Guillain-Barré Syndrome Following Lung Adenocarcinoma Surgery: A Case Report and Literature Review.

BACKGROUND Guillain-Barre syndrome (GBS) is a rare immune-mediated peripheral nerve disorder. Among non-infectious factors, surgery has been identified as a potential trigger of the disease. This report presents the case of a 74-year-old man who developed GBS 15 days after a right lower lobectomy for lung adenocarcinoma. CASE REPORT We present a case of a patient who was a former smoker who underwent uniportal video-assisted (U-VATS) right lower lobectomy for localized lung adenocarcinoma. Fifteen days after surgery, he exhibited bilateral lower-limb weakness, widespread paresthesia, and postural instability. Comprehensive diagnostic workup, including clinical assessment, serological tests, cerebrospinal fluid (CSF) analysis, and nerve conduction studies (NCS), confirmed the diagnosis. Notably, CSF analysis revealed albumin-cytological dissociation, with albumin 453.2 mg/L, protein 757 mg/L, glucose 67 mg/dl, 3 white blood cells (WBC)/uL, and polymorphonucleates (PMN) 33%. NCS demonstrated motor and sensory abnormalities. Prompt administration of intravenous immunoglobulins (IVIG) 2 g/kg daily for 5 days resulted in complete recovery within 3 months. CONCLUSIONS This case emphasizes the importance of prompt recognition and management of GBS as a postoperative complication. Neurological examination, neuroimaging, and electrophysiological studies are essential for accurate diagnosis. IVIG therapy remains a cornerstone in GBS management, with favorable outcomes observed in this case. Enhanced awareness among clinicians about the potential association between surgery and GBS is vital to prevent more serious complications and ensure optimal patient management. Further research is crucial to determine the precise pathogenesis and mechanisms of GBS following lung surgery.

[Effect of glucocorticoids on the efficacy of non-small cell lung cancer patients treated with immune-checkpoint inhibitors].

Lung cancer is a highly lethal malignant tumor worldwide and in China, with non-small cell lung cancer (NSCLC) accounting for approximately 85% of cases globally. In recent years, immune checkpoint inhibitor (ICI) had changed the paradigm of lung cancer treatment, either alone or in combination with chemotherapy and recomended as the first-line treatment for NSCLC. NSCLC patients often required glucocorticoid(GC) due to the cancer itself, tumor complications, or immune-related adverse event (irAE). GC had sparked debates on their impact on the therapeutic effectiveness of ICI in NSCLC patients as a substance with immunomodulatory effects. While some studies suggested that GC use did not influence patients survival, others argued the opposite. Understanding the effects of GC on immunotherapy is crucial for managing complaications in cancer patients and addressing irAE. This review explores the impact of GC on the efficacy of ICI in NSCLC patients, aiming to provide insights for clinical treatment.

Efficacy and safety analysis of anlotinib in combination with immune checkpoint inhibitors for second-line and subsequent extensive-stage small-cell lung cancer.

Currently, there is a lack of effective second-line and subsequent treatments for patients with extensive-stage small-cell lung cancer (ES-SCLC), and the establishment of a standardized treatment protocol is still underway. Considering the potential synergistic therapeutic effects of anti-angiogenic drugs and immune checkpoint inhibitors (ICIs), combination therapy could be a viable option for treating lung cancer. This research concentrates on assessing the efficacy and safety of anlotinib in combination with ICIs for the treatment of ES-SCLC. We undertook a retrospective analysis of patients with extensive-stage SCLC who received anlotinib in combination with ICIs as second-line and subsequent treatment at Zhejiang Cancer Hospital between April 2020 and April 2023. Survival rates were analyzed using the Kaplan-Meier method. Among the 43 patients who received combination therapy, there were no cases of complete response (CR), 16 patients who achieved partial response (PR), 21 patients who had stable disease (SD), and 6 patients who experienced disease progression (PD). This resulted in an overall response rate (ORR) of 37.2% (16/43) and a disease control rate (DCR) of 86.0% (34/43). The median progression-free survival (PFS) was 4.0 months (95% CI: 2.74-5.26), and the median overall survival (OS) time was 10 months (95% CI: 4.8-15.2). Cox multifactorial regression analysis disclosed that the performance score (PS) and the number of metastatic organs were independent factors influencing PFS in ES-SCLC (p<0.001). The combination therapy demonstrated acceptable toxicity, with a total grade 3/4 toxicity rate of 30.2%. The combination therapy showed a notable association with several adverse events, including hand-foot syndrome, hypertension, and fatigue, which were the most significant. Combining anlotinib with immune checkpoint inhibitors has demonstrated favorable efficacy and safety in the treatment of second-line and subsequent extensive-stage small-cell lung cancer.

