Staging Of Non-small Cell Lung Cancer Research Articles

P54.03 Multiple Microarray Analyses Identify Key Genes Associated with the Development of NSCLC from COPD

Chronic obstructive pulmonary disease (COPD) is an independent risk factor of non-small cell lung cancer (NSCLC). This study aimed to analyze the key genes and potential molecular mechanisms that are involved in the development from COPD to NSCLC. Expression profiles of COPD and NSCLC in GSE106899, GSE12472, and GSE12428 were downloaded from the Gene Expression Omnibus (GEO) database, followed by identification of the differentially expressed genes (DEGs) between COPD and NSCLC. Based on the identified DEGs, functional pathway enrichment and lung carcinogenesis-related networks analyses were performed and further visualized with Cytoscape software. Then, principal component analysis (PCA), cluster analysis, and support vector machines (SVM) verified the ability of the top modular genes to distinguish COPD from NSCLC. Additionally, the corrections between these key genes and clinical staging of NSCLC were studied using the UALCAN and HPA websites. Finally, a prognostic risk model was constructed based on multivariate Cox regression analysis. Kaplan-Meier survival curves of the top modular genes on the training and verification sets were generated. A total of 2350, 1914, and 1850 DEGs were obtained from GSE106899, GSE12472, and GSE12428 datasets, respectively. Following analysis of protein-protein interaction networks, the identified modular gene signatures containing H2AFX, MCM2, MCM3, MCM7, POLD1, and RPA1 were identified as markers for discrimination between COPD and NSCLC. The modular gene signatures were mainly enriched in the processes of DNA replication, cell cycle, mismatch repair, and others. Besides, the expression levels of these genes were significantly higher in NSCLC than in COPD, which was further verified by the immunohistochemistry. In addition, the high expression levels of H2AFX, MCM2, MCM7, and POLD1 correlate with poor prognosis of lung adenocarcinoma (LUAD). The Cox regression prognostic risk model showed the similar results and the predictive ability of this model is independent of other clinical variables. This study revealed several key modules that closely relate to NSCLC with underlying disease COPD, which provide a deeper understanding of the potential mechanisms underlying the malignant development from COPD to NSCLC. This study provides valuable prognostic factors in high-risk lung cancer patients with COPD.

A Staging Auxiliary Diagnosis Model for Nonsmall Cell Lung Cancer Based on the Intelligent Medical System.

At present, human health is threatened by many diseases, and lung cancer is one of the most dangerous tumors that threaten human life. In most developing countries, due to the large population and lack of medical resources, it is difficult for doctors to meet patients' needs for medical treatment only by relying on the manual diagnosis. Based on massive medical information, the intelligent decision-making system has played a great role in assisting doctors in analyzing patients' conditions, improving the accuracy of clinical diagnosis, and reducing the workload of medical staff. This article is based on the data of 8,920 nonsmall cell lung cancer patients collected by different medical systems in three hospitals in China. Based on the intelligent medical system, on the basis of the intelligent medical system, this paper constructs a nonsmall cell lung cancer staging auxiliary diagnosis model based on convolutional neural network (CNNSAD). CNNSAD converts patient medical records into word sequences, uses convolutional neural networks to extract semantic features from patient medical records, and combines dynamic sampling and transfer learning technology to construct a balanced data set. The experimental results show that the model is superior to other methods in terms of accuracy, recall, and precision. When the number of samples reaches 3000, the accuracy of the system will reach over 80%, which can effectively realize the auxiliary diagnosis of nonsmall cell lung cancer and combine dynamic sampling and migration learning techniques to train nonsmall cell lung cancer staging auxiliary diagnosis models, which can effectively achieve the auxiliary diagnosis of nonsmall cell lung cancer. The simulation results show that the model is better than the other methods in the experiment in terms of accuracy, recall, and precision.

Multiple microarray analyses identify key genes associated with the development of Non-Small Cell Lung Cancer from Chronic Obstructive Pulmonary Disease.

