factors for pan-cancer species. The differences of tumor characteristics including tumor mutational burden, tumor neoantigen burden, high-microsatellite instability, and microsatellite stable between HDAC pathway CNV altered-type group and wild-type group varied among the various cancer species. In some cancer types, HDAC pathway CNV alteration was positively correlated with loss of heterozygosity, CNV burden, ploidy, and homologous recombination defect score markers, while it was significantly negatively correlated with immune score and stroma score. There were significant differences in immune characteristics such as major histocompatibility complex class I (MHC-I), MHC-II, chemokines, cytolytic-activity, and IFN-γ between the two groups. Immune cycle characteristics varied from one cancer type to another. Conclusion: This study reveals a tumor and immune profile of HDAC pathway CNV as well as its unlimited potential in immune prognosis.

Evolutions in the management of non-small cell lung cancer: A bibliometric study from the 100 most impactful articles in the field.

Objective: The study was designed to explore the evolution of non-small cell lung cancer (NSCLC) management in the last 20 years. Methods: The top 100 most-cited papers on NSCLC treatment were retrieved from the Web of Science Core Collection database. R and VOSviewer were used to extract bibliographic information, including the year of publication, countries/regions, institutions, authors, journals, keywords, impact factor, and total citations. The topic and type of papers were checked independently by authors. Bibliometric analysis was conducted and visualized with R, CiteSpace, Excel and VOSviewer to identify output dynamics, research forces, topics, hotspots, and frontiers in the field. Results: The average citation of each retrieved top 100 most-cited NSCLC management papers was 1,725 (range: 615-7,340). Fifty-seven corresponding authors were from the United States. This country contributed the most papers (n=76), followed by Germany (n=34), France (n=33), and South Korea (n=32). The top contributors were Paz-Ares L. (n=12) and Reck M. (n=12). The Memorial Sloan Kettering Cancer Center published the largest number of papers (n=20). There were two significant citation paths, indicating publications in medicine/medical/clinical journals primarily cited journals in molecular/biology/genetics fields, partly cited health/nursing/medicine fields. Top-cited papers mainly came from the New England Journal of Medicine (n=33, citations=80,427), followed closely by the Journal of Clinical Oncology (n=28, citations=32,408). "Chemotherapy" (n=36) was the keyword with the greatest frequency of co-occurrence. "Open-label" was the keyword with the strongest burst strength (=4.01), followed by "nivolumab" (=3.85), "blockade" (=2.86), and "efficacy" (=2.85). Conclusions: The United States as a nation and the Memorial Sloan Kettering Cancer Center as an institute contributed the most to this field. The New England Journal of Medicine is the most eye-catching journal. Hotspots of NSCLC management have almost undergone an evolution from chemotherapy and radiotherapy to targeted therapy to immunotherapy. Molecular/biological/genetic fields become the main research base for NSCLC treatment. Immunotherapy and combination therapy are research frontiers.

Efficacy and Safety of Rezivertinib (BPI-7711) in Patients With Locally Advanced or Metastatic/Recurrent EGFR T790M-Mutated NSCLC: A Phase 2b Study.

INTRODUCTION: Rezivertinib (BPI-7711) is a novel third-generation EGFR tyrosine kinase inhibitor (TKI) targeting both EGFR-sensitizing mutations and EGFR T790M mutation. This study aimed to evaluate the efficacy and safety of rezivertinib in patients with locally advanced or metastatic/recurrent EGFR T790M-mutated NSCLC. METHODS: Patients with locally advanced or metastatic/recurrent NSCLC with confirmed EGFR T790M mutation who progressed after first-/second-generation EGFR TKI therapy or primary EGFR T790M mutation were enrolled. Patients received rezivertinib at 180 mg orally once daily until disease progression, unacceptable toxicity, or withdrawal of consent. The primary end point was objective response rate (ORR) assessed by blinded independent central review per Response Evaluation Criteria in Solid Tumors version 1.1. Secondary end points included disease control rate (DCR), duration of response, progression-free survival (PFS), overall survival, and safety. This study is registered with Clinical Trials.gov (NCT03812809). RESULTS: A total of 226 patients were enrolled from July 5, 2019, to January 22, 2020. By the data cutoff date on January 24, 2022, the median duration of follow-up was 23.3 months (95% confidence interval [CI]: 22.8-24.0). The ORR by blinded independent central review was 64.6% (95% CI: 58.0%-70.8%), and DCR was 89.8% (95% CI: 85.1%-93.4%). The median duration of response was 12.5 months (95% CI: 10.0-13.9), and median PFS was 12.2 months (95% CI: 9.6-13.9). The median overall survival was 23.9 months (95% CI: 20.0-not calculated [NC]). Among 91 (40.3%) patients with central nervous system (CNS) metastases, the median CNS PFS was 16.6 months (95% CI: 11.1-NC). In 29 patients with more than or equal to one brain target lesion at baseline, the CNS ORR and CNS DCR were 69.0% (95% CI: 49.2%-84.7%) and 100% (95% CI: 88.1%-100%), respectively. Time to progression of CNS was 16.5 months (95% CI: 9.7-NC). Of 226 patients, 188 (83.2%) had at least one treatment-related adverse event, whereas grade more than or equal to 3 occurred in 45 (19.9%) patients. No interstitial lung disease was reported. CONCLUSIONS: Rezivertinib was found to have promising efficacy and favorable safety profile for patients with locally advanced or metastatic/recurrent NSCLC with EGFR T790M mutation.