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A 74-year-old woman, who had been receiving olaparib for the treatment of ovarian cancer for more than a year, visited the emergency department complaining of a fever that had lasted for 1 month. She had been taking antipyretics and antibiotics for her fever, but without any effect. Although she had no symptoms other than fever, she had stopped taking olaparib for 1 week before her visit because she had developed anemia caused by myelosuppression from olaparib. After discontinuing olaparib, her maximum body temperature decreased. On admission, chest X-ray revealed no abnormalities, but chest CT showed diffuse ground-glass opacities. Chest CT taken 5 days later showed partial improvement; therefore, we diagnosed her with interstitial lung disease (ILD) associated with olaparib. After short-term steroid treatment, the ground-glass opacities disappeared, and the patient became afebrile. The CT scan taken for tumor evaluation 2 days before the onset of fever showed a few centrilobular nodular opacities and small patchy ground-glass opacities. These findings could indicate early lesions of ILD, but they seemed inconspicuous and nonspecific, and it might have been difficult to diagnose ILD then. To date, few cases of ILD associated with olaparib have been reported. However, based on previous reports, fever is often seen, and CT findings mainly comprise diffuse ground-glass opacities, and in some cases, centrilobular nodular shadows. Thus, in conjunction with the findings of the present case, these characteristics may be representative of olaparib-induced ILD.

Reversed halo sign (RHS) is a radiological feature described as a focal, rounded area of ground-glass opacity surrounded by a ring of consolidation. In this report we describe two unique radiological cases demonstrating diffuse bilateral infiltrates with multiple RHSs in chest CT scans. Both patients were ultimately diagnosed as having tuberculosis (TB) and had been exposed to silica in the past. This report presents for the first time an association between silica exposure and RHS on CT scans among TB patients. It highlights the importance of having a high index of suspicion for TB in similar scenarios.

Summary: Background: 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. Methods: 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. Findings: 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. Interpretation: Our results provide deeper insights into the indolent nature of GGO and provide a molecular basis for the treatment of GGO-like LUAD. Funding: 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).

The case of 21-year-old man with an asthma history from childhood presenting severe respiratory distress associated with a right lower thoracic pain has been studied. The non–contrast Computed Tomography (CT)-chest scan showed a basal ground-glass opacity (GGO) of the right lung leading to suspicion of COVID-19 pneumonia. However, the molecular Reverse transcription polymerase chain reaction test and blood serology were negative while laboratory analyses revealed high levels of D-dimers (D-D). In addition, 2 repeated COVID-19 tests were negative. A thoracic CT angiography was disclosed due to the persistence of pain at the lower right thoracic side and hemoptysis that shows a bilateral distal pulmonary embolism with a right-sided basal subsegmental ischemia. We discuss a fortuitous discovery of pulmonary embolism associated with peripheral basal ground-glass opacities similar to radiological manifestations of SARS-CoV-2 pneumonia.

Introduction: Although several studies have investigated the prognostic significance of the radiographic appearance of stage IA lung adenocarcinoma, the prognostic impact of solid component size or consolidation-to-tumor ratio (CTR) of part-solid nodules (PSNs) still remains controversial. This study aimed to clarify the combined prognostic impact of the mentioned radiographic features of PSNs and compare it with that of pure solid nodules in the current TNM classification. Methods: We retrospectively investigated 1014 patients with clinical stage IA (TNM eighth edition) adenocarcinoma who underwent curative resection. Overall survival (OS) and pathologic characteristics of pure solid nodules, solid-dominant PSNs (CTR > 0.5), and ground-glass opacity (GGO)-dominant PSNs (CTR ≤ 0.5) were compared according to T category. Results: Patients with pure solid nodules (297 cases) had significantly shorter OS compared with those with PSNs (717 cases) (p < 0.001) but a marginal difference compared with those with solid-dominant PSNs (286 cases) (p = 0.051). No significant difference in OS was found according to T category in those with GGO-dominant PSNs (431 cases). Patients with cT1b and T1c solid-dominant PSNs had significantly worse prognosis compared with those with other PSNs and had comparable prognosis with those with cT1b pure solid nodules (p = 0.892). Higher frequency of nodal and lymphovascular involvement and pathologic upstaging was observed with T category progression in solid-dominant PSNs. Conclusions: An hierarchy of prognosis and pathologic malignant characteristics was observed according to T category in patients with solid-dominant PSNs but not in those with GGO-dominant PSNs, suggesting the importance of classifying PSNs on the basis of solid component size and CTR for accurate prognostic comparison with pure solid nodules.

