Ground-glass Opacity Nodules Research Articles

Comparison of the Patient Demographics, High-Resolution Computed Tomography Features of the Pulmonary Ground-Glass Opacity and Its Diagnostic Value Analysis

Introduction Pulmonary ground-glass opacity (GGO) observed on computed tomography (CT) is widely regarded as a diagnostic feature of lung adenocarcinoma; however, a significant radiological predictive sign remains controversial. In this retrospective study, we conducted a comprehensive analysis of 206 patients with GGO to establish a correlation analysis model between CT images and diagnosis of GGO nodules. Methods Histopathologic specimens were obtained from 206 patients (130 women, 76 men; age range 24–77). The clinical data, pathologic findings, and thin-section CT features of solid, pure GGO (pGGO), and mixed GGO (mGGO) nodules were compared using rigorous statistical methods, such as t-test, Fisher’s exact test, or univariate logistic regression analysis. Results Significant differences were observed among the 3 groups in terms of patient demographics, including gender (P = 0.016), smoking history (P = 0.002), and nodule size (P = 0.002). Morphologic CT characteristics, such as the presence of spiculated sign, lobulated sign, vascular sign, bubble-lucency sign, or pleural retraction, exhibited significant differences among the solid nodule, pGGO, and mGGO groups. However, no significant differences were observed in terms of air-bronchogram sign. Notably, the incidence of malignancy was significantly higher in pGGO nodules (76.52%) than in solid (48.48%) and mGGO (73.86%) nodules. Patients with mGGO had up to 2.988 times higher hazard of malignant lesions than those with solid nodules [P = 0.036, hazard ratio (HR) = 2.988]. Similarly, the hazard of malignant lesions was 2.941 times higher in patients with pGGO than in those with solid nodules (P = 0.007, HR = 2.941). Conclusion Clinical, pathological, and thin-section CT features of solid, pGGO and mGGO nodules were found to be significantly different. Based on our comprehensive analysis, patients presenting with a mGGO or pGGO on CT scans were more likely to be diagnosed with lung cancer.

Immunogenomic features of radiologically distinctive nodules in multiple primary lung cancer

ObjectivesTo provide molecular and immunological attributes mechanistic insights for the management of radiologically distinctive multiple primary lung cancer (MPLC).MethodsThe Bulk RNA-seq data of MPLC were obtained from our center. The Bulk RNA-seq data and CT images of patients with single primary lung cancer (SPLC) were obtained from GSE103584. Immune infiltration algorithms were performed to investigate the disparities in the immunological microenvironment between the two groups. Single-cell gene analysis was used to explore immune cells composition and communication relationships between cells in MPLC.ResultsIn MPLC, 11 pure ground-glass opacity nodules (pGGN) and 10 mixed GGN (mGGN) were identified, while in SPLC, the numbers were 18 pGGN and 22 mGGN, respectively. In MPLC, compared to pGGN, mGGN demonstrated a significantly elevated infiltration of CD8+ T cells. Single-cell gene analysis demonstrated that CD8+ T cells play a central role in the signaling among immune cells in MPLC. The transcription factors including MAFG, RUNX3, and TBX21 may play pivotal roles in regulation of CD8+ T cells. Notably, compared to SPLC nodules for both mGGN and pGGN, MPLC nodules demonstrated a significantly elevated degree of tumor-infiltrating immune cells, with this difference being particularly pronounced in mGGN. There was a positive correlation between the proportion of immune cells and consolidation/tumor ratio (CTR).ConclusionsOur findings provided a comprehensive description about the difference in the immune microenvironment between pGGN and mGGN in early-stage MPLC, as well as between MPLC and SPLC for both mGGN and pGGN. The findings may provide evidence for the design of immunotherapeutic strategies for MPLC.

Increased Scan Speed and Pitch on Ultra-Low-Dose Chest CT: Effect on Nodule Volumetry and Image Quality.

Background and Objectives: This study's objective was to investigate the influence of increased scan speed and pitch on image quality and nodule volumetry in patients who underwent ultra-low-dose chest computed tomography (CT). Material and Methods: One hundred and two patients who had lung nodules were included in this study. Standard-speed, standard-pitch (SSSP) ultra-low-dose CT and high-speed, high-pitch (HSHP) ultra-low-dose CT were obtained for all patients. Image noise was measured as the standard deviation of attenuation. One hundred and sixty-three nodules were identified and classified according to location, volume, and nodule type. Volume measurement of detected pulmonary nodules was compared according to nodule location, volume, and nodule type. Motion artifacts at the right middle lobe, the lingular segment, and both lower lobes near the lung bases were evaluated. Subjective image quality analysis was also performed. Results: The HSHP CT scan demonstrated decreased motion artifacts at the left upper lobe lingular segment and left lower lobe compared to the SSSP CT scan (p < 0.001). The image noise was higher and the radiation dose was lower in the HSHP scan (p < 0.001). According to the nodule type, the absolute relative volume difference was significantly higher in ground glass opacity nodules compared with those of part-solid and solid nodules (p < 0.001). Conclusion: Our study results suggest that HSHP ultra-low-dose chest CT scans provide decreased motion artifacts and lower radiation doses compared to SSSP ultra-low-dose chest CT. However, lung nodule volumetry should be performed with caution for ground glass opacity nodules.

