scholarly journals Comparison of Diagnostic Performance of Spread Through Airspaces of Lung Adenocarcinoma Based on Morphological Analysis and Perinodular and Intranodular Radiomic Features on Chest CT Images

2021 ◽  
Vol 11 ◽  
Author(s):  
Lin Qi ◽  
Xiaohu Li ◽  
Linyang He ◽  
Guohua Cheng ◽  
Yongjun Cai ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Morphological Analysis ◽  
External Validation ◽  
Free Survival ◽  
Poor Differentiation ◽  
Validation Set ◽  
Tumor Edge ◽  
Contrast Ct ◽  
Lung Adenocarcinomas ◽  
Radiologic Features

ObjectSTAS is associated with poor differentiation, KRAS mutation and poor recurrence-free survival. The aims of this study are to evaluate the ability of intra- and perinodular radiomic features to distinguish STAS at non-contrast CT.Patients and MethodsThis retrospective study included 216 patients with pathologically confirmed lung adenocarcinoma (STAS+, n = 56; STAS−, n = 160). Texture-based features were extracted from intra- and perinodular regions of 2, 4, 6, 8, 10, and 20 mm distances from the tumor edge using an erosion and expansion algorithm. Traditional radiologic features were also analyzed including size, consolidation tumor ratio (CTR), density, shape, vascular change, cystic airspaces, tumor–lung interface, lobulation, spiculation, and satellite sign. Nine radiomic models were established by using the eight separate models and a total of the eight VOIs (eight-VOI model). Then the prediction efficiencies of the nine radiomic models were compared to predict STAS of lung adenocarcinomas.ResultsAmong the traditional radiologic features, CTR, unclear tumor–lung interface, and satellite sign were found to be associated with STAS significantly, and the AUCs were 0.796, 0.677, and 0.606, respectively. Radiomic model of combined tumor bodies and all the distances of perinodular areas (eight-VOI model) had better predictive efficiency for predicting STAS+ lung adenocarcinoma. The AUCs of the eight-VOI model in the training and verification sets were 0.907 (95%CI, 0.862–0.947) in the training set, and 0.897 (95%CI, 0.784–0.985) in the testing set, and 0.909 (95%CI, 0.863–0.949) in the external validation set, and the diagnostic accuracy in the external validation set was 0.849.ConclusionRadiomic features from intra- and perinodular regions of nodules can best distinguish STAS of lung adenocarcinoma.

scholarly journals A methylomics-correlated nomogram predicts the recurrence free survival risk of kidney renal clear cell carcinoma

2021 ◽  
Vol 18 (6) ◽  
pp. 8559-8576
Author(s):  
Xiuxian Zhu ◽  
◽  
Xianxiong Ma ◽  
Chuanqing Wu
Keyword(s):  
Dna Methylation ◽  
Cell Carcinoma ◽  
Roc Analysis ◽  
Clear Cell ◽  
Clear Cell Carcinoma ◽  
External Validation ◽  
Renal Clear Cell Carcinoma ◽  
Recurrence Free Survival ◽  
Free Survival ◽  
Validation Set

<abstract> <sec><title>Background</title><p>Various studies have suggested that the DNA methylation signatures were promising to identify novel hallmarks for predicting prognosis of cancer. However, few studies have explored the capacity of DNA methylation for prognostic prediction in patients with kidney renal clear cell carcinoma (KIRC). It's very promising to develop a methylomics-related signature for predicting prognosis of KIRC.</p> </sec> <sec><title>Methods</title><p>The 282 patients with complete DNA methylation data and corresponding clinical information were selected to construct the prognostic model. The 282 patients were grouped into a training set (70%, n = 198 samples) to determine a prognostic predictor by univariate Cox proportional hazard analysis, least absolute shrinkage and selection operator (LASSO) and multivariate Cox regression analysis. The internal validation set (30%, n = 84) and an external validation set (E-MTAB-3274) were used to validate the predictive value of the predictor by receiver operating characteristic (ROC) analysis and Kaplan–Meier survival analysis.</p> </sec> <sec><title>Results</title><p>We successfully identified a 9-DNA methylation signature for recurrence free survival (RFS) of KIRC patients. We proved the strong robustness of the 9-DNA methylation signature for predicting RFS through ROC analysis (AUC at 1, 3, 5 years in internal dataset (0.859, 0.840, 0.817, respectively), external validation dataset (0.674, 0.739, 0.793, respectively), entire TCGA dataset (0.834, 0.862, 0.842, respectively)). In addition, a nomogram combining methylation risk score with the conventional clinic-related covariates was constructed to improve the prognostic predicted ability for KIRC patients. The result implied a good performance of the nomogram.</p> </sec> <sec><title>Conclusions</title><p>we successfully identified a DNA methylation-associated nomogram, which was helpful in improving the prognostic predictive ability of KIRC patients.</p> </sec> </abstract>

