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Purpose: To evaluate the role of systemic arterial embolization for the management of non-emergent hemoptysis in patients with primary or metastatic lung tumors., Materials and Methods: This is a retrospective single center study of consecutive patients who underwent systemic arterial embolization for non-emergent hemoptysis between 2011 and 2023. Study endpoints included technical success, clinical success (partial or complete resolution of hemoptysis) and overall survival. Hemoptysis-free and overall survival were estimated using the Kaplan-Meier method. Predictive factors for hemoptysis-free survival and overall survival were evaluated using univariate analysis (Cox regression). Post-procedural 30-day adverse events were recorded in line with Common Terminology Criteria for Adverse Events (CTCAE) v5.0., Results: A total of 30 patients were identified. Technical success was achieved in 24/30 (80 %) patients. Clinical success following embolization was achieved in 23/30 (76.7 %) patients. Median length of hospitalization was 5 days (Range: 1 to 16 days). Median overall survival was 194 days (95 % CI: 89 to 258). Median hemoptysis-free survival was 286 days (95 % CI: 42 to not reached). No significant clinical or procedural predictors of hemoptysis-free survival or overall survival were identified. Serious adverse events (CTCAE Grade > 3) occurred in 1 patient (3.4 % - fatal respiratory failure)., Conclusion: Embolization of non-emergent hemoptysis in patients with lung malignancies is safe and effective. Recurrence is however high in this patient population, likely due to the nature of the underlying disease., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: E.A. is a paid consultant for Boston Scientific and reports leadership role in Society of Interventional Oncology. S.B.S. is a paid consultant for GE Healthcare, Merck and Obsidian; receives grants or contracts from GE Healthcare and Johnson & Johnson; and reports participation in data safety monitoring board of Candel Therapeutics and Impact Biotech, stock or stock options in Johnson & Johnson. E.Z. receives grant support from AACR-NETF, Memorial Sloan Kettering Cancer Center, Society of Interventional Radiology, Radiographic Society of North America, North American Neuroendocrine Tumor Society, Ethicon, Novartis and TOW Center., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Lung cancer is one of the main causes of cancer burden and death in China, with nearly 800,000 newly diagnosed lung cancer patients each year, nearly half of whom are lung adenocarcinoma (LUAD) patients. According to current clinical guidelines, surgery is the main treatment for stage I LUAD patients, but the 5-year overall survival rate of stage I LUAD patients alone is still unsatisfactory, about 73%-90%, indicating that a considerable number of patients require other means to improve survival benefits. Chemotherapy and targeted therapy have achieved great success in the treatment of locally advanced and metastatic LUAD patients, but there is still controversy over whether they can benefit stage I LUAD postoperative patients. Under the circumstances, many researchers have paid attention to this issue and made beneficial explorations. This review provides a brief review of the factors that affect the acceptance of adjuvant chemotherapy and targeted therapy in stage I LUAD postoperative patients, as well as the relevant clinical research on the application of adjuvant chemotherapy and targeted therapy in stage I LUAD postoperative patients, in order to gain a broader understanding of the latest developments in this field and find new breakthroughs to promote sustained research in this field.
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Angiogenesis, metastasis, and resistance to therapy are all facilitated by cancer-associated fibroblasts (CAFs). A CAF-based risk signature can be used to predict patients' prognoses for Lung adenocarcinoma (LUAD) based on CAF characteristics. The Gene Expression Omnibus (GEO) database was used to gather signal-cell RNA sequencing (scRNA-seq) data for this investigation. The GEO and TCGA databases were used to gather bulk RNA-seq and microarray data for LUAD. The scRNA-seq data were analyzed using the Seurat R program based on the CAF markers. Our goal was to use differential expression analysis to discover differentially expressed genes (DEGs) across normal and tumor samples in the TCGA dataset. Pearson correlation analysis was utilized to discover prognostic genes related with CAF, followed by univariate Cox regression analysis. Using Lasso regression, a risk signature based on CAF-related prognostic genes was created. A nomogram model was created based on the clinical and pathological aspects. 5 CAF clusters were identified in LUAD, 4 of which were associated with prognosis. From 2811 DEGs, 1002 genes were found to be significantly correlated with CAF clusters, which led to the creation of a risk signature with 8 genes. These 8 genes were primarily connected with 41 pathways, such as antigen paocessing and presentation, apoptosis, and cell cycle. Meanwhile, the risk signature was significantly associated with stromal and immune scores, as well as some immune cells. Multivariate analysis revealed that risk signature was an independent prognostic factor for LUAD, and its value in predicting immunotherapeutic outcomes was confirmed. A novel nomogram integrating the stage and CAF-based risk signature was constructed, which exhibited favorable predictability and reliability in the prognosis prediction of LUAD. CAF-based risk signatures can be effective in predicting the prognosis of LUAD, and they may provide new strategies for cancer treatments by interpreting the response of LUAD to immunotherapy., (© 2024. The Author(s).)

The objective is to assess the anti-inflammatory effect of Tao Hong Si Wu Tang combined with anti-PD-1 in a mouse model of COPD combined with lung cancer, elucidating its mechanism through modulation of PD-1/PD-L binding, regulation of Th1/Th2 and Th17/Treg balance, inhibition of IL-4 and IL-17, and promotion of IFN-γ and TGF-β levels in peripheral blood. One hundred male C57/BL6 mice were randomly allocated to five groups: A (blank control), B (model control), C (THSW), D (anti-PD-1), and E (THSW + anti-PD-1), with 20 mice in each group. The COPD model was induced using fumigation and LPS intra-airway drip, followed by the establishment of lung cancer by Lewis cell inoculation. Treatment groups received Tao Hong Si Wu Tang or/and PD-1 monoclonal antibody. Various indicators were assessed, including macroscopic observation, HE staining of lung tissue, ELISA for cytokines, flow cytometry for cell proportions, and immunohistochemistry/western blotting for protein expression. Lung tissue analysis revealed significant differences between groups, with marked tumor formation observed in groups B-E. Serum levels of IL-4, IFN-γ, IL-17, and TGF-β were significantly altered, along with changes in CD4 + T/CD8 + T ratio and cytokine-producing cell populations. Expression levels of key proteins were also significantly affected across treatment groups. Tao Hong Si Wu Tang demonstrated anti-inflammatory effects comparable to anti-PD-1, potentially through modulation of PD-1/PD-L binding, correction of Th1/Th2 and Th17/Treg imbalance, and modulation of cytokine levels. These findings suggest a role for Tao Hong Si Wu Tang in ameliorating inflammation and immune dysregulation in COPD combined with lung cancer., Competing Interests: Declarations Ethical Approval The ethics committee of Liaoning University of traditional Chinese medicine approved the animal experiments conducted in this study (21000042020071). Consent to Participate All authors have their consent to participate. Consent for Publication All authors have their consent to publish their work. Competing Interests The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: The purpose of this study was to analyze the independent risk factors of malignant subpleural pulmonary lesions (SPLs) on B-mode ultrasound (US) images, to construct the combined predictive indicators, and to prospectively verify their predictive efficacy., Methods: A total of 336 patients with SPLs were included in the prospective study, of whom the single-center included patients between September 2019 and December 2019 were the development cohort (DC) (n = 219); Patients who were concurrently enrolled in three centers between January and February 2020 were the validation cohort (VC) (n = 117). The clinical features and B-mode US parameters were collected. Based on the DC, a combined predictive indicators model was developed using binary logistic regression. Then the discrimination was verified externally in the VC. The reference criteria were from the comprehensive diagnosis of clinical-radiological-pathological made by two senior respiratory physicians., Results: The combined predictive indicators model was finally constructed by five parameters: age, borderline, angle between the lesion border and thoracic wall, posterior echo of the lesion and invasion of the pleura. The fitting degree of the model was good (χ 2 = 9.198, p = 0.326). The area under ROC curve of the model was 0.872 (DC) and 0.808 (VC), yielding a higher net benefit than individual risk factors., Conclusion: The combined predictive indicators are useful in the assessment of malignant SPLs and are a useful adjunct diagnostic tool, especially in primary healthcare settings in developing countries., Competing Interests: Conflict of interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this article., (Copyright © 2024. Published by Elsevier Inc.)

