Invasiveness Of Ground-glass Nodules Research Articles

A nomogram based on the quantitative and qualitative features of CT imaging for the prediction of the invasiveness of ground glass nodules in lung adenocarcinoma

PurposeBased on the quantitative and qualitative features of CT imaging, a model for predicting the invasiveness of ground-glass nodules (GGNs) was constructed, which could provide a reference value for preoperative planning of GGN patients.Materials and methodsAltogether, 702 patients with GGNs (including 748 GGNs) were included in this study. The GGNs operated between September 2020 and July 2022 were classified into the training group (n = 555), and those operated between August 2022 and November 2022 were classified into the validation group (n = 193). Clinical data and the quantitative and qualitative features of CT imaging were harvested from these patients. In the training group, the quantitative and qualitative characteristics in CT imaging of GGNs were analyzed by using performing univariate and multivariate logistic regression analyses, followed by constructing a nomogram prediction model. The differentiation, calibration, and clinical practicability in both the training and validation groups were assessed by the nomogram models.ResultsIn the training group, multivariate logistic regression analysis disclosed that the maximum diameter (OR = 4.707, 95%CI: 2.06–10.758), consolidation/tumor ratio (CTR) (OR = 1.027, 95%CI: 1.011–1.043), maximum CT value (OR = 1.025, 95%CI: 1.004–1.047), mean CT value (OR = 1.035, 95%CI: 1.008–1.063; P = 0.012), spiculation sign (OR = 2.055, 95%CI: 1.148–3.679), and vascular convergence sign (OR = 2.508, 95%CI: 1.345–4.676) were independent risk parameters for invasive adenocarcinoma. Based on these findings, we established a nomogram model for predicting the invasiveness of GGN, and the AUC was 0.910 (95%CI: 0.885–0.934) and 0.902 (95%CI: 0.859–0.944) in the training group and the validation group, respectively. The internal validation of the Bootstrap method showed an AUC value of 0.905, indicating a good differentiation of the model. Hosmer–Lemeshow goodness of fit test for the training and validation groups indicated that the model had a good fitting effect (P > 0.05). Furthermore, the calibration curve and decision analysis curve of the training and validation groups reflected that the model had a good calibration degree and clinical practicability.ConclusionCombined with the quantitative and qualitative features of CT imaging, a nomogram prediction model can be created to forecast the invasiveness of GGNs. This model has good prediction efficacy for the invasiveness of GGNs and can provide help for the clinical management and decision-making of GGNs.

Interpretable CT radiomics model for invasiveness prediction in patients with ground-glass nodules

To evaluate the performance of an interpretable computed tomography (CT) radiomic model in predicting the invasiveness of ground-glass nodules (GGNs). The study was conducted retrospectively from 1 August 2017 to 1 August 2022, at three different centres. Two hundred and thirty patients with GGNs were enrolled at centre I as a training cohort. Centres II (n=157) and III (n=156) formed two external validation cohorts. Radiomics features extracted based on CT were reduced by a coarse-fine feature screening strategy. A radiomic model was developed through the use of the LASSO (least absolute shrinkage and selection operator) and XGBoost algorithms. Then, a radiological model was established through multivariate logistic regression analysis. Finally, the interpretability of the model was explored using SHapley Additive exPlanations (SHAP). The radiomic XGBoost model outperformed the radiomic logistic model and radiological model in assessing the invasiveness of GGNs. The area under the curve (AUC) values for the radiomic XGBoost model were 0.885 (95% confidence interval [CI] 0.836-0.923), 0.853 (95% CI 0.790-0.906), and 0.838 (95% CI 0.773-0.902) in the training and the two external validation cohorts, respectively. The SHAP method allowed for both a quantitative and visual representation of how decisions were made using a given model for each individual patient. This can provide a deeper understanding of the decision-making mechanisms within the model and the factors that contribute to its prediction effectiveness. The present interpretable CT radiomics model has the potential to preoperatively evaluate the invasiveness of GGNs. Furthermore, it can provide personalised, image-based clinical-decision support.

Preoperative predicting invasiveness of lung adenocarcinoma manifesting as ground-glass nodules based on multimodal images of dual-layer spectral detector CT radiomics models.

