Lung Adenocarcinoma Lesions Research Articles

The value analysis of high-resolution thin-layer CT in the identification of early lung adenocarcinoma: An observation study.

The aim of this study was to explore the clinical value of high-resolution thin-layer computed tomography (CT) for the identification of early lung adenocarcinoma. Ninety patients with early lung adenocarcinoma who were diagnosed and treated in our hospital were selected as study subjects and divided into noninvasive (NIG, n = 51) and invasive (IG, n = 39) groups according to their pathological findings. Both groups underwent high-resolution target scanning. Differences in lesion size, density, and distribution between the 2 groups were compared. Intergroup differences in the CT signs were examined. A receiver-operating characteristic curve was established to calculate the diagnostic efficacy of high-resolution, thin-layer CT for early lung adenocarcinoma infiltration. The maximum diameter and density of the tumors were significantly higher in the IG than in the NIG (P < .05). The proportions of CT signs of lobulation, spicule, and vessel convergence were higher in the IG patients compared to the NIG (P < .05). High-resolution thin-layer CT for the diagnosis of lung adenocarcinoma infiltration had an AUC of 0.6702 (P < .05), a diagnostic sensitivity of 64.10%, and a diagnostic specificity of 60.78%. High-resolution thin-layer CT had certain differential diagnostic efficacy for early lung adenocarcinoma, which clearly presents various CT signs of early lung adenocarcinoma lesions.

Crizotinib resistance reversal in ALK-positive lung cancer through zeolitic imidazolate framework-based mitochondrial damage

Crizotinib (CRZ), one of anaplastic lymphoma kinase tyrosine kinase inhibitors (ALK-TKIs), has emerged as a frontline treatment for ALK-positive (ALK+) lung adenocarcinoma. However, the overexpression of P-glycoprotein (P-gp, a mitochondrial adenosine triphosphate (ATP)-dependent protein) in lung adenocarcinoma lesions causes multidrug resistance (MDR) and limits the efficacy of CRZ treatment. Herein, a mitochondria-targeting nanosystem, zeolitic imidazolate framework-90@indocyanine green (ZIF-90@ICG), was fabricated to intervene in mitochondria and overcome drug resistance. Due to the zinc ion (Zn2+) interference of ZIF-90 and the photodynamic therapy (PDT) of ICG, this nanosystem is well suited for damaging mitochondrial functions, thus downregulating the intracellular ATP level and inhibiting P-gp expression. In addition, systematic bioinformatics analysis revealed the upregulation of CD44 in CRZ-resistant cells. Therefore, hyaluronic acid (HA, a critical target ligand of CD44) was further modified on the surface of ZIF-90@ICG for active targeting. Overall, this ZIF-90@ICG nanosystem synergistically increased the intracellular accumulation of CRZ and reversed CRZ resistance to enhance its anticancer effect, which provides guidance for nanomedicine design to accurately target tumours and induce mitochondrial damage and represents a viable regimen for improving the prognosis of patients with ALK-TKIs resistance. Statement of significanceThe original aim of our research was to combat multidrug resistance (MDR) in highly aggressive and lethal lymphoma kinase-positive (ALK+) lung adenocarcinoma. For this purpose, a cascade-targeted system was designed to overcome MDR, integrating lung adenocarcinoma-targeted hyaluronic acid (HA), mitochondrion-targeted zeolitic imidazolate framework-90 (ZIF-90), the clinically approved drug crizotinib (CRZ), and the fluorescence imaging agent/photosensitizer indocyanine green (ICG). Moreover, using a “two birds with one stone” strategy, ion interference and oxidative stress induced by ZIF-90 and photodynamic therapy (PDT), respectively, disrupt mitochondrial homeostasis, thus downregulating adenosine triphosphate (ATP) levels, inhibiting MDR-relevant P-glycoprotein (P-gp) expression and suppressing tumour metastasis. Overall, this research represents an attempt to implement the concept of MDR reversal and realize the trade-offs between MDR and therapeutic effectiveness.

A novel approach to evaluation of tumor response for advanced pulmonary adenocarcinoma using the intertumoral heterogeneity response score.