Introduction: Chronic obstructive pulmonary disease (COPD) is an independent risk factor of non-small cell lung cancer (NSCLC). This study aimed to analyze the key genes and potential molecular mechanisms that are involved in the development from COPD to NSCLC.Methods: Expression profiles of COPD and NSCLC in GSE106899, GSE12472, and GSE12428 were downloaded from the Gene Expression Omnibus (GEO) database, followed by identification of the differentially expressed genes (DEGs) between COPD and NSCLC. Based on the identified DEGs, functional pathway enrichment and lung carcinogenesis-related networks analyses were performed and further visualized with Cytoscape software. Then, principal component analysis (PCA), cluster analysis, and support vector machines (SVM) verified the ability of the top modular genes to distinguish COPD from NSCLC. Additionally, the corrections between these key genes and clinical staging of NSCLC were studied using the UALCAN and HPA websites. Finally, a prognostic risk model was constructed based on multivariate Cox regression analysis. Kaplan-Meier survival curves of the top modular genes on the training and verification sets were generated.Results: A total of 2350, 1914, and 1850 DEGs were obtained from GSE106899, GSE12472, and GSE12428 datasets, respectively. Following analysis of protein-protein interaction networks, the identified modular gene signatures containing H2AFX, MCM2, MCM3, MCM7, POLD1, and RPA1 were identified as markers for discrimination between COPD and NSCLC. The modular gene signatures were mainly enriched in the processes of DNA replication, cell cycle, mismatch repair, and others. Besides, the expression levels of these genes were significantly higher in NSCLC than in COPD, which was further verified by the immunohistochemistry. In addition, the high expression levels of H2AFX, MCM2, MCM7, and POLD1 correlate with poor prognosis of lung adenocarcinoma (LUAD). The Cox regression prognostic risk model showed the similar results and the predictive ability of this model is independent of other clinical variables.Conclusions: This study revealed several key modules that closely relate to NSCLC with underlying disease COPD, which provide a deeper understanding of the potential mechanisms underlying the malignant development from COPD to NSCLC. This study provides valuable prognostic factors in high-risk lung cancer patients with COPD.

Molecular Nodal Restaging Based on CEACAM5, FGFR2b and PTPN11 Expression Adds No Relevant Clinical Information in Resected Non-Small Cell Lung Cancer

Background The relapse rate in non-small cell lung cancer (NSCLC) is high, even in localized disease, suggesting that the current approach to pathological staging is insufficiently sensitive to detect occult micrometastases present in resected lymph nodes. Therefore, we aimed to determine the prognostic value of the expression of embryonic molecular markers in histologically-negative lymph nodes of completely-resected NSCLC. Methods 76 completely-resected NSCLC patients were included: 60 pN0 and 16 pN1. Primary tumors and 347 lymph node were studied. CEACAM5, FGFR2b, and PTPN11 expression levels were evaluated through mRNA analysis using real-time RT-qPCR assay. Statistical analyses included the Kruskal-Wallis test, Kaplan Meier curves, and log-rank tests. Results CEACAM5 expression levels were scored as high in of 90 lymph nodes (26%). The molecular-positive lymph nodes lead to the restaging of 37 (62%) pN0 patients as molecular N1 or N2 and 5 (31%) pN1 cases were reclassified as molecular-positive N2. Surprisingly, molecular-positive patients associated with a better OS (overall survival, p = 0,04). FGFR2b overexpression was observed in 41 (12%) lymph nodes leading to the restaging of 17 patients (22%). Again a trend was observed toward a better DFS (disease-free survival) in the restaged patients (p = 0,09). Accordingly, high expression levels of CEACAM5 or FGFR2b in the primary were related to better DFS (p = 0,06; p < 0,02, respectively). Conclusion Molecular nodal restaging based on expression levels of CEACAM5 and/or FGFR2b, does not add relevant clinical information to pathological staging of NSCLC likely related to the better prognosis of their overexpression in primary tumors.

Alternative methods of lymph node staging in lung cancer: a narrative review.

The nodal status indicator in non-small cell lung cancer is one of the most crucial prognostic factors available. However, there are still many arguments among scientists regarding whether the currently used nodal status descriptor should be changed in the forthcoming editions of the Tumor Node Metastasis classification or whether it is precise enough and should be maintained as is. We reviewed studies concerning nodal factor classifications to evaluate their accuracy in non-small cell lung cancer patients and to address the previously mentioned challenge. We reviewed the PubMed database regarding the following classifications: ongoing 8th edition of the Tumor Node Metastasis classification, number of positive lymph nodes, number of negative lymph nodes, number of dissected lymph nodes, lymph node ratio, nodal chains, log odds of positive lymph nodes, zone-based classification and one that is based on the number of lymph node stations involved. Moreover, we analysed data regarding various combinations of these classifications. Our analysis showed that the present nodal staging may not accurately categorize every lung cancer patient. The number of positive lymph nodes and lymph node ratio or the log odds of positive lymph nodes (as the mathematical modification of lymph node ratio) are more legitimate, as they possess very robust data and should be considered initially as additional factors that can be incorporated in ongoing nodal staging systems. Forthcoming non-small cell lung cancer staging systems could benefit from the addition of quantitative-based parameters. Additionally, the minimal extent of lymphadenectomy should be established as staging benefits from it. International, prospective validation studies need to be performed to optimize the cut-off values and prognostic groups and to confirm the superiority of the newly suggested descriptors in non-small cell lung cancer nodal staging.

