Diagnostic Accuracy of a Computed Tomography-Guided Transthoracic Needle Biopsy for Ground-Glass Opacities and Subsolid Pulmonary Nodules.

Purpose The increasing use of computed tomography (CT) imaging has led to the detection of more ground-glass nodules (GGNs) and subsolid nodules (SSNs), which may be malignant and require a biopsy for proper diagnosis. Approximately 75% of persistent GGNs can be attributed to adenocarcinoma in situ or minimally invasive adenocarcinoma. A CT-guided biopsy has been proven to be a reliable procedure with high diagnostic performance. However, the diagnostic accuracy and safety of a CT-guided biopsy for GGNs and SSNs with solid components ≤6 mm are still uncertain. The aim of this study is to assess the diagnostic accuracy of a CT-guided core needle biopsy (CNB) for GGN and SSNs with solid components ≤6 mm. Methods This is a retrospective study of patients who underwent CT-guided CNB for the evaluation of GGNs and SSNs with solid components ≤6 mm between February 2020 and January 2023. Biopsy findings were compared to the final diagnosis determined by definite histopathologic examination and clinical course. Results A total of 22 patients were enrolled, with a median age of 74 years (IQR: 68-81). A total of 22 nodules were assessed, comprising 15 (68.2%) SSNs with a solid component measuring ≤6 mm and seven (31.8%) pure GGNs. The histopathological examination revealed that 12 (54.5%) were diagnosed as malignant, nine (40.9%) as benign, and one (4.5%) as non-diagnostic. The overall diagnostic accuracy and sensitivity for malignancy were 86.36% and 85.7%, respectively. Conclusion A CT-guided CNB for GGNs and SSNs with solid components measuring ≤6 mm appears to have a high diagnostic accuracy.

The radiological characteristics, tertiary lymphoid structures, and survival status associated with EGFR mutation in patients with subsolid nodules like stage I-II LUAD.

BACKGROUND: Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) recommended for the patients with subsolid nodule in early lung cancer stage is not routinely. The clinical value and impact in patients with EGFR mutation on survival outcomes is further needed to be elucidated to decide whether the application of EGFR-TKIs was appropriate in early lung adenocarcinoma (LUAD) stage appearing as subsolid nodules. MATERIALS AND METHODS: The inclusion of patients exhibiting clinical staging of IA-IIB subsolid nodules. Clinical information, computed tomography (CT) features before surgical resection and pathological characteristics including tertiary lymphoid structures of the tumors were recorded for further exploration of correlation with EGFR mutation and prognosis. RESULTS: Finally, 325 patients were enrolled into this study, with an average age of 56.8 ± 9.8 years. There are 173 patients (53.2%) harboring EGFR mutation. Logistic regression model analysis showed that female (OR = 1.944, p = 0.015), mix ground glass nodule (OR = 2.071, p = 0.003, bubble-like lucency (OR = 1.991, p = 0.003) were significant risk factors of EGFR mutations. Additionally, EGFR mutations were negatively correlated with TLS presence and density. Prognosis analysis showed that the presence of TLS was associated with better recurrence-free survival (RFS)(p = 0.03) while EGFR mutations were associated with worse RFS(p = 0.01). The RFS in patients with TLS was considerably excel those without TLS within EGFR wild type group(p = 0.018). Multivariate analyses confirmed that EGFR mutation was an independent prognostic predictor for RFS (HR = 3.205, p = 0.037). CONCLUSIONS: In early-phase LUADs, subsolid nodules with EGFR mutation had specific clinical and radiological signatures. EGFR mutation was associated with worse survival outcomes and negatively correlated with TLS, which might weaken the positive impact of TLS on prognosis. Highly attention should be paid to the use of EGFR-TKI for further treatment as agents in early LUAD patients who carrying EGFR mutation.

Shape-Sensing Robotic-Assisted Bronchoscopy versus Computed Tomography-Guided Transthoracic Biopsy for the Evaluation of Subsolid Pulmonary Nodules.