The correlation between mutation burden and disease free survival in patients with lung adenocarcinomas.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 8550-8550 ◽  
Author(s):  
Changzheng Wang ◽  
Shuang Xin ◽  
Xulian Shi ◽  
Xin Zhao ◽  
Kui Wu ◽  
...  
Keyword(s):  
Survival Analysis ◽  
Lung Adenocarcinoma ◽  
Smoking Status ◽  
Disease Free Survival ◽  
Smoking History ◽  
P Value ◽  
Free Survival ◽  
Mutation Burden ◽  
Lung Adenocarcinomas ◽  
Disease Free

8550 Background: Lung cancer is one of the leading causes of cancerous deaths globally. High mutation burden is a special character in lung adenocarcinoma patients. Mutation burden is usually based on the number of non-synonymous mutations implying the instability of genome. We hypothesize genome-wide mutation burden indicates mutation degree and is correlated with prognostic in lung adenocarcinoma. Methods: Whole-exome sequencing was performed on 98 Chinese lung adenocarcinoma patients with tumor and normal tissue to a mean depth of 49.6ⅹ. The total number of non-synonymous somatic mutations was calculated from the sequencing data of each patient. Patients were divided into high mutation burden and low mutation burden groups in accordance with the mean mutation burden and Kaplan-Meier analysis was performed for survival analysis between these two groups. The association between mutation burden and age or smoking status was analyzed by Wilcoxon rank-sum test. Results: Among these 98 patients, the values of mutation burden varied from 5 to 1121 with mean value 161.8, 36 (36.7%) patients with smoking history and 34 (34.7%) patients were older than 65 years; the numbers of patients in I, II, III stage were 19 (19.4%), 16 (16.3%) and 63 (64.3%) respectively. 32 patients were classified into high mutation burden group, the other 66 patients classified into low mutation burden group. Survival analysis showed a significantly longer disease free survival (DFS) in low mutation burden group (p-value = 0.0133).Mutation burden was significantly associated with age ( < 65 vs ≥65, p-value = 0.0208) and smoking status (p-value = 8.67ⅹ10-4). Conclusions: The association between mutation burden and age or smoking status suggested the high risk for mutation burden accumulation. The significant difference of DFS between high mutation burden and low mutation burden groups reveals the potential of mutation burden as one of the prognostic factors in patients with lung adenocarcinomas.

scholarly journals Radiomics signature on CECT as a predictive factor for invasiveness of lung adenocarcinoma manifesting as subcentimeter ground glass nodules

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Wufei Chen ◽  
Ming Li ◽  
Dingbiao Mao ◽  
Xiaojun Ge ◽  
Jiaofeng Wang ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Predictive Performance ◽  
Ground Glass ◽  
Contrast Enhanced Ct ◽  
Contrast Enhanced ◽  
Enhanced Ct ◽  
Validation Set ◽  
Lung Adenocarcinomas ◽  
Radiomics Signature ◽  
Ground Glass Nodules

