Trastuzumab Deruxtecan‒Related Interstitial Lung Disease/Pneumonitis: Computed Tomography Imaging Patterns to Guide Diagnosis and Management.

PURPOSE: Trastuzumab deruxtecan (T-DXd) is an antibody-drug conjugate approved for the treatment of several advanced cancers; however, severe or fatal interstitial lung disease/pneumonitis can occur. We characterized the computed tomography (CT) patterns of T-DXd‒related pneumonitis as a marker for its clinical severity. MATERIALS AND METHODS: Ninety patients with advanced cancers who developed T-DXd‒related pneumonitis in two completed single-arm clinical trials were included. Three radiologists independently characterized the CT patterns of pneumonitis at diagnosis, for analyses of those patterns' relationships with clinical severity and pneumonitis outcome. RESULTS: T-DXd‒related pneumonitis most commonly presented with cryptogenic organizing pneumonia (COP) pattern, observed in 65 patients (72%), followed by a newly identified COP/hypersensitivity pneumonitis (HP) pattern (13%), acute interstitial pneumonia (AIP)/acute respiratory distress syndrome (ARDS) pattern (11%), and HP pattern (3%). A subset of cases with COP pattern demonstrated an atypical distribution with upper and peripheral lung involvement (6/65; 9%). CT patterns were associated with Common Terminology Criteria for Adverse Events severity grades of pneumonitis, with the AIP/ARDS pattern having higher grades compared with others (P < .0001). Fatal pneumonitis was more common in the AIP/ARDS pattern than in others (P = .005). The onset of pneumonitis was earlier in the AIP/ARDS pattern compared with others (median time to onset: at 17.9 v 32.7 weeks of therapy; P = .019). Pneumonitis was treated by withholding T-DXd with or without corticosteroids in most patients (78/90; 87%). CONCLUSION: T-DXd‒related pneumonitis most commonly demonstrated a COP pattern, with a subset having an atypical distribution. The AIP/ARDS pattern was indicative of severe, potentially fatal pneumonitis, and requires immediate clinical attention to mitigate serious adverse events.

Early Detection of Lung Cancer Using Small RNAs.

INTRODUCTION: Lung cancer remains the deadliest cancer in the world, and lung cancer survival is heavily dependent on tumor stage at the time of detection. Low-dose computed tomography screening can reduce mortality; however, annual screening is limited by low adherence in the United States of America and still not broadly implemented in Europe. As a result, less than 10% of lung cancers are detected through existing programs. Thus, there is a great need for additional screening tests, such as a blood test, that could be deployed in the primary care setting. METHODS: We prospectively recruited 1384 individuals meeting the National Lung Screening Trial demographic eligibility criteria for lung cancer and collected stabilized whole blood to enable the pipetting-free collection of material, thus minimizing preanalytical noise. Ultra-deep small RNA sequencing (20 million reads per sample) was performed with the addition of a method to remove highly abundant erythroid RNAs, and thus open bandwidth for the detection of less abundant species originating from the plasma or the immune cellular compartment. We used 100 random data splits to train and evaluate an ensemble of logistic regression classifiers using small RNA expression of 943 individuals, discovered an 18-small RNA feature consensus signature (miLung), and validated this signature in an independent cohort (441 individuals). Blood cell sorting and tumor tissue sequencing were performed to deconvolve small RNAs into their source of origin. RESULTS: We generated diagnostic models and report a median receiver-operating characteristic area under the curve of 0.86 (95% confidence interval [CI]: 0.84-0.86) in the discovery cohort and generalized performance of 0.83 in the validation cohort. Diagnostic performance increased in a stage-dependent manner ranging from 0.73 (95% CI: 0.71-0.76) for stage I to 0.90 (95% CI: 0.89-0.90) for stage IV in the discovery cohort and from 0.76 to 0.86 in the validation cohort. We identified a tumor-shed, plasma-bound ribosomal RNA fragment of the L1 stalk as a dominant predictor of lung cancer. The fragment is decreased after surgery with curative intent. In additional experiments, results of dried blood spot collection and sequencing revealed that small RNA analysis could potentially be conducted through home sampling. CONCLUSIONS: These data suggest the potential of a small RNA-based blood test as a viable alternative to low-dose computed tomography screening for early detection of smoking-associated lung cancer.

The impact of pathology grossing protocol measures to improve pathologic nodal staging in lung cancer.