To construct and validate conventional and radiomics models based on dual-layer spectral CT radiomics for preoperative prediction of lung ground glass nodules (GGNs) invasiveness. A retrospective study was conducted on 176 GGNs patients who underwent chest non-contrast enhancement scan on dual-layer spectral detector CT at our hospital within 2weeks before surgery. Patients were randomized into the training cohort and testing cohort. Clinical features, imaging features and spectral quantitative parameters were collected to establish a conventional model. Radiomics models were established by extracting 1781 radiomics features form regions of interest of each spectral image [120 kVp poly energetic images (PI), 60keV images and electron density maps], respectively. After selecting the optimal radiomic features and integrating multiple machine learning models, the conventional model, PI model, 60keV model, electron density (ED) model and combined model based on multimodal spectral images were finally established. The performance of these models was assessed through the evaluation of discrimination, calibration, and clinical application. In the conventional model, age, vacuole sign, 60keV and ED were independent risk factors of invasiveness. The combined model using logistic regression-least absolute shrinkage and selection operator classifiers was the optimal model with a higher area under the curve of the training (0.961, 95% confidence interval, CI: 0.932-0.991) and testing set (0.944, 0.890-0.999). The combined models are helpful to predict the invasiveness of GGNs before surgery and guide the individualized treatment of patients.

A semiautomated radiomics model based on multimodal dual-layer spectral CT for preoperative discrimination of the invasiveness of pulmonary ground-glass nodules.

In recent years, spectral computed tomography (CT) has shown excellent performance in the diagnosis of ground-glass nodules (GGNs) invasiveness; however, no research has combined spectral multimodal data and radiomics analysis for comprehensive analysis and exploration. Therefore, this study goes a step further on the basis of the previous research: to investigate the value of dual-layer spectral CT-based multimodal radiomics in accessing the invasiveness of lung adenocarcinoma manifesting as GGNs. In this study, 125 GGNs with pathologically confirmed preinvasive adenocarcinoma (PIA) and lung adenocarcinoma were divided into a training set (n=87) and a test set (n=38). Each lesion was automatically detected and segmented by the pre-trained neural networks, and 63 multimodal radiomic features were extracted. The least absolute shrinkage and selection operator (LASSO) was used to select target features, and a rad-score was constructed in the training set. Logistic regression analysis was conducted to establish a joint model which combined age, gender, and the rad-score. The diagnostic performance of the two models was compared by the receiver operating characteristic (ROC) curve and precision-recall curve. The difference between the two models was compared by the ROC analysis. The test set was used to evaluate the predictive performance and calibrate the model. Five radiomic features were selected. In the training and test sets, the area under the curve (AUC) of the radiomics model was 0.896 (95% CI: 0.830-0.962) and 0.881 (95% CI: 0.777-0.985) respectively, and the AUC of the joint model was 0.932 (95% CI: 0.882-0.982) and 0.887 (95% CI: 0.786-0.988) respectively. There was no significant difference in AUC between the radiomics model and joint model in the training and test sets (0.896 vs. 0.932, P=0.088; 0.881 vs. 0.887, P=0.480). Multimodal radiomics based on dual-layer spectral CT showed good predictive performance in differentiating the invasiveness of GGNs, which could assist in the decision of clinical treatment strategies.

The value of positron emission tomography computed tomography in predicting invasiveness of ground glass nodules: A protocol for systematic review and meta-analysis.

