Pure Ground-glass Nodules Research Articles

Meta-analysis of correlation between CT-based features and invasive properties of pure ground-glass nodules.

Several studies have revealed that computed tomography (CT) features can make a distinction in the invasive properties of pure ground-glass nodules (pGGNs). However, imaging parameters related to the invasive properties of pGGNs are unclear. This meta-analysis was designed to decipher the correlation between the invasiveness of pGGNs and CT-based features, and ultimately to be conducive to making rational clinical decisions. We searched a series of databases, including PubMed, Embase, Web of Science, Cochrane Library, Scopus, wanfang, CNKI, VIP, as well as CBM databases, until September 20, 2022, for the eligible publications only in Chinese or English. This meta-analysis was implemented with the Stata 16.0 software. Ultimately, 17 studies published between 2017 and 2022 were included. According to the meta-analysis, we observed a larger maximum size of lesions in invasive adenocarcinoma (IAC) versus that in preinvasive lesions (PIL) [SMD=1.37, 95% CI (1.07-1.68), P<0.05]. Meanwhile, there were also increased mean CT values of IAC [SMD=0.71, 95% CI (0.35, 1.07), P<0.05], the incidence of pleural traction sign [OR=1.94, 95% CI (1.24, 3.03), P<0.05], the incidence of IAC spiculation [OR=1.55, 95% CI (1.05, 2.29), P<0.05] in comparison to those of PIL. Nevertheless, IAC and PIL exhibited no significant differences in vacuole sign, air bronchogram, regular shape, lobulation and vascular convergence sign (all P>0.05). Therefore, IAC and PIL manifested different CT features of pGGNs. The maximum diameter of lesions, mean CT value, pleural traction sign and spiculation are important indicators to distinguish IAC and PIL. Reasonable use of these features can be helpful to the treatment of pGGNs.

A nomogram for predicting invasiveness of lung adenocarcinoma manifesting as pure ground-glass nodules: incorporating subjective CT signs and histogram parameters based on artificial intelligence.

To construct a nomogram based on subjective CT signs and artificial intelligence (AI) histogram parameters to identify invasiveness of lung adenocarcinoma presenting as pure ground-glass nodules (pGGNs) and to evaluate its diagnostic performance. 187 patients with 228 pGGNs confirmed by postoperative pathology were collected retrospectively and divided into pre-invasive group [atypical adenomatous hyperplasia (AAH) and adenocarcinoma in situ (AIS)] and invasive group [minimally invasive adenocarcinoma (MIA) and invasive adenocarcinoma (IAC)]. All pGGNs were randomly assigned to training cohort (n = 160) and validation cohort (n = 68). Nomogram was developed using subjective CT signs and AI-based histogram parameters by logistic regression analysis. The diagnostic performance was evaluated by receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA) curve. The nomogram was constructed with nodule shape, 3D mean diameter, maximum CT value, and skewness. It showed better discriminative power in differentiating invasive lesions from pre-invasive lesions with area under curve (AUC) of 0.849 (95% CI 0.790-0.909) in the training cohort and 0.831 (95% CI 0.729-0.934) in the validation cohort, which performed better than nodule shape (AUC 0.675, 95% CI 0.609-0.741), 3D mean diameter (AUC 0.762, 95% CI 0.688-0.835), maximum CT value (AUC 0.794, 95% CI 0.727-0.862), or skewness (AUC 0.594, 95% CI 0.506-0.682) alone in training cohort (for all, P < 0.05). For pulmonary pGGNs, the nomogram based on subjective CT signs and AI histogram parameters had a good predictive ability to discriminate invasive lung adenocarcinoma from pre-invasive lung adenocarcinoma, and it has the potential to improve diagnostic efficiency and to help the patient management.

Accurate classification of pulmonary nodules by a combined model of clinical, imaging, and cell-free DNA methylation biomarkers: a model development and external validation study

