BACKGROUND: Immune checkpoint inhibitors (ICIs), including those targeting PD-1, are currently used in a wide range of tumors, but only 20-40% of patients achieve clinical benefit. The objective of our study was to find predictive peripheral blood-based biomarkers for ICI treatment. METHODS: In 41 patients with advanced malignant melanoma (MM) and NSCLC treated with PD-1 inhibitors, we analyzed peripheral blood-based immune subsets by flow cytometry before treatment initialization and the second therapy dose. Specifically, we assessed basic blood differential count, overall T cells and their subgroups, B cells, and myeloid-derived suppressor cells (MDSC). In detail, CD4 + and CD8 + T cells were assessed according to their subtypes, such as central memory T cells (TCM), effector memory T cells (TEM), and naïve T cells (TN). Furthermore, we also evaluated the predictive value of CD28 and ICOS/CD278 co-expression on T cells. RESULTS: Patients who achieved disease control on ICIs had a significantly lower baseline proportion of CD4 + TEM (p = 0.013) and tended to have a higher baseline proportion of CD4 + TCM (p = 0.059). ICI therapy-induced increase in Treg count (p = 0.012) and the proportion of CD4 + TN (p = 0.008) and CD28 + ICOS- T cells (p = 0.012) was associated with disease control. Patients with a high baseline proportion of CD4 + TCM and a low baseline proportion of CD4 + TEM showed significantly longer PFS (p = 0.011, HR 2.6 and p ˂ 0.001, HR 0.23, respectively) and longer OS (p = 0.002, HR 3.75 and p ˂ 0.001, HR 0.15, respectively). Before the second dose, the high proportion of CD28 + ICOS- T cells after ICI therapy initiation was significantly associated with prolonged PFS (p = 0.017, HR 2.51) and OS (p = 0.030, HR 2.69). Also, a high Treg count after 2 weeks of ICI treatment was associated with significantly prolonged PFS (p = 0.016, HR 2.33). CONCLUSION: In summary, our findings suggest that CD4 + TEM and TCM baselines and an early increase in the Treg count induced by PD-1 inhibitors and the proportion of CD28 + ICOS- T cells may be useful in predicting the response in NSCLC and MM patients.

• MeSH
• Inducible T-Cell Co-Stimulator Protein metabolism   MeSH
• Programmed Cell Death 1 Receptor antagonists & inhibitors   MeSH
• CD28 Antigens MeSH
• CD8-Positive T-Lymphocytes immunology   drug effects   metabolism   MeSH
• Adult MeSH
• Immune Checkpoint Inhibitors * therapeutic use   pharmacology   MeSH
• Middle Aged MeSH
• Humans MeSH
• Melanoma * drug therapy   immunology   blood   pathology   MeSH
• Lung Neoplasms * drug therapy   immunology   blood   pathology   MeSH
• Carcinoma, Non-Small-Cell Lung * drug therapy   immunology   blood   pathology   MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

PURPOSE: We report CNS efficacy of first-line osimertinib plus chemotherapy versus osimertinib monotherapy in patients with epidermal growth factor receptor (EGFR)-mutated advanced non-small-cell lung cancer (NSCLC) from the phase III FLAURA2 study according to baseline CNS metastasis status. METHODS: Patients were randomly assigned to osimertinib plus platinum-pemetrexed (combination) or osimertinib monotherapy until disease progression or discontinuation. Brain scans were performed in all patients at baseline and progression and at scheduled assessments until progression for patients with baseline CNS metastases; scans were assessed by neuroradiologist CNS blinded independent central review (BICR). RESULTS: On the basis of baseline CNS BICR, 118 of 279 (combination) and 104 of 278 (monotherapy) randomly assigned patients had ≥one measurable and/or nonmeasurable CNS lesion and were included in the CNS full analysis set (cFAS); 40 of 118 and 38 of 104 had ≥one measurable target CNS lesion and were included in the post hoc CNS evaluable-for-response set (cEFR). In the cFAS, the hazard ratio (HR) for CNS progression or death was 0.58 (95% CI, 0.33 to 1.01). In patients without baseline CNS metastases, the HR for CNS progression or death was 0.67 (95% CI, 0.43 to 1.04). In the cFAS, CNS objective response rates (ORRs; 95% CI) were 73% (combination; 64 to 81) versus 69% (monotherapy; 59 to 78); 59% versus 43% had CNS complete response (CR). In the cEFR, CNS ORRs (95% CI) were 88% (73 to 96) versus 87% (72 to 96); 48% versus 16% had CNS CR. CONCLUSION: Osimertinib plus platinum-pemetrexed demonstrated improved CNS efficacy compared with osimertinib monotherapy, including delaying CNS progression, irrespective of baseline CNS metastasis status. These data support this combination as a new first-line treatment for patients with EGFR-mutated advanced NSCLC, including those with CNS metastases.