Clinical significance of circ-MTHFD2 in diagnosis, pathological staging and prognosis of NSCLC.

To explore the clinical significance of circ-MTHFD2 in the diagnosis, pathological staging, and prognosis of non-small cell lung cancer (NSCLC). A total of 100 pairs of cancer tissues and adjacent tissues were surgically removed from NSCLC patients treated from July 2011 to January 2013 in our hospital were selected. All tissue samples were pathologically confirmed. Real Time-Polymerase Chain Reaction (qRT-PCR) was adopted to detect the expression of circ-MTHFD2 in NSCLC samples and its characteristic as a circular ribonucleic acid (circRNA). The receiver operating characteristic (ROC) curve was drawn to determine the diagnostic potential of circ-MTHFD2 in NSCLC. The relationship between circ-MTHFD2 expression and the clinical characteristics of NSCLC patients was analyzed by the χ2-test. Kaplan-Meier survival curves were depicted to assess the prognostic potential of circ-MTHFD2 in NSCLC. The effect of circ-MTHFD2 on the overall survival rate of NSCLC patients was uncovered by introducing the Cox proportional hazards model. The expression of circ-MTHFD2 in cancer tissues of NSCLC patients was higher than that in adjacent tissues (p<0.05), and there was no remarkable difference in the expression of circ-MTHFD2 before and after RNase R digestion (p>0.05). The area under the curve (AUC) of circ-MTHFD2 ROC was 0.701, with the cut-off value of 3.534, 90% sensitivity and 71% specificity. Circ-MTHFD2 expression was closely associated with smoking history, tumor size, tumor-node-metastasis (TNM) stage, lymph node metastasis, and recurrence in NSCLC patients (p<0.05). The prognosis of NSCLC patients with high expression of circ-MTHFD2 was evidently poorer than those with low expression. High expression of circ-MTHFD2 was an independent risk factor affecting the prognosis in NSCLC (p<0.05). The high expression of circ-MTHFD2 has clinical significance in the diagnosis, pathological staging, and prognosis of NSCLC.

Recent and Current Advances in FDG-PET Imaging within the Field of Clinical Oncology in NSCLC: A Review of the Literature.

Lung cancer is the leading cause of cancer-related deaths around the world, the most common type of which is non-small-cell lung cancer (NSCLC). Computed tomography (CT) is required for patients with NSCLC, but often involves diagnostic issues and large intra- and interobserver variability. The anatomic data obtained using CT can be supplemented by the metabolic data obtained using fluorodeoxyglucose F 18 (FDG) positron emission tomography (PET); therefore, the use of FDG-PET/CT for staging NSCLC is recommended, as it provides more accuracy than either modality alone. Furthermore, FDG-PET/magnetic resonance imaging (MRI) provides useful information on metabolic activity and tumor cellularity, and has become increasingly popular. A number of studies have described FDG-PET/MRI as having a high diagnostic performance in NSCLC staging. Therefore, multidimensional functional imaging using FDG-PET/MRI is promising for evaluating the activity of the intratumoral environment. Radiomics is the quantitative extraction of imaging features from medical scans. The chief advantages of FDG-PET/CT radiomics are the ability to capture information beyond the capabilities of the human eye, non-invasiveness, the (virtually) real-time response, and full-field analysis of the lesion. This review summarizes the recent advances in FDG-PET imaging within the field of clinical oncology in NSCLC, with a focus on surgery and prognostication, and investigates the site-specific strengths and limitations of FDG-PET/CT. Overall, the goal of treatment for NSCLC is to provide the best opportunity for long-term survival; therefore, FDG-PET/CT is expected to play an increasingly important role in deciding the appropriate treatment for such patients.

Hybrid PET/MRI in non-small cell lung cancer (NSCLC) and lung nodules-a literature review.