INTRODUCTION: Lung cancer remains the leading cause of cancer death worldwide. Subsolid nodules (SSN), including ground-glass nodules (GGNs) and part-solid nodules (PSNs), are slow-growing but have a higher risk for malignancy. Therefore, timely diagnosis is imperative. Shape-sensing robotic-assisted bronchoscopy (ssRAB) has emerged as reliable diagnostic procedure, but data on SSN and how ssRAB compares to other diagnostic interventions such as CT-guided transthoracic biopsy (CTTB) are scarce. In this study, we compared diagnostic yield of ssRAB versus CTTB for evaluating SSN. METHODS: A retrospective study of consecutive patients who underwent either ssRAB or CTTB for evaluating GGN and PSN with a solid component less than 6 mm from February 2020 to April 2023 at Mayo Clinic Florida and Rochester. Clinicodemographic information, nodule characteristics, diagnostic yield, and complications were compared between ssRAB and CTTB. RESULTS: A total of 66 nodules from 65 patients were evaluated: 37 PSN and 29 GGN. Median size of PSN solid component was 5 mm (IQR: 4.5, 6). Patients were divided into two groups: 27 in the ssRAB group and 38 in the CTTB group. Diagnostic yield was 85.7% for ssRAB and 89.5% for CTTB (p = 0.646). Sensitivity for malignancy was similar between ssRAB and CTTB (86.4% vs. 88.5%; p = 0.828), with no statistical difference. Complications were more frequent in CTTB with no significant difference (8 vs. 2; p = 0.135). CONCLUSION: Diagnostic yield for SSN was similarly high for ssRAB and CTTB, with ssRAB presenting less complications and allowing mediastinal staging within the same procedure.

Application of computer-aided detection for NCCN-based follow-up recommendation in subsolid nodules: Effect on inter-observer agreement.

RATIONALE AND OBJECTIVES: Computer-aided detection (CAD) of pulmonary nodules reduces the impact of observer variability, improving the reliability and reproducibility of nodule assessments in clinical practice. Therefore, this study aimed to assess the impact of CAD on inter-observer agreement in the follow-up management of subsolid nodules. MATERIALS AND METHODS: A dataset comprising 60 subsolid nodule cases was constructed based on the National Cancer Center lung cancer screening data. Five observers independently assessed all low-dose computed tomography scans and assigned follow-up management strategies to each case according to the National Comprehensive Cancer Network (NCCN) guidelines, using both manual measurements and CAD assistance. The linearly weighted Cohen's kappa test was used to measure agreement between paired observers. Agreement among multiple observers was evaluated using the Fleiss kappa statistic. RESULTS: The agreement of the five observers for NCCN follow-up management categorization was moderate when measured manually, with a Fleiss kappa score of 0.437. Utilizing CAD led to a notable enhancement in agreement, achieving a substantial consensus with a Fleiss kappa value of 0.623. After using CAD, the proportion of major and substantial management discrepancies decreased from 27.5% to 15.8% and 4.8% to 1.5%, respectively (p < 0.01). In 23 lung cancer cases presenting as part-solid nodules, CAD significantly elevates the average sensitivity in detecting lung cancer cases presenting as part-solid nodules (overall sensitivity, 82.6% vs. 92.2%; p < 0.05). CONCLUSION: The application of CAD significantly improves inter-observer agreement in the follow-up management strategy for subsolid nodules. It also demonstrates the potential to reduce substantial management discrepancies and increase detection sensitivity in lung cancer cases presenting as part-solid nodules.

Extent of surgical resection for radiologically subsolid T1N0 invasive lung adenocarcinoma: When is a wedge resection acceptable?

OBJECTIVE: To evaluate whether wedge resection (WR) was appropriate for the patients with peripheral T1 N0 solitary subsolid invasive lung adenocarcinoma. METHODS: Patients with peripheral T1N0 solitary subsolid invasive lung adenocarcinoma who received sublobar resection were retrospectively reviewed. Clinicopathologic characteristics, 5-year recurrence-free survival, and 5-year lung cancer-specific overall survival were analyzed. Cox regression model was used to elucidate risk factors for recurrence. RESULTS: Two hundred fifty-eight patients receiving WR and 1245 patients receiving segmentectomy were included. The mean follow-up time was 36.87 ± 16.21 months. Five-year recurrence-free survival following WR was 96.89% for patients with ground-glass nodule (GGN) ≤2 cm and 0.25< consolidation-to-tumor ratio (CTR) ≤0.5, not statistically different from 100% for those with GGN≤2 cm and CTR ≤0.25 (P = .231). The 5-year recurrence-free survival was 90.12% for patients with GGN between 2 and 3 cm and CTR ≤0.5, significantly lower than that of patients with GGN ≤2 cm and CTR ≤0.25 (P = .046). For patients with GGN≤2 cm and 0.25