Background:The study was conducted to investigate the value of Positron emission tomography computed tomography (PET/CT) in predicting invasiveness of ground glass nodule (GGN) by the method of meta-analysis.Methods:Two researchers independently searched for published literature on PET/CT diagnosis of GGN as of November 30, 2020. After extracting the data, RevMan5.3 was used to evaluate the quality of the included literature. The Stata14 software was used to test the heterogeneity of the original study that met the inclusion criteria, to calculate the combined sensitivity, specificity, positive likelihood ratio and negative likelihood ratio, the prior probability and posttest probability. The summary receiver operator characteristic curve was drawn and the area under the curve was calculated. Using Deeks funnel plot to evaluate publication bias.Results:Five studies were finally included, including 298 GGN cases. The included studies had no obvious heterogeneity and publication bias. The combined sensitivity and specificity of PET/CT for predicting invasive adenocarcinoma presenting as GGN were 0.74 (95% confidence interval [CI]: 0.68–0.79), 0.82 (95% CI: 0.71–0.90), positive likelihood ratio and negative likelihood ratio were 4.1 (95% CI: 2.5–6.9), 0.32 (95% CI: 0.25–0.40), and the diagnostic odds ratio was 13 (95% CI: 7–26). The prior probability is 20%, the probability of GGN being invasive adenocarcinoma when PET/CT was negative was reduced to 7%, and the probability of GGN being invasive adenocarcinoma when PET/CT was positive was increased to 51%. The area under the curve of the summary receiver operator characteristic curve was 0.85.Conclusion:PET/CT has high diagnostic accuracy for invasive adenocarcinoma presenting as GGN.

Deep Learning-Based Stage-Wise Risk Stratification for Early Lung Adenocarcinoma in CT Images: A Multi-Center Study.

Simple SummaryPrediction of the malignancy and invasiveness of ground glass nodules (GGNs) from computed tomography images is a crucial task for radiologists in risk stratification of early-stage lung adenocarcinoma. In order to solve this challenge, a two-stage deep neural network (DNN) was developed based on the images collected from four centers. A multi-reader multi-case observer study was conducted to evaluate the model capability. The performance of our model was comparable or even more accurate than that of senior radiologists, with average area under the curve values of 0.76 and 0.95 for two tasks, respectively. Findings suggest (1) a positive trend between the diagnostic performance and radiologist’s experience, (2) DNN yielded equivalent or even higher performance in comparison with senior radiologists, and (3) low image resolution reduced the model performance in predicting the risks of GGNs.This study aims to develop a deep neural network (DNN)-based two-stage risk stratification model for early lung adenocarcinomas in CT images, and investigate the performance compared with practicing radiologists. A total of 2393 GGNs were retrospectively collected from 2105 patients in four centers. All the pathologic results of GGNs were obtained from surgically resected specimens. A two-stage deep neural network was developed based on the 3D residual network and atrous convolution module to diagnose benign and malignant GGNs (Task1) and classify between invasive adenocarcinoma (IA) and non-IA for these malignant GGNs (Task2). A multi-reader multi-case observer study with six board-certified radiologists’ (average experience 11 years, range 2–28 years) participation was conducted to evaluate the model capability. DNN yielded area under the receiver operating characteristic curve (AUC) values of 0.76 ± 0.03 (95% confidence interval (CI): (0.69, 0.82)) and 0.96 ± 0.02 (95% CI: (0.92, 0.98)) for Task1 and Task2, which were equivalent to or higher than radiologists in the senior group with average AUC values of 0.76 and 0.95, respectively (p > 0.05). With the CT image slice thickness increasing from 1.15 mm ± 0.36 to 1.73 mm ± 0.64, DNN performance decreased 0.08 and 0.22 for the two tasks. The results demonstrated (1) a positive trend between the diagnostic performance and radiologist’s experience, (2) the DNN yielded equivalent or even higher performance in comparison with senior radiologists, and (3) low image resolution decreased model performance in predicting the risks of GGNs. Once tested prospectively in clinical practice, the DNN could have the potential to assist doctors in precision diagnosis and treatment of early lung adenocarcinoma.

Evaluation of Computer-Aided Nodule Assessment and Risk Yield (CANARY) in Korean patients for prediction of invasiveness of ground-glass opacity nodule.