The use of hybrid PET/MRI for clinical staging is growing in several cancer forms and, consequently, PET/MRI has also gained interest in the assessment of non-small cell lung cancer (NSCLC) and lung lesions. However, lung evaluation with PET/MRI is associated with challenges related to technical issues and diagnostic image quality. We, therefore, investigated the published literature on PET/MRI for clinical staging in NSCLC or lung nodule detection specifically addressing diagnostic accuracy and technical issues. The data originates from a systematic search performed in PubMed/MEDLINE, Embase, and Cochrane Library on hybrid PET/MRI in patients with cancer for a scoping review published earlier ( https://doi.org/10.1007/s00259-019-04402-8 ). Studies in English and German evaluating the diagnostic performance of hybrid PET/MRI for NSCLC or lung nodule detection in cancer patients were selected. Data reported in peer-reviewed journals without restrictions to year of publication were included. A total of 3138 publications were identified from which 116 published 2012-2018 were included. Of these, nine studies addressed PET/MRI in NSCLC (4) or lung nodule detection (5). Overall, PET/MRI did not provide advantages in preoperative T- and N-staging in NSCLC compared to PET/CT. The data on M-staging were too few for conclusions to be drawn. The lung nodule detection rate of PET/MRI was comparable to that of PET/CT for FDG-avid nodules larger than 10mm, but the sensitivity of PET/MRI for detection of non-FDG-avid nodules smaller than 5mm was low. PET/MRI did not provide advantages in T- and N-staging of NSCLC compared to PET/CT. PET/MRI had a comparable sensitivity for detection of FDG-avid lung nodules and nodules over 10mm, but PET/CT yielded a higher detection rate in non FDG-avid lung nodules under 5mm. With PET/MRI, the overall detection rate for lung nodules in various cancer types remains inferior to that of PET/CT due to the lower diagnostic performance of MRI than CT in the lungs.

Considerations for the Surgical Management of Early Stage Lung Cancer During the COVID-19 Pandemic

The highly transmissible novel coronavirus (COVID-19) has infected over 8.8 million people globally and has upended the delivery of health care in the United States, creating unprecedented challenges to providing care to patients with early stage non–small cell lung cancer (NSCLC). The initial surge of patients with COVID-19 that have flooded hospitals has put a strain on physical space, workforce, and supplies. In addition, social distancing and the risk of COVID-19 transmission has created significant barriers for thoracic surgeons to diagnose and treat patients. Many hospitals across the country have temporarily suspended elective operations to preserve hospital beds, ventilators, and personal protective equipment. Currently, the pandemic has greatly disrupted the current standard of resection after adequate staging with imaging and/or surgical staging for early stage NSCLC well beyond the initial acute phase; therefore, a new paradigm for effective management will need to be devised until the COVID-19 pandemic is eradicated with systematic vaccination and herd immunity. Thoracic surgeons will need to recalibrate their approach to ensure that patients receive timely and effective treatment for early stage NSCLC. The management of early stage NSCLC during the COVID-19 pandemic should be balanced with available hospital resources, risk of progression of disease, risk of transmission of COVID-19 to patient and surgeon, and the availability of alternative therapies. This article will address the current challenges with treating early stage NSCLC during the COVID-19 pandemic and provide a clinical framework for providing effective surgical therapy while mitigating the risk of transmission of the SARS-CoV-2 virus to patients and surgeons.

UTILITY OF ENDOBRONCHIAL ULTRASOUND-GUIDED LYMPH NODE BIOPSY IN RADIOGRAPHIC STAGE 1 LUNG CANCER

TYPE: Abstract Publication TOPIC: Procedures PURPOSE: Current guidelines recommend using endobronchial ultrasound guided lymph node biopsy (EBUS) in staging non-small cell lung cancer (NSCLC) with evidence of lymphatic metastasis, in primary tumor located centrally, and in tumors > 3cm in size. In patients with radiographic stage 1 (RS1) there are no recommendations on EBUS, yet it is still widely performed. We aim to show that in radiographic stage 1 NSCLC, surveillance of all mediastinal and hilar nodes is not necessary. METHODS: A retrospective study identifying patients that underwent an EBUS from January 2005 to May 2019 in adult patients who underwent both a CT and PET/CT that showed a RS1 lung nodule prior to an EBUS. All included patients had proven NSCLC from the identified nodule. RESULTS: 188 patients were included with demographic data displayed in Table 1. Of those, 13 (6.9%; 95% CI, 4.1%-11.5%) had a positive lymph node with 6 (3.2%; 95% CI, 1.5%-6.8%) were N1 nodes and 7 (3.7%; 95% CI, 1.8%-7.5%) were N2 nodes. Multivariate analysis with the significant variables in univariate anaylsis showed that only the amount of smoking was significant to upstaging lymph nodes (p=0.04). CONCLUSIONS: This study supports the use of EBUS for staging RS1 lung cancer, but with limited lymph node surveillance showing no positive N3 nodes in our cohort which shows sampling of N3 nodes is not indicated in RS1 tumors. CLINICAL IMPLICATIONS: EBUS is stil extremely valuable, but this study supports less lymph node sampling in specific patients. DISCLOSURE: No significant relationships. KEYWORDS: lung cancer, EBUS, Staging