Background: There was limited research data on large-scale locally advanced non-small cell lung cancer (LA-NSCLC) radical radiotherapy (RT) reported in China. This study examined overall survival (OS), progression-free survival (PFS), treatment effectiveness, and toxicity in patients with LA-NSCLC treated with definitive RT in the pre-durvalumab era., Methods: A retrospective analysis of demographic information, clinical characteristics, treatment patterns, and clinical outcomes of 789 patients with LA-NSCLC who underwent radical RT at our center between January 2005 and December 2015 was performed. The Kaplan-Meier method and log-rank test were used for survival comparisons, and Cox regression was used for multivariate analysis., Results: There were 328 patients with stage IIIA disease and 461 with stage IIIB disease. By the last follow-up, there were 365 overall deaths and 576 cases of recurrence, metastasis, or death. The median survival time was 31 months. The OS rates at 1, 2, 5, and 10 years were 83.7%, 59.5%, 28.8%, and 18.9%, respectively. PFS rates at 1, 2, 5, and 10 years were 48%, 24.5%, 11.9%, and 5.5%, respectively. Rates of ≥grade 3 acute radiation pneumonitis or esophagitis were 7.6% and 1.9%, respectively. Rates of ≥grade 3 chronic radiation pneumonitis and esophagitis were 11% and 0.4%, respectively. Multivariate analysis showed that the Karnofsky Performance Status (KPS) score, smoking status, and combined chemotherapy were prognostic factors for OS (p < 0.05). Multivariate analysis revealed that combined chemotherapy and radiation dose were prognostic factors for PFS (p < 0.05)., Conclusions: Our center's data showed that the survival prognosis of locally advanced patients receiving RT and chemotherapy in China was consistent with international levels during the same period. Patients with a KPS score of 80 or higher, who had never smoked or received combined RT, had a more favorable prognosis than those with a KPS of less than 80, who had smoked, or only received RT. The combination of RT and chemotherapy, with a reasonable radiation dose, was the key to improving the therapeutic effect., (© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)

PM 2.5 pollution has been associated with the incidence of lung cancer, but the underlying mechanism is still unclear. PIWI-interacting RNAs (piRNAs), initially identified in germline cells, have emerged as a novel class of small non-coding RNAs (26 - 32 nucleotides) with diverse functions in various diseases, including cancer. However, the role and mechanism of piRNAs in the development of PM 2.5 -induced lung cancer remain to be clarified. In the presented study, we used a PM 2.5 -induced malignant transformation cell model to analyze the change of piRNA profiles. Among the disturbed piRNAs, piR-27222 was identified as an oncogene that inhibited cell death in a m 6 A-dependent manner. Mechanistically, we found that piR-27222 could deubiquitinate and stabilize eIF4B by directly binding to eIF4B and reducing its interaction with PARK2. The enhanced expression of eIF4B, in turn, promoted the expression of WTAP, leading to increased m 6 A modification in the Casp8 transcript. Consequently, the stability of Casp8 transcripts was reduced, rendering lung cancer cells resistant to PANoptosis. Collectively, our findings reveal that PM 2.5 exposure up-regulated piR-27222 expression, which could affect EIF4B/WTAP/m 6 A axis, thereby inhibiting PANoptosis of cells and promoting lung cancer. Our study provides new insights into understanding the epigenetic mechanisms underlining PM 2.5 -induced lung cancer., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objectives: Assess safety and efficacy of thermal ablation for adrenal metastases (AM) secondary to non-small cell lung cancer (NSCLC)., Materials and Methods: This retrospective study included patients with NSCLC AM treated with thermal ablation between 2/2010-11/2021. Local tumor progression free survival (LTPFS) and overall survival (OS) were calculated using Kaplan-Meier method. Adverse events were graded using Common Terminology Criteria for Adverse Events v5., Results: Seven patients (mean age ± SD, 63.9 ± 12.5 years; 6 males) with seven AM were treated in eight sessions. Retreatment was performed in one patient with residual disease. Five sessions were with microwave ablation and 3 with radiofrequency ablation. Mean tumor size was 20.1 ± 7.0 mm. Median number of ablation probes used was 1 (range, 1-5), with a median of 3 activations (range, 1-3), and average ablation time of 14.4 ± 15.0 minutes. Response based on RECIST v 1.1 or PERCIST criteria revealed stable disease in 1 tumor, progression of disease in 3 tumors (one was re-ablated), and partial response in 3 tumors. Median LTPFS was not reached (NR) [95 % CI: 1- NR]. Median OS was 47.97 months (95 % CI: 18.63- NR). Intraprocedural hypertension (blood pressure ≥180 mmHg) occurred during 5/8 (62.5 %) sessions and intraoperative tachycardia occurred during 2/8 (25 %) sessions. Complications within one month of ablation occurred in 3/8 (37.5 %) sessions: grade 2 pneumothorax, grade 1 hematuria, and grade 2 adrenal insufficiency., Conclusions: In this small series, thermal ablation for NSCLC AM resulted in prolonged local control and OS with no major complications., Competing Interests: Declaration of competing interest - Etay Ziv receives research grants from MSK, Druckenmiller, NETRF, AACR, NANETS, SIR, RSNA, Ethicon, and Novartis. - Stephen B. Solomon has received grants from GE healthcare, Elesta, and Johnson & Johnoson. He is a paid consultant for GE Healthcare, XACT, Endoways, Microbot, Varian, Merch, Orchestra Biomed, and MedX. He has stock options for Aperture Medical, Johnson & Johnson, and Lantheus. - Erica S. Alexander is a paid consultant of Boston Scientific. - The remaining authors have no conflicts to disclose., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

A dose-escalation and expansion, phase 1/2 study (ClinicalTrials.gov, NCT04818333) was conducted to assess the novel antibody-drug conjugate SHR-A1811 in pretreated HER2-altered advanced non-small cell lung cancer (NSCLC). Here, we report results from the phase 1 portion. Patients who had previously failed or were intolerant to platinum-based chemotherapy were enrolled and received SHR-A1811 intravenously at doses of 3.2 to 8.0 mg/kg every 3 weeks. Dose escalation followed a Bayesian logistic regression model that included overdose control, with subsequent selection of tolerable levels for dose expansion. Overall, 63 patients were enrolled, including 43 receiving a recommended dose for expansion of 4.8 mg/kg. All patients had HER2-mutant disease. Dose-limiting toxicity occurred in one patient in the 8.0 mg/kg dose cohort. Grade ≥ 3 treatment-related adverse events occurred in 29 (46.0%) patients. One patient in the 6.4 mg/kg cohort died due to interstitial lung disease. As of April 11, 2023, the 4.8 mg/kg cohort showed an objective response rate of 41.9% (95% CI 27.0-57.9), and a disease control rate of 95.3% (95% CI 84.2-99.4). The median duration of response was 13.7 months, with 13 of 18 responses ongoing. The median progression-free survival was 8.4 months (95% CI 7.1-15.0). SHR-A1811 demonstrated favourable safety and clinically meaningful efficacy in pretreated advanced HER2-mutant NSCLC., (© 2024. The Author(s).)

Thioredoxin reductases are frequently overexpressed in various solid tumors as a protective mechanism against heightened oxidative stress. Inhibitors of this system, such as Auranofin, are effective in eradicating cancer cells. However, the clinical significance of thioredoxin reductase 1 (TrxR1) in lung cancer, as well as the potential for its antagonist as a treatment option, necessitated further experimental validation. In this study, we observed significant upregulation of TrxR1 specifically in non-small cell lung cancer (NSCLC), rather than small cell lung cancer. Moreover, TrxR1 expression exhibited associations with survival rate, tumor volume, and histological classification. We developed a novel TrxR1 inhibitor named LW-216 and assessed its antitumor efficacy in NSCLC. Our results revealed that LW-216 is effectively bound with intracellular TrxR1 at sites R371 and G442, facilitating TrxR1 ubiquitination and suppressing TrxR1 expression, while not affecting TrxR2 expression. Treatment of LW-216-induced DNA damage and cell apoptosis in NSCLC cells through the generation of reactive oxygen species (ROS). Importantly, supplementation with N-acetylcysteine (NAC) or ectopic TrxR1 expression reversed LW-216-induced apoptosis. Furthermore, LW-216 displayed potent tumor growth inhibition in NSCLC cell-implanted mice, reducing TrxR1 expression in xenografts. Remarkably, LW-216 exhibited superior antitumor activity compared to Auranofin in vivo. Collectively, our research provides compelling evidence supporting the potential of targeting TrxR1 by LW-216 as a promising therapeutic strategy for NSCLC., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Objectives: The goal of this research is to pinpoint the top 100 most frequently referenced studies on sublobectomy for non-small cell lung cancer., Methods: We identified the top 100 most frequently referenced studies on sublobectomy for non-small cell lung cancer by searching the Web of Science database. We extracted key information from the selected studies, including the author, journal, impact factor, type of article, year of publication, country, organization, and keyword., Results: To the best of our understanding, this is the inaugural bibliometric study on sublobectomy for non-small cell lung cancer. The publication years of the top 100 most frequently referenced studies span from 1994 to 2022, with citation counts ranging from 51 to 795. The majority of the included studies are original (93/100) and primarily retrospective studies (82/93). The United States leads in terms of published articles and citations, with the Annals of Thoracic Surgery being the most frequently sourced journal (n = 27). High-density keywords primarily originate from limited resection, lobectomy, survival, carcinoma, recurrence, randomized trial, radiotherapy, lung cancer, outcome, 2 cm, as revealed by CiteSpace analysis., Conclusions: Our research compiles and analyzes the top 100 most frequently referenced studies in the field of sublobectomy for non-small cell lung cancer. The United States has the most published and cited works on this topic. Currently, the hot keywords for sublobectomy research are gradually shifting towards prognosis and obtaining better evidence-based medical evidence to demonstrate its value in the treatment of non-small cell lung cancer., (© 2024. The Author(s).)