AbstractControversy and challenges remain regarding the cognition of lung adenocarcinomas presented as subcentimeter ground glass nodules (GGNs). Postoperative lymphatic involvement or intrapulmonary metastasis is found in approximately 15% to 20% of these cases. This study aimed to develop and validate a radiomics signature to identify the invasiveness of lung adenocarcinoma appearing as subcentimeter ground glass nodules. We retrospectively enrolled 318 subcentimeter GGNs with histopathology-confirmed adenocarcinomas in situ (AIS), minimally invasive adenocarcinomas (MIA) and invasive adenocarcinomas (IAC). The radiomics features were extracted from manual segmentation based on contrast-enhanced CT (CECT) and non-contrast enhanced CT (NCECT) images after imaging preprocessing. The Lasso algorithm was applied to construct radiomics signatures. The predictive performance of radiomics models was evaluated by receiver operating characteristic (ROC) analysis. A radiographic-radiomics combined nomogram was developed to evaluate its clinical utility. The radiomics signature on CECT (AUC: 0.896 [95% CI 0.815–0.977]) performed better than the radiomics signature on NCECT data (AUC: 0.851[95% CI 0.712–0.989]) in the validation set. An individualized prediction nomogram was developed using radiomics model on CECT and radiographic model including type, shape and vascular change. The C index of the nomogram was 0.915 in the training set and 0.881 in the validation set, demonstrating good discrimination. Decision curve analysis (DCA) revealed that the proposed model was clinically useful. The radiomics signature built on CECT could provide additional benefit to promote the preoperative prediction of invasiveness in patients with subcentimeter lung adenocarcinomas.

scholarly journals Impact on disease-free survival of adjuvant erlotinib or gefitinib in patients with resected lung adenocarcinomas that harbor epidermal growth factor receptor (EGFR) mutations

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 7523-7523
Author(s):  
Y. Y. Janjigian ◽  
B. J. Park ◽  
M. G. Kris ◽  
V. A. Miller ◽  
G. J. Riely ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Egfr Mutation ◽  
Disease Free Survival ◽  
Stage I ◽  
Egfr Mutations ◽  
Free Survival ◽  
Resected Stage ◽  
Lung Adenocarcinomas ◽  
Disease Free ◽  
Exon 19

7523 Background: Patients with stage IV adenocarcinoma whose tumors harbor EGFR mutations have high rates of response (∼ 75%) and prolonged progression free survival after EGFR tyrosine kinase inhibitor (TKI) treatment. Adjuvant cisplatin-based chemotherapy improves disease free survival (DFS) and overall survival (OS) in patients with resected stages IB-IIIA NSCLC. To see if adjuvant treatment with EGFR TKI (gefitinib or erlotinib) improves DFS in patients with EGFR mutation NSCLC, we conducted a retrospective review of patients with resected lung adenocarcinoma harboring EGFR mutations, some of whom received EGFR TKIs postoperatively. Methods: With Institutional Review Board approval, clinical information was obtained on all patients with stage I-III lung adenocarcinoma harboring EGFR exon 19 or 21 mutations that underwent resection at MSKCC between May 2002 and August 2008. Age, gender, type of surgery, histology, EGFR mutation status (exon 19 deletions and exon 21 L858R), stage, perioperative therapy and survival were recorded. Kaplan-Meier analysis and Cox regression analysis were performed. Results: We studied 150 patients (112 women, 38 men) with completely resected stage I-III lung adenocarcinoma whose resection specimens contained EGFR activating mutations in exon 19 or 21. Median age was 69. Forty two patients (28%) received cytotoxic chemotherapy. Forty eight (32%) received either erlotinib (n=26) or gefitinib (n=22) postoperatively. The median time on TKI was 16 months. The median DFS was 43 months in the group that received a TKI vs. 31 months for those that did not. After controlling for stage, individuals who received adjuvant gefitinib or erlotinib had a better DFS (HR=0.38, 95%CI: 0.16–0.90) than the non-TKI group (p=0.03). The median overall survival has not been reached. Conclusions: These data indicate that the adjuvant use of either gefitinib or erlotinib improves DFS in patients with completely resected stage I -III lung adenocarcinomas with mutations in EGFR exons 19 and 21. These data justify a randomized trial in similar patients. [Table: see text]

Decoy Receptor 3 Expression Is Associated With Wild-Type EGFR Status, Poor Differentiation of Tumor, and Unfavorable Patient Outcome

2019 ◽  
Vol 152 (2) ◽  
pp. 207-216
Author(s):  
Wei-Chin Chang ◽  
Yi-Chen Yeh ◽  
Hsiang-Ling Ho ◽  
Shie-Liang Hsieh ◽  
Teh-Ying Chou
Keyword(s):  
Lung Adenocarcinoma ◽  
Growth Factor Receptor ◽  
Disease Free Survival ◽  
Stage I ◽  
Wild Type ◽  
Decoy Receptor ◽  
Decoy Receptor 3 ◽  
Poor Differentiation ◽  
Epidermal Growth ◽  
Lung Adenocarcinomas