Clinical Non–Small Cell Lung Cancer Staging and Tumor Length Measurement Results From U.S. Cancer Hospitals

Examine the accuracy of clinical non-small cell lung cancer staging and tumor length measurements, which are critical to prognosis and treatment planning. Compare clinical and pathological staging and lengths using 10,320 2016 National Cancer Institute Surveillance, Epidemiology, and End Results (SEER) and 559 2010-2018 non-SEER single-institute surgically-treated cases, and analyze modifiable causes of disagreement. The SEER clinical and pathological group-stages agree only 62.3% ± 0.9% over all stage categories. The lymph node N-stage agrees much better at 83.0% ± 1.0%, but the tumor length-location T-stage agrees only 57.7% ± 0.8% with approximately 29% of the cases having a greater pathology than clinical T-stage. Individual T-stage category agreements with respect to the number of pathology cases are Tis, T1a, T1b, T2a, T2b, T3, T4: 89.9% ± 10.0%; 78.7% ± 1.7%; 51.8% ± 1.9%; 46.1% ± 1.3%; 40.5% ± 3.1%; 44.1% ± 2.2%; 56.4% ± 4.7%, respectively. Most of the single-institute results statistically agree with SEER's. Excluding Tis cases, the mean difference in SEER tumor length is ∼1.18 ± 9.26 mm (confidence interval: 0.97-1.39 mm) with pathological lengths being longer than clinical lengths except for small tumors; the two measurements correlate well (Pearson-r >0.87, confidence interval: 0.86-0.87). Reasons for disagreement include the use of family-category descriptors (e.g., T1) instead of their subcategories (e.g., T1a and T1b), which worsens the T-stage agreement by over 15%. Disagreement is also associated with higher tumor grade, larger resected specimens, higher N-stage, patient age, and periodic biases in clinical and pathological tumor size measurements. By including preliminary non-small cell lung cancer clinical stage values in their evaluation, diagnostic radiologists can improve the accuracy of staging and standardize tumor-size measurements, which improves patient care.

Classification of non-small cell lung cancer using one-dimensional convolutional neural network

Non-Small Cell Lung Cancer (NSCLC) is a major lung cancer type. Proper diagnosis depends mainly on tumor staging and grading. Pathological prognosis often faces problems because of the limited availability of tissue samples. Machine learning methods may play a vital role in such cases. 2D or 3D Deep Neural Networks (DNNs) has been the predominant technology in this domain. Contemporary studies tried to classify NSCLC tumors as benign or malignant. The application of 1D CNN in automated staging and grading of NSCLC is not very frequent. The aim of the present study is to develop a 1D CNN model for automated staging and grading of NSCLC. The updated NSCLC Radiogenomics Collection from The Cancer Imaging Archive (TCIA) was used in the study. The segmented tumor images were fed into a hybrid feature detection and extraction model (MSER-SURF). The extracted features were clubbed with the clinical TNM stage and histopathological grade information and fed into the 1D CNN model. The performance of the proposed CNN model was satisfactory. The accuracy and ROC-AUC score were higher than the other leading machine learning methods. The study also did well compared to state-of-the-art studies. The proposed model shows that 1D CNN is equally useful in NSCLC prediction like a conventional 2D/3D CNN model. The model may further be refined by carrying out experiments with varied hyper-parameters. Further studies may be conducted by considering semi-supervised or unsupervised learning techniques.

18F-FDG PET/CT and whole-body MRI diagnostic performance in M staging for non-small cell lung cancer: a systematic review and meta-analysis.

