Background and Objective:MET exon 14 skipping mutation is a significant driver alteration in non-small cell lung cancer (NSCLC). c-Met inhibitors have emerged as a pivotal therapeutic option for targeting this mutation, demonstrating significant efficacy in improving overall survival (OS) and patient outcomes. However, the development of resistance to these inhibitors is inevitable. This review aims to summarize the current landscape of c-Met inhibitors in treating NSCLC with MET exon 14 skipping mutations and to delineate the emerging challenge of drug resistance. Based on existing research evidence, we elaborate on the underlying mechanisms of resistance, with the goal of informing personalized treatment strategies and providing a foundation for future research aimed at overcoming this resistance. Methods:A literature review was conducted using terms related to the treatment of c-Met inhibitors in MET exon 14 skipping NSCLC and mechanisms of resistance. Predefined inclusion or exclusion criteria were not applied, and articles that contained clinical trials, retrospective studies, in vitro experiments and meta-analyses published in English mainly within the last 10 years were selected. Key Content and Findings:In this review, we briefly describe the MET signaling pathway and the MET exon 14 skipping mutation, introduce the efficacy of major c-Met inhibitors in clinical practice, and discuss the main mechanisms of drug resistance, including primary and acquired resistance. Conclusions:The application of c-Met inhibitors has revolutionized the treatment of NSCLC harboring MET exon 14 skipping mutations, substantially improving patient outcomes. However, drug resistance comprising primary and acquired mechanisms poses a major clinical challenge. Current understanding of these resistance mechanisms remains limited. Future research is warranted to further elucidate resistance and to optimize therapeutic strategies, thereby enhancing efficacy and survival benefits for these patients.

Background:Postoperative pulmonary complications (PPCs) remain common after video-assisted thoracoscopic (VATS) lung surgery. Whether sugammadex reduces the incidence of PPCs compared with traditional antagonists remains uncertain. This meta-analysis aimed to evaluate the impact of sugammadex on PPCs in patients undergoing VATS pulmonary resection. Methods:This meta-analysis was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA 2020). PubMed, Web of Science, Cochrane Library, and CNKI were searched from inception to December 13, 2024. Randomized controlled trials (RCTs) and cohort studies comparing sugammadex with other antagonists (e.g., neostigmine or pyridostigmine) in patients undergoing VATS pulmonary resection were included. The primary outcome was overall PPCs. Risk of bias was assessed using the Cochrane risk-of-bias tool for RCTs and the Newcastle-Ottawa Scale (NOS) for cohort studies. Odds ratios (ORs) with 95% confidence intervals (CIs) were pooled using fixed- or random-effects models according to heterogeneity. Results:Nine studies involving 2,240 patients were included, of which eight reported data on overall PPCs and were included in the primary meta-analysis. Sugammadex significantly reduced the incidence of overall PPCs compared with control agents (OR = 0.68, 95% CI: 0.58-0.80, P < 0.001; I² = 23.9%). Subgroup analyses stratified by study design, type of resection, and disease showed consistent results. Among specific PPCs, sugammadex was associated with a lower risk of atelectasis (OR = 0.61, 95% CI: 0.47-0.80, P < 0.001), whereas no significant differences were observed for pneumonia or other complications. Conclusions:Sugammadex may effectively reduce the risk of PPCs, particularly atelectasis, in patients undergoing VATS pulmonary resection. Further large-scale, high-quality studies are warranted.