Silencing of lncRNA LOC105376794 promotes migration, invasion, and Gefitinib resistance of lung adenocarcinoma cells with EGFR 19Del mutation by ATF4/CHOP axis and ERK phosphorylation.

Epidermal growth factor receptor (EGFR) gene exon 19 in-frame deletion (19del) and exon 21 L858R point mutation (21L858R mutation) are prevalent mutations in lung adenocarcinoma. Lung adenocarcinoma patients with 19del presented with a better prognosis than the 21L858R mutation under the same epidermal growth factor receptor tyrosine kinase inhibitor treatment. Our study aimed to uncover the expression of long non-coding RNA LOC105376794 between 19del and 21L858R mutation, and explore the mechanism that regulates cells' biological behavior and gefitinib sensitivity in lung adenocarcinoma cells with 19del. Transcriptome sequencing was conducted to identify differentially expressed lncRNAs between EGFR 19del and 21L858R mutation in serum through the DNBSEQ Platform. Protein-protein interaction network and Kyoto Encyclopedia of Genes and Genomes pathway were conducted to analyze the relationship between lncRNAs and mRNAs through STRING and Dr. TOM. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to measure the expression of lncRNA LOC105376794 in serum and cells. Loss-of-function experiments were used to validate the biological function and gefitinib sensitivity of LOC105376794 in lung adenocarcinoma cells. Protein levels were detected by western blotting. Through transcriptome resequencing and RT-qPCR, we found the expression levels of LOC105376794 in serum were increased in the 19del group compared with the 21L858R mutation group. Inhibition of LOC105376794 promoted proliferation, migration and invasion, and reduced apoptosis of HCC827 and PC-9 cells. The low expression of LOC105376794 reduced gefitinib sensitivity in PC-9 cells. Mechanistically, we found that the knockdown of LOC105376794 suppressed activating transcription factor 4 (ATF4)/C/EBP homologous protein (CHOP) signaling pathway and facilitated the expression of extracellular signal-regulated kinase 1/2 (ERK) phosphorylation. LOC105376794 altered cell biological behavior and gefitinib sensitivity of lung adenocarcinoma cells with 19del through the ATF4/CHOP signaling pathway and the expression of ERK phosphorylation. The results further illustrated the fact that lung adenocarcinoma patients with 19del presented with a more favorable clinical outcome and provided a theoretical basis for treatment strategy for lung adenocarcinoma patients with 19del.

Lower Income, Smoking, Cardiopulmonary Comorbidities, and Higher Symptom Burden Influence the Occurrence of Cough in Patients Receiving Chemotherapy.

OBJECTIVES: To identify subgroups of patients with distinct cough occurrence profiles and evaluate for differences among these subgroups. SAMPLE & SETTING: Outpatients receiving chemotherapy (N = 1,338) completed questionnaires six times over two chemotherapy cycles. METHODS & VARIABLES: Occurrence of cough was assessed using the Memorial Symptom Assessment Scale. Latent class analysis was used to identify subgroups with distinct cough occurrence profiles. Parametric and nonparametric tests were used to evaluate for differences. RESULTS: Four distinct cough profiles were identified (None, Decreasing, Increasing, and High). Risk factors associated with membership in the High class included lower annual household income; history of smoking; self-reported diagnoses of lung disease, heart disease, and back pain; and having lung cancer. IMPLICATIONS FOR NURSING: Clinicians need to assess all patients with cancer for cough and provide targeted interventions.

Tilianin enhances the antitumor effect of sufentanil on non-small cell lung cancer.