Diagnostic accuracy of low-dose dual-input computed tomography perfusion in the differential diagnosis of pulmonary benign and malignant ground-glass nodules

This study aimed to evaluate the value of low-dose dual-input computed tomography perfusion (CTP) imaging in the differential diagnosis of benign and malignant pulmonary ground-glass opacity nodules (GGO). A retrospective study was conducted in patients with GGO who underwent CTP in our hospital from January 2021 to October 2023. All nodules were confirmed via pathological analysis or disappeared during follow-up. Postprocessing analysis was conducted using the dual-input perfusion mode (pulmonary artery and bronchial artery) of the body perfusion software to measure the perfusion parameters of the pulmonary GGOs. A total of 101 patients with pulmonary GGOs were enrolled in this study, including 43 benign and 58 malignant nodules. The dose length product of the CTP (348 mGy.cm) was < 75% of the diagnostic reference level of the unenhanced chest CT (470 mGy.cm). The effective radiation dose was 4.872 mSV. The blood flow (BF), blood volume (BV), mean transit time (MTT), and flow extraction product (FEP) of malignant nodules were higher than those of the benign nodules (p < 0.05). The FEP had the highest accuracy for the diagnosis of malignant nodules (area under the curve [AUC] = 0.821, 95% confidence interval [CI]: 0.735–0.908) followed by BV (AUV = 0.713, 95% CI 0.608–0.819), BF (AUC = 0.688, 95% CI 0.587–0.797), and MTT (AUC = 0.616, 95% CI 0.506–0.726). When the FEP was ≥ 19.12 mL/100 mL/min, the sensitivity was 91.5% and the specificity was 62.8%. To distinguish between benign nodules and malignant nodules, the AUC of the combination of BV and FEP was 0.816 (95% CI 0.728–0.903), whereas the AUC of the combination of BF, BV, MTT, and FEP was 0.814 (95% CI 0.729–0.900). Low-dose dual-input perfusion CT was extremely effective in distinguishing between benign from malignant pulmonary GGOs, with FEP exhibiting the highest diagnostic capability.

The prognostic value of visceral pleural infiltration in ≤3cm non-small cell lung cancer presenting with ground glass opacity: An inverse probability of treatment weighting study.

Visceral pleural infiltration (VPI) has been identified as an important risk factor in non-small cell lung cancer (NSCLC) for many decades. However, for patients who present with ground glass opacity (GGO), the prognostic value of VPI is still elusive. We aimed to investigate whether the VPI is a significant prognostic factor in surgically resected ≤3cm stage I NSCLC who presented with GGO. Patients with primary NSCLC who underwent surgical resection between December 2009 and December 2018 were collected. Stage I tumors that presented as GGO nodule with a tumor size of less than 3cm were included and divided into two groups based on VPI status (positive and negative). Clinical, pathological, and prognostic data were prospectively collected and retrospectively reviewed. Inverse probability of treatment weighting (IPTW) was used to balance baseline characteristics. Overall survival (OS) and recurrence-free survival (RFS) were analyzed using the Cox proportional hazards model and Kaplan-Meier method. A total of 2043 patients were included in this study (VPIs were found in 196 patients). After IPTW weighting, all factors between the two groups were balanced. The median follow-up time was 67.3 months. According to the multivariable Cox models, the VPI was not a significant prognostic factor for OS (HR = 2.00, 95% CI, 0.96-4.17; P= 0.063), but was significant for RFS (HR =2.00, 95% CI, 1.12-3.55; P= 0.019). In subgroup analysis, we found VPI was significant for OS (HR=3.17, 95%CI: 1.09-9.26, P=0.035) and RFS (HR=4.07, 95%CI: 1.76-9.40, P=0.001) in patients with a tumor size >1cm and a consolidation to tumor ratio (CTR) >50%. For patients with a tumor size ≤1cm or a CTR ≤50%, the VPI was not significant. VPI may be a significant risk factor for GGOs in NSCLC patients with a tumor size >1cm and a CTR >50%. Further prospective studies conducted across multi-centers with a larger sample size are needed.