OBJECTIVE: Accurate assessment of lymph node (LN) status is essential for proper staging of resected lung cancer specimens. Here, we assessed pathology-centric interventions to increase the number of peribronchial LNs identified and evaluated in anatomic lung cancer resection specimens as part of a quality improvement initiative. MATERIALS AND METHODS: All non-small cell lung cancer (NSCLC) anatomic resection specimens from 2017 to 2020 were evaluated, comprising two years pre-intervention and one year post-intervention. We instituted 3 measures to increase peribronchial LN yield: 1) educational grossing sessions for pathology assistants and residents, 2) directions to submit additional peribronchial tissue if no LNs were identified grossly, and 3) a hard-stop prior to sign-out by the attending pathologist if no peribronchial LNs were identified. RESULTS: Of the total 227 resection specimens for NSCLC, 107/151 (70.9%) of specimens prior to the intervention had peribronchial LNs identified, whereas after the intervention significantly more (66/76, 86.8%, p < 0.01) specimens had peribronchial LNs identified. In addition, the mean number of peribronchial LNs identified significantly increased from 2.7 ± 3.3 pre-intervention to 4.3 ± 4.0 post-intervention (p < 0.001). Further analysis revealed a strong correlation between peribronchial LN metastases with both overall tumor size and invasive component size (for adenocarcinomas), correlation coefficient 0.974, p < 0.0001. CONCLUSION: Establishing focused grossing measures by pathology led to a significant increase in the number of peribronchial LNs identified and assessed during histopathologic evaluation of anatomic lung cancer resection specimens. Larger tumors are more likely to have occult peribronchial LN metastases, which may warrant more aggressive peribronchial LN assessment for larger tumors.

Vascular remodeling of the small pulmonary arteries and measures of vascular pruning on computed tomography.

Pulmonary hypertension is characterized histologically by intimal and medial thickening in the small pulmonary arteries, eventually resulting in vascular "pruning." Computed tomography (CT)-based quantification of pruning is associated with clinical measures of pulmonary hypertension, but it is not established whether CT-based pruning correlates with histologic arterial remodeling. Our sample consisted of 138 patients who underwent resection for early-stage lung adenocarcinoma. From histologic sections, we identified small pulmonary arteries and measured the relative area comprising the intima and media (VWA%), with higher VWA% representing greater histologic remodeling. From pre-operative CTs, we used image analysis algorithms to calculate the small vessel volume fraction (BV5/TBV) as a CT-based indicator of pruning (lower BV5/TBV represents greater pruning). We investigated relationships of CT pruning and histologic remodeling using Pearson correlation, simple linear regression, and multivariable regression with adjustment for age, sex, height, weight, smoking status, and total pack-years. We also tested for effect modification by sex and smoking status. In primary models, more severe CT pruning was associated with greater histologic remodeling. The Pearson correlation coefficient between BV5/TBV and VWA% was -0.41, and in linear regression models, VWA% was 3.13% higher (95% CI: 1.95-4.31%, p < 0.0001) per standard deviation lower BV5/TBV. This association persisted after multivariable adjustment. We found no evidence that these relationships differed by sex or smoking status. Among individuals who underwent resection for lung adenocarcinoma, more severe CT-based vascular pruning was associated with greater histologic arterial remodeling. These findings suggest CT imaging may be a non-invasive indicator of pulmonary vascular pathology.

COVID-19 Vaccination-Related Uptake on FDG PET/CT: An Emerging Dilemma and Suggestions for Management.

As mass COVID-19 vaccination is underway, radiologists are encountering transient FDG uptake in normal or enlarged axillary, supraclavicular, and cervical lymph nodes after ipsilateral deltoid vaccination. This phenomenon may confound interpretation in patients with cancer undergoing FDG PET/CT. In this article, we present our institutional approach for management of COVID-19 vaccine-related lymphadenopathy on FDG PET/CT according to early experience. We suggest performing PET/CT at least 2 weeks after vaccination in patients with a cancer for which interpretation is anticipated to be potentially impacted by the vaccination but optimally 4-6 weeks after vaccination given increased immunogenicity of mRNA vaccines and potentially longer time for resolution than lymphadenopathy after other vaccines. PET/CT should not be delayed when clinically indicated to be performed sooner. Details regarding vaccination should be collected at the time of PET/CT to facilitate interpretation. Follow-up recommendations for postvaccination lymphadenopathy are provided, considering the lymph node's morphology and likely clinical relevance. Consideration should be given to administering the vaccine in the arm contralateral to a unilateral cancer to avoid confounding FDG uptake on the side of cancer. Our preliminary experience and suggested institutional approach should guide radiologists in management of patients with cancer undergoing PET/CT after COVID-19 vaccination.