Non-small cell cancer (NSCLC) is the most common cancer in the world, but its effective therapeutic methods are limited. Tilianin and sufentanil alleviate various human tumors. This research aimed to clarify the functions and mechanisms of Tilianin and sufentanil in NSCLC. The functions of Tilianin and sufentanil on NSCLC cell viability, apoptosis, mitochondrial dysfunction, and immunity in vitro were examined using Cell Counting Kit-8 assay, flow cytometry, reactive oxygen species level analysis, CD8+ T cell percentage analysis, Western blot, and enzyme-linked immunosorbent assay, respectively. The molecular mechanism regulated by Tilianin and sufentanil in NSCLC was assessed using Western blot, and immunofluorescence assays. Meanwhile, the roles of Tilianin and sufentanil in NSCLC tumor growth, apoptosis, and immunity in vivo were determined by establishing a tumor xenograft mouse model, immunohistochemistry, and Western blot assays. When sufentanil concentration was proximity 2 nM, the inhibition rate of NSCLC cell viability was 50%. The IC50 for A549 cells was 2.36 nM, and the IC50 for H1299 cells was 2.18 nM. The IC50 of Tilianin for A549 cells was 38.7 µM, and the IC50 of Tilianin for H1299 cells was 44.6 µM. Functionally, 0.5 nM sufentanil and 10 µM Tilianin reduced NSCLC cell (A549 and H1299) viability in a dose-dependent manner. Also, 0.5 nM sufentanil and 10 µM Tilianin enhanced NSCLC cell apoptosis, yet this impact was strengthened after a combination of Tilianin and Sufentanil. Furthermore, 0.5 nM sufentanil and 10 µM Tilianin repressed NSCLC cell mitochondrial dysfunction and immunity, and these impacts were enhanced after a combination of Tilianin and Sufentanil. Mechanistically, 0.5 nM sufentanil and 10 µM Tilianin repressed the NF-κB pathway in NSCLC cells, while this repression was strengthened after a combination of Tilianin and Sufentanil. In vivo experimental data further clarified that 1 µg/kg sufentanil and 10 mg/kg Tilianin reduced NSCLC growth, immunity, and NF-κB pathway-related protein levels, yet these trends were enhanced after a combination of Tilianin and Sufentanil. Tilianin strengthened the antitumor effect of sufentanil in NSCLC.

Reinforcement learning for individualized lung cancer screening schedules: A nested case-control study.

BACKGROUND: The current guidelines for managing screen-detected pulmonary nodules offer rule-based recommendations for immediate diagnostic work-up or follow-up at intervals of 3, 6, or 12 months. Customized visit plans are lacking. PURPOSE: To develop individualized screening schedules using reinforcement learning (RL) and evaluate the effectiveness of RL-based policy models. METHODS: Using a nested case-control design, we retrospectively identified 308 patients with cancer who had positive screening results in at least two screening rounds in the National Lung Screening Trial. We established a control group that included cancer-free patients with nodules, matched (1:1) according to the year of cancer diagnosis. By generating 10,164 sequence decision episodes, we trained RL-based policy models, incorporating nodule diameter alone, combined with nodule appearance (attenuation and margin) and/or patient information (age, sex, smoking status, pack-years, and family history). We calculated rates of misdiagnosis, missed diagnosis, and delayed diagnosis, and compared the performance of RL-based policy models with rule-based follow-up protocols (National Comprehensive Cancer Network guideline; China Guideline for the Screening and Early Detection of Lung Cancer). RESULTS: We identified significant interactions between certain variables (e.g., nodule shape and patient smoking pack-years, beyond those considered in guideline protocols) and the selection of follow-up testing intervals, thereby impacting the quality of the decision sequence. In validation, one RL-based policy model achieved rates of 12.3% for misdiagnosis, 9.7% for missed diagnosis, and 11.7% for delayed diagnosis. Compared with the two rule-based protocols, the three best-performing RL-based policy models consistently demonstrated optimal performance for specific patient subgroups based on disease characteristics (benign or malignant), nodule phenotypes (size, shape, and attenuation), and individual attributes. CONCLUSIONS: This study highlights the potential of using an RL-based approach that is both clinically interpretable and performance-robust to develop personalized lung cancer screening schedules. Our findings present opportunities for enhancing the current cancer screening system.

Acceptability of adding a non-contrast abdominal CT scan to screen for kidney cancer and other abdominal pathology within a community-based CT screening programme for lung cancer: A qualitative study.