Treatment response and prognosis estimation in advanced pulmonary adenocarcinoma are challenged by the significant heterogeneity of the disease. The current Response Evaluation Criteria in Solid Tumors (RECIST) criteria, despite providing a basis for solid tumor response evaluation, do not fully encompass this heterogeneity. To better represent these nuances, we introduce the intertumoral heterogeneity response score (THRscore), a measure built upon and expanding the RECIST criteria. This retrospective study included patients with 3-10 measurable advanced lung adenocarcinoma lesions who underwent first-line chemotherapy or targeted therapy. The THRscore, derived from the coefficient of variation in size for each measurable tumor before and 4-6weeks posttreatment, unveiled a correlation with patient outcomes. Specifically, a high THRscore was associated with shorter progression-free survival, lower tumor response rate, and a higher tumor mutation burden. These associations were further validated in an external cohort, confirming THRscore's effectiveness in stratifying patients based on progression risk and treatment response, and enhancing the utility of RECIST in capturing complex tumor behaviors in lung adenocarcinoma. These findings affirm the promise of THRscore as an enhanced tool for tumor response assessment in advanced lung adenocarcinoma, extending the RECIST criteria's utility.

Differential diagnosis of benign and lung adenocarcinoma presenting as larger solid nodules and masses based on multiscale CT radiomics.

To develop a better radiomic model for the differential diagnosis of benign and lung adenocarcinoma lesions presenting as larger solid nodules and masses based on multiscale computed tomography (CT) radiomics. This retrospective study enrolled 205 patients with solid nodules and masses from Center 1 between January 2010 and February 2022 and Center 2 between January 2019 and February 2022. After applying the inclusion and exclusion criteria, we retrospectively enrolled 165 patients from two centers and assigned them to the training dataset (n = 115) or the test dataset (n = 50). Radiomics features were extracted from volumes of interest on CT images. A gradient boosting decision tree (GBDT) was used for data dimensionality reduction to perform the final feature selection. Four models were developed using clinical data, conventional imaging features and radiomics features, namely, the clinical and image model (CIM), the plain CT radiomics model (PRM), the enhanced CT radiomics model (ERM) and the combined model (CM). Model performance was evaluated to determine the best model for identifying benign and lung adenocarcinoma presenting as larger solid nodules and masses. In the training dataset, the areas under the curve (AUCs) for the CIM, PRM, ERM, and CM were 0.718, 0.806, 0.819, and 0.917, respectively. The differential diagnostic capability of the ERM was better than that of the PRM and the CIM. The CM was optimal. Intermediate and junior radiologists and respiratory physicians achieved improved obviously diagnostic results with the radiomics model. The senior radiologists showed slight improved diagnostic results after using the radiomics model. Radiomics may have the potential to be used as a noninvasive tool for the differential diagnosis of benign and lung adenocarcinoma lesions presenting as larger solid nodules and masses.

Association between Contrast-Enhanced Computed Tomography Radiomic Features, Genomic Alterations and Prognosis in Advanced Lung Adenocarcinoma Patients.

Non-invasive methods to assess mutational status, as well as novel prognostic biomarkers, are warranted to foster therapy personalization of patients with advanced non-small cell lung cancer (NSCLC). This study investigated the association of contrast-enhanced Computed Tomography (CT) radiomic features of lung adenocarcinoma lesions, alone or integrated with clinical parameters, with tumor mutational status (EGFR, KRAS, ALK alterations) and Overall Survival (OS). In total, 261 retrospective and 48 prospective patients were enrolled. A Radiomic Score (RS) was created with LASSO-Logistic regression models to predict mutational status. Radiomic, clinical and clinical-radiomic models were trained on retrospective data and tested (Area Under the Curve, AUC) on prospective data. OS prediction models were trained and tested on retrospective data with internal cross-validation (C-index). RS significantly predicted each alteration at training (radiomic and clinical-radiomic AUC 0.95-0.98); validation performance was good for EGFR (AUC 0.86), moderate for KRAS and ALK (AUC 0.61-0.65). RS was also associated with OS at univariate and multivariable analysis, in the latter with stage and type of treatment. The validation C-index was 0.63, 0.79, and 0.80 for clinical, radiomic, and clinical-radiomic models. The study supports the potential role of CT radiomics for non-invasive identification of gene alterations and prognosis prediction in patients with advanced lung adenocarcinoma, to be confirmed with independent studies.