Background: Pulmonary high-grade neuroendocrine carcinomas(pHGNEC) encompassing small cell lung cancer (SCLC) and large cell neuroendocrine carcinoma (LCNEC) are clinically aggressive tumors with poor prognosis. The role of surgery and prognostic factors guiding management remain unclear. We aimed to analyze prognosis following resection and identify predictive variables., Methods: This retrospective study analyzed 259 patients undergoing pHGNEC resection from 2001-2023. Overall survival (OS) and disease-free survival (DFS) were evaluated using Kaplan-Meier curves. Prognostic factors were assessed with Cox regression and visualized using nomogram tools., Results: Minimally invasive surgery was associated with better OS (p = 0.001) and DFS (p = 0.001). Higher T stage predicted worse OS (T2 p = 0.044, T4 p = 0.007) and DFS (T2 p = 0.020, T4 p = 0.004). Advanced TNM stage III (OS p = 0.018; DFS p = 0.015) and IV (OS p < 0.001; DFS p < 0.001) also correlated with poorer prognosis. In the SCLC subgroup, elevated preoperative CEA independently predicted worse OS (p = 0.012) and DFS (p = 0.004). T4 disease (OS p < 0.001; DFS p = 0.002) and advanced TNM staging (stage III OS p = 0.043; DFS p = 0.045; stage IV OS p < 0.001, DFS p < 0.001) were associated with worse outcomes. In LCNEC patients, VATS resection improved OS (p = 0.048) and DFS (p = 0.027) despite conversion. Prior malignancy predicted worse OS (p < 0.001). Advanced TNM disease (stage III OS p = 0.047; stage IV OS p = 0.003, DFS p = 0.005) were also negative prognostic factors. The prognostic nomogram incorporating above variables effectively stratified risk. Calibration plots revealed good correlation between predicted and actual survival., Conclusions: We identified minimally invasive surgery, early TNM stage, younger age, and normal preoperative CEA as positive prognostic factors following pHGNEC resection. Our study provides an applicable prognostic nomogram to facilitate personalized pHGNEC management., (© 2024. The Author(s).)

Background: We investigated the real-world efficacy of adjuvant therapy for stage I lung adenocarcinoma patients with pathological high-risk factors., Methods: Study participants were enrolled from November 1, 2016 and December 31, 2020. Clinical bias was balanced by propensity score matching. Disease-free survival (DFS) outcomes were compared by Kaplan-Meier analysis. The Cox proportional hazards regression was used to identify survival-associated factors. p ≤ 0.05 was the threshold for statistical significance., Results: A total of 454 patients, among whom 134 (29.5%) underwent adjuvant therapy, were enrolled in this study. One hundred and eighteen of the patients who underwent adjuvant therapy were well matched with non-treatment patients. Prognostic outcomes of the treatment group were significantly better than those of the non-treatment group, as revealed by Kaplan-Meier analysis after PSM. Differences in prevention of recurrence or metastasis between the targeted therapy and chemotherapy groups were insignificant. Adjuvant therapy was found to be positive prognostic factors, tumor size and solid growth patterns were negative., Conclusions: Adjuvant therapy significantly improved the DFS for stage I lung adenocarcinoma patients with high-risk factors. Larger prospective clinical trials should be performed to verify our findings., (© 2024. The Author(s).)

Despite epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) have shown remarkable efficacy in patients with EGFR-mutant non-small cell lung cancer (NSCLC), acquired resistance inevitably develops, limiting clinical efficacy. We found that TET2 was poly-ubiquitinated by E3 ligase CUL7 FBXW11 and degraded in EGFR-TKI resistant NSCLC cells. Genetic perturbation of TET2 rendered parental cells more tolerant to TKI treatment. TET2 was stabilized by MEK1 phosphorylation at Ser 1107, while MEK1 inactivation promoted its proteasome degradation by enhancing the recruitment of CUL7 FBXW11 . Loss of TET2 resulted in the upregulation of TNF/NF-κB signaling that confers the EGFR-TKI resistance. Genetic or pharmacological inhibition of NF-κB attenuate the TKI resistance both in vitro and in vivo. Our findings exemplified how a cell growth controlling kinase MEK1 leveraged the epigenetic homeostasis by regulating TET2, and demonstrated an alternative path of non-mutational acquired EGFR-TKI resistance modulated by TET2 deficiency. Therefore, combined strategy exploiting EGFR-TKI and inhibitors of TET2/NF-κB axis holds therapeutic potential for treating NSCLC patients who suffered from this resistance., (© 2024. The Author(s).)

The morbidity and mortality of lung cancer are still the highest among all malignant tumors. Radiotherapy plays an important role in clinical treatment of lung cancer. However, the effect of radiotherapy is not ideal due to the radiation resistance of tumor tissues. Abnormalities in tumor vascular structure and function affect blood perfusion, and oxygen transport is impeded, making tumor microenvironment hypoxic. Tumor hypoxia is the major cause of radiotherapy resistance. By promoting tumor vessel normalization and enhancing vascular transport function, tumor hypoxia can be relieved to reduce radiotherapy resistance and increase tumor radiotherapy sensitivity. In our previous study, a pericytes-targeted tumor necrosis factor alpha (named Z-TNFα) was first constructed and produced by genetically fusing the platelet-derived growth factor receptor β (PDGFRβ)-antagonistic affibody (Z PDGFRβ ) to the TNFα, and the Z-TNFα induced normalization of tumor vessels and improved the delivery of doxorubicin, enhancing tumor chemotherapy. In this study, the tumor vessel normalization effect of Z-TNFα in lung cancer was further clarified. Moreover, the tumor hypoxia improvement and radiosensitizing effect of Z-TNFα were emphatically explored in vivo. Inspiringly, Z-TNFα specifically accumulated in Lewis lung carcinoma (LLC) tumor graft and relieved tumor hypoxia as well as inhibited HIF-1α expression. As expected, Z-TNFα significantly increased the effect of radiotherapy in mice bearing LLC tumor graft. In conclusion, these results demonstrated that Z-TNFα is also a promising radiosensitizer for lung cancer radiotherapy.

Purpose: To assess whether yttrium-90 transarterial radioembolization (TARE) is safe and effective in the treatment of primary lung cancer metastases to the liver (LCML)., Methods and Methods: This retrospective study included 57 patients with LCML who were treated with 79 TARE treatments. Histology included non-small cell lung cancer (NSCLC) (n = 27), small cell lung cancer (SCLC) (n = 17), and lung carcinoid (LC) (n = 13). Survival was calculated using Kaplan-Meier method; differences between groups were estimated using log rank test. Cox proportional hazards model was used to determine factors influencing survival. Adverse events were graded using the Society of Interventional Radiology Adverse Events Classification., Results: Median overall survival (OS) was as follows: NSCLC, 8.3 months (95% confidence interval [CI], 6.3-16.4 months); SCLC, 4.1 months (95% CI, 1.9-6.6 months); and LC, 43.5 months (95% CI, 7.8-61.4 months). For NSCLC, presence of bilobar vs unilobar disease (hazard ratio [HR], 5.24; 95% CI, 1.64-16.79; P = .002); more tumors, 2-5 vs 1 (HR, 4.88; 95% CI, 1.17-20.37; P = .003) and >5 vs 1 (HR, 3.75; 95% CI, 0.95-6.92; P = .05); and lobar vs segmental treatment (HR, 2.56; 95% CI, 0-NA; P = .002) were negative predictors of OS. For SCLC, receipt of >2 lines of chemotherapy vs ≤2 lines (HR, 3.16; 95% CI, 0.95-10.47; P = .05) was a negative predictor of OS. For LC, tumor involvement of >50% was a negative predictor of OS (HR, 3.77 × 10 15 ; 95% CI, 0-NA; P = .002). There were 11 of 79 severe or life-threatening adverse events within 30 days (abdominal pain, altered mental status, nausea/vomiting, acalculous/aseptic cholecystitis, hyponatremia, pancreatitis, renal failure, and death from pneumonia)., Conclusions: TARE has an acceptable safety profile for the treatment of LCML, with survival benefits best seen in LC tumors., (Copyright © 2023 SIR. Published by Elsevier Inc. All rights reserved.)

Background: Classifying and characterizing pulmonary lesions are critical for clinical decision-making process to identify optimal therapeutic strategies. The purpose of this study was to develop and validate a radiomics nomogram for distinguishing between benign and malignant pulmonary lesions based on robust features derived from diffusion images., Material and Methods: The study was conducted in two phases. In the first phase, we prospectively collected 30 patients with pulmonary nodule/mass who underwent twice EPI-DWI scans. The robustness of features between the two scans was evaluated using the concordance correlation coefficient (CCC) and dynamic range (DR). In the second phase, 139 patients who underwent pulmonary DWI were randomly divided into training and test sets in a 7:3 ratio. Maximum relevance minimum redundancy, least absolute shrinkage and selection operator, and logistic regression were used for feature selection and construction of radiomics signatures. Nomograms were established incorporating clinical features, radiomics signatures, and ADC (0, 800) . The diagnostic efficiency of different models was evaluated using the area under the curve (AUC) and decision curve analysis., Results: Among the features extracted from DWI and ADC images, 42.7% and 37.4% were stable (both CCC and DR ≥ 0.85). The AUCs for distinguishing pulmonary lesions in the test set for clinical model, ADC, ADC radiomics signatures, and DWI radiomics signatures were 0.694, 0.802, 0.885, and 0.767, respectively. The nomogram exhibited the best differentiation performance (AUC = 0.923). The decision curve showed that the nomogram consistently outperformed ADC value and clinical model in lesion differentiation., Conclusion: Our study demonstrates the robustness of radiomics features derived from lung DWI. The ADC radiomics nomogram shows superior clinical net benefits compared to conventional clinical models or ADC values alone in distinguishing solitary pulmonary lesions, offering a promising tool for noninvasive, precision diagnosis in lung cancer., (© 2024. The Author(s).)