Diagnostic Yield of Shape-Sensing Robotic-Assisted Bronchoscopy for Ground-Glass Nodules and Subsolid Nodules with a Solid Component Less than 6 mm.

BACKGROUND: Ground-glass pulmonary nodules (GGNs) are most commonly sampled by percutaneous transthoracic biopsy. Diagnostic yield for ground-glass nodules using robotic-assisted bronchoscopy has been scarcely described, with a reported yield of 70.6%. OBJECTIVES: The aim of this study is to assess diagnostic yield for GGNs using shape-sensing robotic-assisted bronchoscopy (ssRAB). METHOD: A retrospective study of patients who underwent ssRAB for evaluation of GGNs, from September 2021 to April 2023. Primary outcome was diagnostic yield of ssRAB for GGNs, secondary outcomes were sensitivity for malignancy, and complications that required admission or intervention. RESULTS: A total of 23 nodules were biopsied from 22 patients. Median age was 71 years (IQR 66-81), 63.6% were female, and 40.9% had a previous history of cancer. Forty-three percent of nodules were in the right upper lobes, and the median lesion size was 1.8 × 1.21. Twelve were subsolid nodules (SSNs), and 11 were pure GGNs. Overall diagnostic yield was 87%, with a sensitivity for malignancy of 88.9%. Adenocarcinoma was the most common malignancy diagnosed (70%). No procedure-related complications were reported. CONCLUSION: The use of ssRAB shows a high diagnostic yield for diagnosing GGN and SSN with less than 6 mm solid component with a low risk for complications.

Software-based quantitative CT analysis to predict the growth trend of persistent nonsolid pulmonary nodules: a retrospective study.

PURPOSE: Persistent nonsolid nodules (NSNs) usually exhibit an indolent course and may remain stable for several years; however, some NSNs grow quickly and require surgical excision. Therefore, identifying quantitative features capable of early discrimination between growing and nongrowing NSNs is becoming a crucial aspect of radiological analysis. The main purpose of this study was to evaluate the performance of an open-source software (ImageJ) to predict the future growth of NSNs detected in a Caucasian (Italian) population. MATERIAL AND METHODS: We retrospectively selected 60 NSNs with an axial diameter of 6-30 mm scanned with the same acquisition-reconstruction parameters and the same computed tomography (CT) scanner. Software-based analysis was performed on thin-section CT images using ImageJ. For each NSNs, several quantitative features were extracted from the baseline CT images. The relationships of NSN growth with quantitative CT features and other categorical variables were analyzed using univariate and multivariable logistic regression analyses. RESULTS: In multivariable analysis, only the skewness and linear mass density (LMD) were significantly associated with NSN growth, and the skewness was the strongest predictor of growth. In receiver operating characteristic curve analyses, the optimal cutoff values of skewness and LMD were 0.90 and 19.16 mg/mm, respectively. The two predictive models that included the skewness, with or without LMD, exhibited an excellent power for predicting NSN growth. CONCLUSION: According to our results, NSNs with a skewness value > 0.90, specifically those with a LMD > 19.16 mg/mm, should require closer follow-up due to their higher growth potential, and higher risk of becoming an active cancer.

Prediction of Interval Growth of Lung Adenocarcinomas Manifesting as Persistent Subsolid Nodules ≤3 cm Based on Radiomic Features.