To evaluate the diagnostic test accuracy of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT), whole-body magnetic resonance imaging (WB-MRI), and whole-body diffusion-weighted imaging (WB-DWI) for the detection of metastases in patients with non-small cell lung cancer (NSCLC). MEDLINE, Embase, and Cochrane Library databases were searched up to June 2019. Studies were selected if they reported data that could be used to construct contingency tables to compare 18F-FDG PET/CT, WB-MRI, and WB-DWI. Two authors independently extracted data on study characteristics and assessed methodological quality using the Quality Assessment of Diagnostic Accuracy Studies. Forest plots were generated for sensitivity and specificity of 18F-FDG PET/CT, WB-MRI, and whole-body diffusion-weighted imaging (WB-DWI). Summary receiver operating characteristic plots were created. The 4 studies meeting inclusion criteria had a total of 564 patients and 559 lesions, 233 of which were metastases. In studies of 18F-FDG PET/CT, the pooled estimates of sensitivity and specificity were 0.83 (95% confidence interval [CI], 0.54-0.95) and 0.93 (95% CI, 0.87-0.96), respectively. For WB-MRI, pooled sensitivity was 0.92 (95% CI, 0.18-1.00) and pooled specificity was 0.93 (95% CI, 0.85-0.95). Pooled sensitivity and specificity for WB-DWI were 0.78 (95% CI, 0.46-0.93) and 0.91 (95% CI, 0.79-0.96), respectively. There was no statistical difference between the diagnostic odds ratio of WB-MRI and WB-DWI compared with that of PET/CT (p = 0.186 for WB-DWI; p = 0.638 for WB-MRI). WB-MRI and DWI are radiation-free alternatives with comparable diagnostic performance to 18F-FDG PET/CT for M staging of NSCLC. • Whole-body MRI with or without diffusion-weighted imaging has a high accuracy for the diagnostic evaluation of metastases in patients with non-small cell lung cancer. • Whole-body MRI may be used as a non-invasive and radiation-free alternative to positron emission tomography with CT with similar diagnostic performance.

Application of computed tomography, positron emission tomography-computed tomography, magnetic resonance imaging, endobronchial ultrasound, and mediastinoscopy in the diagnosis of mediastinal lymph node staging of non-small-cell lung cancer: A protocol for a systematic review.

Background:Ruling out distant metastases, non-small cell lung cancer (NSCLC)treatment depends on the results of mediastinal node staging (N staging). Several diagnostic methods play central roles in mediastinal N staging. This study is intended to evaluate the existing diagnostic methods and report quality, and to search for the best method for staging mediastinal lymph nodes.Methods:We searched PubMed, Embase, and the Cochrane Library to identify relevant studies, including randomized controlled trials and retrospective studies. These studies report the application of computed tomography, positron emission tomography-computed tomography, magnetic resonance imaging, endobronchial ultrasound, and mediastinoscopy in the diagnosis of mediastinal lymph node staging of NSCLC. The quality of the literature was assessed using the Quality Assessment of Diagnostic Accuracy Study 2. The true positive, false positive, true negative, and false negative of each study was extracted. The corresponding sensitivity, specificity, and other indicators were calculated and the Summary Receiver Operating curve was established. Then, head-to-head and indirect comparison meta-analyses will be conducted.Results:The results of this study will be published in a peer-reviewed journal.Conclusion:This study will provide basis for mediastinal lymph node staging of non-small cell lung cancer.PROSPERO registration number:CRD42019145667

The need of a clinically oriented reporting of 18F-FDG PET/CT in non-small cell lung cancer (NSCLC)

In the present review, we aimed to underline the importance of a clinically oriented PET reporting through the discussion of critical aspects that affect the impact of PET in NSCLC patients. Cornerstones for PET reporting related to staging of NSCLC after the publication of the new 8th edition of TNM and emerging issues related to locally advanced disease, to restaging and to response evaluation to innovative therapies are listed and specifically commented. 18F-FDG PET/CT imaging has a prominent role in NSCLC patients both prior to surgery and when evaluating for metastatic disease. The benefit is even most marked in patients at greater risk of distant metastases. In this framework, for patients with stage III, PET imaging has the potential to result in a stage-shift through the identification of asymptomatic occult distant metastases, thus highlighting unexpected stage IV patients. The final PET report is influenced by factors that lie outside the acquired images, from the clinical information available at the time of reporting to the capability of linking these clinical details to further decision-making especially in the settings of response to new therapies. A multidisciplinary approach to cancer patients has a significant impact in their management and outcome. A clinically-oriented report is needed to transfer the relevant information to the clinician to fully exploit PET potential in NSCLC.

MiRNA-200a-3p suppresses the proliferation, migration and invasion of non-small cell lung cancer through targeting IRS2.