A male patient with severe pneumonia due to coronavirus disease 2019 (COVID-19) had acute respiratory distress syndrome (ARDS) which developed in the second week since the first symptoms and improved without mechanical ventilation. The patient had epilepsy as a comorbid disease and his routinely consumed antiepileptic drugs were likely to cause alterations of the immune system. Ground-glass opacity (GGO), consolidation, and reticular pattern are typical radiological features of COVID-19 pneumonia. Less common findings were septal thickening, bronchiectasis, pleural thickening, and subpleural involvement. These radiological abnormalities evolve throughout the course of the disease. In this case report, a GGO lesion was seen in thin-section CT scans on the 30th and 45th day since the onset of symptoms. The consolidation subsided with time and on the 65th day, minimal GGO was seen in CT scan without pulmonary fibrosis and bronchiectasis.

Background: Lymph node (LN) involvement was not rare in patients with radiological solid-predominant part-solid nodules (PSNs). The lymph node dissection (LND) strategy remained unclear., Materials and Methods: Six hundred seventy-two patients with clinical N0 solid-predominant PSNs (0.5 < consolidation-to-tumor ratio < 1) receiving systematic LND (development cohort, n = 598) or limited LND (validation cohort A, n = 74) at 2 Chinese institutions from 2008 to 2016 were collected. The development cohort was utilized to investigate the incidence and pattern of LN metastasis. Lobe-specific LN metastasis pattern was defined as superior mediastinal LN involvement from upper-lobe tumor or inferior mediastinal LN involvement from lower-lobe tumor. To further validate the LN metastasis pattern observed in the development cohort, validation cohort B consisting of 7273 patients with primary lung adenocarcinomas who received surgery from 2016 to 2021 was identified. The clinical outcomes between the development cohort and validation cohort A were compared in order to assess the feasibility of limited LND., Results: LN involvement rate for solid-predominant PSNs was 10.0%. Larger solid component diameter (P = .005) was independently associated with increased risk of LN involvement. In upper/lower lobes solid-predominant PSNs with solid component diameter ≤ 2 cm, a lobe-specific LN involvement pattern was identified. Further validation indicated that the observed mediastinal LN involvement pattern was generalizable, and the oncologic outcomes did not vary by the extent of LND in solid-predominant PSNs with solid component diameter ≤ 2 cm., Conclusion: Lobe-specific LND might be feasible for solid-predominant PSNs with solid component diameter ≤ 2 cm. For other solid-predominant PSNs, systematic LND should be recommended., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Introduction: The objective of this study was to determine whether computed tomography (CT) could be a useful tool for nonsolid lung nodule (NSN) treatment planning, surgery or stereotactic body radiation therapy (SBRT), by assessing the macroscopic and microscopic extension of these nodules., Methods: The study prospectively included 23 patients undergoing anatomic resection at the Foch Hospital in 2020/2021 for NSN with a ground-glass component of more than 50%. Firstly, for each patient, both the macroscopic dimensions of the NSN were assessed on CT and during pathologic analysis. Secondly, the microscopic extension was assessed during pathologic examination. Wilcoxon sign rank tests were used to compare these dimensions. Spearman correlation test and Bland-Altman analysis were used to evaluate the agreement between radiological and pathologic measurements., Results: On CT, the median largest diameter and volume of NSN were 21 mm and 3780 cc, while on pathologic analysis, they were 15 mm and 1800 cc, respectively. Therefore, the largest diameter and volume of the NSN were significantly higher on CT than on pathological analysis. For microscopic extension, the median largest diameter and volume of NSN were 17 mm and 2040 cc, respectively. No significant difference was observed between the macroscopic size and the microscopic extension assessed during pathologic analysis. Moreover, correlation analysis and Bland-Altman plots showed that radiological and pathologic measurements could provide equivalent precision., Conclusion: Our study showed that CT did not underestimate the macroscopic size and microscopic extension of NSN and confirmed that CT can be used for NSN treatment planning., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Accurate segmentation of ground-glass opacity (GGO) is an important premise for doctors to judge COVID-19. Aiming at the problem of mis-segmentation for GGO segmentation methods, especially the problem of adhesive GGO connected with chest wall or blood vessel, this paper proposes an accurate segmentation of GGO based on fuzzy c-means (FCM) clustering and improved random walk algorithm. The innovation of this paper is to construct a Markov random field (MRF) with adaptive spatial information by using the spatial gravity Model and the spatial structural characteristics, which is introduced into the FCM model to automatically balance the insensitivity to noise and preserve the effectiveness of image edge details to improve the clustering accuracy of image. Then, the coordinate values of nodes and seed points in the image are combined with the spatial distance, and the geodesic distance is added to redefine the weight. According to the edge density of the image, the weight of the grayscale and the spatial feature in the weight function is adaptively calculated. In order to reduce the influence of edge noise on GGO segmentation, an adaptive snowfall model is proposed to preprocess the image, which can suppress the noise without losing the edge information. In this paper, CT images of different types of COVID-19 are selected for segmentation experiments, and the experimental results are compared with the traditional segmentation methods and several SOTA methods. The results suggest that the paper method can be used for the auxiliary diagnosis of COVID-19, so as to improve the work efficiency of doctors., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 Elsevier Ltd. All rights reserved.)