RATIONALES AND OBJECTIVES: To investigate the prognostic value of the radiomic-based prediction model in predicting the interval growth rate of persistent subsolid nodules (SSNs) with an initial size of ≤ 3 cm manifesting as lung adenocarcinomas. MATERIALS AND METHODS: A total of 133 patients (mean age, 59.02 years; male, 37.6%) with 133 SSNs who underwent a series of CT examinations at our hospital between 2012 and 2022 were included in this study. Forty-one radiomic features were extracted from each volumetric region of interest. Radiomic features combined with conventional clinical and semantic parameters were then selected for radiomic-based model building. To investigate the model performance in terms of substantial SSN growth and stage shift growth, the model performance was compared by the area under the curve (AUC) obtained by receiver operating characteristic analysis. RESULTS: The mean follow-up period was 3.62 years. For substantial SSN growth, a radiomic-based model (Model 2) based on clinical characteristics, CT semantic features, and radiomic features yielded an AUCs of 0.869 (95% CI: 0.799-0.922). In comparison with Model 1 (clinical characteristics and CT semantic features), Model 2 performed better than Model 1 for substantial SSN growth (AUC model 1:0.793 versus AUC model 2:0.869, p = 0.028). A radiomic-based nomogram combining sex, follow-up period, and three radiomic features was built for substantial SSN growth prediction. For the stage shift growth, a radiomic-based model (Model 4) based on clinical characteristics, CT semantic features, and radiomic features yielded an AUCs of 0.883 (95% CI: 0.815-0.933). Compared with Model 3 (clinical characteristics and CT semantic features), Model 4 performed better than the model 3 for stage shift growth (AUC model 1: 0.769 versus AUC model 2: 0.883, p = 0.006). A radiomic-based nomogram combining the initial nodule size, SSN classification, follow-up period, and three radiomic features was built to predict the stage shift growth. CONCLUSION: Radiomic-based models have superior utility in estimating the prognostic interval growth of patients with early lung adenocarcinomas (≤ 3 cm) than conventional clinical-semantic models in terms of substantial interval growth and stage shift growth, potentially guiding clinical decision-making with follow-up strategies of SSNs in personalized precision medicine.

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

Background and Objective: 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. Methods: 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)". Key Content and Findings: 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). Conclusions: 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.

Lung adenocarcinoma manifesting as subsolid nodule potentially represents tumour in the equilibrium phase of immunoediting.

Lung adenocarcinomas manifesting as subsolid nodules (SSN-LUADs) possess distinct dormant behaviour. This study was designed to compare the immune landscapes of normal lungs (nLungs), SSN-LUADs and LUADs manifesting as solid nodules (SN-LUADs) so as to better understand the status of anti-tumour immunity in SSN-LUADs. Mass cytometry by time-of-flight analysis was performed on 299, 570 single cells from nLung, SSN-LUAD and SN-LUAD tissues. The immune cells were identified by phenotype, and the percentages of different immune cell subclusters were compared between SSN-LUADs, SN-LUADs and nLungs. Elevated percentage of CD8+ T cells were identified in SSN-LUADs compared with in nLungs and SN-LUADs. Elevated CD56bright NK cells and decreased CD56dim NK cells were identified in both SSN-LUADs and SN-LUADs compared with in nLungs. The immune landscape of SSN-LUAD fits the theory of equilibrium phase of immunoediting, thus functional adaptive anti-tumour immunity but impaired innate anti-tumour immunity potentially contributes to the maintaining of its dormant behaviour.

A Nomogram Incorporating Tumor-Related Vessels for Differentiating Adenocarcinoma In Situ from Minimally Invasive and Invasive Adenocarcinoma Appearing as Subsolid Nodules.