Chest CT Diagnosis and Clinical Management of Drug-Related Pneumonitis in Patients Receiving Molecular Targeting Agents and Immune Checkpoint Inhibitors: A Position Paper From the Fleischner Society.

Use of molecular targeting agents and immune checkpoint inhibitors (ICIs) has increased the frequency and broadened the spectrum of lung toxicity, particularly in patients with cancer. The diagnosis of drug-related pneumonitis (DRP) is usually achieved by excluding other potential known causes. Awareness of the incidence and risk factors for DRP is becoming increasingly important. The severity of symptoms associated with DRP may range from mild or none to life-threatening with rapid progression to death. Imaging features of DRP should be assessed in consideration of the distribution of lung parenchymal abnormalities (radiologic pattern approach). The CT patterns reflect acute (diffuse alveolar damage) interstitial pneumonia and transient (simple pulmonary eosinophilia) lung abnormality, subacute interstitial disease (organizing pneumonia and hypersensitivity pneumonitis), and chronic interstitial disease (nonspecific interstitial pneumonia). A single drug can be associated with multiple radiologic patterns. Treatment of a patient suspected of having DRP generally consists of drug discontinuation, immunosuppressive therapy, or both, along with supportive measures eventually including supplemental oxygen and intensive care. In this position paper, the authors provide diagnostic criteria and management recommendations for DRP that should be of interest to radiologists, clinicians, clinical trialists, and trial sponsors, among others.

Chest CT Diagnosis and Clinical Management of Drug-related Pneumonitis in Patients Receiving Molecular Targeting Agents and Immune Checkpoint Inhibitors: A Position Paper from the Fleischner Society.

Use of molecular targeting agents and immune checkpoint inhibitors (ICIs) has increased the frequency and broadened the spectrum of lung toxicity, particularly in patients with cancer. The diagnosis of drug-related pneumonitis (DRP) is usually achieved by excluding other potential known causes. Awareness of the incidence and risk factors for DRP is becoming increasingly important. The severity of symptoms associated with DRP may range from mild or none to life-threatening with rapid progression to death. Imaging features of DRP should be assessed in consideration of the distribution of lung parenchymal abnormalities (radiologic pattern approach). The CT patterns reflect acute (diffuse alveolar damage) interstitial pneumonia and transient (simple pulmonary eosinophilia) lung abnormality, subacute interstitial disease (organizing pneumonia and hypersensitivity pneumonitis), and chronic interstitial disease (nonspecific interstitial pneumonia). A single drug can be associated with multiple radiologic patterns. Treatment of a patient suspected of having DRP generally consists of drug discontinuation, immunosuppressive therapy, or both, along with supportive measures eventually including supplemental oxygen and intensive care. In this position paper, the authors provide diagnostic criteria and management recommendations for DRP that should be of interest to radiologists, clinicians, clinical trialists, and trial sponsors, among others. This article is a simultaneous joint publication in Radiology and CHEST. The articles are identical except for stylistic changes in keeping with each journal's style. Either version may be used in citing this article. Published under a CC BY 4.0 license. Online supplemental material is available for this article.

Assessing invasiveness of subsolid lung adenocarcinomas with combined attenuation and geometric feature models.

The aim of this study was to develop and test multiclass predictive models for assessing the invasiveness of individual lung adenocarcinomas presenting as subsolid nodules on computed tomography (CT). 227 lung adenocarcinomas were included: 31 atypical adenomatous hyperplasia and adenocarcinomas in situ (class H1), 64 minimally invasive adenocarcinomas (class H2) and 132 invasive adenocarcinomas (class H3). Nodules were segmented, and geometric and CT attenuation features including functional principal component analysis features (FPC1 and FPC2) were extracted. After a feature selection step, two predictive models were built with ordinal regression: Model 1 based on volume (log) (logarithm of the nodule volume) and FPC1, and Model 2 based on volume (log) and Q.875 (CT attenuation value at the 87.5% percentile). Using the 200-repeats Monte-Carlo cross-validation method, these models provided a multiclass classification of invasiveness with discriminative power AUCs of 0.83 to 0.87 and predicted the class probabilities with less than a 10% average error. The predictive modelling approach adopted in this paper provides a detailed insight on how the value of the main predictors contribute to the probability of nodule invasiveness and underlines the role of nodule CT attenuation features in the nodule invasiveness classification.