BACKGROUND:Sacituzumab tirumotecan (sac-TMT), a trophoblast cell-surface antigen 2-targeting antibody-drug conjugate, combined with programmed death 1 (PD-1) or programmed death ligand 1 (PD-L1) inhibitors, has shown promising antitumour activity as first-line therapy for non-small-cell lung cancer (NSCLC) in early-phase studies. Our aim was to evaluate the efficacy and safety of sac-TMT plus pembrolizumab as first-line treatment for patients with PD-L1-positive advanced NSCLC without targetable genomic alterations. METHODS:In this randomised, open-label, phase 3 trial (OptiTROP-Lung05) conducted across 68 hospitals in China, eligible patients had locally advanced or metastatic NSCLC without targetable genomic alterations and a PD-L1 tumour proportion score (TPS) of 1% or greater. Patients were randomly assigned (1:1) to receive sac-TMT (4 mg/kg on days 1, 15, and 29) plus pembrolizumab (400 mg fixed dose on day 1), or pembrolizumab alone, administered intravenously every 6 weeks. The primary endpoint was progression-free survival, as assessed by blinded independent central review in the intention-to-treat population. This trial was registered with ClinicalTrials.gov (NCT06448312). Recruitment is complete, with the trial ongoing and the final analysis to be reported later. FINDINGS:Between June 7, 2024, and March 27, 2025, 741 patients were screened and 413 eligible patients were randomly assigned to receive sac-TMT plus pembrolizumab (n=208) or pembrolizumab alone (n=205). At the prespecified interim analysis, conducted after a median follow-up of 10·5 months (IQR 8·7-12·5), median progression-free survival was significantly longer with sac-TMT plus pembrolizumab than with pembrolizumab alone (not reached vs 5·7 months; stratified hazard ratio [HR] 0·35 [95% CI 0·26-0·47]; p<0·0001). The progression-free survival benefit was broadly consistent across subgroups, including patients with PD-L1 TPS of 1-49% (HR 0·28 [95% CI 0·19-0·41]) and those with PD-L1 TPS of 50% or greater (HR 0·47 [0·29-0·77]). Grade 3 or higher treatment-emergent adverse events occurred in 115 (55%) of 208 patients in the sac-TMT plus pembrolizumab group and 64 (31%) of 204 patients in the pembrolizumab group. INTERPRETATION:Among patients with PD-L1-positive advanced NSCLC without targetable genomic alterations, first-line treatment with sac-TMT plus pembrolizumab significantly prolonged progression-free survival compared with pembrolizumab alone. Therefore, sac-TMT plus pembrolizumab has the potential to redefine first-line treatment for patients with PD-L1-positive advanced NSCLC without targetable genomic alterations. FUNDING:Sichuan Kelun-Biotech Biopharmaceutical.

BackgroundBrain metastasis is a major cause of mortality in lung cancer, particularly in small-cell lung cancer (SCLC). Whether genetic susceptibility to lung cancer is associated with brain structural and functional traits relevant to metastatic vulnerability remains unclear. We investigated subtype-specific genetic associations with brain imaging phenotypes and explored the biological context of the SCLC-associated white-matter signal.MethodsBidirectional two-sample Mendelian randomization (MR) was performed using European genome-wide association study summary statistics for three lung cancer subtypes, 3,935 structural MRI phenotypes, and 191 resting-state functional MRI traits. MR findings were evaluated using genetic-correlation and sensitivity analyses. Public single-cell and spatial transcriptomic datasets from brain metastases, computational ligand-receptor inference, and virtual perturbation modeling were used to explore the SCLC-related findings.ResultsSCLC genetic liability showed the clearest white-matter-related pattern, involving the superior cerebellar peduncle and cerebellar-related functional connectivity, whereas lung squamous cell carcinoma was mainly associated with frontal and parietal traits. Single-cell analysis identified mature-like, intermediate, and reactive-like oligodendrocyte states. Reactive-like cells exhibited reduced myelination-associated genes and enhanced stress-response programs. Computational analyses prioritized an FN1-associated tumor-oligodendrocyte interaction program, with neuronal-like malignant SCLC cells as the major predicted sender population. Cross-dataset, spatial, and virtual perturbation analyses provided additional exploratory support for tumor-derived FN1 as a candidate niche-organizing signal associated with reactive oligodendrocyte remodeling.ConclusionsLung cancer subtypes show distinct genetic associations with brain phenotypes. The SCLC findings and exploratory multi-omics analyses support an FN1-centered tumor-oligodendrocyte model that warrants experimental validation.