• MeSH
• Acrylamides * MeSH
• Aniline Compounds therapeutic use   MeSH
• ErbB Receptors genetics   MeSH
• Indoles * MeSH
• Protein Kinase Inhibitors therapeutic use   MeSH
• Humans MeSH
• Mutation MeSH
• Central Nervous System Neoplasms * diagnostic imaging   drug therapy   genetics   MeSH
• Lung Neoplasms * drug therapy   genetics   pathology   MeSH
• Carcinoma, Non-Small-Cell Lung * drug therapy   genetics   pathology   MeSH
• Pemetrexed therapeutic use   MeSH
• Platinum therapeutic use   MeSH
• Pyrimidines * MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Clinical Trial, Phase III MeSH
• Randomized Controlled Trial MeSH

BACKGROUND/AIM: Cemiplimab in patients with non-small cell lung cancer (NSCLC) with PD-L1 (programmed death ligand type 1) expression ≥50% showed a significant improved overall survival (OS) with increasing expression of PD-L1. To our knowledge there exist no similar data published for pembrolizumab regarding the increased OS in relation to the PD-L1 expression. Therefore, the objective of our study was to determine whether improvement in OS reflects increased expression levels of PD-L1 (≥50%) in patients with NSCLC. PATIENTS AND METHODS: Retrospective data from 9 Czech and 1 Polish comprehensive oncology Centers were used. All patients with stage IV NSCLC and PD-L1 expression ≥50% treated with pembrolizumab in daily practice were included. The groups of patients according to the expression of PD-L1 were determined as follows: PD-L1 50-59%, 60-69%, 70-79%, 80-89% and 90-100%. The log-rank test and the Cox regression model were used to compare survival between study groups. RESULTS: A total of 617 patients were included in the study. We did not observe a statistically significant difference in OS between groups of patients with different levels of PD-L1 expression in the pooled comparison (p=0.445). Furthermore, we did not observe a statistically significant difference even when comparing OS in patients with PD-L1expression of 50-59% (reference) with the group of other patients according to the level of expression of PD-L1 in the Cox regression model including the effect covariates. CONCLUSION: PD-L1 expression showed no significant effect on OS in patients with NSCLC with PD-L1≥50% treated with pembrolizumab.

• MeSH
• B7-H1 Antigen * metabolism   genetics   MeSH
• Adult MeSH
• Antibodies, Monoclonal, Humanized * therapeutic use   MeSH
• Middle Aged MeSH
• Humans MeSH
• Biomarkers, Tumor metabolism   MeSH
• Lung Neoplasms * drug therapy   mortality   metabolism   pathology   genetics   MeSH
• Carcinoma, Non-Small-Cell Lung * drug therapy   mortality   metabolism   pathology   genetics   MeSH
• Prognosis MeSH
• Antineoplastic Agents, Immunological therapeutic use   MeSH
• Retrospective Studies MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Neoplasm Staging MeSH
• Treatment Outcome MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