There is an unmet clinical need for accurate non-invasive tests to facilitate the early diagnosis of lung cancer. We propose a combined model of clinical, imaging, and cell-free DNA methylation biomarkers that aims to improve the classification of pulmonary nodules. We conducted a prospective specimen collection and retrospective masked evaluation study. We recruited participants with a solitary pulmonary nodule sized 5-30 mm from 24 hospitals across 20 cities in China. Participants who were aged 18 years or older and had been referred with 5-30 mm non-calcified and solitary pulmonary nodules, including solid nodules, part solid nodules, and pure ground-glass nodules, were included. We developed a combined clinical and imaging biomarkers (CIBM) model by machine learning for the classification of malignant and benign pulmonary nodules in a cohort (n=839) and validated it in two cohorts (n=258 in the first cohort and n=283 in the second cohort). We then integrated the CIBM model with our previously established circulating tumour DNA methylation model (PulmoSeek) to create a new combined model, PulmoSeek Plus (n=258), and verified it in an independent cohort (n=283). The clinical utility of the models was evaluated using decision curve analysis. A low cutoff (0·65) for high sensitivity and a high cutoff (0·89) for high specificity were applied simultaneously to stratify pulmonary nodules into low-risk, medium-risk, and high-risk groups. The primary outcome was the diagnostic performance of the CIBM, PulmoSeek, and PulmoSeek Plus models. Participants in this study were drawn from two prospective clinical studies that were registered (NCT03181490 and NCT03651986), the first of which was completed, and the second of which is ongoing because 25% of participants have not yet finished the required 3-year follow-up. We recruited a total of 1380 participants. 1097 participants were enrolled from July 7, 2017, to Feb 12, 2019; 839 participants were used for the CIBM model training set, and the rest (n=258) for the first CIBM validation set and the PulmoSeek Plus training set. 283 participants were enrolled from Oct 26, 2018, to March 20, 2020, as an independent validation set for the PulmoSeek Plus model and the second validation set for the CIBM model. The CIBM model validation cohorts had area under the curves (AUCs) of 0·85 (95% CI 0·80-0·89) and 0·85 (0·81-0·89). The PulmoSeek Plus model had better discrimination capacity compared with the CIBM and PulmoSeek models with an increase of 0·05 in AUC (PulmoSeek Plus vs CIBM, 95% CI 0·022-0·087, p=0·001; and PulmoSeek Plus vs PulmoSeek, 0·018-0·083, p=0·002). The overall sensitivity of the PulmoSeek Plus model was 0·98 (0·97-0·99) at a fixed specificity of 0·50 for ruling out lung cancer. A high sensitivity of 0·98 (0·96-0·99) was maintained in early-stage lung cancer (stages 0 and I) and 0·99 (0·96-1·00) in 5-10 mm nodules. The decision curve showed that if an invasive intervention, such as surgical resection or biopsy, was deemed necessary at more than the risk threshold score of 0·54, the PulmoSeek Plus model would provide a standardised net benefit of 82·38% (76·06-86·79%), equivalent to correctly identifying approximately 83 of 100 people with lung cancer. Using the PulmoSeek Plus model to classify pulmonary nodules with two cutoffs (0·65 and 0·89) would have reduced 89% (105/118) of unnecessary surgeries and 73% (308/423) of delayed treatments. The PulmoSeek Plus Model combining clinical, imaging, and cell-free DNA methylation biomarkers aids the early diagnosis of pulmonary nodules, with potential application in clinical decision making for the management of pulmonary nodules. The China National Science Foundation, the Key Project of Guangzhou Scientific Research Project, the High-Level University Construction Project of Guangzhou Medical University, the National Key Research & Development Programme, the Guangdong High Level Hospital Construction "Reaching Peak" Plan, the Guangdong Basic and Applied Basic Research Foundation, the National Natural Science Foundation of China, The Leading Projects of Guangzhou Municipal Health Sciences Foundation, the Key Research and Development Plan of Shaanxi Province of China, the Scheme of Guangzhou Economic and Technological Development District for Leading Talents in Innovation and Entrepreneurship, the Scheme of Guangzhou for Leading Talents in Innovation and Entrepreneurship, the Scheme of Guangzhou for Leading Team in Innovation, the Guangzhou Development Zone International Science and Technology Cooperation Project, and the Science and Technology Planning Project of Guangzhou.

Retrospective Analysis of Subsolid Nodules' Frequency Using Chest Computed Tomography Detection in an Outpatient Population.

The study was designed to evaluate the frequency of detection and the characteristics of subsolid nodules (SSNs) in outpatients' chest computed tomography (CT) scans from a private hospital in Southern Brazil. A retrospective analysis of all chest CT scans was performed in adult patients from ambulatory care (non-lung cancer screening population) over a thirty-day period. Inclusion criteria were age > 18 years and lung-scanning protocols, including standard-dose high-resolution chest CT (HRCT), enhanced CT, CT angiography, and low-dose chest CT (LDCT). SSNs main features collected were mean diameter, number, density (pure or heterogenous ground glass nodules and part-solid), and localization. TheLungRADS system and the updated Fleischner Society's pulmonary nodules recommendations were used for categorization only for study purposes, although not specifically fitting the population. The presence of emphysema, as well as calcified and solid nodules were also addressed. Statistical analysis was performed using R software, categorial variables are shown as absolute or relative frequencies, and continuous variables as mean and interquartile ranges. Chest computed tomography were performed in 756 patients during the study period (September 2019), and 650 met the inclusion criteria. The IQR for age was 53/73 years; most participants were female (58.3%) and 10.6% had subsolid nodules detected. The frequency of SSNs detection in patients in daily clinical practice, not related to screening populations, is not negligible. Regardless of the final etiology, follow-up is often indicated, given the likelihood of malignancy for persistent lesions.

Invasiveness identification in pure ground-glass nodules: exploring the generalizability of radiomics based on external validation and stress testing.