OBJECTIVES: To develop a nomogram incorporating the quantity of tumor-related vessels (TRVs) and conventional CT features (CCTFs) for the preoperative differentiation of adenocarcinoma in situ (AIS) from minimally invasive adenocarcinoma (MIA) and invasive adenocarcinoma (IAC) appearing as subsolid nodules. METHODS: High-resolution CT target scans of 274 subsolid nodules from 268 patients were included in this study and randomly assigned to the training and validation groups at a ratio of 7:3. A nomogram incorporating CCTFs with the category of TRVs (CTRVs, using TRVs as categorical variables) and a final nomogram combining the number of TRVs (QTRVs) and CCTFs were constructed using multivariable logistic regression analysis. The performance levels of the two nomograms were evaluated and validated on the training and validation datasets and then compared. RESULTS: The CCTF-QTRV nomogram incorporating abnormal air bronchogram, density, number of dilated and distorted vessels and number of adherent vessels showed more favorable predictive efficacy than the CCTF-CTRV nomogram (training cohort: area under the curve (AUC) = 0.893 vs. 0.844, validation cohort: AUC = 0.871 vs. 0.807). The net reclassification index (training cohort: 0.188, validation cohort: 0.326) and the integrated discrimination improvement values (training cohort: 0.091, validation cohort: 0.125) indicated that the CCTF-QTRV nomogram performed significantly better discriminative ability than the CCTF-CTRV nomogram (all p-value < 0.05). CONCLUSIONS: The nomogram incorporating the QTRVs and CCTFs showed favorable predictive efficacy for differentiating AIS from MIA-IAC appearing as subsolid nodules and may serve as a potential tool to provide individual care for these patients.

Clinical and CT Features of Subsolid Pulmonary Nodules With Interval Growth: A Systematic Review and Meta-Analysis.

Background: Establishing risk-based follow-up management strategies is crucial to the surveillance of subsolid pulmonary nodules (SSNs). However, the risk factors for SSN growth are not currently clear. This study aimed to perform a systematic review and meta-analysis to identify clinical and CT features correlated with SSN growth. Methods: Relevant studies were retrieved from Web of Science, PubMed, Cochrane Library, and EMBASE. The correlations of clinical and CT features with SSN growth were pooled using a random-effects model or fixed-effects model depending on heterogeneity, which was examined by the Q test and I2 test. Pooled odds ratio (OR) or pooled standardized mean differences (SMD) based on univariate analyses were calculated to assess the correlation of clinical and CT features with SSN growth. Pooled ORs based on multivariate analyses were calculated to find out independent risk factors to SSN growth. Subgroup meta-analysis was performed based on nodule consistency (pure ground-glass nodule (pGGN) and part-solid nodule (PSN). Publication bias was examined using funnel plots. Results: Nineteen original studies were included, consisting of 2444 patients and 3012 SSNs. The median/mean follow-up duration of these studies ranged from 24.2 months to 112 months. Significant correlations were observed between SSN growth and eighteen features. Male sex, history of lung cancer, nodule size > 10 mm, nodule consistency, and age > 65 years were identified as independent risk factors for SSN growth based on multivariate analyses results. Eight features, including male sex, smoking history, nodule size > 10 mm, larger nodule size, air bronchogram, higher mean CT attenuation, well-defined border, and lobulated margin were detected to be significantly correlated with pGGNs growth. Smoking history showed no significant correlation with pGGN growth based on the multivariate analysis results. Conclusions: Eighteen clinical and CT features were identified to be correlated with SSN growth, among which male sex, history of lung cancer, nodule size > 10 mm, nodule consistency and age > 65 years were independent risk factors while history of lung cancer was not correlated with pGGN growth. These factors should be considered when making risk-based follow-up plans for SSN patients.

Disparate genomic characteristics of patients with early-stage lung adenocarcinoma manifesting as radiological subsolid or solid lesions.

INTRODUCTION: Early-stage lung adenocarcinoma (LUAD) manifesting as subsolid nodules (SSNs) exhibit more favorable prognosis than solid nodules (SNs). However, the genomic underpinnings behind their indolent tumor behavior remain largely unexplained. METHODS: We identified patients with stage I invasive LUAD who underwent complete surgical resection and broad-panel next-generation sequencing (NGS). Comparative genomic profiling was then performed by radiological subtype (SSNs vs. SNs) regarding the general genomic features, driver genes, oncogenic pathways, therapeutic actionability, and evolutionary trajectory. RESULTS: In total, 177 SSN-LUADs and 133 SN-LUADs were included. Compared with SNs, SSN-LUADs possessed lower somatic mutation count (P < 0.001), genomic alteration count (P = 0.002), and intra-tumor heterogeneity (P = 0.006). In terms of driver genes, SSNs harbored more EGFR mutation (77% vs. 62%), but had lower frequencies of genes such as TP53, ARID1A, PIK3CA, CDKN2A, and BRAF (FDR q < 0.1). Besides, RBM10 mutation was independently associated with SSN-LUADs in multivariate analysis (P = 0.033). Three oncogenic pathways (p53, cell cycle, PI3K) were altered with statistical significance in SNs, while only RNA splicing/processing pathway was significantly altered in SSNs (FDR q < 0.1). Also, SSNs had significantly lower number of pathway alterations (P < 0.001). Finally, SSNs and SNs showed distinct evolutionary trajectories regarding somatic mutations during early-stage LUAD progression. CONCLUSIONS: This study performed the first direct comparative genomic profiling in pathologic stage I invasive LUAD by radiological subtype, highlighting a less complex genomic architecture of SSNs, which might be the molecular interpretation of their indolent tumor behavior.