To uncover the biological role of microRNA-200a-3p (miRNA-200a-3p) in the progression of non-small cell lung cancer (NSCLC) and the underlying mechanism. The expression levels of miRNA-200a-3p and IRS2 in NSCLC tissues and cell lines were examined through quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). The correlation between the miRNA-200a-3p level and pathological characteristics of NSCLC patients was analyzed. The prognostic value of miRNA-200a-3p in NSCLC was assessed through the Kaplan-Meier method. The potential interaction between miRNA-200a-3p and IRS2 was explored through Dual-Luciferase Reporter Gene Assay and Spearman correlation test. The regulatory effects of miRNA-200a-3p/IRS2 on the proliferative, migratory, and invasive abilities of NSCLC were evaluated by Cell Counting Kit-8 (CCK-8) and the transwell assay. The protein levels of the epithelial-mesenchymal transition (EMT)-related genes in NSCLC cells influenced by miRNA-200a-3p were detected by Western blot. MiRNA-200a-3p was downregulated in NSCLC tissues and cell lines. The expression level of miRNA-200a-3p was related to tumor size, TNM staging, and lymphatic metastasis of NSCLC. The low level of miRNA-200a-3p predicted worse prognosis in NSCLC patients. The overexpression of miRNA-200a-3p inhibited A549 cells from proliferating, migrating, and invading. The protein levels of E-cadherin were upregulated, while N-cadherin and Vimentin were downregulated in A549 cells overexpressing miRNA-200a-3p. The Dual-Luciferase Reporter Gene Assay verified the binding between miRNA-200a-3p and IRS2. The level of IRS2 was negatively regulated by miRNA-200a-3p. Moreover, the overexpression of IRS2 could reverse the regulatory role of miRNA-200a-3p in the cellular behaviors of A549 cells. MiRNA-200a-3p suppresses the proliferative, migratory, and invasive abilities of NSCLC by targeting IRS2, thus alleviating the progression of NSCLC.

EBUS-TBNA versus surgical mediastinoscopy for mediastinal lymph node staging in potentially operable non-small cell lung cancer: a systematic review and meta-analysis.

Lung cancer (LC) is one of the leading causes of death worldwide. Accurate mediastinal staging is mandatory in order to assess prognosis and to select patients for surgical treatment. EBUS-TBNA is a minimally invasive procedure that allows sampling of mediastinal lymph nodes (LNs). Some studies have suggested that EBUS-TBNA is preferable to surgical mediastinoscopy for mediastinal staging of LC. The objective of this systematic review and meta-analysis was to compare EBUS-TBNA and mediastinoscopy in terms of their effectiveness for mediastinal LN staging in potentially operable non-small cell lung cancer (NSCLC). This was a systematic review and meta-analysis, in which we searched various databases. We included studies comparing the accuracy of EBUS-TBNA with that of mediastinoscopy for mediastinal LN staging in patients with NSCLC. In the meta-analysis, we calculated sensitivity, specificity, positive likelihood ratios, and negative likelihood ratios. We also analyzed the risk difference for the reported complications associated with each procedure. The search identified 4,201 articles, 5 of which (with a combined total of 532 patients) were selected for inclusion in the meta-analysis. There were no statistically significant differences between EBUS-TBNA and mediastinoscopy in terms of the sensitivity (81% vs. 75%), specificity (100% for both), positive likelihood ratio (101.03 vs. 95.70), or negative likelihood ratio (0.21 vs. 0.23). The area under the summary ROC curve was 0.9881 and 0.9895 for EBUS-TBNA and mediastinoscopy, respectively. Although the number of complications was higher for mediastinoscopy, the difference was not significant (risk difference: -0.03; 95% CI: -0.07 to 0.01; I2 = 76%). EBUS-TBNA and mediastinoscopy produced similar results for mediastinal staging of NSCLC. EBUS-TBNA can be the procedure of first choice for LN staging in patients with NSCLC.

Simplified, standardized methods to assess the accuracy of clinical cancer staging