This study aimed to apply external validation and stress tests to evaluate the generalizability of radiomics models built using various machine-learning methods for identifying the invasiveness of lung adenocarcinomas manifesting as pure ground-glass nodules (pGGNs). This retrospective study enrolled 495 patients (514 pGGNs) confirmed as lung adenocarcinomas by postoperative pathology from three centers. All nodules were included in the primary cohort (randomly divided into training and test cohorts), two external validation cohorts, and two stress test cohorts. Six machine-learning radiomics models were constructed in the training cohort using the optimal features. Performance of radiomics models and clinical models were compared in primary cohort and external validation cohorts. The stress tests included stratified performance evaluation and shifted performance evaluation and contrastive evaluation under three single-condition modification settings. The predictive performance was validated by area under curve (AUC) of receiver operating characteristic (ROC). Of the six radiomics models, the best logistic regression (LR) model was able to maintain high differential diagnostic capability (AUC: 0.849 ± 0.049) and good stability (relative standard deviation, 5.719%), but it showed poorer performance (AUC= 0.835) than the clinical model (AUC= 0.862) in the external validation cohort E1. The stress tests suggested LR model had no significant difference in performance between subgroups after stratification and had good consistency in the predictions before and after the three transformations (Kappa = 0.960, 0.840, and 0.933, respectively; p < 0.05, all). The rigorous testing procedure facilitates the selection of high-performance radiomics models with good clinical generalizability.

Different nodal upstaging rates and prognoses for patients with clinical T1N0M0 lung adenocarcinoma classified according to the presence of solid components in the lung and mediastinal windows.

Little is known about the correlation between nodal upstaging and pulmonary nodules classified according to the presence of solid components in the lung and mediastinal windows. This study thus aimed to analyze the risk factors of nodal upstaging and prognosis based on different imaging features, clinical characteristics, and pathological results from patients with clinical stage T1N0M0 lung adenocarcinoma. A total of 340 patients between January 2016 and June 2017 were selected from the Affiliated Hospital of Qingdao University database. Imaging features, clinical characteristics, and pathological results were collected for survival and analysis of nodal upstaging risk factors. We used logistic regression models to identify important metastatic risk factors for nodal upstaging. Survival rates were calculated using Kaplan-Meier (KM) survival curves and compared with the log-rank test. Significant prognostic risk factors were identified using the Cox proportional hazards model. A total of 340 patients, with an average age of 64.89 (±8.775) years, were enrolled. Among them, nonnodal upstaging occurred both in 77 (22.6%) patients with pure ground-glass nodules (pGGNs) and in 30 (8.8%) patients with heterogenous ground-glass nodules (hGGNs). Compared to the 92 (27.1%) patients with real part-solid nodules (rPSNs), the 141 (41.5%) patients with solid nodules were significantly different in terms of in nodal upstaging (P<0.001). Moreover, preoperative carcinoembryonic antigen (CEA) level >3.4 µg/L [odds ratio (OR): 2.931; 95% confidence interval (CI): 1.511-5.688; P=0.001], imaging tumor size >18.3 mm (OR, 3.482; 95% CI: 1.609-7.535; P=0.002), and consolidation tumor ratio (CTR) >0.788 (OR 8.791; 95% CI: 3.570-21.651; P<0.001) were independent risk factors for nodal upstaging. The KM survival curve results showed that patients with pGGNs and those with hGGNs had a much better 5-year disease-free survival (DFS) and 5-year overall survival (OS) than did those with rPSNs and those with solid nodules (DFS: 98.7% vs. 100% vs. 81.4% vs. 73.7%, P<0.001; OS: 97.4% vs. 100% vs. 90.2% vs. 83.7%, P=0.003). In the multivariate Cox regression analysis of patients with rPSNs and solid nodules, tumor location and pathological lymph node grade were found to be independent risk factors for DFS and OS. Patients with pGGNs and those with hGGNs were more likely to be free of nodal upstaging and had better prognosis than did those with clinical stage IA rPSNs and solid nodules. The patients with pGGNs or hGGNs with preoperative CEA level <3.4 µg/L, imaging tumor size <18.3 mm, and CTR <0.788 can choose systematic lymph node sampling (SLNS) or decline lymph node dissection to avoid postoperative complications.

Proposal of Modified Lung-RADS in Assessing Pulmonary Nodules of Patients with Previous Malignancies: A Primary Study

Background: In addition to the diameters of pulmonary nodules, the number and morphology of blood vessels in pure ground-glass nodules (pGGNs) were closely related to the occurrence of lung cancer. Moreover, the benign and malignant signs of nodules were also valuable for the identification of nodules. Based on these two points, we tried to revise Lung-RADS 2022 and proposed our Modified Lung-RADS. The aim of the study was to verify the diagnostic performance of Modified Lung-RADS for pulmonary solid nodules (SNs) and pure ground-glass nodules (pGGNs) in patients with previous malignancies. Methods: The chest CT and clinical data of patients with prior cancer who underwent pulmonary nodulectomies from 1 January 2018 to 30 November 2021 were enrolled according to inclusion and exclusion criteria. A total of 240 patients with 293 pulmonary nodules were included in this study. In contrast with the original version, the risk classification of pGGNs based on the GGN–vascular relationships (GVRs), and the SNs without burrs and with benign signs, could be downgraded to category 2. The sensitivity, specificity, and agreement rate of the original Lung-RADS 2022 and Modified Lung-RADS for pGGNs and SNs were calculated and compared. Results: Compared with the original version, the sensitivity and agreement rate of the Modified version for pGGNs increased from 0 and 23.33% to 97.10% and 92.22%, respectively, while the specificity decreased from 100% to 76.19%. As regards SNs, the specificity and agreement rate of the Modified version increased from 44.44% to 75.00% (p &lt; 0.05) and 88.67% to 94.09% (p = 0.052), respectively, while the sensitivity was unchanged (98.20%). Conclusions: In general, the diagnostic efficiency of Modified Lung-RADS was superior to that of the original version, and Modified Lung-RADS could be a preliminary attempt to improve Lung-RADS 2022.