Introduction: Cough is a major complication after lung cancer surgery, potentially impacting lung function and quality of life. However, effective treatments for managing long-term persistent postoperative cough remain elusive. In this study, we investigated the potential of a pulmonary rehabilitation training program to effectively address this issue., Methods: Between January 2019 and December 2022, a retrospective review was conducted on patients with non-small cell lung cancer (NSCLC) who underwent lobectomy and lymph node dissection via video-assisted thoracoscopic surgery (VATS) at Daping hospital. Based on their postoperative rehabilitation methods, the patients were categorized into 2 groups: the traditional rehabilitation group and the pulmonary rehabilitation group. All patients underwent assessment using the Leicester cough questionnaire (LCQ) on the third postoperative day. Additionally, at the 6-month follow-up, patients' LCQ scores and lung function were re-evaluated to assess the long-term effects of the pulmonary rehabilitation training programs., Results: Among the 276 patients meeting the inclusion criteria, 195 (70.7%) were in the traditional rehabilitation group, while 81 (29.3%) participated in the pulmonary rehabilitation group. The pulmonary rehabilitation group showed a significantly lower incidence of cough on the third postoperative day (16.0% vs 29.7%, P = .018) and higher LCQ scores in the somatic dimension (5.09 ± .81 vs 4.15 ± 1.22, P = .007) as well as in the total score (16.44 ± 2.86 vs 15.11 ± 2.51, P = .018, whereas there were no significant differences in psychiatric and sociological dimensions. At the 6-month follow-up, the pulmonary rehabilitation group continued to have a lower cough incidence (3.7% vs 12.8%, P = .022) and higher LCQ scores across all dimensions: somatic (6.19 ± .11 vs 5.75 ± 1.20, P = .035), mental (6.37 ± 1.19 vs 5.85 ± 1.22, P = .002), sociological (6.76 ± 1.22 vs 5.62 ± 1.08, P < .001), and total (18.22 ± 2.37 vs 16.21 ± 2.53, P < .001). Additionally, lung function parameters including FVC, FVC%, FEV1, FEV1%, MVV, MVV%, DLCO SB, and DLCO% were all significantly higher in the pulmonary rehabilitation group compared to the traditional group., Conclusion: Pulmonary rehabilitation exercises significantly reduced the incidence of postoperative cough and improved cough-related quality of life in patients undergoing lobectomy, with sustained benefits observed at the 6-month follow-up. Additionally, these exercises demonstrated superior lung function outcomes compared to traditional rehabilitation methods., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

This study aimed to explore the interaction between the tumor-associated macrophage (TAM) and enhancer of zeste homolog 2 (EZH2) in tumor microenvironment of lung cancer are obscure. M2 type of TAM was induced by interleukin-4 (IL-4) and interleukin-13 (IL-13) in RAW264.7 cells. Subsequently, the co-culture system of the M2 RAW264.7 treating LLC-1 cells were constructed to evaluate the cell proliferation, migration and invasion abilities. On top of that, the M2 RAW264.7 was injected into the LLC-1 cells-bearing mice. Tumor growth and the number of metastatic nodes were observed. Moreover, DNA methylation, EZH2 expression, target genes of EZH2 and the M2 type TAM-related markers were detected in vivo and in vitro . Further experiments of EZH2 function in lung cancer were carried out by the addition of EZH2 inhibitor (GSK126) and si-EZH2. M2 type of TAM was induced with IL-4 and IL-13 with increased expression of CD206, CD68, CD163 and Arg1. Following co-culture with M2 type TAM, the proliferative, invasive, migrative abilities, tumor growth and metastasis, and the DNA methylation, EZH2 level were strengthened whereas the target genes of EZH2, including p21, CDKN2A, CDKN2B were reduced in LLC-1 cells and LLC-1 cell-bearing mice. Of note, GSK126 and si-EZH2 offset the M2 type TAM's effects, and inhibited the LLC-1 cell metastasis, DNA methylation and tumor growth. M2 type TAM promoted DNA methylation in LLC-1 cells and LLC-1 cell-bearing mice, which is related to the intensified EZH2., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

BACKGROUND. Pure ground-glass nodules (pGGNs) on chest CT representing invasive adenocarcinoma (IAC) warrant lobectomy with lymph node resection. For pGGNs representing other entities, close follow-up or sublobar resection without node dissection may be appropriate. OBJECTIVE. The purpose of this study was to develop and validate an automated deep learning model for differentiation of pGGNs on chest CT representing IAC from those representing atypical adenomatous hyperplasia (AAH), adenocarcinoma in situ (AIS), and minimally invasive adenocarcinoma (MIA). METHODS. This retrospective study included 402 patients (283 women, 119 men; mean age, 53.2 years) with a total of 448 pGGNs on noncontrast chest CT that were resected from January 2019 to June 2022 and were histologically diagnosed as AAH ( n = 29), AIS ( n = 83), MIA ( n = 235), or IAC ( n = 101). Lung-PNet, a 3D deep learning model, was developed for automatic segmentation and classification (probability of IAC vs other entities) of pGGNs on CT. Nodules resected from January 2019 to December 2021 were randomly allocated to training ( n = 327) and internal test ( n = 82) sets. Nodules resected from January 2022 to June 2022 formed a holdout test set ( n = 39). Segmentation performance was assessed with Dice coefficients with radiologists' manual segmentations as reference. Classification performance was assessed by ROC AUC and precision-recall AUC (PR AUC) and compared with that of four readers (three radiologists, one surgeon). The code used is publicly available (https://github.com/XiaodongZhang-PKUFH/Lung-PNet.git). RESULTS. In the holdout test set, Dice coefficients for segmentation of IACs and of other lesions were 0.860 and 0.838, and ROC AUC and PR AUC for classification as IAC were 0.911 and 0.842. At threshold probability of 50.0% or greater for prediction of IAC, Lung-PNet had sensitivity, specificity, accuracy, and F1 score of 50.0%, 92.0%, 76.9%, and 60.9% in the holdout test set. In the holdout test set, accuracy and F1 score ( p values vs Lung-PNet) for individual readers were as follows: reader 1, 51.3% ( p = .02) and 48.6% ( p = .008); reader 2, 79.5% ( p = .75) and 75.0% ( p = .10); reader 3, 66.7% ( p = .35) and 68.3% ( p < .001); reader 4, 71.8% ( p = .48) and 42.1% ( p = .18). CONCLUSION. Lung-PNet had robust performance for segmenting and classifying (IAC vs other entities) pGGNs on chest CT. CLINICAL IMPACT. This automated deep learning tool may help guide selection of surgical strategies for pGGN management.

Exosomal miRNAs (exo-miRNAs) have arisen as novel diagnostic biomarkers for various cancers. However, few reports on exo-miRNAs related to bone metastasis (BM) in lung cancer exist. This study aims to screen out key exo-miRNAs and estimate their prognostic values for predicting BM in lung cancer. The differentially expressed exo-miRNAs between the highly-metastatic (95D) and lowly-metastatic (A549) human lung cancer cell lines were comprehensively analyzed using high-throughput sequencing followed by bioinformatic analyses. 29 candidate exo-miRNAs were identified, and 101 BM-related target genes were predicted. Enrichment analysis revealed that these target genes were mainly involved in regulating transcription and pathways in cancer. An exosomal miRNA-mRNA regulatory network consisting of 7 key miRNAs and 10 hub genes was constructed. Further function analysis indicated that these 10 hub genes were mainly enriched in regulating cancer's apoptosis and central carbon metabolism. The survival analysis indicated that 7 of 10 hub genes were closely related to prognosis. Mutation analysis showed that lung cancer patients presented certain genetic alterations in the 7 real hub genes. GSEA for a single hub gene suggested that 6 of 7 real hub genes had close associations with lung cancer development. Finally, ROC analysis revealed that hsa-miR-151a-3p and hsa-miR-877-5p provided high diagnostic accuracy in discriminating patients with bone metastasis (BM+) from patients without bone metastasis (BM-). These findings provided a comprehensive analysis of exo-miRNAs and target genes in the regulatory network of BM in lung cancer. In particular, hsa-miR-151a-3p and hsa-miR-877-5p may be novel biomarkers for predicting BM in lung cancer.

Purpose: Surgical strategy for second primary lung cancer (SPLC) may be more conservative due to influence of first primary lung cancer (FPLC). The optimal surgical method for SPLC warrants discussion. We aimed to explore a more suitable surgical approach for early-stage (T1-T2N0, ≤ 3 cm) SPLC and provide insights for clinical practice., Methods: A retrospective study was conducted using data from the Surveillance, Epidemiology and End Results database between 2004 and 2018, and data of patients with early-stage SPLC who underwent secondary surgery were collected. Propensity score matching (PSM) reduced potential bias between lobar and sublobar resection groups. The effect of lobar and sublobar resection on overall survival (OS) was assessed in all patients and subgroups., Results: A total of 714 patients who met the study entry criteria were enrolled, including 476 patients in the sublobar resection group (66.67%) and 238 patients in the lobar resection group (33.33%). There was no difference in OS between the lobar and sublobar resection groups before and after PSM (P = 0.289) and (P = 0.608), respectively. Subgroup analyses showed that lobar resection achieved a significantly better OS than sublobar resection only in patients with an SPLC tumor size of 2-3 cm (P < 0.05)., Conclusion: The OS of sublobar resection was not significantly different from that of lobar resection for early-stage SPLC. For SPLC with a 2-3 cm tumor size, lobar resection is more advantageous than sublobar resection., (© 2023. The Author(s).)