OBJECTIVES: The Yorkshire Kidney Screening Trial (YKST) is a feasibility study of adding non-contrast abdominal CT scanning to screen for kidney cancer and other abdominal malignancies to community-based CT screening for lung cancer within the Yorkshire Lung Screening Trial (YLST). This study explored the acceptability of the combined screening approach to participants and healthcare professionals (HCPs) involved in the trial. METHODS: We conducted semi-structured interviews with eight HCPs and 25 participants returning for the second round of scanning within YLST, 20 who had taken up the offer of the additional abdominal CT scan and five who had declined. Transcripts were analysed using thematic analysis, guided by the Theoretical Framework of Acceptability. RESULTS: Overall, combining the offer of a non-contrast abdominal CT scan alongside the low-dose thoracic CT was considered acceptable to participants, including those who had declined the abdominal scan. The offer of the additional scan made sense and fitted well within the process, and participants could see benefits in terms of efficiency, cost and convenience both for themselves as individuals and also more widely for the NHS. Almost all participants made an instant decision at the point of initial invitation based more on trust and emotions than the information provided. Despite this, there was a clear desire for more time to decide whether to accept the scan or not. HCPs also raised concerns about the burden on the study team and wider healthcare system arising from additional workload both within the screening process and downstream following findings on the abdominal CT scan. CONCLUSIONS: Adding a non-contrast abdominal CT scan to community-based CT screening for lung cancer is acceptable to both participants and healthcare professionals. Giving potential participants prior notice and having clear pathways for downstream management of findings will be important if it is to be offered more widely.

Pulmonary Capillary Hemangiomatosis as a Rare Underlying Cause of Primary Pulmonary Hypertension: A Case Report in an Adolescent.

Despite its rarity, pulmonary capillary hemangiomatosis (PCH) presents a significant diagnostic challenge. Due to its similarity to other pulmonary vascular diseases, such as pulmonary veno-occlusive disease, it is characterized by abnormal pulmonary capillary proliferation, which is a rare cause of primary pulmonary hypertension. This case was the first reported instance of PCH in Shahid Rajaee Heart Hospital in Tehran, Iran, in 2023, which was confirmed by genetic testing. It highlighted the importance of considering PCH among the differential diagnoses for pulmonary hypertension, even in adolescent patients. The 13-year-old patient's main complaints were progressive exertional dyspnea and chest pain. He had no previous medical history and had not taken any pharmaceutical or herbal medications. Critical clinical findings included a heart murmur, an electrocardiogram revealing right ventricular hypertrophy, and echocardiogram evidence of pulmonary hypertension. The main diagnosis was PCH, as shown by CT findings of pulmonary artery dilatation and diffuse nodular ground glass opacities. Genetic tests indicated pathogenic EIF2AK4 mutations and suspicion of PCH. Therapeutic intervention included vasodilator therapy, which exacerbated the patient's condition. This case emphasized the importance of maintaining a high index of suspicion for rare causes of pulmonary hypertension, such as PCH. The outcome was to prepare the patient for lung transplantation. To differentiate PCH from other pulmonary vascular diseases, a combination of clinical presentation, radiologic studies, genetic analysis, and response to treatment is required to determine appropriate management, particularly lung transplantation.

CD161+CD127+CD8+ T cell subsets can predict the efficacy of anti-PD-1 immunotherapy in non-small cell lung cancer with diabetes mellitus.

The role of CD161+CD127+CD8+ T cells in non-small cell lung cancer (NSCLC) patients with diabetes remains unexplored. This study determined the prevalence, phenotype, and function of CD8+ T cell subsets in NSCLC with diabetes. We recruited NSCLC patients (n = 436) treated with anti-PD-1 immunotherapy as first-line treatment. The progression-free survival (PFS), overall survival (OS), T cells infiltration, and peripheral blood immunological characteristics were analyzed in NSCLC patients with or without diabetes. NSCLC patients with diabetes exhibited shorter PFS and OS (p = 0.0069 and p = 0.012, respectively) and significantly lower CD8+ T cells infiltration. Mass cytometry by time-of-flight (CyTOF) showed a higher percentage of CD161+CD127+CD8+ T cells among CD8+T cells in NSCLC with diabetes before anti-PD-1 treatment (p = 0.0071) than that in NSCLC without diabetes and this trend continued after anti-PD-1 treatment (p = 0.0393). Flow cytometry and multiple-immunofluorescence confirmed that NSCLC with diabetes had significantly higher CD161+CD127+CD8+ T cells to CD8+T cells ratios than NSCLC patients without diabetes. The RNA-sequencing analysis revealed immune-cytotoxic genes were reduced in the CD161+CD127+CD8+ T cell subset compared to CD161+CD127-CD8+ T cells in NSCLC with diabetes. CD161+CD127+CD8+ T cells exhibited more T cell-exhausted phenotypes in NSCLC with diabetes. NSCLC patients with diabetes with ≥ 6.3% CD161+CD127+CD8+ T cells to CD8+T cells ratios showed worse PFS. These findings indicate that diabetes is a risk factor for NSCLC patients who undergo anti-PD-1 immunotherapy.CD161+CD127+CD8+ T cells could be a key indicator of a poor prognosis in NSCLC with diabetes. Our findings would help in advancing anti-PD-1 therapy in NSCLC patients with diabetes.