Circular RNAs (circRNAs) have played an essential role in cancer development. This study aimed to illustrate the impact and potential mechanism of circRACGAP1 action in NSCLC development. The expression patterns of circRACGAP1, miR-1296, and CDK2 in NSCLC tissues and cell lines were analysed by RT-qPCR. The function of circRACGAP1 in NSCLC cell proliferation and apoptosis was investigated using the CCK-8 assay, flow cytometry, TUNEL staining, and Western blot. The interaction among circRACGAP1, miR-1296, and CDK2 was clarified by dual-luciferase reporter assay while the correlation was confirmed by the Pearson correlation coefficient. The expression of circRACGAP1 and CDK2 was up-regulated in NSCLC tissues, while the expression of miR-1296 was down-regulated. Cell function studies further revealed that circRACGAP1 could promote NSCLC cell proliferation, accelerate the cell cycle process, up-regulate B-cell lymphoma 2 (Bcl2) expression, and down-regulate Bcl2-associated X (Bax) expression. miR-1296 was identified as a downstream target to reverse circRACGAP1-mediated cell proliferation. miR-1296 directly targeted the 3'-UTR of CDK2 to regulate proliferation and apoptosis of NSCLC cells. Additionally, the dual-luciferase reporter assay and Pearson correlation coefficient analysis proved that circRACGAP1 acted in NSCLC cells by negatively regulating miR-1296 expression and positively regulating CDK2 expression. In summary, our study revealed that circRACGAP1 promoted NSCLC cell proliferation by regulating the miR-1296/CDK2 pathway, providing potential diagnostic and therapeutic targets for NSCLC.

• MeSH
• Apoptosis * genetics   MeSH
• Cyclin-Dependent Kinase 2 * metabolism   genetics   MeSH
• RNA, Circular * genetics   metabolism   MeSH
• Humans MeSH
• MicroRNAs * genetics   metabolism   MeSH
• Cell Line, Tumor MeSH
• Lung Neoplasms * genetics   pathology   metabolism   MeSH
• Carcinoma, Non-Small-Cell Lung * genetics   pathology   metabolism   MeSH
• Cell Proliferation * genetics   MeSH
• GTPase-Activating Proteins genetics   metabolism   MeSH
• Gene Expression Regulation, Neoplastic MeSH
• Signal Transduction genetics   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH

DNA ligase 1 (LIG1) plays a key role in DNA synthesis and DNA damage repair pathways. LIG1 has been shown to be up-regulated in human non-small cell lung cancer (NSCLC); however, its role and molecular regulatory mechanism in NSCLC cell proliferation are still not fully understand. In this study, we aimed to explore the role of LIG1 and post-transcripional regulators in NSCLC. Utilizing bioinformatic tools and qRT-PCR, our investigation substantiated the up-regulation of LIG1 within NSCLC cell lines and tumour tissues. Remarkably, individuals exhibiting elevated levels of LIG1 had diminished survival rates. Functionally, the depletion of LIG1 inhibited cell proliferation and migration, contrasting with the increased proliferation and migration upon LIG1 over-expression. Prediction from the TargetScanHuman database and results of dual luciferase reporter assays indicated that miR-325 could directly bind to and negatively regulate LIG1. Moreover, our findings demonstrated that the mimicry of miR-325 decreased cell viability, whereas its inhibition correspondingly increased viability, indicative of the tumour-suppressive role of miR-325 through the down-regulation of LIG1. Collectively, our findings show that LIG1 could promote tumour progression and knockdown of LIG1 could exert suppressive effects on NSCLC. As the post-transcriptional factor of LIG1, miR-325 could negatively regulate the expression of LIG1 to inhibit tumour progression in vitro. These findings suggest that LIG1 and miR-325 might be potential therapeutic targets for NSCLC treatment.

• MeSH
• DNA Ligase ATP * metabolism   genetics   MeSH
• Humans MeSH
• MicroRNAs * genetics   metabolism   MeSH
• Cell Line, Tumor MeSH
• Lung Neoplasms * pathology   genetics   metabolism   MeSH
• Carcinoma, Non-Small-Cell Lung * genetics   pathology   metabolism   MeSH
• Cell Movement * MeSH
• Cell Proliferation * MeSH
• Gene Expression Regulation, Neoplastic MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