A computerized tomography-based radiomic model for assessing the invasiveness of lung adenocarcinoma manifesting as ground-glass opacity nodules

BackgroundClinically differentiating preinvasive lesions (atypical adenomatous hyperplasia, AAH and adenocarcinoma in situ, AIS) from invasive lesions (minimally invasive adenocarcinomas, MIA and invasive adenocarcinoma, IA) manifesting as ground-glass opacity nodules (GGOs) is difficult due to overlap of morphological features. Hence, the current study was performed to explore the diagnostic efficiency of radiomics in assessing the invasiveness of lung adenocarcinoma manifesting as GGOs.MethodsA total of 1018 GGOs pathologically confirmed as lung adenocarcinoma were enrolled in this retrospective study and were randomly divided into a training set (n = 712) and validation set (n = 306). The nodules were delineated manually and 2446 intra-nodular and peri-nodular radiomic features were extracted. Univariate analysis and least absolute shrinkage and selection operator (LASSO) were used for feature selection. Clinical and semantic computerized tomography (CT) feature model, radiomic model and a combined nomogram were constructed and compared. Decision curve analysis (DCA) was used to evaluate the clinical value of the established nomogram.Results16 radiomic features were selected and used for model construction. The radiomic model exhibited significantly better performance (AUC = 0.828) comparing to the clinical-semantic model (AUC = 0.746). Further analysis revealed that peri-nodular radiomic features were useful in differentiating between preinvasive and invasive lung adenocarcinomas appearing as GGOs with an AUC of 0.808. A nomogram based on lobulation sign and radiomic features showed the best performance (AUC = 0.835), and was found to have potential clinical value in assessing nodule invasiveness.ConclusionsRadiomic model based on both intra-nodular and peri-nodular features showed good performance in differentiating between preinvasive lung adenocarcinoma lesions and invasive ones appearing as GGOs, and a nomogram based on clinical, semantic and radiomic features could provide clinicians with added information in nodule management and preoperative evaluation.

Multivariate Analysis on Development of Lung Adenocarcinoma Lesion from Solitary Pulmonary Nodule.

Objective To analyze multiple factors developing lung adenocarcinoma lesion from solitary pulmonary nodule (SPN). Methods A total of 70 patients diagnosed with lung adenocarcinoma after finding SPN by chest CT and treated in our hospital (01, 2018–01, 2021) were selected as the malignant lesion group, and another 70 patients diagnosed with benign lesion after finding SPN by CT in the same period were included in the benign lesion group. All patients had complete medical records. With univariate analysis and multivariate logistic regression, the independent risk factors for developing lung adenocarcinoma lesions from SPN were analyzed. Results By conducting univariate analysis of patients' general information (age, course of disease, BMI, nodule diameter, and gender), smoking status (smoking history and number of cigarettes smoked per year), medical history (family history of lung cancer, history of extrapulmonary malignant tumor, and history of autoimmune diseases), basic complications (hypertension and diabetes), and laboratory examinations (CEA, NSE, CYFRA21-1, SCC-Ag, and CA125), it was concluded that age, course of disease, nodule diameter, CEA positive, CYFRA21-1 positive, and CA125 positive were significantly different between the two groups (P < 0.05); the logistic regression results showed that high age, increased nodule diameter, and CYFRA21-1 positive were the independent risk factors developing lung adenocarcinoma from SPN (P < 0.05). Conclusion In patients with SPN, higher age, longer course of disease, greater nodule diameter, and CYFRA21-1 positive imply increased risk for triggering lung adenocarcinoma lesion. Therefore, high attention should be paid in the clinic to such SPN patients for early diagnosis and treatment.

Intertumoural Heterogeneity and Branch Evolution of Synchronous Multiple Primary Lung Adenocarcinomas by Next-Generation Sequencing Analysis.

ObjectivesMultiple primary lung cancers (MPLCs) are an increasingly well-known clinical phenomenon, but there is a lack of high-level evidence for their optimal clinical diagnosis and therapeutic approaches. Thus, we analysed genetic variation to determine the intertumoural heterogeneity and branch evolution of synchronous multiple primary lung adenocarcinomas.MethodsWe performed multiplex mutational sequencing on 93 synchronous multiple primary lung adenocarcinoma lesions from 42 patients who underwent surgical resection.ResultsThe high discordance rate of mutation was 92.9% (n=39) between tumours in individual patients. EGFR, TP53 and KRAS mutations were detected in 57 (61.3%), 19 (20.4%) and 11 (11.8%) of the 93 tumours, respectively. 16 cases of multiple primary lung adenocarcinomas simultaneously harboured EGFR mutations and TP53 mutations. Matching mutations between paired tumours were observed in 1 (2.4%) patient for P20. The genotypes were all EGFR L858R mutations, but the pathological type of P20T1 was lepidic predominant, and P20T2 was adenocarcinoma in situ. In the phylogenetic tree, genetic variations were divided into trunk, shared and branch subtypes. Branch mutations accounted for 91.09% of variations in sMPLA, while the ratio of trunk (4.95%) and shared (3.96%) variations was significantly lower.ConclusionsRemarkable intertumoural heterogeneity and frequent branch mutations were found in synchronous multiple primary lung adenocarcinomas.