Candidate tumor-specific CD8+ T cell subsets identified in the malignant pleural effusion of advanced lung cancer patients by single-cell analysis.

Isolation of tumor-specific T cells and their antigen receptors (TCRs) from malignant pleural effusions (MPE) may facilitate the development of TCR-transduced adoptive cellular immunotherapy products for advanced lung cancer patients. However, the characteristics and markers of tumor-specific T-cells in MPE are largely undefined. To this end, to establish the phenotypes and antigen specificities of CD8+ T cells, we performed single-cell RNA and TCR sequencing of samples from three advanced lung cancer patients. Dimensionality reduction on a total of 4,983 CD8+ T cells revealed 10 clusters including naïve, memory, and exhausted phenotypes. We focused particularly on exhausted T cell clusters and tested their TCR reactivity against neoantigens predicted from autologous cancer cell lines. Four different TCRs specific for the same neoantigen and one orphan TCR specific for the autologous cell line were identified from one of the patients. Differential gene expression analysis in tumor-specific T cells relative to the other T cells identified CXCL13, as a candidate gene expressed by tumor-specific T cells. In addition to expressing CXCL13, tumor-specific T cells were present in a higher proportion of T cells co-expressing PDCD1(PD-1)/TNFRSF9(4-1BB). Furthermore, flow cytometric analyses in advanced lung cancer patients with MPE documented that those with high PD-1/4-1BB expression have a better prognosis in the subset of 57 adenocarcinoma patients (p = .039). These data suggest that PD-1/4-1BB co-expression might identify tumor-specific CD8+ T cells in MPE, which are associated with patients' prognosis. (233 words).

Clinical investigation of former workers exposed to asbestos: the health surveillance experience of an Italian University Hospital.

Background: The need for health surveillance of former workers exposed to asbestos was provided by law in Italy after the asbestos ban in 1992. Objectives: We describe the results of the health surveillance of former workers exposed to asbestos, conducted over 27 years, from 1994 to 2020, at the Operative Unit of Occupational Medicine of the University Hospital of Bari. Materials and methods: We adopted the health surveillance protocol, which was validated at the national level in 2018. Results: A total of 1,405 former workers exposed to asbestos were examined. We proceeded with diagnosing pathologies in 339 cases (24% of the cohort subjected to surveillance), with diagnoses of some cases involving multiple pathologies. Specifically, pleural plaques were diagnosed in 49.2% of the 339 cases, asbestosis in 35.9%, malignant pleural mesothelioma (MPM) in 20.3%, mesothelioma of the vaginal tunic of the testis (MTVT) in 9.1%, lung cancer in 5.8%, and laryngeal cancer in 0.8%. Conclusion: Despite the 1992 asbestos ban, asbestos-related diseases remain a serious public health issue. It is important to establish criteria that ensure the health surveillance of formerly exposed workers minimizes costs, reduces the number of invasive examinations, and optimizes achievable results.

Feline lung-digit syndrome: A differential diagnosis for shifting, waxing and waning lameness in a cat.

The clinical presentation, cytologic findings, radiographic findings, and postmortem assessment of a cat with primary pulmonary adenocarcinoma with multiple digital metastasis are described. An unusual shifting, waxing and waning pattern of lameness, suspected to be an early manifestation of digital metastasis before any gross lesions were visible, was documented. Initial cytologic finding of a lung nodule was equivocal for diagnosis of neoplasia despite being strongly suspicious. Palliative management was short-lived, with rapid progression culminating in widespread metastasis to multiple digits, muscles, and other organs. The diagnosis of pulmonary adenocarcinoma was confirmed via necropsy and histopathology. Key clinical message: This case report highlights that feline lung-digit syndrome is an important differential diagnosis for an acute, waxing and waning, shifting leg lameness in an older cat. This pattern of lameness should raise the index of suspicion for an underlying primary lung neoplasm, and thoracic imaging (radiographs) should be considered.

