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Aims: This study aims to assess whether consensus clustering, based on computed tomography (CT) radiomics from both intratumoral and peritumoral regions, can effectively stratify the risk of non-small cell lung cancer (NSCLC) patients and predict their postoperative recurrence-free survival (RFS)., Materials and Methods: A retrospective analysis was conducted on the data of surgical patients diagnosed with NSCLC between December 2014 and April 2020. After preprocessing CT images, radiomic features were extracted from a 9-mm region encompassing both the tumor and its peritumoral area. Consensus clustering was utilized to analyze the radiomics features and categorize patients into distinct clusters. A comparison of the differences in clinical pathological characteristics was conducted among the clusters. Kaplan-Meier survival analysis was employed to investigate differences in survival among the clusters., Results: A total of 266 patients were included in this study, and consensus clustering identified three clusters (Cluster 1: n=111, Cluster 2: n=61, Cluster 3: n=94). Multiple clinical risk factors, including pathological TNM staging, programmed cell death ligand 1 (PD-L1), and epidermal growth factor receptor (EGFR) expression status exhibit significant differences among the three clusters. Kaplan-Meier survival analysis demonstrated significant variations in RFS across the clusters (P<0.001). The 3-year cumulative recurrence-free survival rates were 76.5% (95% CI: 68.6-84.4) for Cluster 1, 45.9% (95% CI: 33.4-58.4) for Cluster 2, and 41.5% (95% CI: 31.6-51.5) for Cluster 3., Conclusions: Consensus clustering of CT radiomics based on intratumoral and peritumoral regions can stratify the risk of postoperative recurrence in patients with NSCLC., (Copyright © 2024 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

Aims: This study aimed to predict the expression of programmed death-1 (PD-1) in non-small cell lung cancer (NSCLC) using intratumoral and peritumoral computed tomography (CT) radiomics nomogram., Materials and Methods: Two hundred patients pathologically diagnosed with NSCLC from two hospitals were retrospectively analyzed. Of these, 159 NSCLC patients from our hospital were randomly divided into a training cohort (n=96) and an internal validation cohort (n=63) at a ratio of 6:4, while 41 NSCLC patients from another medical institution served as the external validation cohort. The radiomic features of the gross tumor volume (GTV) and peritumoral volume (PTV) were extracted from the CT images. Optimal radiomics features were selected using least absolute shrinkage and selection operator regression analysis. Finally, a CT radiomics nomogram of clinically independent predictors combined with the best rad-score was constructed., Results: Compared with the 'GTV' and 'PTV' radiomics models, the combined 'GTV + PTV' radiomics model showed better predictive performance, and its area under the curve (AUC) values in the training, internal validation, and external validation cohorts were 0.90 (95% confidence interval [CI]: 0.83-0.97), 0.85 (95% CI: 0.74-0.96) and 0.78 (95% CI: 0.63-0.92). The nomogram constructed by the rad-score of the 'GTV + PTV' radiomics model combined with clinical independent predictors (prealbumin and monocyte) had the best performance, with AUC values in each cohort being 0.92 (95% CI: 0.85-0.98), 0.88 (95% CI: 0.78-0.97), and 0.80 (95% CI: 0.66-0.94), respectively., Conclusion: The intratumoral and peritumoral CT radiomics nomogram may facilitate individualized prediction of PD-1 expression status in patients with NSCLC., (Copyright © 2024 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