Growth assessment of pure ground-glass nodules on CT: comparison of density and size measurement methods.

To investigate the differences of size and density measurements in assessing pure ground-glass nodules (pGGNs) growth, and compare the growth rates and growth proportions of the two methods during follow-up period. Ninety patients with at least 3 consecutive thin-section chest CTs and confirmed 103 pGGNs on baseline CT were enrolled retrospectively. Using the two definitions of size and density to evaluate pGGNs growth with semi-automated segmentation. Then, the two methods were compared to assess differences in pGGNs growth. For the size and density methods to assess nodule growth, 50.5% and 26.2% showed interval growth at the last CT (p < 0.001). Among the 19 nodules that grew in both size and density, the volume doubling time (VDT) of solid component (mean, 317.1; standard deviation, 224.8days) was shorter than total VDT (median, 942.8; range, 400.1-2315.9days) (p < 0.001). Of the 27 growth pGGNs assessed by the density method, the growth rates at years 1 and 2 were 25.9% and 63.0%, while the growth rates of 52 growing nodules assessed by size method were 11.5% and 48.1%, respectively. Twenty of 103 (19.4%) nodules were classified into category 4A lesions, and 7 (6.8%) were 4B lesions. Compared to size measurements, observed density increases have a higher proportion of early growth and faster growth rates in growing nodules. Clinicians need to pay close attention to the nodules of new solid components and make timely decision management.

European guidelines for the surgical management of pure ground-glass opacities and part-solid nodules: Task Force of the European Association of Cardio-Thoracic Surgery and the European Society of Thoracic Surgeons.

Pulmonary nodules are often encountered by respiratory physicians, radiologists, and thoracic surgeons alike. The European Society of Thoracic Surgery (ESTS) and European Association of Cardiothoracic Surgery (EACTS) established a multidisciplinary collaboration of clinicians with expertise in managing pulmonary nodules with the aim of producing the first joint comprehensive review of the scientific literature, with a specific focus on the management of pure ground glass opacities and part-solid nodules. The scope of the document has been defined by the EACTS and ESTS governing bodies and focuses on six areas of main interest agreed upon by the Task Force. These include: management of solitary and multiple pure ground glass nodules, solitary part-solid nodules, identifying the non-palpable lesion, the role of minimally invasive surgery and the decision making behind sub-lobar versus lobar resection. The literature revealed that with the increasing use of incidental CT scans and CT lung cancer screening programs, the detection of early-stage lung cancer is going to rise with a higher number of potential cancers presenting on the ground glass and part-solid nodule spectrum. Given that the gold standard for improved survival is surgical resection, there is an urgent need for comprehensive characterisation of these nodules and guidelines that are directed towards their surgical management. It is recommended that standard decision-making tools are used to determine the risk of malignancy and thus guide referral for surgical management and decisions for surgical resection are made in a multidisciplinary setting with equitable consideration given to radiological characteristics, the evolution of the lesion, presence of solid component, patient fitness and co-morbidities. Given the recent surge in robust level I data comparing sublobar and lobar resection with the release of JCOG0802 and CALGB140503 data, a global overview of an individual case must be adopted into clinical practice. This set of recommendations are based on the available literature; however, close collaboration in the design and conduct of randomized controlled trials is still of utmost importance to answer further questions in this rapidly evolving field.

Watershed analysis in wedge resection of pulmonary pure ground-glass nodules hardly localized by CT-guided puncture

BackgroundTo investigate the feasibility and safety of watershed analysis after target pulmonary vascular occlusion for the wedge resection in patients with non-palpable and non-localizable pure ground-glass nodules during uniport thoracoscopic surgery.MethodsA total of 30 patients with pure ground-glass nodules < 1 cm in diameter, localized in the lateral third of the lung parenchyma, were enrolled. Three-dimensional reconstruction of thin-section computed tomography (CT) data was performed using Mimics software before surgery to observe and identify the target pulmonary vessels supplying the lung tissue in the area where the pulmonary nodules were localized and to temporarily block the target pulmonary vessels during surgery. Next, the extent of the watershed was determined with the expansion-collapse method, and finally, wedge resection was performed. After wedge resection of the target lung tissue, the blocked pulmonary vessel was released, thus allowing operators to complete the procedure without damaging pulmonary vessels.ResultsNone of the patients experienced postoperative complications. The chest CT of all patients was reviewed six months after the operation, revealing no tumor recurrence.ConclusionsOur results suggest that watershed analysis following target pulmonary vascular occlusion for wedge resection in pulmonary pure ground-glass nodules is a safe and feasible approach.