PURPOSE: Recent papers suggested a correlation between the risk of distant metastasis (DM) and dose outside the PTV, though conclusions in different publications conflicted. This study resolves these conflicts and provides a compelling explanation of prognostic factors. MATERIALS AND METHODS: A dataset of 478 NSCLC patients treated with SBRT (IMRT or VMAT) was analyzed. We developed a deep learning model for DM prediction and explainable AI was used to identify the most significant prognostic factors. Subsequently, the prognostic power of the extracted features and clinical details were analyzed using conventional statistical methods. RESULTS: Treatment technique, tumor features, and dosiomic features in a 3 cm wide ring around the PTV (PTV3cm) were identified as the strongest predictors of DM. The Hazard Ratio (HR) for Dmean,PTV3cm was significantly above 1 (p < 0.001). There was no significance of the PTV3cm dose after treatment technique stratification. However, the dose in PTV3cm was found to be a highly significant DM predictor (HR > 1, p = 0.004) when analyzing only VMAT patients with small and spherical tumors (i.e., sphericity > 0.5). CONCLUSIONS: The main reason for conflicting conclusions in previous papers was inconsistent datasets and insufficient consideration of confounding variables. No causal correlation between the risk of DM and dose outside the PTV was found. However, the mean dose to PTV3cm can be a significant predictor of DM in small spherical targets treated with VMAT, which might clinically imply considering larger PTV margins for smaller, more spherical tumors (e.g., if IGTV > 2 cm, then margin ≤ 7 mm, else margin > 7 mm).

• MeSH
• Radiotherapy Dosage * MeSH
• Deep Learning * MeSH
• Middle Aged MeSH
• Humans MeSH
• Neoplasm Metastasis MeSH
• Lung Neoplasms * pathology   radiotherapy   MeSH
• Carcinoma, Non-Small-Cell Lung * radiotherapy   pathology   MeSH
• Radiotherapy Planning, Computer-Assisted methods   MeSH
• Prognosis MeSH
• Radiosurgery * methods   MeSH
• Radiotherapy, Intensity-Modulated methods   MeSH
• Aged MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

BACKGROUND: Adjuvant therapy with durvalumab, with or without tremelimumab, may have efficacy in patients with limited-stage small-cell lung cancer who do not have disease progression after standard concurrent platinum-based chemoradiotherapy. METHODS: In a phase 3, double-blind, randomized, placebo-controlled trial, we assigned patients to receive durvalumab at a dose of 1500 mg, durvalumab (1500 mg) plus tremelimumab at a dose of 75 mg (four doses only), or placebo every 4 weeks for up to 24 months. Randomization was stratified according to disease stage (I or II vs. III) and receipt of prophylactic cranial irradiation (yes vs. no). Results of the first planned interim analysis of the two primary end points of overall survival and progression-free survival (assessed on the basis of blinded independent central review according to the Response Evaluation Criteria in Solid Tumors, version 1.1) with durvalumab as compared with placebo (data cutoff date, January 15, 2024) are reported; results in the durvalumab-tremelimumab group remain blinded. RESULTS: A total of 264 patients were assigned to the durvalumab group, 200 to the durvalumab-tremelimumab group, and 266 to the placebo group. Durvalumab therapy led to significantly longer overall survival than placebo (median, 55.9 months [95% confidence interval {CI}, 37.3 to not reached] vs. 33.4 months [95% CI, 25.5 to 39.9]; hazard ratio for death, 0.73; 98.321% CI, 0.54 to 0.98; P = 0.01), as well as to significantly longer progression-free survival (median 16.6 months [95% CI, 10.2 to 28.2] vs. 9.2 months [95% CI, 7.4 to 12.9]; hazard ratio for progression or death, 0.76; 97.195% CI, 0.59 to 0.98; P = 0.02). The incidence of adverse events with a maximum grade of 3 or 4 was 24.4% among patients receiving durvalumab and 24.2% among patients receiving placebo; adverse events led to discontinuation in 16.4% and 10.6% of the patients, respectively, and led to death in 2.7% and 1.9%. Pneumonitis or radiation pneumonitis with a maximum grade of 3 or 4 occurred in 3.1% of the patients in the durvalumab group and in 2.6% of those in the placebo group. CONCLUSIONS: Adjuvant therapy with durvalumab led to significantly longer overall survival and progression-free survival than placebo among patients with limited-stage small-cell lung cancer. (Funded by AstraZeneca; ADRIATIC ClinicalTrials.gov number, NCT03703297.).