Objective: The purpose was to compare the results of the RT-PCR test, with the findings of Chest CT and to determine the features of CT for the diagnosis of COVID-19 and how to approach RT-PCR negative patients., Material Method: Chest CT findings of 569 COVID-19 diagnosed patients, followed up at the pandemic wards between March and June 2020 were retrospectively examined. Patients were grouped according to RT-PCR results, gender, and age., Results: 284 (49%) were RT-PCR(+), 285 (50.8%) were RT-PCR(-) of total 569 patients. 11 (1.9%) of RT-PCR(+) had no involvement in Chest CT while all the RT-PCR(-) patients were CT(+). The distribution of lesions in CT were; 544 (95.6%) bilateral, 553 (97.2%) multilobar, 557(98%) peripherally 151 (26.5%) posteriorly localized. The most common findings were; 539 (94.7%) ground-glass opacity (GGO), 365 (64.1%) consolidation, 160 (28.1%) crazy paving interlobular septal thickening. CO-RADS mean value was 5.4 ± 0.7. GGO and reticulation in RT-PCR(-) patients were 280 (98.2%) and 24 (8.4%); while they were 259 (91.2%) and 12 (4.2%) in RT-PCR(+) patients, were significantly higher (p < 0.05). No significant difference was observed, in CT findings for gender. Only the findings of crazy paving interlobular septal thickening and reticulation in 18-64 age group were significantly higher than that in 65-94 age group, 105 (24.8%)-55 (37.9%), 19 (4.5%)-17 (11.7%) respectively (p < 0.05)., Conclusion: The typical findings of COVID-19 pneumonia in Chest CT are: GGO, consolidation and crazy paving in bilateral, peripheral, posterior localization. CT plays an essential role for diagnosis, isolation and treatment in cases of COVID-19 and RT-PCR negative test should be verified by CT., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Introduction: Because several articles have reported a prognostic association with the radiologic features of ground-glass opacity, we explored whether the histologic presence of a lepidic component had similar significance., Methods: We retrospectively evaluated 380 consecutive surgically resected lung adenocarcinomas (ADCs) of pathologic (p)stage IA. The tumors were classified into lepidic-positive and lepidic-negative ADCs. Clinicopathologic characteristics, radiographic ground-glass opacity status, and disease-free survival were compared between lepidic-positive and lepidic-negative ADCs and between part-solid and solid nodules on computed tomography images., Results: Of the 380 cases, 176 (46.3%) were lepidic-positive ADCs. Of the overall patients with pT1, lepidic-positive ADCs were found to have significantly better recurrence-free survival (5 y, 95.4% versus 87.0%, p = 0.005), but this significance was not reproduced in pT1 subcategories (pT1a, pT1b, and pT1c). Furthermore, the presence of the lepidic component was not an independent prognostic factor in the multivariate analysis (hazard ratio = 0.46 [95% confidence interval: 0.19-1.14], p = 0.09). We also analyzed the extent of the lepidic component with 10% incremental valuables. Although we found that a 10% or greater extent of lepidic component made the recurrence-free survival difference the largest, a clear prognostic impact was not obtained with this cutoff point., Conclusions: Although lepidic-positive ADCs tended to have a favorable outcome, the lepidic component was not a clear independent prognostic factor in pstage I ADC., (Copyright © 2021 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