Pre-operative Prediction of Ki-67 Expression in Various Histological Subtypes of Lung Adenocarcinoma Based on CT Radiomic Features.

Purpose: The aims of this study were to combine CT images with Ki-67 expression to distinguish various subtypes of lung adenocarcinoma and to pre-operatively predict the Ki-67 expression level based on CT radiomic features.Methods: Data from 215 patients with 237 pathologically proven lung adenocarcinoma lesions who underwent CT and immunohistochemical Ki-67 from January 2019 to April 2021 were retrospectively analyzed. The receiver operating curve (ROC) identified the Ki-67 cut-off value for differentiating subtypes of lung adenocarcinoma. A chi-square test or t-test analyzed the differences in the CT images between the negative expression group (n = 132) and the positive expression group (n = 105), and then the risk factors affecting the expression level of Ki-67 were evaluated. Patients were randomly divided into a training dataset (n = 165) and a validation dataset (n = 72) in a ratio of 7:3. A total of 1,316 quantitative radiomic features were extracted from the Analysis Kinetics (A.K.) software. Radiomic feature selection and radiomic classifier were generated through a least absolute shrinkage and selection operator (LASSO) regression and logistic regression analysis model. The predictive capacity of the radiomic classifiers for the Ki-67 levels was investigated through the ROC curves in the training and testing groups.Results: The cut-off value of the Ki-67 to distinguish subtypes of lung adenocarcinoma was 5%. A comparison of clinical data and imaging features between the two groups showed that histopathological subtypes and air bronchograms could be used as risk factors to evaluate the expression of Ki-67 in lung adenocarcinoma (p = 0.005, p = 0.045, respectively). Through radiomic feature selection, eight top-class features constructed the radiomic model to pre-operatively predict the expression of Ki-67, and the area under the ROC curves of the training group and the testing group were 0.871 and 0.8, respectively.Conclusion: Ki-67 expression level with a cut-off value of 5% could be used to differentiate non-invasive lung adenocarcinomas from invasive lung adenocarcinomas. It is feasible and reliable to pre-operatively predict the expression level of Ki-67 in lung adenocarcinomas based on CT radiomic features, as a non-invasive biomarker to predict the degree of malignant invasion of lung adenocarcinoma, and to evaluate the prognosis of the tumor.

P30.04 Clinical Research on Patients With Surgically Resected Lung Adenocarcinoma Lesions: Are Heterogeneous GGNs Different From Part Solid Nodules?

To evaluate the natural course of patients with surgically resected lung adenocarcinoma (Ad) lesions with heterogenous GGN, and clarify the difference between heterogeneous GGNs and part solid nodules.

Landscape and dynamics of single tumor and immune cells in early and advanced-stage lung adenocarcinoma.

BackgroundLung adenocarcinoma (LUAD) patients with different American Joint Committee on Cancer stages have different overall 5‐year survival rates. The tumor microenvironment (TME) and intra‐tumor heterogeneity (ITH) have been shown to play a crucial role in the occurrence and development of tumors. However, the TME and ITH in different lesions of LUAD have not been extensively explored.MethodsWe present a 204,157‐cell catalog of the TME transcriptome in 29 lung samples to systematically explore the TME and ITH in the different stages of LUAD. Traditional RNA sequencing data and complete clinical information were downloaded from publicly available databases.ResultsBased on these high‐quality cells, we constructed a single‐cell network underlying cellular and molecular features of normal lung, early LUAD, and advanced LUAD cells. In contrast with early malignant cells, we noticed that advanced malignant cells had a remarkably more complex TME and higher ITH level. We also found that compared with other immune cells, more differences in CD8+/CTL T cells, regulatory T cells, and follicular B cells were evident between early and advanced LUAD. Additionally, cell‐cell communication analyses, revealed great diversity between different lesions of LUAD at the single‐cell level. Flow cytometry and qRT‐PCR were used to validate our results.ConclusionOur results revealed the cellular diversity and molecular complexity of cell lineages in different stages of LUAD. We believe our research, which serves as a basic framework and valuable resource, can facilitate exploration of the pathogenesis of LUAD and identify novel therapeutic targets in the future.