• MeSH
• Chemotherapy, Adjuvant adverse effects   MeSH
• Survival Analysis MeSH
• Chemoradiotherapy * adverse effects   MeSH
• Progression-Free Survival * MeSH
• Adult MeSH
• Double-Blind Method MeSH
• Antibodies, Monoclonal, Humanized * therapeutic use   adverse effects   MeSH
• Kaplan-Meier Estimate MeSH
• Cranial Irradiation adverse effects   MeSH
• Middle Aged MeSH
• Humans MeSH
• Small Cell Lung Carcinoma * drug therapy   mortality   MeSH
• Antibodies, Monoclonal * therapeutic use   adverse effects   MeSH
• Lung Neoplasms * drug therapy   mortality   pathology   therapy   MeSH
• Antineoplastic Agents, Immunological therapeutic use   adverse effects   MeSH
• Antineoplastic Combined Chemotherapy Protocols * therapeutic use   adverse effects   MeSH
• Aged MeSH
• Neoplasm Staging MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Clinical Trial, Phase III MeSH
• Multicenter Study MeSH
• Randomized Controlled Trial MeSH

OBJECTIVES: IMbrella A is a Phase III extension study that allowed rollover from Roche/Genentech-sponsored atezolizumab trials, including IMpower133, a Phase I/III trial of first-line atezolizumab or placebo plus carboplatin/etoposide in extensive-stage small cell lung cancer. We report outcomes from an exploratory analysis of IMpower133 with extended time-to-event data for patients who rolled over to IMbrella A. MATERIALS AND METHODS: IMpower133 patients could roll over to IMbrella A to receive atezolizumab 1200 mg intravenously every three weeks if they continued to receive atezolizumab at IMpower133 closure or were in survival follow-up after atezolizumab discontinuation. Overall survival and safety were assessed; only serious adverse events and AEs of special interest were collected in IMbrella A. RESULTS: Eighteen of 26 eligible patients rolled over to IMbrella A. At clinical cutoff (March 16, 2023), median follow-up in the atezolizumab plus carboplatin/etoposide arm (IMpower133 and IMbrella A) was 59.4 months. The three-, four-, and five-year overall survival (95 % CI) estimates were 16 % (11 %-21 %), 13 % (8 %-18 %), and 12 % (7 %-17 %), respectively. In IMbrella A, serious adverse events occurred in three patients (16.7 %), and one adverse event of special interest was reported (grade two hypothyroidism). CONCLUSION: This long-term analysis of patients from IMbrella A previously enrolled in IMpower133 provides the first report of five-year overall survival outcomes in patients with extensive-stage small cell lung cancer treated with first-line cancer immunotherapy and chemotherapy. While limited by small patient numbers and lack of long-term data for the IMpower133 control arm, exploratory overall survival analyses in patients treated with atezolizumab plus carboplatin/etoposide compared favorably with historical data with chemotherapy alone. NCT03148418.

• MeSH
• Adult MeSH
• Etoposide administration & dosage   therapeutic use   MeSH
• Antibodies, Monoclonal, Humanized * therapeutic use   administration & dosage   adverse effects   MeSH
• Carboplatin * administration & dosage   therapeutic use   MeSH
• Middle Aged MeSH
• Humans MeSH
• Small Cell Lung Carcinoma * drug therapy   mortality   pathology   MeSH
• Survival Rate MeSH
• Lung Neoplasms * drug therapy   mortality   pathology   MeSH
• Follow-Up Studies MeSH
• Antineoplastic Combined Chemotherapy Protocols * therapeutic use   adverse effects   MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Neoplasm Staging MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Clinical Trial, Phase III MeSH
• Multicenter Study MeSH
• Randomized Controlled Trial MeSH