The Growth Rate of Subsolid Lung Adenocarcinoma Nodules at Chest CT.

Background Confirming that subsolid adenocarcinomas show exponential growth is important because it would justify using volume doubling time to assess their growth. Purpose To test whether the growth of lung adenocarcinomas manifesting as subsolid nodules at chest CT is accurately represented by an exponential model. Materials and Methods Patients with lung adenocarcinomas manifesting as subsolid nodules surgically resected between January 2005 and May 2018, with three or more longitudinal CT examinations before resection, were retrospectively included. Overall volume (for all nodules) and solid component volume (for part-solid nodules) were measured over time. A linear mixed-effects model was used to identify the growth pattern (linear, exponential, quadratic, or power law) that best represented growth. The interactions between nodule growth and clinical, CT morphologic, and pathologic parameters were studied. Results Sixty-nine patients (mean age, 70 years ± 9 [standard deviation]; 48 women) with 74 lung adenocarcinomas were evaluated. Overall growth and solid component growth were better represented by an exponential model (adjusted R2 = 0.89 and 0.95, respectively) than by a quadratic model (r2 = 0.88 and 0.93, respectively), a linear model (r2 = 0.87 and 0.92, respectively), or a power law model (r2 = 0.82 and 0.93, respectively). Faster overall volume growth was associated with a history of lung cancer (P < .001), a baseline nodule volume less than 500 mm3 (P = .03), and histologic findings of invasive adenocarcinoma (P < .001). The median volume doubling time of noninvasive adenocarcinoma was significantly longer than that of invasive adenocarcinoma (939 days [interquartile range, 588-1563 days] vs 678 days [interquartile range, 392-916 days], respectively; P = .01). Conclusion The overall volume growth of adenocarcinomas manifesting as subsolid nodules at chest CT was best represented by an exponential model compared with the other tested models. This justifies the use of volume doubling time for the growth assessment of these nodules. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Kuriyama and Yanagawa in this issue.

Preoperative bronchial cytology for the assessment of tumor spread through air spaces in lung adenocarcinoma resection specimens.

BACKGROUND: Tumor spread through air spaces (STAS), a significant prognostic indicator, has been described recently as a pattern of invasion in pulmonary carcinomas. However, questions remain regarding preoperative identification of STAS and whether it represents an in vivo phenomenon versus an ex vivo artifact. METHODS: We retrospectively reviewed 67 paired preoperative bronchoalveolar lavage (BAL) or bronchial washing (BW) cytology specimens with the subsequent lung adenocarcinoma surgical resection specimen to determine whether preoperative cytology could predict STAS. Other clinical, radiologic, and pathologic features of the resected lesions were also correlated with preoperative bronchial cytology results. RESULTS: Positive bronchial cytology was observed in 28 cases (41.8%), 24 of which had STAS (85.7%); however, negative BAL/BW cytology was observed in 39 cases (58.2%), 29 of which had STAS (74.4%) (x2  = 1.27, P = .26, not significant). High-STAS burden was observed in 44 cases (83.0%), 21 (47.7%) with negative BAL/BW and 23 (52.3%) with positive BAL/BW. Low-STAS burden was observed in 9 cases (17.0%), 8 (88.9%) with negative BAL/BW and only 1 (11.1%) with positive BAL/BW (x2  = 5.11, P = .024, significant). For tumors with STAS, a statistically significant difference was identified in the maximal STAS distance from the main tumor edge between BAL/BW-positive and BAL/BW-negative groups (P = .007). Of the remaining clinicopathologic and radiologic features, only visceral pleural invasion was significantly associated with BAL/BW positivity. CONCLUSION: Presurgical bronchial cytology alone cannot adequately predict tumor STAS; however, it may provide useful information regarding the extent and overall burden of STAS on the subsequent resection specimen.

Growth Assessment of Pulmonary Adenocarcinomas Manifesting as Subsolid Nodules on CT: Comparison of Diameter-Based and Volume Measurements.