Abstract PO-118: Novel mechanisms of EGFR-TKI resistance and clonal evolution of lung adenocarcinoma by overexpression of a cell adhesion molecule, CADM1

Abstract Evolution of cancer and generation of its heterogeneity are most dynamically demonstrated in the process of cancer cells acquiring resistance to molecular targeted therapy. Lung adenocarcinoma is the best solid tumor to which molecular targeted therapy is established and clinically available. However, tumors resistant against targeted drugs develop frequently, providing the biggest challenge in current treatment of lung adenocarcinoma. The tumors resistant to the initial treatment also show more malignant features, such as invasion and metastasis. Thus, it is interesting to investigate possible mechanisms to link EGFR-TKI resistance to malignant progression in lung adenocarcinoma. A cell adhesion molecule, CADM1, is originally identified as a tumor suppressor in lung adenocarcinoma. CADM1 is involved in the formation and maintenance of an epithelial cell structure. On the other hand, CADM1 is frequently inactivated by promoter methylation in various cancers in their advanced stages. In lung adenocarcinoma, CADM1 was expressed in the cell-cell attachment sites in lepidic growth components, whereas CADM1 expression was frequently lost in invasive lesions, conferring heterogenous features to cancer tissue. We have also reported that CADM1 inhibits HGF-induced epithelial mesenchymal transition of canine kidney cells, MDCK, by associating with MET and intervening with MET signaling on the cell membrane. Here, we demonstrate significant expression of CADM1 in a lung adenocarcinoma cell, HCC827, but not in its gefitinib-resistant derivatives, HCC827GR5 or GR6, which express significant amounts of phosphorylated MET (p-MET). Introducing CADM1 expression into HCC827GR5 restores the sensitivity to gefitinib in association with decreasing amount of pMET. In contrast, CADM1 is not effective at restoring gefitinib sensitivity in PC9 cells carrying T790M mutation of EGFR. Dox-inducible CADM1 expression in HCC827GR5 also showed restoration of gefitinib sensitivity both in vivo and in vitro. Finally, intra-tumoral injection of adenoviruses expressing CADM1, but not control adenoviruses, significantly suppressed subcutaneous tumor formation only when treated with gefitinib to nude mice. These results suggest that exogenous expression of CADM1 could provide a unique approach to overcome EGFR-TKI resistance of lung adenocarcinoma caused by MET overexpression. Inversely, loss of CADM1 and cancer cell adhesion could promote EGFR-TKI resistance caused by MET overexpression. Considering that CADM1 expression is lost selectively and clonally in microinvasive lesions of lung adenocarcinoma, disruption of cancer cell adhesion would be involved in generation of cell clones resistant to molecular targeted drugs and resultant heterogeneity in a subset of lung adenocarcinoma. Citation Format: Takehiro Tsuchiya, Hideki Kuwano, Takeshi Ito, Masayoshi Nagata, Taketo Kawai, Yumi Tsuboi, Daisuke Matsubara, Isami Okamoto, Kenji Tamura, Jun Nakajima, Motoi Oba, Yoshinori Murakami. Novel mechanisms of EGFR-TKI resistance and clonal evolution of lung adenocarcinoma by overexpression of a cell adhesion molecule, CADM1 [abstract]. In: Proceedings of the AACR Virtual Special Conference on Tumor Heterogeneity: From Single Cells to Clinical Impact; 2020 Sep 17-18. Philadelphia (PA): AACR; Cancer Res 2020;80(21 Suppl):Abstract nr PO-118.

Diffusion kurtosis imaging: correlation analysis of quantitative model parameters with molecular features in advanced lung adenocarcinoma.