The influence of different previous cancer histories on the diagnostic efficacy of Lung Imaging Reporting and Data System.

For lung cancer screening in patients with previous malignant tumors, Lung Imaging Reporting and Data System (Lung-RADS) and other lung cancer screening tools are controversial in terms of requirements for the previous cancer history. This study investigated the effect of the length and type of malignancy history on the diagnostic efficacy of Lung Imaging Reporting and Data System (Lung-RADS) 2022 in pulmonary nodules (PNs). Chest computed tomography and clinical data of PNs in patients with a history of cancer who underwent surgical resection in The First Affiliated Hospital of Chongqing Medical University from January 1, 2018, to November 30, 2021, were retrospectively collected and evaluated based on Lung-RADS. All PNs were divided into 2 groups: the prior lung cancer (PLC) and the prior extrapulmonary cancer (PEPC) groups. Each group was divided into the ≥5 years and <5 years groups based on the duration of cancer history. The diagnostic agreement of Lung-RADS was evaluated based on the pathological diagnosis of nodules after operation. The diagnostic agreement rate (AR) of Lung-RADS and the composition ratios of different types between different groups were calculated and compared. A total of 451 patients with 565 PNs were included in this study. These patients were divided into the PLC group (<5 years: 135 cases, 175 PNs; ≥5 years: 9 cases, 12 PNs) and the PEPC group (<5 years: 219 cases, 278 PNs; ≥5 years: 88 cases, 100 PNs). The diagnostic AR of partial solid nodules (93.0%; 95% CI: 88.7-97.2%) and solid nodules (88.1%; 95% CI: 84.1-92.1%) was close (P=0.13), while both were higher than that of the pure ground-glass nodules (24.0%; 95% CI: 17.5-30.4%; all P values <0.001). Within 5 years, the composition ratio of PNs and the diagnostic AR (PLC: 58.9%, 95% CI: 51.5-66.2%; PEPC: 76.6%, 95% CI: 71.6-81.6%) between the PLC and PEPC groups were all different (all P values <0.001), and the others [composition ratio of PNs & the diagnostic AR: PLC (≥5 years) vs. PEPC (≥5 years); PLC (<5 years) vs. PLC (≥5 years); PEPC (<5 years) vs. PEPC (≥5 years)] were similar (all P values >0.05; range: 0.10-0.93). The length of prior cancer history may affect the diagnostic agreement of Lung-RADS, especially for patients with prior lung cancer within 5 years.

Thin-slice computed tomography enables to classify pulmonary subsolid nodules into pre-invasive lesion/minimally invasive adenocarcinoma and invasive adenocarcinoma: a retrospective study

The aim was to investigate the ability of thin-slice computed tomography (TSCT) to differentiate invasive pulmonary adenocarcinomas (IACs) from pre-invasive/minimally invasive adenocarcinoma (AAH-MIAs), manifesting as subsolid nodules (SSNs) of diameter less than 30 mm. The CT findings of 810 patients with single subsolid nodules diagnosed by pathology of resection specimens were analyzed (atypical adenomatous hyperplasia, n = 13; adenocarcinoma in situ, n = 175; minimally invasive adenocarcinoma, n = 285; and invasive adenocarcinoma, n = 337). According to the classification of lung adenocarcinoma published by WHO classification of thoracic tumors in 2015, TSCT features of 368 pure ground-glass nodules (pGGN) and 442 part-solid nodules (PSNs) were compared AAH-MIAs with IACs. Logistic regression and receiver operating characteristic (ROC) curve analyses were performed. In pGGNs, multivariate analysis of factors found to be significant by univariate analysis revealed that higher mean-CT values (p = 0.006, OR 1.006, 95% CI 1.002–1.010), larger tumor size (p < 0.001, OR 1.483, 95% CI 1.304–1.688) with air bronchogram and non-smooth margins were significantly associated with IACs. The optimal cut-off tumor diameter for AAH-MIAs lesions was less than 10.75 mm (sensitivity, 82.8%; specificity, 80.6%) and optimal cut-off mean-CT value − 629HU (sensitivity, 78.1%; specificity, 50.7%). In PSNs, multivariate analysis of factors found to be significant by univariate analysis revealed that smaller tumor diameter (p < 0.001, OR 0.647, 95% CI 0.481–0.871), smaller size of solid component (p = 0.001, OR 83.175, 95% CI 16.748–413.079),and lower mean-CT value of solid component (p < 0.001, OR 1.009, 95% CI 1.004–1.014) were significantly associated with AAH-MIAs (p < 0.05). The optimal cut-off tumor diameter, size of solid component, and mean-CT value of solid component for AAH-MIAs lesions were less than 14.595 mm (sensitivity, 71.1%; specificity, 83.4%), 4.995 mm (sensitivity, 97.8%; specificity, 92.3%) and − 227HU (sensitivity, 65.6%; specificity, 76.3%), respectively. In subsolid nodules, whether pGGN or PSNs, the characteristics of TSCT can help in distinguishing IACs from AAH-MIAs.

Reticulation Sign on Thin-Section CT: Utility for Predicting Invasiveness of Pure Ground-Glass Nodules.