RATIONALE AND OBJECTIVES: To analyze the performances of diameter-based measurements, either using diameters, or by calculating diameter-based volumes, as compared to volume measurements in assessing growth of pulmonary adenocarcinomas manifesting as subsolid nodules on CT. MATERIALS AND METHODS: In this IRB-approved, retrospective study, 74 pulmonary adenocarcinomas presenting as subsolid nodules and resected in 69 patients (21 men, 48 women, mean age 70 ± 9 years) were included. Three CTs were available for each patient. Nodule size on each CT was assessed with diameter measurements, calculated volume based on diameter measurements, and measured volume. Nodule growth was defined as an increase of measured volume ≥25% between two sequential CTs. Sensitivity, specificity, accuracy, positive and negative predictive values of diameter-based measurements for growth assessment were calculated. Nodule characteristics were compared with nonparametric tests and analysis of variance. RESULTS: There were fewer growing nodules during CT1-CT2 interval (n = 22, 30%) than during CT2-CT3 interval (n = 33, 45%, p =.060). Specificity and negative predictive value of diameter-based measurements for growth assessment ranged respectively from 52 to 77% and 81 to 83% between CT1 and CT2, and from 66 to 76% and 79 to 90% between CT2 and CT3. Nongrowing nodules tended to be larger, regardless how size was measured, and some of these differences in size were statistically significant (p =.002 to .046). CONCLUSION: For pulmonary adenocarcinomas presenting as subsolid nodules on CT, diameter-based assessment of nodule volume is reasonably accurate at confirming a lack of nodule growth but may overestimate actual growth, as compared to growth assessment based on measured volume.

Inter-observer agreement in identifying traction bronchiectasis on computed tomography: its improvement with the use of the additional criteria for chronic fibrosing interstitial pneumonia.

PURPOSE: To assess inter-observer variability in identifying traction bronchiectasis on computed tomography (CT) using additional criteria for chronic fibrosing interstitial pneumonia. METHODS: Seven experts categorized CT image set representing 39 patients into three groups on the basis of the presence of traction bronchiectasis, using a three-point scale: 3-definitely/probably yes; 2-possibly yes; and 1-definitely/probably no. This scale served as a reference standard. The image set included cases of chronic fibrosing interstitial pneumonia, non-interstitial lung disease, and difficult-to-determine cases. Forty-eight observers similarly assessed the same image set, first according to the Fleischner Society definition, and second with additional criteria, in which traction bronchiectasis was observed exclusively in chronic fibrosing interstitial pneumonia. The agreement level between the reference standard and each observer's evaluation in each session was calculated using weighted kappa values which were compared between the two sessions using a paired t test. RESULTS: The mean weighted kappa value for all observers was significantly higher in the second reading session (mean 0.75) than in the first reading session (mean 0.62) (p < 0.001). CONCLUSION: Inter-observer agreement in identifying traction bronchiectasis improves when using the additional criteria which specify chronic fibrosing interstitial pneumonia as the underlying disease.

Radiographic pulmonary vessel volume, lung function and airways disease in the Framingham Heart Study.

Radiographic abnormalities of the pulmonary vessels, such as vascular pruning, are common in advanced airways disease, but it is unknown if pulmonary vascular volumes are related to measures of lung health and airways disease in healthier populations.In 2388 participants of the Framingham Heart Study computed tomography (CT) sub-study, we calculated total vessel volumes and the small vessel fraction using automated CT image analysis. We evaluated associations with measures of lung function, airflow obstruction on spirometry and emphysema on CT. We further tested if associations of vascular volumes with lung function were present among those with normal forced expiratory volume in 1 s and forced vital capacity.In fully adjusted linear and logistic models, we found that lower total and small vessel volumes were consistently associated with worse measures of lung health, including lower spirometric volumes, lower diffusing capacity and/or higher odds of airflow obstruction. For example, each standard deviation lower small vessel fraction (indicating more severe pruning) was associated with a 37% greater odds of obstruction (OR 1.37, 95% CI 1.11-1.71, p=0.004). A similar pattern was observed in the subset of participants with normal spirometry.Lower total and small vessel pulmonary vascular volumes were associated with poorer measures of lung health and/or greater odds of airflow obstruction in this cohort of generally healthy adults without high burdens of smoking or airways disease. Our findings suggest that quantitative CT assessment may detect subtle pulmonary vasculopathy that occurs in the setting of subclinical and early pulmonary and airways pathology.

Visceral Pleural Invasion in Pulmonary Adenocarcinoma: Differences in CT Patterns between Solid and Subsolid Cancers.