ABSTRACT Typical carcinoid tumors (TC) are a low‐grade neuroendocrine tumor characterized by low proliferation activity and an overall favorable prognosis. Lympho‐vascular invasion is uncommon in TC and is more frequently associated with atypical carcinoid. We reported a 46‐year‐old non‐smoking woman who underwent right lower lobectomy for a right pulmonary hilar mass after multidisciplinary team (MDT) evaluation (cT1cN0M0, AJCC 9th edition, IA3). Postoperative histopathological examination confirmed typical carcinoid tumor with a low Ki‐67 proliferation index (< 2%), and no tumor necrosis was identified, fulfilling the diagnostic criteria for typical carcinoid according to the current WHO classification of thoracic tumors. Unexpectedly, focal lympho‐vascular invasion in the form of tumor emboli was identified. Additionally, the resected lung showed caseating granulomatous inflammation with acid‐fast bacilli, suggestive of a non‐tuberculous mycobacteria (NTM) infection; however, species‐level identification was not performed. No lymph node metastasis was detected (pT1cN0M0, AJCC 9th edition, IA3). The patient had minimal pleural effusion on the surgical side postoperatively, and no signs of recurrence or metastasis have been detected during 20 months of follow‐up to date. This report highlights a pathological discordance between the low proliferation index and the presence of lympho‐vascular invasion in TC. The concomitant granulomatous inflammation may have contributed to diagnostic complexity, although a causal relationship cannot be established. This case underscores the importance of careful histopathological evaluation for invasive features in typical carcinoid tumors, even in the context of low proliferative activity. Surgical treatment alone might be safe in this specific scenario.

ALK gene fusions occur in approximately 6.7% of non-small cell lung cancer (NSCLC) cases. These fusions drive constitutive activation of the ALK tyrosine kinase domain, which can be therapeutically targeted with tyrosine kinase inhibitors (TKIs). However, non-rearrangement alterations are rare, and the efficacy of TKIs against them remains unclear. Here we report a NSCLC patient with mixed squamous cell carcinoma and adenocarcinoma experiencing rapid progression after conventional radiochemotherapy. DNA sequencing revealed an ALK exon 19 frameshift mutation instead of rearrangement, accompanied by positive ALK protein expression. After 7 months of alectinib treatment, the primary and metastatic lesions significantly shrank. This case suggests that non-rearrangement ALK variants may also drive NSCLC and could respond to TKI therapy.

Cancer-associated fibroblast (CAF)-derived extracellular vesicles (EVs) mediate lung adenocarcinoma (LUAD) progression, but the role of their protein cargo remains poorly defined. Through quantitative proteomic profiling of EVs from patient-derived CAFs, we identify the V-ATPase subunit ATP6V1C1 as a protein highly enriched in pro-migratory CAF-EVs that critically mediates LUAD metastasis. Mechanistically, EV-delivered ATP6V1C1 suppresses insulin-like growth factor binding protein 3 (IGFBP3) expression by downregulating the transcriptional regulator ID1. This suppression of IGFBP3 induces epithelial-mesenchymal transition in LUAD cells and amplifies the oncogenic IGF1/IGF1R/Akt/ERK signaling cascade initiated by CAF-secreted IGF1. This dual action establishes a feedforward loop that exacerbates metastatic progression. Our findings identify ATP6V1C1 as a dual regulator of LUAD metastasis and suggest a potential stroma-targeted therapeutic approach.

To determine the association between preoperative geriatric nutritional risk index (GNRI) and postoperative complications in surgical esophageal cancer patients. PubMed, Web of Science EMBASE and CNKI databases were searched from inception up to December 16, 2024. Primary outcome was the overall complication. Secondary outcomes included the postoperative pulmonary complication (PPC), anastomotic leakage, chylothorax, vocal code paresis, pneumonia, arrhythmia, incision infection, gastrointestinal complication, respiratory failure and heart failure. Odds ratios (ORs) and 95 https://doi.org/10.37766/inplasy2025.9.0012 ).