Differential Diagnosis of Nonabsorbable Inflammatory and Malignant Subsolid Nodules with a Solid Component ≤5 mm.

Purpose: To investigate the differential clinical and computed tomography (CT) characteristics of pulmonary nonabsorbable inflammatory and malignant subsolid nodules (SSNs) with a solid component ≤5 mm. Patients and Methods: We retrospectively analyzed 576 consecutive patients who underwent surgical resection and had SSNs with a solid component ≤5 mm on CT images. These patients were divided into inflammatory and malignant groups according to pathology. Their clinical and imaging data were analyzed and compared. Multiple logistic regression analysis was used to identify independent prognostic factors differentiating inflammatory from malignant SSNs. Furthermore, 146 consecutive patients were included as internal validation cohort to test the prediction efficiency of this model. Results: Significant differences in 11 clinical characteristics and CT features were found between both groups (P < 0.05). Presence of respiratory symptoms, distribution of middle/lower lobe, irregular shape, part-solid nodule (PSNs), CT value of ground-glass opacity (GGO) areas <-657 Hu, presence of abnormal intra-nodular vessel sign, and interlobular septal thickening were the most effective factors for diagnosing nonabsorbable inflammatory SSNs, with an AUC (95% CI), accuracy, sensitivity, and specificity of 0.843 (95% CI: 0.811-0.872), 89.76%, 72.86%, and 81.23%, respectively. The internal validation cohort obtained an AUC (95% CI), accuracy, sensitivity, and specificity of 0.830 (95% CI: 0.759-0.887), 83.56%, 73.91%, and 76.42%, respectively. Conclusion: Nonabsorbable inflammatory and malignant SSNs with a solid component ≤5 mm exhibited different clinical and imaging characteristics.

Predicting the Ki-67 proliferation index in pulmonary adenocarcinoma patients presenting with subsolid nodules: construction of a nomogram based on CT images.

BACKGROUND: The Ki-67 proliferation index (PI) reflects the proliferation of cells. However, the conventional methods for the acquisition of the Ki-67 PI, such as surgery and biopsy, are generally invasive. This study investigated a potential noninvasive method of predicting the Ki-67 PI in patients with lung adenocarcinoma presenting with subsolid nodules. METHODS: This retrospective study enrolled 153 patients who presented with pulmonary adenocarcinoma appearing as subsolid nodules (SSNs) on computed tomography (CT) images between January 2015 and December 2018. Presence of LUAD with SSNs was confirmed by histopathology. Of these participants, 107 patients were from institution 1 and were divided into a training cohort and an internal validation cohort in a 7:3 ratio. The other 46 patients were from institution 2 and were enrolled as an external validation cohort. All patients underwent conventional CT scans with thin-slice (≤1.25 mm) reconstruction, and 1,316 quantitative radiomic features were extracted from the CT images for each nodule. The minimum redundancy maximum relevance and the least absolute shrinkage and selection operator were used for feature selection, and the radiomics signature was constructed based on these selected features. Clinical features were examined using univariate logistic regression analysis. The nomogram was developed based on the radiomics signature and the independent clinical risk factors. The Delong test and t test were employed for statistical analysis. The performance of different models was assessed by the receiver operating characteristic (ROC) curve. RESULTS: The diameter of the nodules [odds ratio (OR) =1.17; P=0.003] was identified as an independent predictive parameter. Both the radiomics signature and the nomogram suggested a good predictive probability for Ki-67 expression. For the radiomics signature, the area under the ROC curve (AUC) for the training cohort, the internal validation cohort, and the external validation cohort was 0.86 [95% confidence interval (CI): 0.77 to 0.95], 0.81 (95% CI: 0.64 to 0.98), and 0.77 (95% CI: 0.62 to 0.91), respectively. For the nomogram, the AUC for the training cohort, the internal validation cohort, and the external validation cohort was 0.86 (95% CI: 0.77 to 0.95), 0.80 (95% CI: 0.64 to 0.97), and 0.79 (95% CI: 0.65 to 0.94), respectively. There were no statistical differences in the AUCs between the radiomics signature and the radiomic nomogram in the training cohort or the validation cohorts (all P>0.05). CONCLUSIONS: The nomogram provides a novel strategy for determining the Ki-67 PI in predicting the proliferation of subsolid nodules, which may be beneficial for the management of patients with SSNs.