Abstract Objectives The role of decoy receptor 3 (DcR3) in lung cancer, particularly adenocarcinoma, has not been well studied. In this study, we aim to investigate the expression profile and the clinicopathologic implications of DcR3 expression in lung adenocarcinoma. Methods Immunohistochemistry was used to examine DcR3 expression in 461 lung adenocarcinomas. The differences in DcR3 expression among the various histopathologic patterns were analyzed. The relationship between DcR3 expression and clinicopathologic parameters, including epidermal growth factor receptor (EGFR) mutation, was also investigated. Results DcR3 expression was more frequently expressed in solid, micropapillary, and acinar patterns (P < .0001) and in tumors with wild-type EGFR status (P = .018). In addition, DcR3 expression portends a less favorable disease-free survival in stage I patients (P = .012). Conclusions The expression of DcR3 might be involved in the differentiation and progression of lung adenocarcinoma. Therefore, DcR3 may be applied clinically for prediction of tumor progression in stage I lung adenocarcinoma.

scholarly journals Comparative postoperative outcomes of GGN-dominant vs single lesion lung adenocarcinomas.

2020 ◽  
Author(s):  
Takamasa Hotta ◽  
Yukari Tsubata ◽  
Akari Tanino ◽  
Mika Nakao ◽  
Yoshihiro Amano ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Disease Free Survival ◽  
Asian Population ◽  
Ground Glass ◽  
Significant Extent ◽  
Free Survival ◽  
Lung Adenocarcinomas ◽  
Different Characteristics ◽  
Ground Glass Nodules

Abstract Background: Multiple synchronous ground glass nodules (GGNs) are known to be malignant, however, they tend to progress slowly. Multiple synchronous lesions in the same patient which show different characteristics must be treated individually.Methods: This was a retrospective review of 34 lung adenocarcinoma patients with multiple synchronous GGNs in an Asian population. One hundred twenty-seven single lung adenocarcinoma patients were included for comparison purposes. The follow-up period was 5 years for all patients. Results: The 5-year overall survival (OS) patients with multiple lesions did not differ from that of the patients with single lesions to a statistically significant extent (Single: 81.8% vs. Multiple: 88.2%, P=0.3602). Dominant tumors (DTs) with a ground glass component and consolidation were divided into three categories based on the consolidation-to-tumor ratio on radiological imaging. No significant differences were observed among the three DT categories. Twenty-four patients had unresected GGNs, while a progression of the unresected GGN occurred in 10 of these cases. The OS and disease-free survival (DFS) curves of patients with and without GGN progression did not differ to a statistically significant extent (OS: 80% vs. 92.9%, P=0.3870; DFS: 80% vs. 100%, P=0.0977).Conclusions: The outcomes were best predicted by the stage of the DT. After surgery patients require a careful follow-up because unresected GGNs may show progression. At the same time, the increase in residual lesions and the appearance of new GGNs were not related to OS. The management of such patients should be determined according to the DT with the worst prognosis.

scholarly journals Tumor Margin Contains Prognostic Information: Radiomic Margin Characteristics Analysis in Lung Adenocarcinoma Patients

Cancers ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1676
Author(s):  
Geewon Lee ◽  
Hyunjin Park ◽  
Ho Yun Lee ◽  
Joong Hyun Ahn ◽  
Insuk Sohn ◽  
...  
Keyword(s):  
Overall Survival ◽  
Lung Adenocarcinoma ◽  
External Validation ◽  
Quantitative Computed Tomography ◽  
Prognostic Information ◽  
Tumor Margin ◽  
Clinical Variables ◽  
Characteristics Analysis ◽  
Selection Operator ◽  
Lung Adenocarcinomas

We aimed to investigate the relationship between tumor radiomic margin characteristics and prognosis in patients with lung cancer. We enrolled 334 patients who underwent complete resection for lung adenocarcinoma. A quantitative computed tomography analysis was performed, and 76 radiomic margin characteristics were extracted. The radiomic margin characteristics were correlated with overall survival. The selected clinical variables and radiomic margin characteristics were used to calculate a prognostic model with subsequent internal and external validation. Nearly all of the radiomic margin characteristics showed excellent reproducibility. The least absolute shrinkage and selection operator (LASSO) method was used to select eight radiomic margin characteristics. When compared to the model with clinical variables only (C-index = 0.738), the model incorporating clinical variables and radiomic margin characteristics (C-index = 0.753) demonstrated a higher C-index for predicting overall survival. In the model integrating both clinical variables and radiomic margin characteristics, convexity, a Laplace of Gaussian (LoG) kurtosis of 3, and the roundness factor were each independently predictive of overall survival. In addition, radiomic margin characteristics were also correlated with the micropapillary subtype, and the sphericity value was able to predict the presence of the micropapillary subtype. In conclusion, our study showed that radiomic margin characteristics helped predict overall survival in patients with lung adenocarcinomas, thus implying that the tumor margin contains prognostic information.