Syndrome pulmonaire-digital félin : un diagnostic différentiel des boiteries changeantes, croissantes et décroissantes chez un chatLa présentation clinique, les résultats cytologiques, les résultats radiographiques et l'évaluation post mortem d'un chat atteint d'adénocarcinome pulmonaire primaire avec métastases numériques multiples sont décrits. Un schéma inhabituel de boiterie, variable, croissante et décroissante, suspecté d'être une manifestation précoce de métastases digitales avant que des lésions macroscopiques ne soient visibles, a été documenté. La découverte cytologique initiale d'un nodule pulmonaire était équivoque pour le diagnostic de néoplasie bien qu'elle soit fortement suspecte. La prise en charge palliative a été de courte durée, avec une progression rapide aboutissant à des métastases généralisées à plusieurs doigts, muscles et autres organes. Le diagnostic d'adénocarcinome pulmonaire a été confirmé par autopsie et histopathologie.Message clinique clé :Ce rapport de cas souligne que le syndrome pulmonaire-digital félin est un diagnostic différentiel important pour une boiterie aiguë, croissante et décroissante et mobile des pattes chez un chat ágé. Ce type de boiterie devrait faire suspecter une tumeur primaire du poumon sous-jacente, et une imagerie thoracique (radiographies) devrait être envisagée.(Traduit par Dr Serge Messier).

The rapidly changing field of predictive biomarkers of non-small cell lung cancer.

Lung cancer is a leading cause of cancer-related death worldwide in both men and women, however mortality in the US and EU are recently declining in parallel with the gradual cut of smoking prevalence. Consequently, the relative frequency of adenocarcinoma increased while that of squamous and small cell carcinomas declined. During the last two decades a plethora of targeted drug therapies have appeared for the treatment of metastasizing non-small cell lung carcinomas (NSCLC). Personalized oncology aims to precisely match patients to treatments with the highest potential of success. Extensive research is done to introduce biomarkers which can predict the effectiveness of a specific targeted therapeutic approach. The EGFR signaling pathway includes several sufficient targets for the treatment of human cancers including NSCLC. Lung adenocarcinoma may harbor both activating and resistance mutations of the EGFR gene, and further, mutations of KRAS and BRAF oncogenes. Less frequent but targetable genetic alterations include ALK, ROS1, RET gene rearrangements, and various alterations of MET proto-oncogene. In addition, the importance of anti-tumor immunity and of tumor microenvironment has become evident recently. Accumulation of mutations generally trigger tumor specific immune defense, but immune protection may be upregulated as an aggressive feature. The blockade of immune checkpoints results in potential reactivation of tumor cell killing and induces significant tumor regression in various tumor types, such as lung carcinoma. Therapeutic responses to anti PD1-PD-L1 treatment may correlate with the expression of PD-L1 by tumor cells. Due to the wide range of diagnostic and predictive features in lung cancer a plenty of tests are required from a single small biopsy or cytology specimen, which is challenged by major issues of sample quantity and quality. Thus, the efficacy of biomarker testing should be warranted by standardized policy and optimal material usage. In this review we aim to discuss major targeted therapy-related biomarkers in NSCLC and testing possibilities comprehensively.

A Visual Analysis of the Research Dynamics in Resistance to EGFR Inhibitors for NSCLC.