BackgroundHospitals lack intuitive methods to monitor their accuracy of clinical cancer staging, which is critical to treatment planning, prognosis, refinements, and registering quality data. MethodsWe introduce a tabulation framework to compare clinical staging with the reference-standard pathological staging, and quantify systematic errors. As an example, we analyzed 9,644 2016 U.S. National Cancer Institute SEER surgically-treated non-small cell lung cancer (NSCLC) cases, and computed concordance with different denominators to compare with incompatible past results. ResultsThe concordance for clinical versus pathological lymph node N-stage is very good, 83.4 ± 1.0%, but the tumor length-location T-stage is only 58.1 ± 0.9%. There are intuitive insights to the causes of discordance. Approximately 29% of the cases are pathological T-stage greater than clinical T-stage, and 12% lower than the clinical T-stage, which is due partly to the fact that surgically-treated NSCLC are typically lower-stage cancer cases, which results in a bounded higher probability for pathological upstaging. Individual T-stage categories Tis, T1a, T1b, T2a, T2b, T3, T4 invariant percent-concordances are 85.2 ± 9.7 + 10.3%; 72.7 ± 1.6 + 11.3%; 46.6 ± 1.8 + 10.9%; 54.6 ± 1.6 – 20.5%; 41.6 ± 3.3 – 0.1%; 54.7 ± 2.8 – 24.1%; 55.2 ± 4.7 + 2.6%, respectively. Each percent-concordance is referenced to an averaged number of pathological and clinical cases. The first error number quantifies statistical fluctuations; the second quantifies clinical and pathological staging biases. Lastly, comparison of over and under staging versus clinical characteristics provides further insights. ConclusionsClinical NSCLC staging accuracy and concordance with pathological values can improve. As a first step, the framework enables standardizing comparing staging results and detecting possible problem areas. Cancer hospitals and registries can implement the efficient framework to monitor staging accuracy.

Comparison of Conventional TNM and Novel TNMB Staging Systems for Non–Small Cell Lung Cancer

Improved staging for non-small cell lung cancer (NSCLC) represents a critical unmet need. External validations of the eighth edition of the TNM staging system have yielded disappointing results, with persistently high mortality observed in early-stage disease. To determine whether incorporation of a molecular prognostic classifier into conventional TNM staging for NSCLC improves estimation of disease-free survival. This cohort study was conducted at an academic, quaternary care medical center from 2012 to 2018. A consecutive series of 238 patients underwent surgical resection of stage I to IIIC nonsquamous NSCLC and had molecular prognostic classifier testing performed. Data analysis was conducted in May 2019. Patients were restaged according to the seventh and eighth editions of the TNM staging system and the novel TMMB staging system, which maintains the order and structure of the eighth edition of the TNM but downstages or upstages according to low or high molecular risk, respectively. The primary outcome was disease-free survival 3 years from the time of surgical resection. Reclassification statistics were then used to evaluate performance and improvement measures of the TNM seventh and eighth editions and the TNMB staging system. Two hundred thirty-eight patients (144 [60.5%] female; median [interquartile range] age, 70 [63-75] years) were analyzed. The median (interquartile range) follow-up was 25 (14-40) months, and the disease-free survival rate was estimated to be 58.3% (95% CI, 45.7% to 69.0%). One hundred fifty-nine patients (66.8%) were reclassified by the TNMB staging system. Overall model fit remained the same for the seventh and eighth editions of the TNM staging system, whereas the R2 statistic (change from 0.22 to 0.31), concordance index (change from 0.68 to 0.73), and log-rank χ2 (change from 38 to 108) were all associated with improvements after TNMB adoption. The TNMB system, compared with the TNM eighth edition, was associated with enhanced identification of high-risk patients and better differentiation of those without recurrence from those who had recurrence (net reclassification improvement, 0.28; 95% CI, 0.08 to 0.46; P < .001), whereas the eighth edition compared with the seventh edition was not associated with improvement of this measure (net reclassification improvement, 0.02; 95% CI, -0.18 to 0.21; P = .87). The TNMB staging system was associated with improved estimation of disease-free survival compared with conventional TNM staging. Incorporation of a molecular prognostic classifier into staging for NSCLC may lead to better identification of high-risk patients.

The added value of18F-FDG PET/CT in staging non-small cell lung cancer

BackgroundNon-small cell lung cancer (NSCLC) accounts for about 80% of all lung cancers. The current criteria for its staging are based on the TNM system that determines treatment options and predicts survival rate in patients. The aim of the study was to evaluate the diagnostic accuracy of 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography PET/CT in staging of NSCLC patients.MethodsA retrospective study was conducted. We reviewed the CT and PET/CT examinations done in our institution on pathologically proven patients of NSCLC, in the period between October 2018 and end of July 2019.ResultsA total of 40 patients were evaluated with the age ranging from 37 to 77 years old, and the mean was 55.63 years (SD ± 10.29). There were 31 male cases and 9 female cases. When we compared contrast enhanced CT (CECT) to PET-CT for staging, PET-CT helped upstage disease in 10 of 40 patients (25%) and downstage in 3 of 40 patients (7.5%).ConclusionPET/CT is a useful imaging tool in initial staging of the newly diagnosed patients with NSCLC. It is better thаn СT alone fоr detection of malignant lesions for accurate staging. It can change the strategy of treatment according to its findings.