Aims: In response to the COVID-19 pandemic, guidelines on reduced fractionation for patients treated with curative-intent radiotherapy were published, aimed at reducing the number of hospital attendances and potential exposure of vulnerable patients to minimise the risk of COVID-19 infection. We describe the changes that took place in the management of patients with stage I-III lung cancer from April to October 2020., Materials and Methods: Lung Radiotherapy during the COVID-19 Pandemic (COVID-RT Lung) is a prospective multicentre UK cohort study. The inclusion criteria were: patients with stage I-III lung cancer referred for and/or treated with radical radiotherapy between 2nd April and 2nd October 2020. Patients who had had a change in their management and those who continued with standard management were included. Data on demographics, COVID-19 diagnosis, diagnostic work-up, radiotherapy and systemic treatment were collected and reported as counts and percentages. Patient characteristics associated with a change in treatment were analysed using multivariable binary logistic regression., Results: In total, 1553 patients were included (median age 72 years, 49% female); 93 (12%) had a change to their diagnostic investigation and 528 (34%) had a change to their treatment from their centre's standard of care as a result of the COVID-19 pandemic. Age ≥70 years, male gender and stage III disease were associated with a change in treatment on multivariable analysis. Patients who had their treatment changed had a median of 15 fractions of radiotherapy compared with a median of 20 fractions in those who did not have their treatment changed. Low rates of COVID-19 infection were seen during or after radiotherapy, with only 21 patients (1.4%) developing the disease., Conclusions: The COVID-19 pandemic resulted in changes to patient treatment in line with national recommendations. The main change was an increase in hypofractionation. Further work is ongoing to analyse the impact of these changes on patient outcomes., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: The purpose of this study was to investigate the correlations of hsa&#95;circ&#95;0046264 expression with the onset, pathological stage, and chemotherapy resistance of lung cancer., Patients and Methods: Firstly, gene expression profiling microarrays were applied to screen the differentially expressed circular ribonucleic acids (circRNAs) in the tumor tissues of patients with non-small cell lung cancer (NSCLC). Secondly, quantitative Reverse Transcription-Polymerase Chain Reaction (RT-qPCR) assay was adopted to further verify the circRNAs with significant differences. Thirdly, the correlations of hsa&#95;circ&#95;0046264 expression level with the clinical features of NSCLC patients were explored via statistical analysis. Fourthly, Kaplan-Meier survival analysis and receiver operating characteristic (ROC) curve were utilized to investigate the influence of hsa&#95;circ&#95;0046264 expression level on the survival of the patients. Finally, the role of hsa&#95;circ&#95;0046264 in the process of lung cancer was probed using in vitro experimental methods., Results: It was shown in the results of gene microarray assay that hsa&#95;circ&#95;0046264 was the most prominently upregulated gene, and RT-qPCR assay further proved that hsa&#95;circ&#95;0046264 expression was upregulated remarkably in the tissues of tumor patients. Clinical analysis indicated that the expression level of hsa&#95;circ&#95;0046264 was notably associated with the patient's age, tumor size, tumor-node-metastasis (TNM) stage, and lymph node metastasis (p<0.01). In addition, Kaplan-Meier statistical analysis manifested that the patients in hsa&#95;circ&#95;0046264 low-expression group had a markedly longer survival than those in hsa&#95;circ&#95;0046264 high-expression group. In the tumor tissues and serum of the patients, the area under ROC curve of hsa&#95;circ&#95;0046264 was 0.971 and 0.915, the specificity was 0.973 and 0.957, and the sensitivity was 0.951 and 0.927, while the Youden Index was 0.924 and 0.884 respectively. The results of Cell Counting Kit-8 (CCK-8) assay revealed that the proliferative ability of lung cancer A549 cells was significantly enhanced at 36, 48, and 72 h in hsa&#95;circ&#95;0046264 overexpression group. According to the results of wound-healing assay, the migratory ability of A549 cells was distinctly strengthened in hsa&#95;circ&#95;0046264 overexpression group compared with that in the control group (p<0.05). Moreover, the transwell assay results pointed out that the invasive ability of A549 cell lines at 48 h after overexpression of hsa&#95;circ&#95;0046264 was evidently stronger than that in control group (p<0.05). Under the stimulation of different doses of cisplatin, hsa&#95;circ&#95;0046264 overexpression group had a clearly raised survival rate of A549 cells in comparison with control group, and the differences in data were statistically significant (p<0.01)., Conclusions: Hsa&#95;circ&#95;0046264 may serve as a potential biomarker for the diagnosis and prognosis and a possible therapeutic target of lung cancer.

Objective: To explore the safety and therapeutic effect of programmed death 1 (PD-1) antibody combined with chemotherapy as a neoadjuvant therapy for patients with stage Ⅱ to Ⅲ non-small cell lung cancer (NSCLC). Methods: Thirteen patients, who had been diagnosed as stage Ⅱ-Ⅲ NSCLC and received PD-1 inhibitor plus chemotherapy as a neoadjuvant treatment in National Cancer Center/Cancer Hospital were recruited. The patients received consecutive neoadjuvant chemotherapy for 21 days as a cycle and the therapeutic efficacy was evaluated after two cycles. Results: At the last time of follow-up on December 2, 2019, the objective response rate (ORR) and disease control rate (DCR) of these patients were 61.5% (95% CI 30.9%-92.1%) and 100%, respectively. The downregulation rate of disease stage was 61.5% (8/13). The resectable rate was 38.5% (5/13), among them, the major pathologic response (MPR) was 60.0% (3/5) and the complete pathologic response (CPR) was 20.0% (1/5). The neoadjuvant chemotherapy displayed a low incidence of adverse reaction. The main grade 3 to 4 toxicities were neutropenia (38.5%) and leukopenia (23.1%). There was no significant immune-related toxicity. The safety and tolerability of perioperative period of patients underwent resection were promising. Conclusions: Immunotherapy combined with chemotherapy as a neoadjuvant treatment is an effective, low-toxicity treatment manner, which has perioperative safety and high rate of MPR for patients with resectable NSCLC. It is a promising treatment option for patients with stage Ⅱ to Ⅲ NSCLC.