Differentiating the invasiveness of ground-glass nodules (GGN) is clinically important, and several institutions have attempted to develop their own solutions by using computed tomography images. The purpose of this study is to evaluate Computer-Aided Analysis of Risk Yield (CANARY), a validated virtual biopsy and risk-stratification machine-learning tool for lung adenocarcinomas, in a Korean patient population. To this end, a total of 380 GGNs from 360 patients who underwent pulmonary resection in a single institution were reviewed. Based on the Score Indicative of Lung Cancer Aggression (SILA), a quantitative indicator of CANARY analysis results, all of the GGNs were classified as “indolent” (atypical adenomatous hyperplasia, adenocarcinomas in situ, or minimally invasive adenocarcinoma) or “invasive” (invasive adenocarcinoma) and compared with the pathology reports. By considering the possibility of uneven class distribution, statistical analysis was performed on the 1) entire cohort and 2) randomly extracted six sets of class-balanced samples. For each trial, the optimal cutoff SILA was obtained from the receiver operating characteristic curve. The classification results were evaluated using several binary classification metrics. Of a total of 380 GGNs, the mean SILA for 65 (17.1%) indolent and 315 (82.9%) invasive lesions were 0.195±0.124 and 0.391±0.208 (p < 0.0001). The area under the curve (AUC) of each trial was 0.814 and 0.809, with an optimal threshold SILA of 0.229 for both. The macro F1-score and geometric mean were found to be 0.675 and 0.745 for the entire cohort, while both scored 0.741 in the class-equalized dataset. From these results, CANARY could be confirmed acceptable in classifying GGN for Korean patients after the cutoff SILA was calibrated. We found that adjusting the cutoff SILA is needed to use CANARY in other countries or races, and geometric mean could be more objective than F1-score or AUC in the binary classification of imbalanced data.

Determining the invasiveness of ground-glass nodules using a 3D multi-task network.

The aim of this study was to determine the invasiveness of ground-glass nodules (GGNs) using a 3D multi-task deep learning network. We propose a novel architecture based on 3D multi-task learning to determine the invasiveness of GGNs. In total, 770 patients with 909 GGNs who underwent lung CT scans were enrolled. The patients were divided into the training (n = 626) and test sets (n = 144). In the test set, invasiveness was classified using deep learning into three categories: atypical adenomatous hyperplasia (AAH) and adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA), and invasive pulmonary adenocarcinoma (IA). Furthermore, binary classifications (AAH/AIS/MIA vs. IA) were made by two thoracic radiologists and compared with the deep learning results. In the three-category classification task, the sensitivity, specificity, and accuracy were 65.41%, 82.21%, and 64.9%, respectively. In the binary classification task, the sensitivity, specificity, accuracy, and area under the ROC curve (AUC) values were 69.57%, 95.24%, 87.42%, and 0.89, respectively. In the visual assessment of GGN invasiveness of binary classification by the two thoracic radiologists, the sensitivity, specificity, and accuracy of the senior and junior radiologists were 58.93%, 90.51%, and 81.35% and 76.79%, 55.47%, and 61.66%, respectively. The proposed multi-task deep learning model achieved good classification results in determining the invasiveness of GGNs. This model may help to select patients with invasive lesions who need surgery and the proper surgical methods. • The proposed multi-task model has achieved good classification results for the invasiveness of GGNs. • The proposed network includes a classification and segmentation branch to learn global and regional features, respectively. • The multi-task model could assist doctors in selecting patients with invasive lesions who need surgery and choosing appropriate surgical methods.

Can peritumoral regions increase the efficiency of machine-learning prediction of pathological invasiveness in lung adenocarcinoma manifesting as ground-glass nodules?

BackgroundThe peri-tumor microenvironment plays an important role in the occurrence, growth and metastasis of cancer. The aim of this study is to explore the value and application of a CT image-based deep learning model of tumors and peri-tumors in predicting the invasiveness of ground-glass nodules (GGNs).MethodsPreoperative thin-section chest CT images were reviewed retrospectively in 622 patients with a total of 687 pulmonary GGNs. GGNs are classified according to clinical management strategies as invasive lesions (IAC) and non-invasive lesions (AAH, AIS and MIA). The two volumes of interest (VOIs) identified on CT were the gross tumor volume (GTV) and the gross volume of tumor incorporating peritumoral region (GPTV). Three dimensional (3D) DenseNet was used to model and predict GGN invasiveness, and five-fold cross validation was performed. We used GTV and GPTV as inputs for the comparison model. Prediction performance was evaluated by sensitivity, specificity, and area under the receiver operating characteristic curve (AUC).ResultsThe GTV-based model was able to successfully predict GGN invasiveness, with an AUC of 0.921 (95% CI, 0.896–0.937). Using GPTV, the AUC of the model increased to 0.955 (95% CI, 0.939–0.971).ConclusionsThe deep learning method performed well in predicting GGN invasiveness. The predictive ability of the GPTV-based model was more effective than that of the GTV-based model.