Lymph node (LN) metastasis is one of the predominant metastatic routes of non-small cell lung cancer (NSCLC) and is considered as a leading cause for the unsatisfactory prognosis of patients. Although lymphangiogenesis is well-recognized as a crucial process in mediating LN metastasis, the regulatory mechanism involving lymphangiogenesis and LN metastasis in NSCLC remains unclear. In this study, we employed high-throughput sequencing to identify a novel circular RNA (circRNA), circTLCD4-RWDD3, which was significantly upregulated in extracellular vesicles (EVs) from LN metastatic NSCLC and was positively associated with deteriorated OS and DFS of patients with NSCLC from multicenter clinical cohort. Downregulating the expression of EV-packaged circTLCD4-RWDD3 inhibited lymphangiogenesis and LN metastasis of NSCLC both in vitro and in vivo. Mechanically, circTLCD4-RWDD3 physically interacted with hnRNPA2B1 and mediated the SUMO2 modification at K108 residue of hnRNPA2B1 by upregulating UBC9. Subsequently, circTLCD4-RWDD3-induced SUMOylated hnRNPA2B1 was recognized by the SUMO interaction motif (SIM) of ALIX and activated ALIX to recruit ESCRT-III, thereby facilitating the sorting of circTLCD4-RWDD3 into NSCLC cell-derived EVs. Moreover, EV-packaged circTLCD4-RWDD3 was internalized by lymphatic endothelial cells to activate the transcription of PROX1, resulting in the lymphangiogenesis and LN metastasis of NSCLC. Importantly, blocking EV-mediated transmission of circTLCD4-RWDD3 via mutating SIM in ALIX or K108 residue of hnRNPA2B1 inhibited the lymphangiogenesis and LN metastasis of NSCLC in vivo. Our findings reveal a precise mechanism underlying SUMOylated hnRNPA2B1-induced EV packaging of circTLCD4-RWDD3 in facilitating LN metastasis of NSCLC, suggesting that EV-packaged circTLCD4-RWDD3 could be a potential therapeutic target against LN metastatic NSCLC., (© 2023. The Author(s).)

Background: The optimal extent of mediastinal lymph node dissection is still under debate. This study aimed to investigate the prognostic impact of complete dissection of right paratracheal lymph nodes (LNs) in right-sided non-small cell lung cancer (NSCLC) and evaluate the potential patient population who will particularly benefit from right paratracheal node dissection (RPND)., Methods: Between January 2009 and December 2019, we retrospectively reviewed 2650 patients with primary right-sided NSCLC who underwent pulmonary surgery with lymphadenectomy in the Western China Lung Cancer Database. A total of 2447 patients received both 2R and 4R LNs dissection (complete RPND group), 162 patients received only 2R or 4R LNs dissection (incomplete RPND group), and 41 patients received neither 2R nor 4R LNs dissection (no RPND group). Overall survival (OS) was analyzed., Results: The metastasis rates in stations 2R and 4R were 6.5% and 8.0%, respectively. In stage N2 patients, the frequency of involvement of stations 2R/4R was 74.8%. The complete RPND group had a significantly better survival than the incomplete and no RPND group (5-year OS, 79.5% vs. 72.7% vs. 65.5%; p < 0.001). In the multivariate analysis, status of RPND (incomplete RPND vs. complete RPND: HR 1.45, 95% CI: 1.10-1.90; p = 0.009; no RPND vs. complete RPND: HR 2.25, 95% CI: 1.37 to 3.69; p = 0.001), age, gender, tumor size, histological type, pTNM stage, pT stage, pN stage, and adjuvant treatment were independent factors for OS., Conclusions: Complete RPND brings survival benefits to patients with right-sided NSCLC. We suggest complete RPND as a standard procedure for patients with right-sided NSCLC., (© 2023 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

Mammalian sirtuin 6 (SIRT6) regulates a spectrum of vital biological processes and has long been implicated in the progression of cancer. However, the mechanisms underlying the regulation of SIRT6 in tumorigenesis remain elusive. Here, we report that the tumor-suppressive function of SIRT6 in non-small cell lung cancer (NSCLC) is regulated by acetylation. Specifically, males absent on the first (MOF) acetylates SIRT6 at K128, K160, and K267, resulting in a decreased deacetylase activity of SIRT6 and attenuated SIRT6 tumor-suppressive function in NSCLC. Mechanistically, MOF-mediated SIRT6 acetylation hinders the interaction between SIRT6 and transcriptional factor FOXA2, which in turn leads to the transcriptional activation of ZEB2, thus promoting NSCLC progression. Collectively, these data indicate an acetylation-dependent mechanism that modulates SIRT6 tumor-suppressive function in NSCLC. Our findings suggest that the MOF-SIRT6-ZEB2 axis may represent a promising therapeutic target for the management of NSCLC., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: To assess the predictive values of primary tumor FDG uptake for patients with inoperable stage III non-small cell lung cancer (NSCLC) after concurrent chemoradiotherapy (CCRT)., Methods: A total of 107 patients with diagnosis of stage III NSCLC and CCRT were enrolled. The tumor maximum uptake value (SUVmax) was standardized by calculating several ratios between tumor and each background tissues. The receiver operating characteristics curve (ROC) was used to compare the predictive power of prognostic models. The tumor objective response rate (ORR) and overall survival (OS) were compared and analyzed by the Kaplan-Meier method and univariate and multivariate Cox regression models., Results: The areas under ROC curve (AUCs) ranged from 0.72 to 0.81 among these tumor SUVmax and standardized SUVmax ratios, and the tumor SUVmax and tumor SUVmax-to-liver SUVmean ratio (TLMR) were more predictive of ORR (AUC, 0.81; 95% CI, 0.73-0.88 for tumor SUVmax and AUC, 0.84; 95%CI, 0.76-0.91 for TLMR) than any of other SUVmax ratios. The patients with lower tumor SUVmax, SUVmean and SUVmax ratios had a significantly better OS than those with their corresponding higher ones. Moreover, both univariate and multivariable analyses revealed that TLMR was significantly associated with better ORR and OS after adjustment with other prognostic variables., Conclusions: TLMR, a standardized tumor SUVmax, was an independent prognostic predictor for tumor ORR and OS of patients with stage III NSCLC after CCRT., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Non-small cell lung cancer (NSCLC) occupies 87% of all lung cancer cases. Due to delayed diagnosis, the prognosis of NSCLC is unfavorable. To improve the survival of patients with NSCLC, more effective therapeutic targets urgently need to be identified. Recently, circular RNAs (circRNAs) have been revealed to play a crucial role in NSCLC progression., Purpose: This research focused on the influence of circTADA2A on the malignant phenotype of NSCLC cells and its in-depth regulatory mechanisms., Methods: RT-qPCR and western blot assays were done to examine the level of gene/protein of interest. Wound healing and transwell assays were conducted to monitor the migration and invasion of NSCLC cells. Bioinformatics tools and mechanistic assays were utilized to delve into the underlying mechanism of circTADA2A in NSCLC cells., Results: The results demonstrated that circTADA2A presented a high expression in NSCLC. CircTADA2A knockdown was revealed to hamper migration and invasion of NSCLC cells. Mechanistically, circTADA2A elevated MAPK8 expression through sequestering miR-214-3p and recruiting EIF4A3., Conclusion: CircTADA2A enhances MAPK8 expression by serving as a miR-214-3p sponge and EIF4A3 decoy, consequently promoting invasion and migration of NSCLC cells., (©The Author(s) 2023. Open Access. This article is licensed under a Creative Commons CC-BY International License.)

Background: The purpose of this analysis was to investigate the effectiveness of afatinib compared to that of osimertinib in patients with non-small cell lung cancer (NSCLC) who harbored uncommon epidermal growth factor receptor (EGFR) mutations., Methods: A PubMed database-based literature review was conducted to retrieve related studies. Patients harboring EGFR mutations besides the deletion in exon 19 (19del) and point mutation of L858R were included in this analysis. The primary outcome events were the objective response rate (ORR) and progression-free survival (PFS). Propensity score matching (PSM) at a ratio of 1:1 was used between afatinib and osimertinib groups to control the confounding factors. Uncommon EGFR mutations were categorized into 4 groups: insertion in exon 20 (ex20ins), non-ex20ins single uncommon EGFR mutations, compound EGFR mutations that with 19del or L858R, and compound EGFR mutations without 19del or L858R., Results: After PSM, 71 patients in either the afatinib or osimertinib group were matched. The afatinib group had an ORR of 60.6%, slightly higher than the osimertinib group's (50.3%), the difference was not statistically significant (P = .610). However, the afatinib group showed a significantly superior PFS benefit than the osimertinib group (11.0 vs. 7.0 months, P = .044). In addition, patients harboring non-ex20ins single uncommon EGFR mutations yield the best ORR and PFS, following treatment of either afatinib (ORR: 76.7%, mPFS: 14.1 months) or osimertinib (ORR: 68.8%, mPFS: 15.1 months). Moreover, there was no significant difference in terms of ORR or PFS between the cohort of patients treated with afatinib or osimertinib, regardless of whether or not the patients had brain metastases., Conclusions: Both afatinib and osimertinib displayed favorable clinical activities toward uncommon EGFR mutations. Afatinib showed a more profound and durable PFS benefit than osimertinib, although no efficacy advantage was observed., (© The Author(s) 2023. Published by Oxford University Press.)