Primary lung cancer in children and adolescents

PurposePrimary lung cancer is extremely rare in children and adolescents. The aim of this study is to clarify clinical features and outcomes of primary lung cancer in children and adolescents.MethodsYoung patients (aged ≤ 20 years) diagnosed as primary lung cancer between 2012 and 2023 were retrospective reviewed. According to radiological appearance of the nodules, they were divided into solid nodule (SN) group and ground glass opacity (GGO) group.ResultsA total of 74 patients were identified, with a median age at diagnosis of 18 years old (range: 11–20), including 7 patients in SN group and 67 patients in GGO group. In the GGO group, none of the nodules enlarged or changed during an average surveillance period of 10.8 months before surgery, except one. Wedge resection was the most common procedure (82.1%), followed by segmentectomy (16.4%) and lobectomy (1.5%). Histopathological analysis revealed that 64.2% of GGO nodules were adenocarcinoma in situ and minimally invasive adenocarcinomas, while the remaining 35.8% were invasive adenocarcinomas. Mutational analysis was performed in nine patients, with mutations identified in all cases. After a mean follow-up period of 1.73 ± 1.62 years, two patients in the SN group died due to multiple distant metastases, while all patients in the GGO group survived without recurrence. The overall survival (100%) of the GGO group was significantly higher than SN group (66.7%).ConclusionsPrimary lung cancer in children and adolescents are rare and histopathological heterogeneous. Persistent GGO nodules may indicate early-stage lung adenocarcinoma in children and adolescents.

Clinical application of serum seven tumour-associated autoantibodies in patients with pulmonary nodules

BackgroundThe incidence of pulmonary nodules is increasing because of the promotion and popularisation of low-dose computed tomography (LDCT) screening for populations with suspected lung cancer. However, a high rate of false positives and concerns regarding the radiation-related cancer risk of repeated CT scanning remain major obstacles to its wide application. This study aimed to investigate the clinical value of seven tumour-associated autoantibodies (7-TAAbs) in the differentiation of malignant pulmonary tumours from benign ones and the early detection of lung cancer in routine clinical practice. MethodsWe included 377 patients who underwent both the 7-TAAbs panel test and LDCT screening, and were diagnosed with pulmonary nodules using LDCT. An enzyme-linked immunosorbent assay (ELISA) was used to measure the serum levels antibodies for P53, PGP9.5, SOX2, GAGE7, GBU4-5, CAGE, and MAGE-A1. The relationships between the positive rates of the 7-TAAbs and the patient sex, and age, and the number, size, and composition of pulmonary nodules were analysed. We then statistically evaluated the clinical application value. ResultsThe positive rates of the 7-TAAbs did not correlate with sex, age, number, size, or composition of pulmonary nodules. The serum antibody level of GBU4-5 in patients with pulmonary nodules tended to increase with age; the serum antibody level of SOX2 tended to increase with nodule size and was the highest among patients with mixed ground-glass opacity (mGGO) nodules. The antibody positive rate for CAGE in female patients with pulmonary nodules was significantly higher than that in male patients (P < 0.05). The positive rate of GBU4-5 antibody in patients aged 60 years and above was higher than that in younger patients (P < 0.05). The positive rate of GAGE7 antibody in patients with pulmonary nodules sized 8–20 mm was also significantly higher than that in patients with pulmonary nodules sized less than 8 mm (P < 0.01). Significant differences were observed in the GAGE7 antibody levels of patients with pulmonary nodules of different compositions (P < 0.01). The positive rate of the 7-TAAbs panel test in patients with lung cancer was significantly higher than in patients with pulmonary nodules (P < 0.01). Serum levels of P53, SOX2, GBU4-5, and MAGE-A1 antibodies were significantly higher in patients with lung cancer than in those with pulmonary nodules (P < 0.05). ConclusionThe low positive rates of serum 7-TAAbs in patients with lung cancer and pulmonary nodules may be related to different case selection, population differences, geographical differences, different degrees of progression, and detection methods. The combined detection of 7-TAAbs has some clinical value for screening and early detection of lung cancer.