Dependence of radiomic features on pixel size affects the diagnostic performance of radiomic signature for the invasiveness of pulmonary ground-glass nodule.

To investigate the effect of reducing pixel size on the consistency of radiomic features and the diagnostic performance of the downstream radiomic signatures for the invasiveness for pulmonary ground-glass nodules (GGNs) on CTs. We retrospectively collected the clinical data of 182 patients with GGNs on high resolution CT (HRCT). The CT images of different pixel sizes (0.8mm, 0.4mm, 0.18 mm) were obtained by reconstructing the single HRCT scan using three combinations of field of view and matrix size. For each pixel size setting, radiomic features were extracted for all GGNs and radiomic signatures for the invasiveness of GGNs were built through two modeling pipelines for comparison. The study finally extracted 788 radiomic features. 87% radiomic features demonstrated inter pixel size variation. By either modeling pipeline, the radiomic signature under small pixel size performed significantly better than those under middle or large pixel sizes in predicting the invasiveness of GGNs (p's value <0.05 by Delong test). With the independent modeling pipeline, the three pixel size bounded radiomic signatures shared almost no common features. Reducing pixel size could cause inconsistency in most radiomic features and improve the diagnostic performance of the downstream radiomic signatures. Particularly, super HRCTs with small pixel size resulted in more accurate radiomic signatures for the invasiveness of GGNs. The dependence of radiomic features on pixel size will affect the performance of the downstream radiomic signatures. The future radiomic studies should consider this effect of pixel size.

Radiomics nomogram: A noninvasive tool for preoperative evaluation of the invasiveness of pulmonary adenocarcinomas manifesting as ground-glass nodules

In this study, we aimed to establish a radiomics nomogram that noninvasively evaluates the invasiveness of pulmonary adenocarcinomas manifesting as ground-glass nodules (GGNs). Computed tomography (CT) images of 509 patients manifesting as GGNs were collected: 70% of cases were included in the training cohort and 30% in the validation cohort. The Max-Relevance and Min-Redundancy (mRMR) and the least absolute shrinkage and selection operator (LASSO) algorithm were used to select the radiomics features and construct a radiomics signature. Univariate and multivariate logistic regression were used to select the invasiveness-related clinical and CT morphological predictors. Age, smoking history, long diameter, and average CT value were retained as independent predictors of GGN invasiveness. A radiomics nomogram was established by integrating clinical and CT morphological features with the radiomics signature. The radiomics nomogram showed good predictive ability in the training set (area under the curve [AUC], 0.940; 95% confidence interval [CI], 0.916–0.964) and validation set (AUC, 0.946; 95% CI, 0.907–0.986). This radiomics nomogram may serve as a noninvasive and accurate predictive tool to determine the invasiveness of GGNs prior to surgery and assist clinicians in creating personalized treatment strategies.

Predicting the invasiveness of lung adenocarcinomas appearing as ground-glass nodule on CT scan using multi-task learning and deep radiomics.

BackgroundDue to different treatment method and prognosis of different subtypes of lung adenocarcinomas appearing as ground-glass nodules (GGNs) on computed tomography (CT) scan, it is important to classify invasive adenocarcinomas from non-invasive adenocarcinomas. The purpose of this paper is to build and evaluate the performance of deep learning networks on the differentiation the invasiveness of lung adenocarcinoma appearing as GGNs.MethodsThis retrospective study included 886 GGNs from 794 pathological confirmed patients with lung adenocarcinoma for training and testing the proposed networks. Three deep learning networks, namely XimaNet (deep learning-based classification model), XimaSharp (classification and nodule segmentation model), and Deep-RadNet (deep learning and radiomics combined classification model, i.e., deep radiomics) were built. Three classification tasks, namely task 1: classification of AAH/AIS and MIA, task 2: classification of MIA and IAC, and task 3: classification of non-invasive adenocarcinomas and invasive adenocarcinomas (AAH/AIS&MIA and IAC) were conducted to evaluate the model performance. The Z-test was used to compare the model performance.ResultsThe AUC for classification of AAH/AIS with MIA were 0.891, 0.841 and 0.779 for Deep-RadNet, XimaNet and XimaSharp respectively. The AUC for classification of MIA with IAC were 0.889, 0.785 and 0.778 for three networks and AUC for classification of AAH/AIS&MIA with IAC were 0.941, 0.892 and 0.827 respectively. The performance of deep_RadNet was better than the other two models with the Z-test (P<0.05).ConclusionsDeep-RadNet with the visual heat map could evaluate the invasiveness of GGNs accurately and intuitively, providing a theoretical basis for individualized and accurate medical treatment of patients with GGNs.