Purpose: Activating mutations in epidermal growth factor receptor (EGFR) have been identified as key predictive biomarkers for the customized treatment with EGFR tyrosine kinase inhibitors (TKIs) in non-small cell lung cancer (NSCLC), aiding in improving patient response rates and survival. However, resistance challenges the efficacy of these treatments, with limited understanding of post-resistance therapeutic strategies. A deep understanding of the biology and resistance mechanisms of EGFR-mutant NSCLC is crucial for developing new treatment approaches. This study, through bibliometric analysis, summarizes the trends in research on resistance to EGFR-TKIs. Methods: Research papers on NSCLC with EGFR inhibitor resistance were collected from the Web of Science Core Collection (WoSCC). The analysis utilized bibliometric tools like CiteSpace, VOSviewer, and other platforms for comprehensive analysis and visualization of the outcomes. Results: The WoSCC database contains a total of 5866 documents on resistance to EGFR-TKIs treatment, including 4727 articles (93.48%) and 1139 reviews (6.52%), spanning 81 countries and regions, 4792 institutions, with the involvement of 23,594 authors. Since 2016, there has been a significant increase in publications in this field. China has the highest publication output, while the United States has the highest citation count for papers. Harvard University leads in terms of the number of publications. Among the top ten journals with the highest output, Clinical Cancer Research has the highest impact factor at 11.5, with 90% of the journals classified in Q1 or Q2. Rafael Rosell is one of the most influential authors in this field, ranking second in publication volume and fourth in citation count. Research on EGFR-TKIs resistance mainly focuses on genetic testing, resistance mechanisms, and post-resistance treatment strategies. Conclusion: This study provides researchers with a reliable basis and guidance for finding authoritative references, understanding research trends, and exploring potential directions.

Intrathoracic Lymph Node Microcalcifications are Associated With a High Prevalence of Malignancy and Anaplastic Lymphoma Kinase Rearrangement: The "Calce" Study.

BACKGROUND: Microcalcifications are acknowledged as a malignancy risk factor in multiple cancers. However, the prevalence and association of intrathoracic lymph node (ILN) calcifications with malignancy remain unexplored. METHODS: In this cross-sectional study, we enrolled patients with known/suspected malignancy and an indication for endosonography for diagnosis or ILN staging. We assessed the prevalence and pattern of calcified ILNs and the prevalence of malignancy in ILNs with and without calcifications. In addition, we evaluated the genomic profile and PD-L1 expression in lung cancer patients, stratifying them based on the presence or absence of ILN calcifications. RESULTS: A total of 571 ILNs were sampled in 352 patients. Calcifications were detected in 85 (24.1%) patients and in 94 (16.5%) ILNs, with microcalcifications (78/94, 83%) being the predominant type. Compared with ILNs without calcifications (214/477, 44.9%), the prevalence of malignancy was higher in ILNs with microcalcifications (73/78, 93.6%; P<0.0001) but not in those with macrocalcifications (7/16, 43.7%; P=0.93). In patients with lung cancer, the high prevalence of metastatic involvement in ILNs displaying microcalcifications was independent of lymph node size (< or >1 cm) and the clinical stage (advanced disease; cN2/N3 disease; cN0/N1 disease). The anaplastic lymphoma kinase (ALK) rearrangement was significantly more prevalent in patients with than in those without calcified ILNs (17.4% vs. 1.7%, P<0.001), and all of them exhibited microcalcifications. CONCLUSION: ILN microcalcifications are common in patients undergoing endosonography for suspected malignancy, and they are associated with a high prevalence of metastatic involvement and ALK rearrangement.

Role of drug-eluting bead bronchial arterial chemoembolisation in the treatment of non-small cell lung cancer: protocol for a meta-analysis.

BACKGROUND: Non-small cell lung cancer (NSCLC) has a poor prognosis. Transvascular intervention is an important approach for treating NSCLC. Drug-eluting bead bronchial artery chemoembolisation (DEB-BACE) is a technique of using DEBs loaded with chemotherapeutic drugs for BACE. This study aims to conduct a meta-analysis to comprehensively assess the effectiveness and safety of DEB-BACE in treating NSCLC and investigate a novel therapeutic strategy for NSCLC. METHODS AND ANALYSIS: Wanfang, China National Knowledge Infrastructure, Medline (via PubMed), Cochrane Library, Scopus and Embase databases will be searched in November 2024. A meta-analysis will be conducted to assess the effectiveness and safety of DEB-BACE in the treatment of NSCLC. The following keywords will be applied: "Carcinoma, Non-Small-Cell Lung", "Non-Small Cell Lung Cancer", "Drug-Eluting Bead Bronchial Arterial Chemoembolization" and "drug-eluting beads". Reports in Chinese or English comparing the efficacy of DEB-BACE with other NSCLC treatment options will be included. Case reports, single-arm studies, conference papers, abstracts without full text and reports published in languages other than English and Chinese will not be considered. The Cochrane Handbook for Systematic Reviews of Interventions will be used to independently assess the risk of bias for each included study. In case of significant heterogeneity between studies, possible sources of heterogeneity will be explored through subgroup and sensitivity analysis. For the statistical analysis of the data, RevMan V.5.3 will be used. ETHICS AND DISSEMINATION: This meta-analysis will seek publication in a peer-reviewed journal on completion. Ethical approval is not required for this study as it is a database-based study. PROSPERO REGISTRATION NUMBER: CRD42023411392.