Pulmonary nodular lymphoid hyperplasia presenting as multifocal subsolid nodules: A case report and literature review.

Pulmonary nodular lymphoid hyperplasia (PNLH) is a rare, benign lymphoproliferative disease, which is characterized by nonclonal lymphoproliferation. PNLH is usually asymptomatic and usually detected incidentally on imaging studies. Common imaging findings include a solitary nodule, multiple nodules, or focal consolidation. Atypically, PNLH may present with persistent subsolid nodules, mimicking adenocarcinoma. Here, we report a rare case of PNLH presenting as multifocal subsolid nodules in both lower lobes. During follow-up, persistency and growth of the subsolid nodules suggested the possibility of malignancy. Wedge resection was performed bilaterally, and PNLH was confirmed on pathological examination.

The Impact of EGFR Tyrosine Kinase Inhibitor on the Natural Course of Concurrent Subsolid Nodules in Patients with Non-Small Cell Lung Cancer.

PURPOSE: The role of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) in the management of persistent subsolid nodules (SSNs) is unclear. This study aimed to investigate the impact of EGFR-TKIs on concurrent SSNs in patients with stage IV non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: Patients who received an EGFR-TKI for at least 1 month for stage IV NSCLC and had concurrent SSN(s) that had existed for at least 3 months on chest computed tomography were included in this retrospective study. Size change of each nodule before and after EGFR-TKI therapies were evaluated using a cutoff value of 2 mm; increase (≥ 2 mm), decrease (≤ -2 mm), and no change (-2 mm < size change < +2 mm). RESULTS: A total of 77 SSNs, 51 pure ground-glass (66.2%) and 26 part-solid nodules (33.8%), were identified in 59 patients who received gefitinib (n=45) and erlotinib (n=14). Among 58 EGFR mutation analysis performed for primary lung cancer, 45 (77.6%) were EGFR mutant. The proportions of decrease group were 19.5% (15/77) on per-nodule basis and 25.4% (15/59) on per-patient basis. Four SSNs (5.2%) disappeared completely. On per-patient based multivariable analysis, EGFR exon 19 deletion positivity for primary lung cancer was associated with a decrease after initial EGFR-TKI therapy (adjusted odds ratio, 4.29; 95% confidence interval, 1.21 to 15.29; p=0.025). CONCLUSION: Approximately 20% of the concurrent SSNs decreased after the initial EGFR-TKI therapy. EGFR exon 19 deletion positivity for primary lung cancer was significantly associated with the size change of concurrent SSNs.

Establishment and validation a prediction model for discrimination of invasive adenocarcinomas for patients with peripheral pulmonary subsolid nodules.