Fine particulate matter (PM 2.5 ) exposure causes DNA mutations and abnormal gene expression leading to lung cancer, but the detailed mechanisms remain unknown. Here, analysis of genomic and transcriptomic changes upon a PM 2.5 exposure-induced human bronchial epithelial cell-based malignant transformed cell model in vitro showed that PM 2.5 exposure led to APOBEC mutational signatures and transcriptional activation of APOBEC3B along with other potential oncogenes. Moreover, by analyzing mutational profiles of 1117 non-small cell lung cancers (NSCLCs) from patients across four different geographic regions, we observed a significantly higher prevalence of APOBEC mutational signatures in non-smoking NSCLCs than smoking in the Chinese cohorts, but this difference was not observed in TCGA or Singapore cohorts. We further validated this association by showing that the PM 2.5 exposure-induced transcriptional pattern was significantly enriched in Chinese NSCLC patients compared with other geographic regions. Finally, our results showed that PM 2.5 exposure activated the DNA damage repair pathway. Overall, here we report a previously uncharacterized association between PM 2.5 and APOBEC activation, revealing a potential molecular mechanism of PM 2.5 exposure and lung cancer.

Non-small cell lung cancer (NSCLC) accounts for 80-85% of all lung cancers, which has the highest cancer-related mortality worldwide. Regardless of the therapeutic effects of chemotherapy or targeted therapy, drug resistance will occur after 1 year. Heat shock proteins (HSPs) are a class of molecular chaperones participated in protein stability and multiple intracellular signaling pathways. It has been widely reported that HSPs family is over expressed in non-small cell lung cancer, and these molecules are also associated with protein stability and multiple intracellular signaling pathways. The effect of chemotherapy drugs or targeted drugs on cancer cells is usually to induce apoptosis. It is necessary to explore the interaction between heat shock protein family and apoptosis pathway in NSCLC. Here we provide a brief review of how HSPs affect the apoptotic pathway in NSCLC., Competing Interests: The authors declare no conflict of interest., (© 2023 The Author(s). Published by IMR Press.)

Numerous studies have revealed that ambient long-term exposure to fine particulate matter (PM 2.5 ) is significantly related to the development of lung cancer, but the molecular mechanisms of PM 2.5 exposure-induced lung cancer remains unknown. As an important epigenetic regulator, microRNAs (miRNAs) play vital roles in responding to environment exposure and various diseases including lung cancer development. Here we constructed a PM 2.5 -induced malignant transformed cell model and found that miR-200 family, especially miR-200a-3p, was involved in the process of PM 2.5 induced lung cancer. Further investigation of the function of miR-200 family (miR-200a-3p as a representative revealed that miR-200a-3p promoted cell migration by directly suppressing TNS3 expression. These results suggested that ambient PM 2.5 exposure may increase the expression of miR-200 family and then promote the proliferation and migration of lung cancer cells. Our study provided novel model and insights into the molecular mechanism of ambient PM 2.5 exposure-induced lung cancer., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Clinically, activated EGFR mutation associated chemo-drugs resistance has severely threaten NSCLC patients. Nanoparticle based small interfering RNA (siRNA) therapy representing another promising alternative by silencing specific gene while still suffered from charge associated toxicity, strong immunogenicity and poor targetability. Herein, we reported a novel EGFR-mutant NSCLC therapy relying on edible and cation-free kiwi-derived extracellular vesicles (KEVs), which showed sevenfold enhancement of safe dosage compared with widely used cationic liposomes and could be further loaded with Signal Transducer and Activator of Transcription 3 interfering RNA (siSTAT3). siSTAT3 loaded KEVs (STAT3/KEVs) could be easily endowed with EGFR targeting ability (STAT3/EKEVs) and fluorescence by surface modification with tailor-making aptamer through hydrophobic interaction. STAT3/EKEVs with a controlled size of 186 nm displayed excellent stability, high specificity and good cytotoxicity towards EGFR over-expressing and mutant PC9-GR4-AZD1 cells. Intriguingly, the systemic administration of STAT3/EKEVs significantly suppressed subcutaneous PC9-GR4-AZD1 tumor xenografts in nude mice by STAT3 mediated apoptosis. This safe and robust KEVs has emerged as the next generation of gene delivery platform for NSCLC therapy after multiple drug-resistance., (© 2023. The Author(s).)

Background: Systemic inflammation is crucial for the development and progression of cancers. The advanced lung cancer inflammation index (ALI) is considered to be a better indicator of systemic inflammation than current biomarkers. However, the prognostic value of the ALI in gastrointestinal neoplasms remains unclear. We performed the first meta-analysis to explore the association between ALI and gastrointestinal oncologic outcomes to help physicians better evaluate the prognosis of those patients., Methods: Eligible articles were retrieved using PubMed, the Cochrane Library, EMBASE, and Google Scholar by December 29, 2022. Clinical outcomes were overall survival (OS), disease-free survival (DFS), progression-free survival (PFS), and cancer-specific survival (CSS)., Results: A total of 18 articles with 6898 patients were included in this meta-analysis. The pooled results demonstrated that a low ALI was correlated with poor OS (HR = 1.914, 95% CI: 1.514-2.419, P < 0.001), DFS (HR = 1.631, 95% CI: 1.197-2.224, P = 0.002), and PFS (HR = 1.679, 95% CI: 1.073-2.628, P = 0.023) of patients with gastrointestinal cancers. Subgroup analysis revealed that a low ALI was associated with shorter OS (HR = 2.279, 95% CI: 1.769-2.935, P < 0.001) and DFS (HR = 1.631, 95% CI: 1.197-2.224, P = 0.002), and PFS (HR = 1.911, 95% CI: 1.517-2.408, P = 0.002) of patients with colorectal cancer. However, the ALI was not related to CSS in the patients with gastrointestinal malignancy (HR = 1.121, 95% CI: 0.694-1.812, P = 0.640). Sensitivity analysis supported the stability and dependability of the above results., Conclusion: The pre-treatment ALI was a useful predictor of prognosis in patients with gastrointestinal cancers., (© 2023. The Author(s).)

Background: Results from Lung ART and PORT-C trials suggest that postoperative radiotherapy (PORT) cannot routinely be recommended as standard treatment in completely resected pIIIA-N2 NSCLC patients, but their effects on the real-world practice of PORT in China remain unclear., Methods: A national cross-section survey was conducted by using an online survey service. Participants were voluntarily recruited using a river sampling strategy. A link to the survey was posted on websites of radiation oncologist associations and tweets from public WeChat accounts. The survey collected the real names of participants to ensure that they were board-certified radiation oncologists., Results: A total of 484 radiation oncologists were included with a median age of 40 years (IQR, 35-47). A total of 377 (77.9%) participants were male, and 282 (58.1%) had more than 10 years of clinical experience practicing thoracic radiotherapy. Before Lung ART and PORT-C trials were published, 313 (64.7%) respondents recommended PORT, 11 (2.3%) did not recommend it, and 160 (33.1%) reported that they made decisions based on risk factors. After the presentation of two trials, only 42 (8.7%) did not recommend PORT, while 108 (22.3%) recommended it, and 334 (69.0%) made decisions based on risk factors. The five most commonly considered risk factors among these 334 respondents were as follows: nodal extracapsular extension, the highest lymph node (LN) station involved, the number of dissected mediastinal LN stations, the number of positive mediastinal LN stations, and surgical approaches. In addition, the majority of all 484 respondents recommended a total dose of 50 Gy, lung stump + ipsilateral hilus + regions containing positive LNs as the targeted region, lung V20 < 25%, and heart V30 < 40% as dose constraints for PORT., Conclusion: Most Chinese radiation oncologists recommended PORT for completely resected IIIA-N2 NSCLC patients based on risk factors, especially status of LN station., (© 2023. The Author(s).)