Background:Due to development of magnetic resonance-based functional imaging, it is easier to detect micro-structural alterations of tumor tissues. The aim of this study was to conduct a preliminary evaluation of the correlation of non-Gaussian diffusion kurtosis imaging (DKI) parameters with expression of molecular markers (epidermal growth factor receptor [EGFR]; anaplastic lymphoma kinase [ALK]; Ki-67 protein) in patients with advanced lung adenocarcinoma, using routine diffusion-weighted imaging as the reference standard.Methods:Data from patients with primary lung adenocarcinoma diagnosed at Cancer Hospital, Chinese Academy of Medical Sciences (CHCAMS) from 2016 to 2019 were collected for retrospective analysis. The pathologic and magnetic resonance imaging data of 96 patients who met the inclusion criteria were included in this study. Specifically, the Kapp and Dapp parameters measured from the DKI model; apparent diffusion coefficient (ADC) value from the diffusion-weighted imaging model; and the EGFR, ALK, and Ki-67 biomarkers detected by immunohistochemistry and/or molecular biology techniques after biopsy or surgery were evaluated. The relations between quantitative parameters (ADC, Kapp, Dapp) and pathologic outcomes (EGFR, ALK, and Ki-67 expression) were analyzed by Spearman correlation test.Results:Of the 96 lung adenocarcinoma lesions (from 96 patients), the number of EGFR- and ALK-positive and high Ki-67 expressing lesions were 53, 12, and 83, respectively. The Kapp values were significantly higher among patients with EGFR-positive mutations (0.81 ± 0.12 vs. 0.66 ± 0.10, t = 6.41, P < 0.001), ALK rearrangement-negative (0.76 ± 0.12 vs. 0.60 ± 0.15, t = 4.09, P < 0.001), and high Ki-67 proliferative index (PI) (0.76 ± 0.12 vs. 0.58 ± 0.13, t = 4.88, P < 0.001). The Dapp values were significantly lower among patients with high Ki-67 PI (3.19 ± 0.69 μm2/ms vs. 4.20 ± 0.83 μm2/ms, t = 4.80, P < 0.001) and EGFR-positive mutations (3.11 ± 0.73 μm2/ms vs. 3.59 ± 0.77 μm2/ms, t = 3.12, P = 0.002). The differences in mean Dapp (3.73 ± 1.26 μm2/ms vs. 3.26 ± 0.68 μm2/ms, t = 1.96, P = 0.053) or ADC values ([1.34 ± 0.81] × 10−3 mm2/s vs. [1.33 ± 0.41] × 10−3 mm2/s, t = 0.07, P = 0.941) between the groups with or without ALK rearrangements were not statistically significant. The ADC values were significantly lower among patients with EGFR-positive mutation ([1.19 ± 0.37] × 10−3 mm2/s vs. [1.50 ± 0.53] × 10−3 mm2/s, t = 3.38, P = 0.001) and high Ki-67 PI ([1.28 ± 0.39] × 10−3 mm2/s vs. [1.67 ± 0.77] × 10−3 mm2/s, t = 2.88, P = 0.005). Kapp was strongly positively correlated with EGFR mutations (r = 0.844, P = 0.008), strongly positively correlated with Ki-67 PI (r = 0.882, P = 0.001), and strongly negatively correlated with ALK rearrangements (r = −0.772, P = 0.001). Dapp was moderately correlated with EGFR mutations (r = −0.650, P = 0.024) or Ki-67 PI (r = −0.734, P = 0.012). ADC was moderately correlated with Ki-67 PI (r = −0.679, P = 0.033).Conclusions:The Kapp value of DKI parameters was strongly correlated with different expression of EGFR, ALK, and Ki-67 in advanced lung adenocarcinoma. The results potentially indicate a surrogate measure of the status of different molecular markers assessed by non-invasive imaging tools.

Can texture features improve the differentiation of infiltrative lung adenocarcinoma appearing as ground glass nodules in contrast-enhanced CT?

ObjectivesTo investigate the validity and efficacy of comparing texture features from contrast-enhanced images with non-enhanced images in identifying infiltrative lung adenocarcinoma represented as ground glass nodules (GGN). Materials and methodsA retrospective cohort study was conducted with patients presenting with lung adenocarcinoma and treated at a single centre between January 2015 to December 2017. All patients underwent standard and contrast-enhanced thoracic CT scans with 0.5 mm collimation and 1 mm slice reconstruction thickness before surgery. A total of 34 lung adenocarcinoma patients (representing 34 lesions) were analysed; including 21 instances of invasive adenocarcinoma (IAC) lesions, 4 instances of adenocarcinoma in situ (AIS) lesions, and 9 minimally invasive adenocarcinoma (MIA) lesions. After radiologists manually segmented the lesions, texture features were quantitatively extracted using Artificial Intelligence Kit (AK) software. Then, multivariate logistic regression analysis based on standard and contrast-enhanced CT texture features was employed to analyse the invasiveness of lung adenocarcinoma lesions appearing as GGNs. A receiver operating characteristic (ROC) curve analysis was used to evaluate the performance of those models. ResultsA total of 21 quantitative texture features were extracted using the AK software. After dimensionality reduction, 5 and 3 features extracted from thin-section unenhanced and contrast-enhanced CT, respectively, were used to establish the model. The area under the ROC curve (AUC) values for unenhanced CT and enhanced CT features were 0.890 and 0.868, respectively. There was no significant difference (P = 0.190) in the AUC between models based on non-enhanced and contrast-enhanced CT texture features. ConclusionCompared with unenhanced CT, texture features extracted from contrast-enhanced CT provided no benefit in improving the differential diagnosis of infiltrative lung adenocarcinoma from non-infiltrative malignancies appearing as GGNs.