The objective of this study was to evaluate the significance of preoperative heart rate variability (HRV) as a surrogate marker for vagus nerve activity in predicting the incidence of postoperative pneumonia (POP) and lung function recovery in patients undergoing lung cancer surgery. A prospective observational study was conducted at a single center. Patients were categorized into two groups: the POP group, which included those who developed pneumonia post-surgery, and the non-POP group, comprising patients who did not experience POP. A total of 257 subjects met the inclusion criteria and were ultimately included in the study. 33 patients presented POP, accounting for 12.8

BACKGROUND:Certain patients with stage IIIA-N2IIIB non-small cell lung cancer (NSCLC) have surgical opportunities after induction therapy. Two to four cycles of neoadjuvant chemoimmunotherapy (NCIT) are commonly used. However, whether the number of cycles of NCIT has an impact on the pathological response has not been extensively investigated. The intent of this study was to explore the impact of the number of NCIT cycles on the pathological response of patients with stage IIIA-N2IIIB NSCLC. PATIENTS AND METHODS:This retrospective single-center study reviewed patients with stage IIIA-N2IIIB NSCLC without positive driver genes who received two to four cycles of NCIT followed by complete resection. The primary endpoint was the major pathological response (MPR) rate. Univariate and multivariate logistic regression analyses were performed to explore the risk factors for the MPR. The objective response rate (ORR) was also compared between different cycles of NCIT. RESULTS:Among the 170 patients included in our final analysis, the MPR rate was 58.24%, and the pathological complete response (pCR) rate was 37.06% in the overall cohort. The MPR rates were 58.97%, 62.50%, and 50.00% in the two-, three- and four-cycle NCIT groups, respectively. Multivariate regression analysis revealed that preoperative assessment of the radiographic response to NCIT, partial response/complete response (PR/CR), was the only independent prognostic factor for the MPR (p < 0.001). CONCLUSIONS:We confirmed that preoperative PR/CR was important in predicting the MPR, whereas the number of cycles of NCIT did not influence the MPR rate in patients with stage IIIA-N2IIIB NSCLC.

Background:Perioperative airway management is critical for patient safety and optimal surgical outcomes. Effective airway management reduces postoperative pulmonary complications and accelerates recovery. This expert consensus aims to update the earlier consensus based on the latest research and emphasize aspects that were previously overlooked. Methods:A comprehensive search up to June 2024 was performed. Earlier consensus documents were reviewed to ensure thorough coverage. A modified Delphi method involved 62 domestic experts from various surgical and anesthetic specialties who discussed and voted on preliminary recommendations in face-to-face meetings, requiring ≥70% agreement. Drafts were then reviewed by 18 international experts via email to incorporate diverse insights. Results:Through the modified Delphi method, consensus was achieved with ≥70% agreement among the 62 domestic experts, ensuring that the preliminary recommendations were robust and widely supported. Additionally, feedback from the 18 international experts provided diverse insights that further refined and validated the recommendations. Recommendations were established for preoperative airway preparation, anesthesia management, surgical approach, postoperative airway management, and managing coexisting respiratory diseases. These recommendations update the perspectives of earlier consensus documents based on the latest research and emphasize non-intubated surgery, inhalation therapy, and individualized treatment for patients with coexisting pulmonary diseases. Conclusions:This expert consensus provides a valuable reference for clinical practice. Further technological optimization and clinical research are needed to improve perioperative airway management.