A distinctive histological variant of poorly differentiated, sarcomatoid, non-small cell lung carcinoma characterized by a discohesive population of giant tumor cells associated with prominent interstitial inflammatory cell infiltrates is described. The tumors occurred in 7 women and 7 men, 42 to 72 years of age (mean: 56 y). They predominantly affected the upper lobes and measured 1.3 to 9 cm in greatest diameter (mean: 4.6 cm). The tumor cells were characterized by large pleomorphic nuclei with prominent nucleoli, ample cytoplasm, and frequent abnormal mitoses, and were surrounded by a dense inflammatory cell infiltrate, often associated with emperipolesis. Immunohistochemical stains were positive in the tumor cells for cytokeratin AE1/AE3 and CK8/18 and negative for TTF1, napsin A, p40, and CK5/6. Next-generation sequencing was performed in all cases using the Oncomine Precision Assay; the most common abnormalities found included TP53 mutations (9 cases) and AKT1 amplification (8 cases), followed by KRAS mutations (4 cases) and MAP2K1/2 mutations (4 cases). Clinical follow-up was available in 13 patients. Three patients presented with metastases as the initial manifestation of disease; 8 patients died of their tumors from 6 months to 8 years (mean: 2.7 y); 3 patients were alive and well from 4 to 6 years; and 2 patients had metastases when last seen but were lost to follow-up thereafter. The importance of recognizing this distinctive and aggressive variant of non-small cell lung carcinoma lies in avoiding confusion with a sarcoma or other types of malignancy.

• MeSH
• Adult MeSH
• Immunohistochemistry * MeSH
• Middle Aged MeSH
• Humans MeSH
• Mutation MeSH
• DNA Mutational Analysis MeSH
• Biomarkers, Tumor * genetics   analysis   MeSH
• Lung Neoplasms * genetics   pathology   chemistry   MeSH
• Carcinoma, Non-Small-Cell Lung genetics   pathology   mortality   MeSH
• Carcinoma, Giant Cell * pathology   genetics   chemistry   mortality   MeSH
• Predictive Value of Tests MeSH
• Aged MeSH
• High-Throughput Nucleotide Sequencing * MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

INTRODUCTION: Despite many technological advances, the diagnostic yield of bronchoscopic peripheral lung nodule analysis remains limited due to frequent mispositioning. Needle-based confocal laser endomicroscopy (nCLE) enables real-time microscopic feedback on needle positioning, potentially improving the sampling location and diagnostic yield. Previous studies have defined and validated nCLE criteria for malignancy, airway and lung parenchyma. Larger studies demonstrating the effect of nCLE on diagnostic yield are lacking. We aim to investigate if nCLE-imaging integrated with conventional bronchoscopy results in a higher diagnostic yield compared with conventional bronchoscopy without nCLE. METHODS AND ANALYSIS: This is a parallel-group randomised controlled trial. Recruitment is performed at pulmonology outpatient clinics in universities and general hospitals in six different European countries and one hospital in the USA. Consecutive patients with a for malignancy suspected peripheral lung nodule (10-30 mm) with an indication for diagnostic bronchoscopy will be screened, and 208 patients will be included. Web-based randomisation (1:1) between the two procedures will be performed. The primary outcome is diagnostic yield. Secondary outcomes include diagnostic sensitivity for malignancy, needle repositionings, procedure and fluoroscopy duration, and complications. Pathologists will be blinded to procedure type; patients and endoscopists will not. ETHICS AND DISSEMINATION: Primary approval by the Ethics Committee of the Amsterdam University Medical Center. Dissemination involves publication in a peer-reviewed journal. SUPPORT: Financial and material support from Mauna Kea Technologies. TRIAL REGISTRATION NUMBER: NCT06079970.

• MeSH
• Bronchoscopy * methods   MeSH
• Needles MeSH
• Microscopy, Confocal * methods   MeSH
• Humans MeSH
• Multicenter Studies as Topic MeSH
• Lung Neoplasms * pathology   diagnosis   diagnostic imaging   MeSH
• Lung pathology   diagnostic imaging   MeSH
• Randomized Controlled Trials as Topic MeSH
• Solitary Pulmonary Nodule * pathology   diagnostic imaging   diagnosis   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Multicenter Study MeSH
• Clinical Trial Protocol MeSH
• Randomized Controlled Trial MeSH