The Invasiveness Classification of Ground-Glass Nodules Using 3D Attention Network and HRCT.

The early stage lung cancer often appears as ground-glass nodules (GGNs). The diagnosis of GGN as preinvasive lesion (PIL) or invasive adenocarcinoma (IA) is very important for further treatment planning. This paper proposes an automatic GGNs' invasiveness classification algorithm for the adenocarcinoma. 1431 clinical cases and a total of 1624 GGNs (3-30mm) were collected from Shanghai Cancer Center for the study. The data is in high-resolution computed tomography (HRCT) format. Firstly, the automatic GGN detector which is composed by a 3D U-Net and a 3D multi-receptive field (multi-RF) network detects the location of GGNs. Then, a deep 3D convolutional neural network (3D-CNN) called Attention-v1 is used to identify the GGNs' invasiveness. The attention mechanism was introduced to the 3D-CNN. This paper conducted a contract experiment to compare the performance of Attention-v1, ResNet, and random forest algorithm. ResNet is one of the most advanced convolutional neural network structures. The competition performance metrics (CPM) of automatic GGN detector reached 0.896. The accuracy, sensitivity, specificity, and area under curve (AUC) value of Attention-v1 structure are 85.2%, 83.7%, 86.3%, and 92.6%. The algorithm proposed in this paper outperforms ResNet and random forest in sensitivity, accuracy, and AUC value. The deep 3D-CNN's classification result is better than traditional machine learning method. Attention mechanism improves 3D-CNN's performance compared with the residual block. The automatic GGN detector with the addition of Attention-v1 can be used to construct the GGN invasiveness classification algorithm to help the patients and doctors in treatment.

Use of a Radiomics Model to Predict Tumor Invasiveness of Pulmonary Adenocarcinomas Appearing as Pulmonary Ground-Glass Nodules.

Background It is important to distinguish the classification of lung adenocarcinoma. A radiomics model was developed to predict tumor invasiveness using quantitative and qualitative features of pulmonary ground-glass nodules (GGNs) on chest CT. Materials and Methods A total of 599 GGNs [including 202 preinvasive lesions and 397 minimally invasive and invasive pulmonary adenocarcinomas (IPAs)] were evaluated using univariate, multivariate, and logistic regression analyses to construct a radiomics model that predicted invasiveness of GGNs. In primary cohort (comprised of patients scanned from August 2012 to July 2016), preinvasive lesions were distinguished from IPAs based on pure or mixed density (PM), lesion shape, lobulated border, and pleural retraction and 35 other quantitative parameters (P <0.05) using univariate analysis. Multivariate analysis showed that PM, lobulated border, pleural retraction, age, and fractal dimension (FD) were significantly different between preinvasive lesions and IPAs. After logistic regression analysis, PM and FD were used to develop a prediction nomogram. The validation cohort was comprised of patients scanned after Jan 2016. ResultsThe model showed good discrimination between preinvasive lesions and IPAs with an area under curve (AUC) of 0.76 [95% CI: 0.71 to 0.80] in ROC curve for the primary cohort. The nomogram also demonstrated good discrimination in the validation cohort with an AUC of 0.79 [95% CI: 0.71 to 0.88]. Conclusions For GGNs, PM, lobulated border, pleural retraction, age, and FD were features discriminating preinvasive lesions from IPAs. The radiomics model based upon PM and FD may predict the invasiveness of pulmonary adenocarcinomas appearing as GGNs.