ALK fusions, such as the classic EML4-ALK, are known drivers of lung cancer and effective therapeutic targets. However, variant ALK fusions, including intergenic fusions like LOC388942-ALK (LA), have been detected in increasing numbers of patients, with their roles in tumorigenesis and ALK inhibitor resistance remaining unclear. Using CRISPR/Cas9, we generated the LA fusion in A549 and H441 cells, confirming elevated ALK expression via qRT-PCR and immunohistochemistry (IHC) staining. Functional analyses showed that LA significantly promoted tumor growth in vitro and in vivo while conferring increased resistance to alectinib. RNA-seq revealed upregulation of the FOS pathway in LA tumors, identifying FOS as a potential therapeutic target. Subsequently, we demonstrated that FOS disruption and inhibition sensitized LA tumors to treatment. RNA-seq profiling demonstrated that FOS depletion in LOC388942-ALK tumor significantly downregulated multiple oncogenic pathways related to cell cycle progression, DNA replication fidelity, and extracellular matrix remodeling, suggesting a pivotal role of FOS in maintaining tumor growth. These findings establish LOC388942-ALK as a novel oncogenic driver in lung cancer, highlighting its role in tumor growth and ALK inhibitor resistance. Targeting FOS may provide a promising therapeutic strategy for tumors harboring this intergenic fusion.

Identification of lesion demarcation during thoracoscopic anatomical lesion resection is fundamental for treating children with congenital lung malformation. Existing lesion demarcations do not always meet the needs of clinical practice. This study aimed to explore the safety and efficacy of near-infraredfluorescence imaging with nebulized inhalation of indocyanine green for thoracoscopic anatomical lesion resection in children with congenital lung malformation. Under the fluorescence scope, the area of uniform green fluorescence was produced when indocyanine green was distributed into normal lung tissue, and lesions showed little or no green fluorescence, thus delineating a clear fluorescent lesion demarcation. Under the guidance of fluorescent demarcation, all the patients except one case of extralobar sequestration underwent thoracoscopic anatomical lesion resection successfully.

Background: Alveolar regeneration represents a critical research direction in respiratory disease treatment. Despite the surge in studies following the COVID-19 pandemic, comprehensive bibliometric analysis to systematically evaluate global research trends and future directions remains lacking. Methods: This study employed bibliometric methodology to analyze 1564 publications related to alveolar regeneration from 1974 to 2024 using the Web of Science Core Collection database. Data visualization and analysis were conducted using VOSviewer (version 1.6.19), CiteSpace (version 6.2.R3), and the biblioshiny R package. Results: The analysis encompassed 68 countries, 1930 institutions, and 9150 researchers across 658 journals. The United States leads with 601 publications and 32,172 citations, with Harvard University as the most influential institution. The American Journal of Respiratory and Critical Care Medicine has the highest impact factor (19.3), while the American Journal of Physiology-Lung Cellular and Molecular Physiology has the most co-citations (2,402). Edward E. Morrisey is the most prolific author, and C. E. Barkauskas has the highest co-citations. Keyword analysis revealed six major research clusters: stem cells and regenerative medicine, acute lung injury and fibrosis, COVID-19-related research, chronic lung disease repair, cellular behavior and molecular mechanisms, and post-pneumonectomy regeneration. Thematic mapping indicates future research should prioritize lung injury repair mechanisms, matrix environment in tissue regeneration, stem cell therapeutics, and immune regulation in lung injury repair. Conclusion: This first comprehensive 50-year bibliometric analysis of alveolar regeneration reveals the evolutionary trend from basic mechanistic exploration toward clinical translational applications, providing important reference for researchers and funding agencies.

The ultimate goal of enhanced recovery after surgery (ERAS) is to achieve risk-free and pain-free care. It is necessary in establishing perioperative comfort-oriented wards for medical technology advancement and economic development. This article discusses the clinical practices of comfort-oriented wards at the Lung Cancer Center of West China Hospital, Sichuan University and focuses on the following aspects: concept, framework, and team-building; current clinical application status, challenges, and implementation strategies; analysis of related construction models and plans; and clinical outcomes and future prospects. This work aims to promote a shift in the ERAS evaluation system toward a patient-centered concept and the application of comfort-oriented wards.