Computed tomography-guided percutaneous microwave ablation for treatment of peripheral ground-glass opacity-Lung adenocarcinoma: A pilot study.

The purpose of the study is to retrospectively evaluate the safety and efficacy of microwave ablation (MWA) for the treatment of ground-glass opacity (GGO)-lung adenocarcinoma. From December 2013 to June 2017, a total of 51 patients (22 males and 29 females, mean age of 69.4 ± 10.1 years) were included in this study, with 51 lung adenocarcinoma lesions showing GGO (mean long-axis diameter of 18.7 ± 6.05 mm). They received a total of 52 sessions of percutaneous computed tomography-guided (CT-guided) MWA. First, lung adenocarcinoma with GGO was histologically defined by needle biopsy under the guidance of CT. Second, the efficacy of CT-guided MWA was analyzed, including the feasibility, safety, 3 years local progression-free survival (LPFS), 3 years disease-specific survival, and 3 years overall survival (OS). Final, complications after MWA were also summarized. The technical success rate was 100%, without MWA procedure-related death. At the median follow-up period (27.02, range: 7-45 months), the rates of 3 years LPFS, cancer-specific survival, and OS were 98%, 100%, and 96%, respectively. The complications after MWA included pneumothorax (48.1%, 25/52), hemoptysis (28.8%, 14/52), pleural effusion (23.1%, 12/52), and pulmonary infection (7.7%, 4/52). CT-guided percutaneous MWA was a feasible, safe, and effective therapeutic approach for treating GGO-lung adenocarcinoma.

Inverse correlation between galectin-4 and TTF-1 in lung adenocarcinoma.

We have previously shown that galectin-4 expression is an independent predictor for lymph node metastasis and serves as an adverse prognostic indicator in patients with acinar adenocarcinoma of the lung. In contrast, thyroid transcription factor-1 (TTF-1) expression in non-small cell lung carcinoma has been shown to be associated with a favorable prognosis. In the present study, 208 cases of acinar adenocarcinoma of the lung and 36 cases with distant metastatic lesions of lung adenocarcinoma were immunohistochemically examined for expression of galectin-4 and TTF-1 to elucidate their correlation with clinicopathological factors. TTF-1 expression was observed in 145 cases (69.7%) and associated with smaller tumor size, infrequent pleural invasion, and lower TNM stage. Galectin-4 expression was observed in 86 cases (41.3%). Furthermore, galectin-4-positive carcinoma cells and TTF-1-positive carcinoma cells existed exclusively within the same lesion. Expressions of TTF-1 and galectin-4 were favorable and adverse prognostic factors, respectively. Approximately 40% (15/36 cases) of lung adenocarcinoma at the distant metastatic sites were immunohistochemically negative for TTF-1. Four out of five galectin-4-positive metastatic lesions were negative for TTF-1. We found an inverse correlation between galectin-4 and TTF-1 expressions in acinar adenocarcinoma, and this phenomenon was also found to be present in metastatic sites. These findings suggest that we should not exclude the possibility of metastatic adenocarcinoma of the lung, even if the tumor cells are immunohistochemically negative for TTF-1 in the primary unknown tumor, because aggressive lung adenocarcinomas often lack TTF-1 expression.

Innate Immune Landscape in Early Lung Adenocarcinoma by Paired Single-Cell Analyses

To guide the design of immunotherapy strategies for patients with early stage lung tumors, we developed a multiscale immune profiling strategy to map the immune landscape of early lung adenocarcinoma lesions to search for tumor-driven immune changes. Utilizing a barcoding method that allows a simultaneous single-cell analysis of the tumor, non-involved lung, and blood cells, we provide a detailed immune cell atlas of early lung tumors. We show that stage I lung adenocarcinoma lesions already harbor significantly altered Tcell and NK cell compartments. Moreover, we identified changes in tumor-infiltrating myeloid cell (TIM) subsets that likely compromise anti-tumor Tcell immunity. Paired single-cell analyses thus offer valuable knowledge of tumor-driven immune changes, providing a powerful tool for the rational design of immune therapies. VIDEO ABSTRACT.

EGFR L858R mutation is associated with lung adenocarcinoma patients with dominant ground-glass opacity.