The tyrosine kinase TEK is differentially expressed in non-small cell lung adenocarcinomas.

2020 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
United States ◽  
Tyrosine Kinase ◽  
Lung Adenocarcinoma ◽  
Microarray Data ◽  
The United States ◽  
Small Cell ◽  
Small Cell Lung ◽  
Significant Differential Expression ◽  
Lung Cancers ◽  
Lung Adenocarcinomas

Non-small cell lung adenocarcinoma (NSCLC) is a leading cause of death in the United States and worldwide (1, 2). We mined published microarray data (3, 4, 5) to discover genes associated with NSCLC. We identified significant differential expression of the tyrosine kinase TEK in tumors from patients with NSCLC. TEK may be of relevance to the initiation, progression or maintenance of non-small cell lung cancers.

scholarly journals Immunogenomic Gene Signature of Cell-Death Associated Genes with Prognostic Implications in Lung Cancer

Cancers ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 155
Author(s):  
Pankaj Ahluwalia ◽  
Meenakshi Ahluwalia ◽  
Ashis K. Mondal ◽  
Nikhil Sahajpal ◽  
Vamsi Kota ◽  
...  
Keyword(s):  
Lung Cancer ◽  
T Cells ◽  
Cell Death ◽  
T Cell ◽  
High Risk ◽  
Lung Adenocarcinoma ◽  
Risk Group ◽  
High Risk Group ◽  
Free Survival ◽  
Cell Death Pathways

Lung cancer is one of the leading causes of death worldwide. Cell death pathways such as autophagy, apoptosis, and necrosis can provide useful clinical and immunological insights that can assist in the design of personalized therapeutics. In this study, variations in the expression of genes involved in cell death pathways and resulting infiltration of immune cells were explored in lung adenocarcinoma (The Cancer Genome Atlas: TCGA, lung adenocarcinoma (LUAD), 510 patients). Firstly, genes involved in autophagy (n = 34 genes), apoptosis (n = 66 genes), and necrosis (n = 32 genes) were analyzed to assess the prognostic significance in lung cancer. The significant genes were used to develop the cell death index (CDI) of 21 genes which clustered patients based on high risk (high CDI) and low risk (low CDI). The survival analysis using the Kaplan–Meier curve differentiated patients based on overall survival (40.4 months vs. 76.2 months), progression-free survival (26.2 months vs. 48.6 months), and disease-free survival (62.2 months vs. 158.2 months) (Log-rank test, p < 0.01). Cox proportional hazard model significantly associated patients in high CDI group with a higher risk of mortality (Hazard Ratio: H.R 1.75, 95% CI: 1.28–2.45, p < 0.001). Differential gene expression analysis using principal component analysis (PCA) identified genes with the highest fold change forming distinct clusters. To analyze the immune parameters in two risk groups, cytokines expression (n = 265 genes) analysis revealed the highest association of IL-15RA and IL 15 (> 1.5-fold, p < 0.01) with the high-risk group. The microenvironment cell-population (MCP)-counter algorithm identified the higher infiltration of CD8+ T cells, macrophages, and lower infiltration of neutrophils with the high-risk group. Interestingly, this group also showed a higher expression of immune checkpoint molecules CD-274 (PD-L1), CTLA-4, and T cell exhaustion genes (HAVCR2, TIGIT, LAG3, PDCD1, CXCL13, and LYN) (p < 0.01). Furthermore, functional enrichment analysis identified significant perturbations in immune pathways in the higher risk group. This study highlights the presence of an immunocompromised microenvironment indicated by the higher infiltration of cytotoxic T cells along with the presence of checkpoint molecules and T cell exhaustion genes. These patients at higher risk might be more suitable to benefit from PD-L1 blockade or other checkpoint blockade immunotherapies.

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