A systematic review and dose-response meta-analysis of prospective cohort studies on coffee consumption and risk of lung cancer.

Studies on the association between coffee consumption and risk of lung cancer have been conflicting. The aim of this study was to systematically review the current evidence on the association between coffee consumption and risk of lung cancer and to quantify this association by performing a meta-analysis. A comprehensive systematic search was performed on online databases up to July 2023 investigating the association between coffee consumption and risk of lung cancer. All prospective cohort studies reporting odds ratios (ORs), rate or risk ratios (RRs), or hazard ratios (HRs) and 95% confidence intervals (CIs) in this context were included. The overall effect size was calculated using the random-effects model and statistical between-studies heterogeneity was examined using Cochrane's Q test and I2. A total of 14 prospective cohort studies were included in this systematic review and meta-analysis. We found a significant positive association between coffee consumption and risk of lung cancer (RR: 1.28; 95% CI: 1.12, 1.47). This association remained significant when we included a pooled analysis paper and excluded 5 cohort studies (RR: 1.37; 95% CI: 1.12, 1.66). We observed no proof of significant publication bias using Egger's test (P = 0.58). Moreover, dose-response analysis showed that each one cup/day increase in coffee consumption was related with a 6% higher lung cancer risk (RR: 1.06; 95% CI: 1.03, 1.09). In conclusion, we found a significant positive association between coffee consumption and risk of lung cancer.

Machine learning identifies prognostic subtypes of the tumor microenvironment of NSCLC.

The tumor microenvironment (TME) plays a fundamental role in tumorigenesis, tumor progression, and anti-cancer immunity potential of emerging cancer therapeutics. Understanding inter-patient TME heterogeneity, however, remains a challenge to efficient drug development. This article applies recent advances in machine learning (ML) for survival analysis to a retrospective study of NSCLC patients who received definitive surgical resection and immune pathology following surgery. ML methods are compared for their effectiveness in identifying prognostic subtypes. Six survival models, including Cox regression and five survival machine learning methods, were calibrated and applied to predict survival for NSCLC patients based on PD-L1 expression, CD3 expression, and ten baseline patient characteristics. Prognostic subregions of the biomarker space are delineated for each method using synthetic patient data augmentation and compared between models for overall survival concordance. A total of 423 NSCLC patients (46% female; median age [inter quantile range]: 67 [60-73]) treated with definite surgical resection were included in the study. And 219 (52%) patients experienced events during the observation period consisting of a maximum follow-up of 10 years and median follow up 78 months. The random survival forest (RSF) achieved the highest predictive accuracy, with a C-index of 0.84. The resultant biomarker subtypes demonstrate that patients with high PD-L1 expression combined with low CD3 counts experience higher risk of death within five-years of surgical resection.

Advancing neoadjuvant therapies in resectable non-small cell lung cancer: implications for novel treatment strategies and biomarker discovery.

The delivery of neoadjuvant and perioperative therapies for non-small cell lung cancer has been radically altered by significant advances and by the incorporation of targeted therapies as well as immune checkpoint inhibitors alone or alongside conventional chemotherapy. This evolution has been particularly notable in the incorporation of immunotherapy and targeted therapy into the treatment of resectable NSCLC, where recent FDA approvals of drugs such as nivolumab and pembrolizumab, in combination with platinum doublet chemotherapy, have led to considerable improvements in pathological complete response rates and the potential for enhanced long-term survival outcomes. This review emphasizes the growing importance of biomarkers in optimizing treatment selection and explores the impact of emerging studies that challenge existing treatment paradigms and investigate novel therapeutic combinations poised to redefine standard of care practices. Furthermore, the discussion extends to the unmet needs within perioperative treatment assessment and prognostication, highlighting the prospective value of biomarkers in evaluating treatment responses and prognosis.