Background: The purpose of this study was to investigate the outcomes of gefitinib and erlotinib in patients with non-small cell lung cancer (NSCLC) with uncommon epidermal growth factor receptor (EGFR) mutations., Methods: Relevant researches were identified by a literature search of the PubMed database. Patients with EGFR mutations other than exon 19 deletion and L858R were eligible for the study. Clinical outcomes included objective response rate (ORR), progression free survival (PFS), and overall survival (OS). We categorized all uncommon EGFR mutations as: single uncommon EGFR mutations and compound mutations that containing 2 or more kinds of EGFR mutations. We also assessed outcomes in patients categorized by EGFR-TKIs: (1) gefitinib group; (2) erlotinib group., Results: A total of 438 patients with NSCLC harboring uncommon EGFR mutations were included in this study. The ORR for gefitinib and erlotinib was 43.8 %, with a median PFS (mPFS) of 6.00 months and a median OS (mOS) of 20.50 months. Patients with compound mutations had an ORR of 56.3 % and an mPFS of 8.10 months. Both of them were significantly better than these in patients with single uncommon EGFR mutation, which were 29.3 % and 3.90 months, respectively (odds ratio (ORa): 2.74, 95 % confidence interval (CI): 1.86-4.05, P < 0.001; hazard ratio (HR): 0.58, 95 % CI: 0.48-0.71, P < 0.001). Moreover, patients with compound mutations containing 19 deletion or L858R had a superior response and survival benefits compared to patients with other compound mutation patterns. In addition, the gefitinib group showed a favorable efficacy advantage (P = 0.003) and PFS benefit (P = 0.021) compared to the erlotinib group., Conclusions: Uncommon EGFR mutations exhibit favorable but inconsistent treatment responses and survival outcomes to gefitinib and erlotinib, which are closely related to the mutation pattern, the cooccurring partner mutant genes, and the type of EGFR-TKIs received., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: This study aimed to identify whether NTR is the independent risk factor for progression-free survival (PFS) and overall survival (OS) in patients treated with concurrent chemo-radiotherapy (cCRT)., Methods: We retrospectively studied 106 T1-4N1-3M0 non-small cell lung cancer patients treated with cCRT. The maximum standardized uptake value (SUVTumor) of the primary tumor and the metastatic lymph nodes (SUVLN) were measured. The prognostic significance of NTR for predicting PFS and OS was assessed. A multi-adjusted spline regression model was conducted to provide more precise estimates and examine the shape of the associations between NTR and the risk of progression., Results: From 2012 to 2017, 106 eligible patients were analyzed. The median follow-up time was 15.3 months (3.5-44.6 months). We determined the maximizing area under the time-dependent receiver operating characteristic curve was at an NTR of 0.73 for predicting PFS. The two-year PFS was significantly lower in the high-NTR group (35.7% vs. 55.4%, P = 0.02) and two-year OS (43.4% vs. 61.1%, P = 0.03 was also significantly worse. Multivariable analysis revealed that only NTR was an independent prognostic factor for PFS (hazard ratio [HR]: 10.04, P < 0.001) and OS (HR: 4.19, P = 0.03). The restricted cubic spline regression model showed that NTR had a non-linear relationship with log relative risk for progression., Conclusion: NTR was an independent risk factor for predicting PFS and OS in T1-4N1-3M0 non-small cell lung cancer patients treated with cCRT., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Lung adenocarcinoma (LUAD) belongs to non-small cell lung cancer. In addition to surgical resection, chemotherapy and radiotherapy cause great side effects and low 5-year survival rates. MiRNAs are closely related to cancer development. This study aimed to analyze the molecular mechanism of miRNA-144-5p targeting CDCA3 to inhibit LUAD proliferation., Methods: MiRNA and mRNA data were downloaded from TCGA-LUAD dataset for differential expression analysis. TargetScan and miRTarBase databases were adopted to predict the target genes of miRNA, and the signaling pathways involved were analyzed by gene set enrichment analysis. The functions of LUAD cells were analyzed by CCK-8, colony formation assay, stem cell spheroidization assay, and flow cytometry. The expression levels of CDCA3, p53, and cell cycle-associated proteins were evaluated by Western blot., Results: The expression of miRNA-144-5p was significantly down-regulated in LUAD, but overexpression of it repressed proliferation and spheroidization, and promoted apoptosis of LUAD cells. By bioinformatics prediction and dual-luciferase reporter assay, miRNA-144-5p was validated to target CDCA3, thereby regulating proliferation of LUAD cells. Besides, the results of cell experiments showed that miRNA-144-5p targeting CDCA3 affected cell proliferation and apoptosis in LUAD by regulating cell cycles, and miRNA-144-5p/CDCA3 mediated the p53 signaling pathway to affect the growth of LUAD cells., Significance: Through the study of the pathogenesis of miRNA-144-5p regulating LUAD, we can better understand the molecular mechanism underlying LUAD development., Competing Interests: Conflict of Interest Statement The authors deny that they have any intention to obtain any financial interests., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: High immune infiltration is associated with favourable prognosis in patients with non-small-cell lung cancer (NSCLC), but an automated workflow for characterizing immune infiltration, with high validity and reliability, remains to be developed., Methods: We performed a multicentre retrospective study of patients with completely resected NSCLC. We developed an image analysis workflow for automatically evaluating the density of CD3 + and CD8 + T-cells in the tumour regions on immunohistochemistry (IHC)-stained whole-slide images (WSIs), and proposed an immune scoring system "I-score" based on the automated assessed cell density., Results: A discovery cohort (n = 145) and a validation cohort (n = 180) were used to assess the prognostic value of the I-score for disease-free survival (DFS). The I-score (two-category) was an independent prognostic factor after adjusting for other clinicopathologic factors. Compared with a low I-score (two-category), a high I-score was associated with significantly superior DFS in the discovery cohort (adjusted hazard ratio [HR], 0.54; 95% confidence interval [CI] 0.33-0.86; P = 0.010) and validation cohort (adjusted HR, 0.57; 95% CI 0.36-0.92; P = 0.022). The I-score improved the prognostic stratification when integrating it into the Cox proportional hazard regression models with other risk factors (discovery cohort, C-index 0.742 vs. 0.728; validation cohort, C-index 0.695 vs. 0.685)., Conclusion: This automated workflow and immune scoring system would advance the clinical application of immune microenvironment evaluation and support the clinical decision making for patients with resected NSCLC., (© 2022. The Author(s).)

Purpose: Growing numbers of clinical trials test the efficacy of radiotherapy (RT) plus immune checkpoint inhibitors (ICIs), but the number of irradiated sites is not uniform. We aimed to evaluate the efficacy of single-site RT plus immunotherapy in oligometastatic non-small cell lung cancer (NSCLC) with smaller disease burdens and low tumor heterogeneity., Methods: We retrospectively identified oligometastatic NSCLC (< 4 metastatic sites) patients treated with PD-1 pathway inhibitors with or without RT to a single lesion in our institution between 2018 and 2020. The primary endpoints were the best objective response rate (ORR) and progression-free survival (PFS)., Results: Of the 152 patients enrolled, 93 and 59 were identified as the ICI alone group and the ICI plus RT group, respectively. The addition of RT to ICI therapy significantly increased the best ORR from 31.2% to 50.8% (p = 0.015). The out-of-field (abscopal effect) response rate could reach 41.3% (95%CI 26.5%-56.1%) in the ICI plus RT group. Median PFS was 8.9 months (95%CI 4.7-13.1 months) with ICI alone versus 13.8 months (95%CI 9.5-18.1 months) with ICI plus radiotherapy (hazard ratio [HR] 0.556; p = 0.035). In an exploratory subgroup analysis of PFS, the addition of RT brought greater benefits in patients aged < 65 years (p = 0.016), patients with ECOG PS = 0 (p = 0.048), and patients with 1-2 metastatic sites (p = 0.024). No unexpected adverse events or significantly increased toxicities were observed in the experimental arm., Conclusion: Single-site RT plus anti-PD-1 inhibitors significantly increased systemic responses and improved survival outcomes in oligometastatic NSCLC patients., (© 2021. The Author(s).)

Background: For early stage non-small cell lung cancer, whether limited resection can yield comparable outcomes to those of lobectomy hasn't been established. We compared Overall survival (OS) and lung cancer-specific survival (LCSS) after segmentectomy or lobectomy in stage IA1 (≤10 mm) lung adenocarcinoma (LUAD) patients., Research Design and Methods: We retrospectively recruited patients who'd been diagnosed with lung cancer for the first time and treated with segmentectomy or lobectomy, with or without previous other malignancy., Results: 1788 patients were included. After propensity score matching: 5-year OS were 85.6% for segmentectomy and 84.7% for lobectomy (p=0.951); 5-year LCSS were 93.5% for segmentectomy; and 93.0% for lobectomy (p=0.726). Cox regression analysis revealed segmentectomy was comparable to lobectomy in OS and LCSS. Having a second lung cancer later in life was associated with a worse LCSS for lobectomy (p<0.05) rather than segmentectomy. After patients were stratified according to malignancy history, subgroup analyses showed no significant prognosis differences between two surgeries., Conclusions: For stage IA1 LUAD patients who were diagnosed with lung cancer for the first time, with or without previous other malignancy, segmentectomy yields comparable outcomes to those of lobectomy. It may provide better outcomes for patients with multiple suspicious nodules.