PURPOSE: To analyze the incidence and CT patterns of visceral pleural invasion (VPI) in adenocarcinomas on the basis of their CT presentation as solid or subsolid nodules. MATERIALS AND METHODS: A total of 286 adenocarcinomas in direct contact with a pleural surface, resected at an institution between 2005 and 2016, were included in this retrospective, institutional review board-approved study. CT size and longest contact length with a pleural surface were measured and their ratios computed. Pleural deviation, pleural thickening, spiculations, different pleural tag types, pleural effusion, and the CT appearance of transgression into an adjacent lobe or infiltration of surrounding tissue were evaluated. Fisher exact tests and simple and multiple logistic regression models were used. RESULTS: Of the 286 nodules, 179 of 286 (62.6%) were solid and 107 of 286 (37.4%) were subsolid. VPI was present in 49 of 286 (17.1%) nodules and was significantly more frequent in solid (44 of 179; 24.6%) than in subsolid nodules (five of 107; 4.7%; P < .001). In solid nodules, multiple regression analysis showed an association of higher contact length-to-size ratio (adjusted odds ratio [OR], 1.02; P = .007) and the presence of multiple pleural tag types (adjusted OR, 5.88; P = .002) with VPI. In subsolid nodules, longer pleural contact length of the solid nodular component (adjusted OR, 1.27; P = .017) and the CT appearance of transgression or infiltration (adjusted OR, 10.75; P = .037) were associated with VPI. CONCLUSION: During preoperative evaluation of adenocarcinomas for the likelihood of VPI, whether a tumor manifests as a solid or a subsolid nodule is important to consider because the incidence of VPI is significantly higher in solid than in subsolid nodules. In addition, this study showed that the CT patterns associated with VPI differ between solid and subsolid nodules.© RSNA, 2019Supplemental material is available for this article.See also the commentary by Elicker in this issue.

Pathologic T Descriptor of Nonmucinous Lung Adenocarcinomas Now Based on Invasive Tumor Size: How Should Pathologists Measure Invasion?

OBJECTIVES: The eighth edition of the American Joint Committee on Cancer staging manual now stratifies nonmucinous lung adenocarcinomas (nmLACAs) by the size of the invasive component only. This is determined by direct gross or microscopic measurement; however, a calculated invasive size based on the percentage of invasive growth patterns has been proposed as an alternative option. METHODS: To compare radiologic with different pathologic assessments of invasive tumor size, we retrospectively reviewed a cohort of resected nmLACAs with a part-solid appearance on computed tomography (CT) scan (n = 112). RESULTS: The median direct microscopic pathologic invasive measurements were not significantly different from the median calculated pathologic invasive measurements; however, the median CT invasive measurements were 0.26 cm larger than the median direct pathologic measurements (P < .001). CONCLUSIONS: Our results show that pathologic calculated invasive tumor measurements are comparable to direct microscopic measurements of invasive tumor, thereby supporting the recommendation for use of calculated invasive tumor size by the pathologist if necessary.

CT Manifestations of Tumor Spread Through Airspaces in Pulmonary Adenocarcinomas Presenting as Subsolid Nodules.

PURPOSE: The aim of this study was to identify potential computed tomography manifestations of pulmonary adenocarcinomas presenting as subsolid nodules and associated with the histologic evidence of spread of tumor through air spaces (STAS). MATERIALS AND METHODS: From a radiologic-pathologic repository of resected pulmonary adenocarcinomas including 203 subsolid nodules, 40 STAS-positive nodules were randomly selected and matched to 40 STAS-negative nodules. Total average diameter, as well as average and long-axis diameters of the solid component, was measured. The proportion of solid component diameter to total average diameter was calculated. Measurements and proportions between STAS-positive and STAS-negative nodules were compared with paired samples t test, χ test, or the Fisher exact test. RESULTS: The total average diameter in STAS-positive nodules was significantly larger than in STAS-negative nodules (P=0.024). The average and long-axis diameters of the solid component of STAS-positive nodules were significantly larger than that of STAS-negative nodules (P=0.001 and 0.003). The proportion of solid component to total average diameter was significantly larger in STAS-positive than in STAS-negative nodules (P=0.041). At a threshold of ≥10 mm for the average and the solid component long-axis diameters, significantly more nodules were STAS-positive than STAS-negative (P=0.015 and 0.001). CONCLUSIONS: Total average diameter, average and long-axis diameters of the solid component, and a high proportion of solid component diameter compared with total average diameter are computed tomography manifestations of subsolid pulmonary adenocarcinomas with STAS. These findings could serve as an in-vivo tool for the likelihood estimation of STAS, and consequently influence management of subsolid adenocarcinomas.