Background: The optimal management of patients with subsolid pulmonary nodules is of growing clinical concern. This study sought to develop and validate a more precise predictive model to evaluate the pathological invasiveness of patients with lung peripheral subsolid nodules (SSNs). Methods: The data of 1,140 patients with peripheral SSNs who underwent surgical resection at Shanghai Renji Hospital from January 2014 to December 2018 were retrospectively analyzed. The patients were randomly assigned to a training and validation cohort (at a ratio of 2 to 1). Clinical parameters and imaging features were collected to estimate the independent predictors of pathological invasiveness of SSNs. A nomogram model was developed and applied to the validation cohort. The predictive performance of the nomogram model was evaluated by a calibration curve analysis, an area under the receiver operating characteristic curve (AUC) analysis, and a decision curve analysis (DCA), which was also compared with other diagnostic models. Results: In the multivariate analysis, the nodule diameter (P<0.001), solid component size (P<0.001), mean CT attenuation (P=0.001), spiculation (P<0.001), and pleura indentation (P=0.011) were identified as independent predictors of the pathological invasiveness of SSNs. A nomogram model based on the results of the multivariate analysis was developed and showed a robust discrimination in the validation cohort, with an AUC of [0.890; 95% confidence interval (CI), 0873-0.907], which was higher than another two reported models. The calibration curve showed optimal agreement between the pathological invasive probability as predicted by the nomogram and the actual probability. Conclusions: We developed and validated a nomogram model to evaluate the risk of the pathological invasiveness for patients with lung SSNs. The AUC of this nomogram model was higher than another two reported models. Our nomogram model may help clinicians to make individualized treatment more precisely.

Manejo de los nódulos pulmonares subsólidos: resultados quirúrgicos basados en algoritmo local / Pulmonary subsolid nodules: surgical outcomes based on institutional algorithm

INTRODUCCIÓN: en la actualidad no existe un consenso respecto al manejo de los nódulos pulmonares subsólidos (NPSS). OBJETIVO: describir los resultados del manejo quirúrgico de los NPSS, basados en un algoritmo local. MATERIAL Y MÉTODOS: estudio descriptivo de corte transversal. Se revisaron las fichas clínicas electrónicas de los pacientes operados por NPSS, sugerentes de ser malignos, a juicio de un equipo multidisciplinario, entre enero de 2014 y enero de 2018, en el Departamento de Cirugía de Adultos de Clínica Las Condes. RESULTADOS: se estudió un total de 35 pacientes. La edad promedio fue de 65,8 años. El tamaño promedio de los nódulos fue de 15 mm. Todos los pacientes fueron abordados por cirugía videotoracoscópica asistida. El 88,6% de las biopsias demostró la presencia de una neoplasia maligna. CONCLUSIONES: la adopción de un algoritmo local, instituido por un equipo multidisciplinario, es una alternativa para el manejo adecuado de los portadores de NPSS.

BACKGROUND: Nowadays, there is no consensus in the management of pulmonary subsolid nodules (SSNs). AIM: describe the results of surgical management of SSNs, based on institutional algorithm. MATERIAL AND METHODS: cross-sectional, descriptive study, with revision of clinical electronic records, that included all patients intervened for SSNs, suggestive of malignancy, by the judgment of a multi-disciplinary team, from January 2014 to January 2018 at the Department of Adult Surgery, Clinica Las Condes. RESULTS: 35 patients were studied. The average age was 65.8 years. The average size of the nodules was 15 mm. All patients were approached by video-assisted thoracoscopic surgery. 88.6% of biopsies turned out to be malignant neoplasm. CONCLUSIONS: the acquisition of a local algorithm established by a multidisciplinary team is an appropriate alternative for the management of the patients with SSNs.

[Expert Consensus for Thermal Ablation of Pulmonary Subsolid Nodules (2021 Edition)].

"The Expert Group on Tumor Ablation Therapy of Chinese Medical Doctor Association, The Tumor Ablation Committee of Chinese College of Interventionalists, The Society of Tumor Ablation Therapy of Chinese Anti-Cancer Association and The Ablation Expert Committee of the Chinese Society of Clinical Oncology" have organized multidisciplinary experts to formulate the consensus for thermal ablation of pulmonary subsolid nodules or ground-glass nodule (GGN). The expert consensus reviews current literatures and provides clinical practices for thermal ablation of GGN. The main contents include: (1) clinical evaluation of GGN, (2) procedures, indications, contraindications, outcomes evaluation and related complications of thermal ablation for GGN and (3) future development directions.
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