BACKGROUND. Pure ground-glass nodules (pGGNs) may represent a diverse range of histologic entities of varying aggressiveness. OBJECTIVE. The purpose of this study was to evaluate the use of the reticulation sign on thin-section CT images for predicting the invasiveness of pGGNs. METHODS. This retrospective study included 795 patients (mean age, 53.4 ± 11.1 [SD] years; 254 men, 541 women) with a total of 876 pGGNs on thin-section CT that underwent resection between January 2015 and April 2022. Two fellowship-trained thoracic radiologists independently reviewed unenhanced CT images to assess the pGGNs for a range of features, including diameter, attenuation, location, shape, air bronchogram, bubble lucency, vascular change, lobulation, spiculation, margins, pleural indentation, and the reticulation sign (defined as multiple small linear opacities resembling a mesh or a net); differences were resolved by consensus. The relationship between the reticulation sign and lesion invasiveness on pathologic assessment was evaluated. RESULTS. On pathologic assessment, the 876 pGGNs included 163 nonneoplastic and 713 neoplastic pGGNs (323 atypical adenomatous hyperplasias [AAHs] or adenocarcinomas in situ [AISs], 250 minimally invasive adenocarcinomas [MIAs], and 140 invasive adenocarcinomas [IACs]). Interobserver agreement for the reticulation sign, expressed as kappa, was 0.870. The reticulation sign was detected in 0.0% of nonneoplastic lesions, 0.0% of AAHs/AISs, 6.8% of MIAs, and 54.3% of IACs. The reticulation sign had sensitivity of 24.0% and specificity of 100.0% for a diagnosis of MIA or IAC and sensitivity of 54.3% and specificity of 97.7% for a diagnosis of IAC. In multivariable regression analyses including all of the assessed CT features, the reticulation sign was a significant independent predictor of IAC (OR, 3.64; p = .001) but was not a significant independent predictor of MIA or IAC. CONCLUSION. The reticulation sign, when observed in a pGGN on thin-section CT, has high specificity (albeit low sensitivity) for invasiveness and is an independent predictor of IAC. CLINICAL IMPACT. Those pGGNs that show the reticulation sign should be strongly suspected to represent IAC; this suspicion may guide risk assessments and follow-up recommendations.

CT-based three-dimensional invasiveness analysis of adenocarcinoma presenting as pure ground-glass nodules.

We invest computed tomography (CT) image differences between non-invasive adenocarcinomas (NIAs) and invasive adenocarcinomas (IAs) presenting as pure ground glass nodules (GGNs). From 2013 to 2019, 48 pure GGNs were surgically resected in 45 patients. Of these, 40 were pathologically diagnosed as non-small cell lung cancers (NSCLCs). We assessed them using the Synapse Vincent (Fujifilm Co., Ltd., Tokyo, Japan) three-dimensional (3D) analysis system; we drew histograms of the CT densities. We calculated the maximum, minimum, means, and standard deviations of the densities. The proportions of GGNs of high CT density were compared between the two groups. The diagnostic performance was investigated via receiver operating curve (ROC) analysis. Of the 40 pure GGNs, 20 were NIAs (4 adenocarcinomas in situ and 16 minimally IAs) and 20 IAs. Significant correlations were evident between histological invasiveness and the maximum and mean CT densities and the standard deviation. Neither the nodule volume nor the minimum CT density significantly predicted invasiveness. A CT volume density proportion >-300 Hounsfield units optimally predicted the invasiveness of pure GGNs; the cutoff was 5.41% with a sensitivity of 85% and a specificity of 95%. CT density reflected the invasiveness of pure GGNs. A CT volume proportion density >-300 Hounsfield units may significantly predict histological invasiveness.

Long-term follow-up of persistent pulmonary subsolid nodules: Natural course of pure, heterogeneous, and real part-solid ground-glass nodules.

Previous studies have suggested the applicability of three classifications of subsolid nodules (SSNs). However, few studies have unraveled the natural history of the three types of SSNs. A retrospective study from two medical centers between November 2007 and November 2017 was conducted to explore the long-term follow-up results of three different types of SSNs, which were divided into pure ground-glass nodules (pGGNs), heterogeneous ground-glass nodules (hGGNs), and real part-solid nodules (rPSNs). A total of 306 consecutive patients, including 361 SSNs with long-term follow-up, were reviewed. The median growth times of pGGNs, hGGNs, and rPSNs were 7.7, 6.0, and 2.0 years, respectively. For pGGNs, the median period of development into rPSNs was 4.6 years, while that of hGGNs was 1.8 years, and the time from pGGNs to hGGNs was 3.1 years (p < 0.05). In SSNs with an initial lung window consolidation tumor ratio (LW-CTR) >0.5 and mediastinum window (MW)-CTR >0.2, all cases with growth were identified within 5 years. Meanwhile, in SSNs whose LW-CTR and MW-CTR were 0, it took over 5 years to detect nodular growth. Pathologically, 90.6% of initial SSNs with LW-CTR >0 were invasive carcinomas (invasive adenocarcinoma and micro-invasive adenocarcinoma). Among patients with rPSNs in the initial state, 100.0% of the final pathological results were invasive carcinoma. Cox regression showed that age (p=0.038), initial maximal diameter (p < 0.001), and LW-CTR (p=0.002) were independent risk factors for SSN growth. pGGNs, hGGNs, and rPSNs have significantly different natural histories. Age, initial nodule diameter, and LW-CTR are important risk factors for SSN growth.