Abstract 4097: LNP-mRNA neoantigen vaccines to intercept progression of pre-invasive to invasive lung adenocarcinoma

Abstract The widespread use of chest computed tomography in lung cancer screening has led to the detection of ground-glass opacity (GGO) nodules, which typically harbor pre-invasive or minimally invasive adenocarcinoma and 20-40% of GGO nodules progress to invasive lung adenocarcinoma within 4 years. Lack of approved treatments to intercept disease progression has imposed challenges in the clinical management of patients with GGOs. Previous studies showed that GGO nodules have substantially lower rates of HLA deletions than invasive/metastatic lung cancer, suggesting that GGO nodules constitute a critical window of vulnerability for immune interception. We therefore sought to identify the most immunogenic and cytotoxic neoantigens in patients with GGO nodules and to develop LNP-mRNA cancer vaccines to intercept the disease progression from pre-invasive to invasive adenocarcinoma. Whole exome and RNA sequencing of a large cohort (&amp;gt;300) patients identified potential neoantigen candidates, with KRAS-G12C, KRAS-G12D and EGFR-L858R as the most frequently predicted shared neoantigens consistent with &amp;gt;40% GGO patient population harboring either mutant KRAS or EGFR driver oncogenes. LNP-mRNA vaccines targeting KRAS-G12C and EGFR-L858R showed marked immunogenicity as determined by ELISPOT assays. Moreover, KRAS-G12C vaccination induced CD4+ T cell responses whereas EGFR-L858R vaccination triggered CD8+ T cell responses. Both these vaccines are being tested in GGO immunoprevention studies. Our data suggest the potential of KRAS and EGFR vaccines in the treatment of early disease, particularly in EGFR mutant patients who fail to respond to immunotherapy. Citation Format: Yongfeng He, Sijin Luo Zhong, Bhavneet Bhinder, Geoffrey Markowitz, Arshdeep Singh, Eric Gardner, Myung Soo Ko, Nasser K. Altorki, Shaoyi Jiang, Vivek Mittal. LNP-mRNA neoantigen vaccines to intercept progression of pre-invasive to invasive lung adenocarcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4097.

A clinical spectrum of resectable lung adenocarcinoma with micropapillary component (MPC) concurrently presenting as mixed ground-glass opacity nodules.

In clinical practice, preoperative identification of mixed ground-glass opacity (mGGO) nodules with micropapillary component (MPC) to facilitate the implementation of individualized therapeutic strategies and avoid unnecessary surgery is increasingly importantOBJECTIVE: This study aimed to build a predictive model based on clinical and radiological variables for the early identification of MPC in lung adenocarcinoma presenting as mGGO nodules. The enrolled 741 lung adenocarcinoma patients were randomly divided into a training cohort and a validation cohort (3:1 ratio). The pathological specimens and preoperative images of malignant mGGO nodules from the study subjects were retrospectively reviewed. Furthermore, in the training cohort, selected clinical and radiological variables were utilized to construct a predictive model for MPC prediction. The MPC was found in 228 (43.3%) patients in the training cohort and 72 (41.1%) patients in the validation cohort. Based on the predictive nomogram, the air bronchogram was defined as the most dominant independent risk factor for MPC of mGGO nodules, followed by the maximum computed tomography (CT) value (> 200), adjacent to pleura, gender (male), and vacuolar sign. The nomogram demonstrated good discriminative ability with a C-index of 0.783 (95%[CI] 0.744-0.822) in the training cohort and a C-index of 0.799 (95%[CI] 0.732-0.866) in the validation cohort Additionally, by using the bootstrapping method, this predictive model calculated a corrected AUC of 0.774 (95% CI: 0.770-0.779) in the training cohort. This study proposed a predictive model for preoperative identification of MPC in known lung adenocarcinomas presenting as mGGO nodules to facilitate individualized therapy. This nomogram model needs to be further externally validated by subsequent multicenter studies.

Development and evaluation of an integrated model based on a deep segmentation network and demography-added radiomics algorithm for segmentation and diagnosis of early lung adenocarcinoma.

Non-invasive early detection and differentiation grading of lung adenocarcinoma using computed tomography (CT) images are clinically important for both clinicians and patients, including determining the extent of lung resection. However, these are difficult to accomplish using preoperative images, with CT-based diagnoses often being different from postoperative pathologic diagnoses. In this study, we proposed an integrated detection and classification algorithm (IDCal) for diagnosing ground-glass opacity nodules (GGN) using CT images and other patient informatics, and compared its performance with that of other diagnostic modalities. All labeling was confirmed by a thoracic surgeon by referring to the patient's CT image and biopsy report. The detection phase was implemented via a modified FC-DenseNet to contour the lesions as elaborately as possible and secure the reliability of the classification phase for subsequent applications. Then, by integrating radiomics features and other patients' general information, the lesions were dichotomously reclassified into "non-invasive" (atypical adenomatous hyperplasia, adenocarcinoma in situ, and minimally invasive adenocarcinoma) and "invasive" (invasive adenocarcinoma). Data from 168 GGN cases were used to develop the IDCal, which was then validated in 31 independent CT scans. IDCal showed a high accuracy of GGN detection (sensitivity, 0.970; false discovery rate, 0.697) and classification (accuracy, 0.97; f1-score, 0.98; ROAUC, 0.96). In conclusion, the proposed IDCal detects and classifies GGN with excellent performance. Thus, it can be suggested that our multimodal prediction model has high potential as an auxiliary diagnostic tool of GGN to help clinicians.