E-cigarettes are devices that generate an aerosol by heating a fluid containing multiple chemicals, such as nicotine, additives, and flavorings. They were developed to aid in smoking cessation and were promoted as socially acceptable, healthier, cheaper than conventional cigarettes. Multiple lung disorders related to e-cigarette use are reported, and they range from mild cases of pneumonitis to life-threatening lung disorders that may require intubation and mechanical ventilation. Most of the complications are due to the generation of various unknown and potentially harmful chemicals within the aerosol generated in the e-cigarette. These disorders are known collectively as e-cigarette/Vaping-associated lung injury (EVALI). E-cigarettes are marketed as safer alternatives to traditional cigarettes, with the highest rates of use are noted in young smokers. Given the significant prevalence of e-cigarettes use and their pulmonary complications, EVALI should be considered a potential etiology in the broad differential diagnosis of patients with pulmonary disease and a history of vaping. Herein, we present a case of cryptogenic organizing pneumonia with a chest C.T. showing a crazy-paving pattern in a patient with a history of vaping., (Published by Elsevier Inc. on behalf of University of Washington.)

Deep learning based medical image segmentation is an important step within diagnosis, which relies strongly on capturing sufficient spatial context without requiring too complex models that are hard to train with limited labelled data. Training data is in particular scarce for segmenting infection regions of CT images of COVID-19 patients. Attention models help gather contextual information within deep networks and benefit semantic segmentation tasks. The recent criss-cross-attention module aims to approximate global self-attention while remaining memory and time efficient by separating horizontal and vertical self-similarity computations. However, capturing attention from all non-local locations can adversely impact the accuracy of semantic segmentation networks. We propose a new Dynamic Deformable Attention Network (DDANet) that enables a more accurate contextual information computation in a similarly efficient way. Our novel technique is based on a deformable criss-cross attention block that learns both attention coefficients and attention offsets in a continuous way. A deep U-Net (Schlemper et al., 2019) segmentation network that employs this attention mechanism is able to capture attention from pertinent non-local locations and also improves the performance on semantic segmentation tasks compared to criss-cross attention within a U-Net on a challenging COVID-19 lesion segmentation task. Our validation experiments show that the performance gain of the recursively applied dynamic deformable attention blocks comes from their ability to capture dynamic and precise attention context. Our DDANet achieves Dice scores of 73.4% and 61.3% for Ground-glass opacity and consolidation lesions for COVID-19 segmentation and improves the accuracy by 4.9% points compared to a baseline U-Net and 24.4% points compared to current state of art methods (Fan et al., 2020)., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Introduction: Surgical resection with minimally invasive approach is the gold standard for both definitive diagnosis and treatment of solitary pulmonary nodules (SPNs); however, it can be difficult to pinpoint small, deep, or subsolid nodes without palpating lung parenchyma. The primary endpoint of this study is showing that radioguided surgery is a cost-effective strategy to improve the effectiveness of video-thoracoscopic localization/resection of SPNs/ground-glass opacities (GGOs). Secondary endpoints are analyzing the morbidity of this technique and tips and tricks to better manage this method., Methods: SPN smaller than 20 mm and/or with a distance from the visceral pleura ≥5 mm underwent minimally invasive resection after computed tomography-guided injection of a solution composed of 0.1/0.2 mL of 99Tc-labeled human serum albumin microspheres and 0.1 mL of nonionic contrast. In the operating theater, a collimated probe connected to a gamma ray detector allowed localization of the target area., Results: Between 1997 and 2018, a total of 451 patients with SPN/GGO underwent minimally invasive surgery with a radioguided technique at our hospital. The mean SPN diameter was 13 mm (range, 5-20 mm), and the mean distance from the visceral pleura was 15 mm (range, 6-29 mm). The mean time to a localizing nodule was 3 minutes (range, 1-5 minutes). No significant injection-related complications were reported; only 3.3% of patients (15 of 451) developed pneumothorax. Both 30- to 60-day and 90-day mortality were 0%. The rate of postoperative complications was 2.53% (prolonged air leak). The conversion rate to thoracotomy was 1.55% (7 of 451)., Conclusions: Our 20-year experience shows that radioguided thoracoscopic surgery is a safe and feasible strategy to treat suspicious SPN/GGO, with a success rate of 98%., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Introduction: Recent studies have indicated that the presence of ground-glass opacity (GGO) components is associated with favorable survival. The purpose of this study was to reveal the prognostic value of GGO components and differences in prognostic factors for part-solid and solid lesions in invasive stage I NSCLC., Methods: The cases of 2010 patients with completely resected invasive pathological stage I NSCLC were reviewed according to the eighth edition of the TNM classification. Patients were categorized into the pure-GGO, part-solid, and solid groups based on consolidation-to-tumor ratio. Cox multivariate proportional hazard analyses were conducted to identify independent prognostic factors in each group., Results: Of the 2010 patients, 146 (7.3%) were in the pure-GGO group, 732 (36.4%) were in the part-solid group, and 1132 (56.3%) were in the solid group. Cox multivariate analyses revealed that GGO absence was a strong independent risk factor for worse recurrence-free survival (p < 0.001). For the pure-GGO group, there was no recurrence in spite of the invasive stage. For the part-solid group, visceral pleural invasion could not predict recurrence-free survival in general (p = 0.514) or in each tumor size group (for tumors size ≤1 cm, p = 0.664; for tumors size >1 to 2 cm, p = 0.456; for tumors size >2 to 3 cm, p = 0.900; and for tumors size >3 to 4 cm, p = 0.397). For the solid group, adenocarcinoma subtype was not a prognostic factor for recurrence-free survival in general (p = 0.162) or in each tumor size group (for tumors size ≤ 2 cm, p = 0.092; for tumors size >2 to 3 cm, p = 0.330; and for tumors size >3 to 4 cm, p = 0.885)., Conclusions: The presence of GGO components was a strong predictor in patients with invasive pathological stage I NSCLC. Risk factors were distinct in the part-solid and solid groups. There was no prognostic value of visceral pleural invasion in the part-solid group. Adenocarcinoma subtype did not have prognostic value in the solid group., (Copyright © 2019 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