Computer-Aided Detection of Subsolid Nodules on Chest Computed Tomography: Assessment of Visualization on Vessel-Suppressed Images.

This study aimed to clarify the performance of automatic detection of subsolid nodules by commercially available software on computed tomography (CT) images of various slice thicknesses and compare it with visualization on the accompanying vessel-suppression CT (VS-CT) images. A total of 95 subsolid nodules from 84 CT examinations of 84 patients were included. The reconstructed CT image series of each case with 3-, 2-, and 1-mm slice thicknesses were loaded into a commercially available software application (ClearRead CT) for automatic detection of subsolid nodules and generation of VS-CT images. Automatic nodule detection sensitivity was assessed for 95 nodules on each series of images acquired at 3 slice thicknesses. Four radiologists subjectively evaluated visual assessment of the nodules on VS-CT. ClearRead CT automatically detected 69.5% (66/95 nodules), 68.4% (65/95 nodules), and 70.5% (67/95 nodules) of all subsolid nodules in 3-, 2-, and 1-mm slices, respectively. The detection rate was higher for part-solid nodules than for pure ground-glass nodules at all slice thicknesses. In the visualization assessment on VS-CT, 3 nodules at each slice thickness (3.2%) were judged as invisible, while 26 of 29 (89.7%), 27 of 30 (90.0%), and 25 of 28 (89.3%) nodules, which were missed by computer-aided detection, were judged as visible in 3-, 2-, and 1-mm slices, respectively. The automatic detection rate of subsolid nodules by ClearRead CT was approximately 70% at all slice thicknesses. More than 95% of subsolid nodules were visualized on VS-CT, including nodules undetected by the automated software. Computed tomography acquisition at slices thinner than 3 mm did not confer any benefits.

A narrative review of the clinical approach to subsolid pulmonary nodules.

The widespread use of chest computed tomography (CT) for lung cancer screening has led to increased detection of subsolid pulmonary nodules. The management of subsolid nodules (SSNs) is challenging since they are likely to grow slowly and a long-term follow-up is needed. In this review, we discuss the characteristics, natural history, genetic features, surveillance, and management of SSNs. PubMed and Google Scholar were searched to identify relevant articles published in English between January 1998 and December 2022 using the following keywords: "subsolid nodule", "ground-glass nodule (GGN)", and "part-solid nodule (PSN)". The differential diagnosis of SSNs includes transient inflammatory lesions, focal fibrosis, and premalignant or malignant lesions. Long-term CT surveillance follow-up is needed to manage SSNs that persist for >3 months. Although most SSNs have an indolent clinical course, PSNs may have a more aggressive clinical course than pure GGNs. The proportion of growth and the time to grow is higher and shorter in PSN than pure GGN. In lung adenocarcinoma manifesting as SSNs, EGFR mutations were the major driver mutations. Guidelines are available for the management of incidentally detected and screening-detected SSNs. The size, solidity, location, and number of SSNs are important factors in determining the need for surveillance and surgical resection, as well as the interval of follow-up. Positron emission tomography/CT and brain magnetic resonance imaging (MRI) are not recommended for the diagnosis of SSNs, especially for pure GGNs. Periodic CT surveillance and lung-sparing surgery are the main strategies for the management of persistent SSNs. Nonsurgical treatment options for persistent SSNs include stereotactic body radiotherapy (SBRT) and radiofrequency ablation (RFA). For multifocal SSNs, the timing of repeated CT scans and the need for surgical treatment are decided based on the most dominant SSN(s). The SSN is a heterogeneous disease and a personalized medicine approach is required in the future. Future studies of SSNs should focus on their natural history, optimal follow-up duration, genetic features, and surgical and nonsurgical treatments to improve the corresponding clinical management. All these efforts will lead to the personalized medicine approach for the SSNs.

Radiomics-based analysis of CT imaging for the preoperative prediction of invasiveness in pure ground-glass nodule lung adenocarcinomas

ObjectiveThe purpose of the study is to investigate the performance of radiomics-based analysis in prediction of pure ground-glass nodule (pGGN) lung adenocarcinomas invasiveness using thin-section computed tomography images.MethodsA total of 382 patients surgically resected single pGGN and pathologically confirmed were enrolled in the retrospective study. The pGGN cases were divided into two groups: the noninvasive group and the invasive adenocarcinoma (IAC) group. 330 patients were randomly assigned to the training and testing cohorts with a ratio of 7:3 (245 noninvasive lesions, 85 IAC lesions), while 52 patients (30 noninvasive lesions, 22 IAC lesions) were assigned to the external validation cohort. A model, radiomics model, and combined clinical-radiographic-radiomic model were built using the LASSO and multivariate backward stepwise regression analysis on the basis of the selected and radiomics features. The area under the curve (AUC) and decision curve analysis (DCA) were used to evaluate and compare the model performance for invasiveness discrimination among the three cohorts.ResultsThree clinical-radiographic features (including age, gender and the mean CT value) and three radiomics features were selected for model building. The combined model and radiomics model performed better than the clinical-radiographic model. The AUCs of the combined model in the training, testing, and validation cohorts were 0.856, 0.859, and 0.765, respectively. The DCA demonstrated the radiomics signatures incorporating clinical-radiographic feature was clinically useful in predicting pGGN invasiveness.ConclusionsThe proposed radiomics-based analysis incorporating the clinical-radiographic feature could accurately predict pGGN invasiveness, providing a noninvasive biomarker for the individualized and precise medical treatment of patients.