Expression Changes in Programmed Death Ligand 1 from Precancerous Lesions to Invasive Adenocarcinoma in Subcentimeter Pulmonary Nodules: A Large Study of 2022 Cases in China.

This large-scale, multicenter, retrospective observational study aimed to evaluate the clinicopathological and molecular profiles associated with programmed death-ligand 1 (PD-L1) expression in precancerous lesions and invasive adenocarcinoma in subcentimeter pulmonary nodules. Patients with histologically confirmed atypical adenomatous hyperplasia (AAH), adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA), and invasive adenocarcinoma (ADC) were included. PD-L1 expression was evaluated at each center using a PD-L1 immunohistochemistry 22C3 pharmDx kit (Agilent, Santa Clara, CA, USA). The tumor proportion score (TPS) cutoff values were set at ≥ 1% and ≥ 50%. A total of 2022 nodules from 1844 patients were analyzed. Of these, 9 (0.45%) nodules had PD-L1 TPS ≥ 50%, 187 (9.25%) had PD-L1 TPS 1-49%, and 1826 (90.30%) had PD-L1 TPS < 1%. A total of 378 (18.69%), 1016 (50.25%), and 628 (31.06%) nodules were diagnosed as AAH/AIS, MIA, and ADC, respectively, by pathology. A total of 1377 (68.10%), 591 (25.67%), and 54 (2.67%) nodules were diagnosed as pure ground-glass opacity (GGO), mixed GGO, and solid nodules, respectively, by computed tomography. There was a significant difference between PD-L1 expression and anaplastic lymphoma kinase (ALK) mutation status (P < 0.001). PD-L1 expression levels were significantly different from those determined using the International Association for the Study of Lung Cancer (IASLC) grading system (P < 0.001). PD-L1 expression was significantly associated with radiological and pathological invasiveness and driver mutation status in subcentimeter pulmonary nodules. The significance of PD-L1 expression in the evolution of early-stage lung adenocarcinoma requires further investigation.

Differences of molecular events driving pathological and radiological progression of lung adenocarcinoma.

Ground-glass opacity (GGO)-like lung adenocarcinoma (LUAD) has been detected increasingly in the clinic and its inert property and superior survival indicate unique biological characteristics. However, we do not know much about them, which hampers identification of key reasons for the inert property of GGO-like LUAD. Using whole-exome sequencing and RNA sequencing, taking into account both radiological and pathological classifications of the same 197 patients concomitantly, we systematically interrogate genes driving the progression from GGO to solid nodule and potential reasons for the inertia of GGO. Using flow cytometry and IHC, we validated the abundance of immune cells and activity of cell proliferation. Identifying the differences between GGO and solid nodule, we found adenocarcinoma in situ/minimally invasive adenocarcinoma (AIS/MIA) and GGO-like LUAD exhibited lower TP53 mutation frequency and less active cell proliferation-related pathways than solid nodule in LUAD. Identifying the differences in GGO between AIS/MIA and LUAD, we noticed that EGFR mutation frequency and CNV load were significantly higher in LUAD than in AIS/MIA. Regulatory T cell was also higher in LUAD, while CD8+ T cell decreased from AIS/MIA to LUAD. Finally, we constructed a transcriptomic signature to quantify the development from GGO to solid nodule, which was an independent predictor of patients' prognosis in 11 external LUAD datasets. Our results provide deeper insights into the indolent nature of GGO and provide a molecular basis for the treatment of GGO-like LUAD. This study was supported in part by the National Natural Science Foundation of China (32170657), the National Natural Science Foundation of China (82203037), and Shanghai Sailing Program (22YF1408900).

Clinical, radiological, and pathological features of minute pulmonary meningothelial-like nodules and diffuse pulmonary meningotheliomatosis.