Purpose: The Japan Clinical Oncology Group Study 0201 has proposed radiologic criteria on thin-slice computed tomography to diagnose pathologic less invasive lung adenocarcinoma that could be a candidate for sublobar resection based on the previous tumor, node, metastasis classification system (TNM). The aim of this study was to propose the new radiologic criteria for predicting pathologic less invasive cancer according to the 8th edition TNM., Patients and Methods: We analyzed 744 patients who had peripheral clinical Tis-T1cN0M0 non-small-cell lung cancer of 3 cm or less and underwent complete resection by lobectomy from 2003 to 2011. We defined lung cancer with no nodal involvement and no vessel invasion pathologically as a pathologic less invasive cancer and investigated the radiologic criteria on the basis of the solid component size and by the consolidation-to-tumor (C/T) ratio (calculated with the maximum solid component diameter divided by the maximum tumor diameter) by using preoperative thin-slice computed tomography to predict them with a specificity of 97% or more, and evaluated overall survival., Results: Patients with clinical Tis/T1mi/T1a disease had no pathologic invasive cancer except for one patient (specificity, 99%). From the investigation with the C/T ratio, only the criterion of C/T ratio 0.5 or less met the standard (specificity, 100%). The final specificity after combining these criteria was 99.6%, and they showed excellent prognosis (5-year overall survival rate, 96.2%)., Conclusion: Lung cancer with clinical Tis/T1mi/T1a or a C/T ratio of 0.5 or less can be completely cured by sublobar resection with sufficient margin because of its less invasive nature pathologically., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Purpose: Intraoperative localization and resection of ill-defined pulmonary ground-glass opacities (GGOs) during minimally invasive pulmonary resection is technically challenging. Current preoperative techniques to facilitate localization of GGOs include microcoil and hook wire placement, both of which have logistic limitations, carry safety concerns, and do not help with margin assessment. In this clinical trial, we explored an alternative method involving near-infrared molecular imaging with a folate receptor-targeted agent, OTL38, to improve localization of GGOs and confirmation of resection margins., Methods: In a human trial, 20 subjects with pulmonary GGOs who were eligible for video-assisted thoracoscopic surgery (VATS) resection received 0.025 mg/kg of OTL38 before the resection. The primary objectives were to (1) determine whether use of OTL38 allows safe localization of GGOs and assessment of margins during VATS and (2) determine patient, radiographic, and histopathologic variables that predict the amount of fluorescence during near-infrared imaging., Results: We observed no toxicity. Of the 21 GGOs, 20 accumulated OTL38 and displayed fluorescence upon in situ or back table evaluation. Intraoperatively, near-infrared imaging localized 15 of 21 lesions whereas VATS alone localized 10 of 21 (p = 0.05). The addition of molecular imaging affected care of nine of 21 subjects by improving intraoperative localization (n = 6) and identifying close margins (n = 3). This approach was most effective for subpleural lesions measuring less than 2 cm. For lesions deeper than 1.5 cm from the pleural surface, intraoperative localization using fluorescent feedback was limited., Conclusions: This approach provides a safe alternative for intraoperative localization of small, peripherally located pulmonary lesions. In contrast to alternative localization techniques, use of OTL38 also allows confirmation of adequate margins. Future studies will compare this approach to alternative localization techniques in a clinical trial., (Copyright © 2018 International Association for the Study of Lung Cancer. All rights reserved.)