Besides traditional treatment strategies, including surgery, radiotherapy, and chemotherapy for lung cancer as the leading cause of cancer incidence and death, immunotherapy has also emerged as a new treatment strategy. The goal of immunotherapy is to stimulate the immune system responses against cancer, using various approaches such as therapeutic vaccines, monoclonal antibodies, immune checkpoint inhibitors, and T-cell therapy. Chimeric antigen receptor (CAR)-T cells, one of the most popular cancer immunotherapy approaches in the last decade, are genetically engineered T-cells to redirect patients' immune responses to recognize and eliminate tumor-associated antigens (TAA)-expressing tumor cells. CAR-T cell therapy provides promising benefits in lung tumors. In this review, we summarize different immunotherapy approaches for lung cancer, the structure of CAR-T cells, currently undergoing CARs in clinical trials, and various TAAs are being investigated as potential targets in designing CAR-T cells for lung cancer., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: The safety of thoracic radiotherapy (TRT) after programmed death 1/programmed death ligand 1 (PD-(L)1) inhibitor treatment in patients with lung cancer was scarcely reported. This retrospective study was conducted to evaluate the incidence, severity, and risk factors of symptomatic treatment-related pneumonitis in patients with lung cancer who received this sequential combination., Methods: We conducted a retrospective study of a cohort of patients with lung cancer who received TRT after at least two cycles of PD-(L)1 inhibitor treatment between January 2018 and August 2020. Treatment-related pneumonitis was evaluated and analyzed to illustrate the safety profile of this sequential combination. Potential risk factors were explored by univariate and multivariate logistic regression analyses., Results: Among the 828 patients with prior PD-(L)1 inhibitor treatment, 96 patients receiving subsequent TRT were included in the analysis. Of these, 49 patients (51%) received radical TRT while 47 patients (49%) received palliative TRT. The median total dose was 52 Gy (IQR 50-60 Gy). The median time from the initiation of PD-(L)1 inhibitor treatment to TRT was 4.8 months (1.6-14.1 months) with most of the patients (74%) administering no less than four cycles of PD-(L)1 inhibitor. During follow-up, 47 patients (48.96%) developed symptomatic treatment-related pneumonitis (grade 2 n = 28, grade ≥3 n = 19) while six patients (6.25%) suffered from fatal toxicity. The median time of pneumonitis onset after completion of TRT was 35 days (0-177 days) with six patients developing during TRT. Pulmonary emphysema and lung V20 were demonstrated to be independent risk factors of symptomatic pneumonitis (OR: 5.67, 95% CI: 1.66-19.37, p = 0.006; OR: 3.49, 95% CI: 1.41-8.66, p = 0.007, respectively)., Conclusion: TRT after PD-(L)1 inhibitor treatment resulted in significantly increased incidence and severity of treatment-related pneumonitis in patients with lung cancer. Intensive attention should be emphasized to the safety of this sequential combination in clinical practice., (© 2021 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Aim: To further elucidate the prognostic factors of non-small-cell lung cancer (NSCLC) patients with T2aN0M0 (stage IB) who underwent surgical treatment., Methods: We retrospectively analyzed the data of stage IB NSCLC patients who underwent surgical treatment at our center from October 2013 to September 2016. Eighty patients were enrolled. We analyzed their overall survival (OS) and disease-free survival (DFS) using the Kaplan-Meier method., Results: In univariable analysis, adenosquamous carcinoma (ASC) was significantly associated with inferior DFS (p = 0.036, p = 0.037) and OS (p = 0.001, p = 0.003) in all stage IB patients and those who only accepted surgery. Patients with a number of N2 lymph node dissections of ≥3 regions (N2-LSNDr) exhibited better DFS (p = 0.020, p = 0.005) and OS (p = 0.003, p = 0.001) in all stage IB patients and those who only accepted surgery. In addition, advanced age (≥70 years old) is an adverse factor for DFS (p = 0.049) and OS (p = 0.018) among patients who did not receive adjuvant chemotherapy following surgery. In multivariable analyses, patients with N2-LSNDr exhibited a longer OS (p = 0.045) in all enrolled patients; patients with N2-LSNDr (p = 0.016) and younger age (p = 0.021) demonstrated a superior OS in patients who only received surgery., Conclusions: We found that N2-LSNDr were independent influencing factors affecting the prognosis in all included stage IB patients and stage IB patients without adjuvant chemotherapy. ASC was associated with worse prognosis of T2aN0M0 NSCLC. Older age is an independent prognostic factor of the worst OS in stage IB patients without adjuvant chemotherapy., (© 2021 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

Objective: Circular RNA&#95;0001946 (circ&#95;0001946) inhibits tumor progression but promotes chemosensitivity in non-small-cell lung cancer (NSCLC); however, its correlation with tumor features and prognosis in NSCLC patients is still unclear; therefore, this study aimed to investigate these issues., Methods: A total of 284 NSCLC patients were retrospectively analyzed. Circ&#95;0001946 expression in tumor (n = 284) and adjacent (n = 125) tissues was detected by the reverse transcription-quantitative polymerase chain reaction. Meanwhile, patients' clinical characteristics, recurrence, and survival data were extracted from the electrical database., Results: Circ&#95;0001946 expression in adjacent tissues was over 3-folds as that in tumor tissues (P < .001). Meanwhile, higher tumor circ&#95;0001946 expression was correlated with less lymph node metastasis (P < .001) and decreased TNM stage (P = .001), but did not correlate with other clinicopathological features. Moreover, higher tumor circ&#95;0001946 expression was associated with prolonged disease-free survival (DFS) (P < .001) and overall survival (OS) (P < .001), respectively. Subgroup analyses revealed that higher tumor circ&#95;0001946 was correlated with improved DFS in patients with TNM stage I, II, or III, respectively (all P < .05), while only correlated with prolonged OS in patients with TNM stage III (P = .037), but not in patients with TNM stage I or II. Further multivariate Cox's proportional hazard regression analyses suggested that higher tumor circ&#95;0001946 expression could independently predict improved DFS (P < .001, hazard ratio (HR) = 0.719) and OS (P < .001, HR = 0.746), respectively., Conclusion: Circ&#95;0001946 is insufficiently expressed in tumor tissues, whereas its higher expression correlates with less lymph node metastasis, reduced TNM stage, and improved prognosis in NSCLC patients., (© 2021 The Authors. Journal of Clinical Laboratory Analysis published by Wiley Periodicals LLC.)

Opportunistic screening for osteoporosis can be performed using low-dose computed tomography (LDCT) imaging obtained for other clinical indications. In this study we explored the CT-derived bone mineral density (BMD) and prevalence of osteoporosis from thoracic LDCT in a large population cohort of Chinese men and women. A total of 69,095 adults (40,733 men and 28,362 women) received a thoracic LDCT scan for the purpose of lung cancer screening between 2018 and 2019, and data were obtained for analysis from the China Biobank Project, a prospective nationwide multicenter population study. Lumbar spine (L 1 -L 2 ) trabecular volumetric bone mineral density (vBMD) was derived from these scans using quantitative computed tomography (QCT) software and the American College of Radiology QCT diagnostic criteria for osteoporosis were applied. Geographic regional differences in the prevalence of osteoporosis were assessed and the age-standardized, population prevalence of osteoporosis in Chinese men and women was estimated from the 2010 China census. The prevalence of osteoporosis by QCT for the Chinese population aged >50 years was 29.0% for women and 13.5% for men, equating to 49.0 million and 22.8 million, respectively. In women, this rate is comparable to estimates from dual-energy X-ray absorptiometry (DXA), but in men, the prevalence is double. Prevalence varied geographically across China, with higher rates in the southwest and lower rates in the northeast. Trabecular vBMD decreased with age in both men and women. Women had higher peak trabecular vBMD (185.4 mg/cm 3 ) than men (176.6 mg/cm 3 ) at age 30 to 34 years, but older women had lower trabecular vBMD (62.4 mg/cm 3 ) than men (92.1 mg/cm 3 ) at age 80 years. We show that LDCT-based opportunistic screening could identify large numbers of patients with low lumbar vBMD, and that future cohort studies are now required to evaluate the clinical utility of such screening in terms of fracture prevention and supporting national health economic analyses. © 2020 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).., (© 2020 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).)

Introduction: The optimal extent of lymphadenectomy during esophagectomy remains unclear. In this trial, we aim to clarify whether three-field (cervical-thoracic-abdominal) lymphadenectomy improved patient survival over two-field (thoracic-abdominal) lymphadenectomy for esophageal cancer., Methods: Between March 2013 and November 2016, a total of 400 patients with middle and lower thoracic esophageal cancer were included and randomly assigned to undergo esophagectomy with either three- or two-field lymphadenectomy at a 1:1 ratio. Analyses were done according to the intention-to-treat principle. The primary end point was overall survival (OS), calculated from the date of randomization to the date of death from any cause., Results: Demographic characteristics were similar in the two arms. The median follow-up time was 55 months (95% confidence interval [CI]: 52-58). OS (hazard ratio [HR] = 1.019, 95% CI: 0.727-1.428, p = 0.912) and the disease-free survival (DFS) (HR = 0.868, 95% CI: 0.636-1.184, p = 0.371) were comparable between the two arms. The cumulative 5-year OS was 63% in the three-field arm, as compared with 63% in the two-field arm; 5-year DFS was 59% and 53%, respectively. On the basis of whether the patients had mediastinal or abdominal lymph node metastasis or not, OS was also comparable between the two arms. In this cohort, only advanced tumor stage (pathologic TNM stages III-IV) was identified as the risk factor associated with reduced OS (HR = 3.330, 95% CI: 2.140-5.183, p < 0.001)., Conclusions: For patients with middle and lower thoracic esophageal cancer, there was no improvement in OS or DFS after esophagectomy with three-field lymphadenectomy over two-field lymphadenectomy., (Copyright © 2020 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)