Minute pulmonary meningothelial-like nodules (MPMNs) and diffuse pulmonary meningotheliomatosis (DPM) are both rare lung diseases that involve the proliferation of cells of meningothelial origin in the lungs. However, few studies have focused on the clinical, pathological, and radiological features of MPMNs and DPMs. The clinicopathological data of 167 cases diagnosed as MPMNs and 13 cases diagnosed as DPM in the China National Center for Respiratory Medicine were examined. Based on clinical data, CT images, and morphological features, this study analyzed the similarities and differences between MPMNs and DPM. The detection rates of MPMNs and DPM were 1.9 and 0.15%, respectively. Compared to MPMNs, DPM patients were all women (100% vs. 79.4%, P = 0.066), had a younger age (51.4 ± 7.7 vs. 57.9 ± 8.5, P < 0.01), and had higher pulmonary function (P < 0.01 or P < 0.05). The chest CT of DPM patients showed diffuse ground-glass opacity nodules measuring 2.0-8.0 mm in diameter, with the number of nodules ranging from 40 to >600 per lung. There were no significant differences in nodule volume [28.0 (12.1, 65.1) mm3 vs. 28.7 (17.1, 48.9) mm3, P = 0.451] and CT values [-646.8 (-732.5, -514.5) Hu vs. -588 (-674, -480) Hu, P = 0.215] between MPMNs and DPM. MPMNs are characterized by reactive hyperplasia pulmonary nodules, which can be solitary or multiple. This study suggests that there are many different characteristics between patients with MPMNs and DPM. The limited findings challenge the notion that DPM is a rare subtype of MPMNS.

Correlation exploration among CT imaging, pathology and genotype of pulmonary ground-glass opacity.

To analyse the clinical features, imaging manifestation, pathological typing and genetic testing results of patients undergoing surgery for ground-glass opacity (GGO) nodules, and explore the reasonable diagnosis and treatment program for GGO patients as to provide the basis for the establishment of GGO treatment process. This study is an exploratory study. 465 cases with GGO confirmed by HRCT, undergoing surgery and approved by pathologic diagnosis in Shanghai pulmonary hospital were enrolled in this study. All the patients with GGO were cases with single lesion. The relationship between the clinical, imaging, pathological and molecular biological data of single GGO were statistically studied. (1) Among 465 cases, the median age was 58 years and females were 315 (67.7%); there were 397 (85.4%) non-smoking, and 354 cases (76.1%) had no clinical symptoms. There were 33 cases of benign and 432 cases of malignant GGO. Significant differences were observed on the size, vacuole sign, pleural indentation and blood vessel sign of GGO between two groups (p < 0.05). Of 230 mGGO, there were no AAH, 13 cases of AIS, 25 cases of MIA and 173 cases of invasive adenocarcinoma. The probability of solid nodules in invasive adenocarcinoma was higher than that in micro invasive carcinoma, and the difference was statistically significant (p < 0.05). 360 cases were followed up with the average follow-up time of 6.05 months, and GGO of 34 cases (9.4%) increased. (2) In 428 adenocarcinoma samples approved by pathologic diagnosis, there were 262 (61.2%) lesions of EGFR mutation, 14 (3.3%) lesions of KRAS mutation, 1 (0.2%) lesion of Braf mutation, 9 (2.1%) lesions of EML4-ALK gene fusion and 2 (0.5%) lesions of ROS1 fusion. The detection rate of gene mutation in mGGO was higher than that of pGGO. During the follow-up period, genetic testing results of 32 GGO showed that EGFR mutation rate was 53.1%, ALK positive rate of 6.3%, KRAS mutation rate of 3.1% and no ros1 and BRAF gene mutation. No statistically significant difference was observed in comparison with unchanged GGO. (3) EGFR mutation rate of invasive adenocarcinoma was the highest (168/228, 73.7%), mainly in the 19Del and L858R point mutations. No KRAS mutation was found in atypical adenoma hyperplasia. No significant difference was observed on the mutation rate of KRAS between different types of GGO (p = 0.811). EML4-ALK fusion gene was mainly detected in invasive adenocarcinoma (7/9). GGO tends to occur in young, non-smoking women. The size of GGO is related to the degree of malignancy. Pleural depression sign, vacuole sign and vascular cluster sign are all characteristic images of malignant GGO. pGGO and mGGO reflect the pathological development of GGO. During the follow-up, it is found that GGO increases and solid components appear, which is the indication of surgical resection. The detection rate of EGFR mutations in mGGO and invasive adenocarcinoma is high. pGGO has heterogeneity in imaging, pathology and molecular biology. Heterogeneity research helps to formulate correct individualized diagnosis and treatment plans.