Objective: Adenosquamous carcinoma of lung is an uncommon subtype with more aggressive behavior and poor prognosis than adenocarcinoma and squamous cell carcinoma. This study was aimed to investigate the clinicopathological characteristics and prognostic factors of lung adenosquamous carcinoma. Methods: The pathological features and follow-up data of 133 patients were collected and the prognostic factors of these patients were retrospectively analyzed. Results: Among the 133 patients, 81 cases (60.9%) smoked. Among the 62 patients whose percentage of histological components were identified, 45 cases had >50% adenocarcinoma components, and 17 cases had >50% squamous cell carcinoma components. 55 patients had lymph node metastasis at the first visit. All patients accepted at least one test of tumor driven gene mutation, and the results showed that the mutation rate of EGFR was 50.8% (67/132), the mutation rate of K-ras was 8.6% (11/128), the ALK-positive rate was 4.2% (2/48). The gender, smoking status, and the proportion of pathological components were the main influence factors of EGFR mutation status. The median overall survival was 28 months, the rates of 1-year, 3-year, and 5-year survival were 72.9%, 23.3%, and 9.0%, respectively. EGFR tyrosine kinase inhibitors (TKIs) treatment was an independent risk factor for prognose of these patients ( P =0.024). Conclusions: Lung adenosquamous carcinoma is a rare subtype with high malignancy and poor prognosis. Early diagnosis and driven-mutation-based individualized therapy may improve the survival of patients with lung adenosquamous carcinoma.

Objective: To investigate the efficacy of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) on patients with lung adenosquamous carcinoma, and to analyze relative factors. Methods: From August 2007 to July 2017, 40 patients who were pathologically diagnosed as lung adenosquamous carcinoma in our hospital and received EGFR TKIs treatment were retrospectively analyzed. All patients underwent EGFR mutation detection, resulted in 11 wild type, 13 19Del, 13 21L858R mutations, and 3 uncommon EGFR mutations in 20 exon and 19/21 complex mutation. A higher frequency of EGFR mutation was found in non-smokers and patients with adenocarcinoma components over 50.0%. Results: Twenty-six (65.0%) patients had disease progression after EGFR TKIs treatment, with a median progression-free survival (PFS) of 5.5 months (95% CI 0.52-10.49 months). A total of 20 (50.0%) patients died with an median overall survival (OS) of 15 months (95% CI 11.03-18.97 months). Multivariate analysis showed that gender, age, smoking, histopathological subtypes, EGFR mutations, and brain metastasis had no influence on PFS (all P >0.05). Gender, age, smoking, histopathological subtypes, and the presence of brain metastasis during TKI treatment had no influence on OS ( P >0.05), while EGFR mutation is the only influencing factor of OS ( P <0.05) in the current study. Conclusions: EGFR TKIs had modest efficacy in lung adenosquamous carcinoma, especially in patients with EGFR mutation. Based on the pathological features, EGFR mutation and EGFR TKIs treatment should be introduced into the routine clinical practice to improve the survival of patients with lung adenosquamous carcinoma.

Gemcitabine is a chemotherapeutic drug widely used in the treatment of non-small cell lung carcinoma, especially in advanced lung adenocarcinoma. However, many patients with advanced lung adenocarcinoma show a resistance to gemcitabine. Overexpression of COX-2 has been found in human non-small cell lung cancer tissues and itA s cell lines. Evidences show that COX-2 is involved in drug resistance of tumor. However, It is unknown whether COX-2 inhibitor can augment the efficacy of gemcitabine against lung adenocarcinoma. In this study, A549 cells were treated with gemcitabine and/or NS-398. The cell viability was examined by MTT assay. The cell cycle distribution and apoptotic ratio were tested by flow cytometry. The levels of p21WAF1, p27KIP1, p16INK4a and p15INK4b expression were detected by western blotting. After the cells were treated with gemcitabine along with NS-398, more cells were arrested in G1 phase and went to apoptosis. The levels of p21WAF1 and p27KIP1 protein were elevated, while the levels of p16INK4a and p15INK4b protein were not changed. It can be concluded that NS-398 enhances the efficacy of gemcitabine against lung adenocarcinoma and the efficacy is associated with up-regulation of p21WAF1 and p27KIP1protein.

Multistage modeling incorporating a time-dependent exposure pattern is applied to lung cancer mortality data obtained from a cohort of 2802 arsenic-exposed copper-smelter workers who worked 1 or more years during the period 1940-1964 at a copper smelter at Tacoma, Washington. The workers were followed for death through 1976. There were 100 deaths due to lung cancer during the follow-up period. Exposures to air arsenic levels measured in micrograms/m3 were estimated from departmental air arsenic and workers urinary arsenic measurements. Relationships of different temporal variables with excess death rates are examined to judge qualitatively the implications of the multistage cancer process. Analysis to date indicates a late stage effect of arsenic although an additional early stage effect cannot be ruled out.