Spectral Dual-Layer Computed Tomography Can Predict the Invasiveness of Ground-Glass Nodules: A Diagnostic Model Combined with Thymidine Kinase-1.

Few studies have explored the use of spectral dual-layer detector-based computed tomography (SDCT) parameters, thymidine kinase-1 (TK1), and tumor abnormal protein (TAP) for the detection of ground-glass nodules (GGNs). Therefore, we aimed to evaluate the quantitative and qualitative parameters generated from SDCT for predicting the pathological subtypes of GGN-featured lung adenocarcinoma combined with TK1 and TAP. Between July 2021 and September 2022, 238 patients with GGNs were retrospectively enrolled in this study. SDCT and tests for TK1 and TAP were performed preoperatively, and the lesions were divided into glandular precursor lesions (PGL), minimally invasive adenocarcinoma (MIA), and invasive adenocarcinoma (IAC), according to the pathological results. A receiver operating characteristic (ROC) curve was used to compare the diagnostic performance of these parameters. Multivariate logistic regression analysis was performed to construct a joint diagnostic model and create a nomogram. This study included 238 GGNs, including 41 atypical adenomatous hyperplasias (AAH), 62 adenocarcinomas in situ (AIS), 49 MIA, and 86 IAC, with a high proportion of women, non-smokers, and pure ground-glass nodule (pGGN). CT100 keV (a/v), electronic density (EDW) (a/v), Daverage, Dsolid, TK1, and TAP of MIA and IAC were higher than those of PGL. The effective atomic number (Zeff (a/v)) was lower in MIA and IAC than in PGL (all p < 0.05). Logistic regression analysis showed that Zeff (a), EDW (a), TK1, Daverage, and internal bronchial morphology were crucial factors in predicting the aggressiveness of GGN. Zeff (a) had the highest diagnostic performance with an area under the ROC curve (AUC) = 0.896, followed by EDW (a) (AUC = 0.838) and CT100 keVa (AUC = 0.819). The diagnostic model and nomogram constructed using these five parameters (Zeff (a) + EDW (a) + CT100 keVa + Daverage + TK1) had an AUC = 0.933, which was higher than the individual parameters (p < 0.05). Multiple quantitative and functional parameters can be selected based on SDCT, especially Zeff (a) and EDW (a), which have high sensitivity and specificity for predicting GGNs' invasiveness. Additionally, the combination of TK1 can further improve diagnostic performance, and using a nomogram is helpful for individualized predictions.

Natural progression of persistent pure ground-glass nodules 10mm or smaller: long-term observation and risk factor assessment.

Semi-automatic segmentation was used to investigate the natural progression of pure ground-glass nodules (pGGNs) of 5-10mm in long-term follow-up and to analyze independent risk factors for subsequent growth. A total of 154 pGGNs of 5-10mm from 132 patients with 698 follow-up CT scans were retrospectively identified. Subsequently, enrolled pGGNs were semiautomatically segmented on initial and follow-up CT to obtain diameter, density and volume, thus calculating mass, volume doubling time (VDT), and mass doubling time (MDT). Kaplan‒Meier analysis and multivariate Cox proportional risk regression were performed to explore independent predictors of pGGN growth. We analyzed growth differences among different pathological results of pGGNs confirmed by surgery. The prognosis was analyzed using the total diameter or solid size of the nodules on the last preoperative CT. Among the 85 (55.2%) pGGNs with growth, 5.9%, 51.8%, and 80.0% showed growth within 1, 3, and 5years, respectively. The median VDT and MDT were 1206.4 (range 349.8-5134.4) days and 1161.3 (range 339.4-6630.4) days, respectively. The multivariate Cox risk regression analysis showed that mean CT attenuation (m-CTA) [hazard ratio (HR) = 2.098, p = 0.010] and roundness index (HR = 1.892, p = 0.021) were independent risk factors for pGGN growth. In total, 67.6% of surgically resected and growing pGGNs were invasive non-mucinous adenocarcinoma (IA), including 2 cases of endpoint events, showing a PSN with solid components of 5.6mm and a solid nodule with a diameter of 19.9mm. pGGNs of 5-10mm showed an indolent clinical course. Follow-up CT imaging of pGGNs in the latter half of the first two years should be a rational management strategy. Small pGGNs with a larger overall m-CTA and roundness index on baseline CT are more likely to grow.