A pyramid input augmented multi-scale CNN for GGO detection in 3D lung CT images

This paper proposes a new convolutional neural network (CNN) with multi-scale processing for detecting ground-glass opacity nodules (GGO) in 3D computed tomography (CT) images, which is referred to as PiaNet for short. PiaNet consists of a feature-extraction module and a prediction module. The former module is constructed by introducing pyramid multi-scale source connections into a contracting-expanding structure. Besides, a new multi-receptive-field convolution block (MRCB) is presented to fuse the convolutions with multiple kernels of varying sizes for capturing features in each scale of information better. The latter module includes a bounding-box regressor and a classifier that are employed to simultaneously recognize GGO nodules and estimate bounding boxes at multiple scales. To train the proposed PiaNet, a two-stage transfer learning strategy is developed. In the first stage, the feature-extraction module is embedded into a classifier network that is trained on a large data set of GGO and non-GGO patches, which are generated by performing data augmentation from a small number of annotated CT scans. In the second stage, the pretrained feature-extraction module is loaded into PiaNet, and then PiaNet is fine-tuned using the annotated CT scans. We evaluate the proposed PiaNet with the LIDC-IDRI dataset. The experimental results demonstrate that our method outperforms state-of-the-art counterparts, including the Subsolid CAD and Aidence systems and CPM-Net and S4ND and GA-SSD methods. PiaNet achieves a sensitivity of 93.6% with only one false positive per scan.

Availability of virtual-assisted lung mapping affects procedure selection for early-stage lung cancer: a web-based cross-sectional study

The availability of new techniques may affect surgeons' procedure selection and thereby affect clinical outcomes. This study aimed to evaluate the effect of the availability of virtual-assisted lung mapping (VAL-MAP) on the selection of lung resection methods. Members of the Japanese Association for Chest Surgeons were invited to participate in a web-based survey. Participants were divided into those who had never used VAL-MAP (group 0), those who had used only VAL-MAP 1.0 (multiple dye marks on the pleural surface; group 1) and those who had used VAL-MAP 2.0 (multiple dye marks and intrabronchial microcoils for three-dimensional mapping; group 2). Participants were shown chest computed tomography images of 6 ground-glass opacity nodules and asked to choose surgical procedures to resect the nodules with sufficient resection margins greater than the lesion diameter or 2 cm. There were 197 surgeons in group 0, 49 in group 1 and 26 in group 2. All groups showed a similar trend of avoiding wedge resection for deeply located nodules. However, group 1 showed a trend of disagreeing with the selection of wedge resection compared with group 0 as measured by a Likert scale (1-5) by -0.21 points (95% confidence interval, -0.41 to -0.008 points, P = 0.042). This tendency disappeared in group 2. The availability of VAL-MAP 1.0 led to the selection of segmentectomy, while the availability of VAL-MAP 2.0 led to aggressive deep wedge resection.

Distinct Prognostic Factors of Ground Glass Opacity and Pure-Solid Lesion in Pathological Stage I Invasive Lung Adenocarcinoma.

Ground glass opacity (GGO) is associated with favorable survival in lung cancer. However, the relevant evidence of the difference in prognostic factors between GGO and pure-solid nodules for pathological stage I invasive adenocarcinoma (IAC) is limited. We aimed to identify the impact of GGO on survival and find prognostic factor for part-GGO and pure-solid patients. Between December 2007 and August 2018, patients with pathological stage I IAC were retrospectively reviewed and categorized into the pure-GGO, part-GGO, and pure-solid groups. Survival curves were analyzed by the Kaplan-Meier method and compared by log-rank tests. Least absolute shrinkage and selection operator and Cox regression models were used to obtained prognostic factors for disease-free survival (DFS) and overall survival (OS). The number of patients with pure-GGO, part-GGO, and pure-solid was 134, 540, and 396, respectively. Part-GGO patients with consolidation-tumor-ratio (CTR) > 0.75 had similar outcome to those with pure-solid nodules. In part-GGO patients, CTR was negatively associated with OS (P = 0.007) and solid tumor size (STS) was negatively associated with DFS (P < 0.001). Visceral pleural invasion (VPI) was negatively associated with OS (P = 0.040) and DFS (P = 0.002). Sublobectomy was negatively associated with OS (P = 0.008) and DFS (P = 0.005), while extended N1 stations examination was associated with improved DFS (P = 0.005) in pure-solid patients. Though GGO component is a positively prognostic factors of patients with pathological stage I IAC, a small proportion of GGO components is not associated with favorable survival. VPI, STS and CTR are the significant predictors for part-GGO patients. Sublobectomy, especially wedge resection should be used cautiously in pure-solid patients.

An Automatic Random Walker Algorithm for Segmentation of Ground Glass Opacity Pulmonary Nodules.