To retrospectively identify quantitative computed tomographic (CT) features that correlate with the three major driver gene mutations in surgically resected lung adenocarcinomas with dominant ground-glass opacity (GGO) stratified by the International Association for the Study of Lung Cancer (IASLC), American Thoracic Society (ATS), and European Respiratory Society (ERS) classification in a Chinese cohort of patients. Surgically resected lung adenocarcinomas from Shanghai Pulmonary Hospital were enrolled. EGFR, KRAS and EML4-ALK mutations were detected by qPCR. Clinical and pathological characteristics including gender, age, TNM stage, smoking status and CT pattern were analyzed. Histologic subtype was classified according to IASLC/ATS/ERS classification. At preoperative chest CT, the percentage of GGO volume, diameter, solid volume and total tumor volume of each tumor were measured by using a semiautomated algorithm. Distribution of driver gene mutations was evaluated by using the Fisher exact test, the Student's t test, and Pearson correlation analysis. 788 in total and 158 GGO tumors were taken in this cohort. GGO pattern occurred at a significantly higher frequency in younger, female and non-smoking patients. EGFR/KRAS mutations and EML4-ALK fusions were similar between GGO and solid adenocarcinomas. GGO volume and diameter showed correlation with EGFR mutation. With regard to association between lung adenocarcinoma histological subtypes and GGO features, GGO proportion was significantly higher in lepidic predominant adenocarcinomas, including adenocarcinoma in situ, minimally invasive adenocarcinoma, and lepidic predominant invasive adenocarcinoma. No significant differences of driver gene mutations were found between subtypes of lung adenocarcinoma. It is important that we understand GGO lesions of lung adenocarcinoma to identify molecular biomarkers including EGFR, KRAS and EML4-ALK. These markers would offer useful information for determining the appropriate strategy to treat lung adenocarcinoma with GGO lesions detected by helical CT.

Analysis of pre‐invasive lung adenocarcinoma lesions on thin‐section computerized tomography

Recent studies have revealed a potential relationship between the presence of ground glass opacity (GGO) on regular computerized tomography (CT) and adenocarcinomas. To investigate features of pre-invasive lung adenocarcinoma lesions on thin-section CT. We evaluated 59 cases of atypical adenomatous hyperplasia (AAH) and 35 cases of adenoma in situ (AIS) confirmed by histopathology. Comparison of thin-section CT features, such as size, shape, margin, internal characteristics, and adjacent structures of pre-invasive lesions were analyzed. Lesions were further classified to pure ground glass opacity (pGGO) and mixed ground glass opacity (mGGO). Differences were analyzed using Chi-square or Fisher tests. There were significant differences in lobulation, spiculation, and bubble lucency between pGGO and mGGO (P < 0.05), while no differences in air bronchogram, pleural indentation, or vascular morphological changes were identified (P > 0.05). In the group of pGGO, AAH and AIS lesions did not differ significantly in size (P > 0.05), while significant differences were found with respect to lobulation, spiculation, pleural indentation, and vascular morphological changes (P < 0.05). In the group of mGGO, AAH and AIS lesions were significantly different with respect to size (P < 0.05), while no differences were found in lobulation, spiculation, bubble lucency, air bronchogram, or pleural indentation (P > 0.05). Only vascular morphological changes were significantly different between AAH and AIS lesions (P < 0.05). The features of thin-slice CT of AAH and AIS reflected the corresponding morphological changes from AAH progressing to AIS or adenocarcinoma.

Radiographic and pathological analysis of small lung adenocarcinoma using the new IASLC classification

To analyse the correlation between computed tomography (CT) findings of small lung adenocarcinomas and the International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society Classification of Lung Adenocarcinoma. A retrospective review of 300 lung adenocarcinoma lesions (size ≤20mm) after surgical resection in 295 consecutive patients was performed. Tumours were defined as air-containing type if the ratio of the maximum dimension of the tumour on mediastinal windows to the maximum dimension of the tumour on lung windows was ≤50%, and as solid-density type if the ratio was >50%. The incidence between CT findings (air bronchogram, vascular involvement, pleural tags, notches, and spiculation) and pathological findings were investigated. Of the 142 air-containing lesions, 114 were adenocarcinoma in situ (AIS), 28 were minimally invasive adenocarcinoma (MIA), and none of the lesions were invasive adenocarcinoma. Of the 158 solid-density lesions, 30 were AIS, 24 were MIA, and 104 were invasive adenocarcinoma. Notches and pleural tags were commonly observed in cases of invasive adenocarcinoma (p<0.05). In the air-containing type of small lung adenocarcinomas, AIS and MIA were observed but no cases of invasive adenocarcinoma were found. The presence of notches and pleural tags were a significant factor in invasive adenocarcinoma.