Automatic and accurate segmentation of ground glass opacity (GGO) nodules still remains challenging due to inhomogeneous interiors, irregular shapes, and blurred boundaries from different patients. Despite successful applications in the image processing domains, the random walk has some limitations for segmentation of GGO pulmonary nodules. In this paper, an improved random walker method is proposed for the segmentation of GGO nodules. To calculate a new affinity matrix, intensity, spatial, and texture features are incorporated. It strengthens discriminative power between two adjacent nodes on the graph. To address the problem of robustness in seed acquisition, the geodesic distance is introduced and a novel local search strategy is presented to automatically acquire reliable seeds. For segmentation, a label constraint term is introduced to the energy function of original random walker, which alleviates the accumulation of errors caused by the initial seeds acquisition. Massive experiments conducted on Lung Images Dataset Consortium (LIDC) demonstrate that the proposed method achieves visually satisfactory results without user interactions. Both qualitative and quantitative evaluations also demonstrate that the proposed method obtains better performance compared with conventional random walker method and state-of-the-art segmentation methods in terms of the overlap score and F-measure.

Deep learning analysis to predict EGFR mutation status in lung adenocarcinoma manifesting as pure ground-glass opacity nodules on CT.

BackgroundEpidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) showed potency as a non-invasive therapeutic approach in pure ground-glass opacity nodule (pGGN) lung adenocarcinoma. However, optimal methods of extracting information about EGFR mutation from pGGN lung adenocarcinoma images remain uncertain. We aimed to develop, validate, and evaluate the clinical utility of a deep learning model for predicting EGFR mutation status in lung adenocarcinoma manifesting as pGGN on computed tomography (CT).MethodsWe included 185 resected pGGN lung adenocarcinomas in the primary cohort. The patients were divided into training (n = 125), validation (n = 23), and test sets (n = 37). A preoperative CT-based deep learning model with clinical factors as well as clinical and radiomics models was constructed and applied to the test set. We evaluated the clinical utility of the deep learning model by applying it to 83 GGNs that received EGFR-TKI from an independent cohort (clinical validation set), and treatment response was regarded as the reference standard.ResultsThe prediction efficiencies of each model were compared in terms of area under the curve (AUC). Among the 185 pGGN lung adenocarcinomas, 122 (65.9%) were EGFR-mutant and 63 (34.1%) were EGFR-wild type. The AUC of the clinical, radiomics, and deep learning with clinical models to predict EGFR mutations were 0.50, 0.64, and 0.85, respectively, for the test set. The AUC of deep learning with the clinical model in the validation set was 0.72.ConclusionsDeep learning approach of CT images combined with clinical factors can predict EGFR mutations in patients with lung adenocarcinomas manifesting as pGGN, and its clinical utility was demonstrated in a real-world sample.

Comprehensive characterization of genomic and radiologic features reveals distinct driver patterns of RTK/RAS pathway in ground-glass opacity pulmonary nodules.

Ground-glass opacity (GGO)-associated pulmonary nodules have been known as a radiologic feature of early-stage lung cancers and exhibit an indolent biological behavior. However, the correlation between driver genes and radiologic features as well as the immune microenvironment remains poorly understood. We performed a custom 1021-gene panel sequencing of 334 resected pulmonary nodules presenting as GGO from 262 Chinese patients. A total of 130 multiple pulmonary nodules were sampled from 58 patients. Clinical-pathologic and radiologic parameters of these pulmonary nodules were collected. Immunohistochemistry (IHC) and multiplex immunofluorescent staining (mIF) were applied to analyze proliferation and immune cell markers of GGO-associated pulmonary nodules. Compared with pure GGO nodules, mixed GGO nodules were enriched for invasive adenocarcinoma (IAC) (182/216 vs 73/118, P &lt; .001). Eighty-eight percent (294/334) of GGO-associated nodules carried at least one mutation in EGFR/ERBB2/BRAF/KRAS/MAP2K1 of the RTK/RAS signaling pathway, and the alterations in these driver genes were mutually exclusive. The analysis of multifocal pulmonary nodules from the same patient revealed evidence of functional convergence on RTK/RAS pathways. Nodules with ERBB2/BRAF/MAP2K1 mutations tended to be more indolent than those with EGFR and KRAS mutations. IHC and mIF staining showed that KRAS-mutant GGO nodules displayed higher infiltration of CD4+ T cell and CD8+ T cell as well as stronger proliferation and immune inhibitory signals. Our study demonstrates a driver landscape of radiologically detectable GGO-associated pulmonary nodules in Chinese patients and supports that different driver patterns in RTK/RAS pathway are corresponding to different radiologic features.