Introduction: We retrospectively investigated the high-resolution computed tomography features that distinguish benign lesions (BLs) from malignant lesions (MLs) appearing as persistent solitary subsolid nodules (SSNs)., Materials and Methods: In 2015, the data from patients treated in our department with persistent solitary SSNs 5 to 30 mm in size were analyzed retrospectively. The demographic data and HRCT findings were analyzed and compared between those with BLs and MLs., Results: Of the 1934 SSNs, 94 were BLs and 1840 were MLs. One half of the MLs (920 SSNs) were randomly selected and analyzed. The BLs were classified into 2 subgroups: 28 pure ground-glass nodules (pGGNs) and 66 part-solid nodules (PSNs). After matching in each group, 56 pGGNs and 132 PSNs in the ML group were selected. In the pGGN subgroup, multivariate analysis found that a well-defined border (odds ratio [OR], 4.320; 95% confidence interval [CI], 1.534-12.168; P = .006; area under the curve, 0.705; 95% CI, 0.583-0.828; P = .002) and a higher average CT value (OR, 1.007; 95% CI, 1.001-1.013; P = .026; area under the curve, 0.715; 95% CI, 0.599-0.831; P = .001) favored the diagnosis of malignancy. In the PSN subgroup, multivariate analysis revealed that a larger size (OR, 1.084; 95% CI, 1.015-1.158; P = .016), a well-defined border (OR, 3.447; 95% CI, 1.675-7.094; P = .001), and a spiculated margin (OR, 2.735; 95% CI, 1.359-5.504; P = .005) favored the diagnosis of malignancy., Conclusion: In pGGNs, a well-defined lesion border and a larger average CT value can be valuable discriminators to distinguish between MLs and BLs. In PSNs, a larger size, well-defined border, and spiculated margin had greater predictive value for malignancy., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: While lepidic-predominant lung adenocarcinomas are known to have better outcomes than similarly sized solid tumors, the impact of smaller noninvasive foci within predominantly solid tumors is less clearly characterized. We tested the hypothesis that lung adenocarcinomas with even a small ground-glass opacity (GGO) component have a better prognosis than otherwise similar pure solid (PS) adenocarcinomas., Patients and Methods: The maximum total and solid-component diameters were determined by preoperative computed tomography in patients who underwent lobar or sublobar resection of clinical N0 adenocarcinomas without induction therapy between May 2003 and August 2013. Survival between patients with PS tumors (0% GGO) or tumors with a minor ground-glass (MGG) component (1%-25% GGO) was compared by Kaplan-Meier and Cox analyses., Results: A total of 123 patients met the inclusion criteria, comprising 54 PS (44%) and 69 MGG (56%) whose mean ground-glass component was 18 ± 7%. The solid component tumor diameter was not significantly different between the groups (2.3 ± 1.2 cm vs. 2.5 ± 1.3 cm, P = .2). Upstaging to pN1-2 was more common for the PS group (13% [7/54] vs. 3% [2/69], P = .04), but the distribution of pathologic stage was not significantly different between the groups (PS 76% stage I [41/54] vs. MGG 80% stage I [55/69], P = .1). Having a MGG component was associated with markedly better survival in both univariate analysis (MGG 5-year overall survival 86.7% vs. PS 64.5%, P = .001) and multivariable survival analysis (hazard ratio, 0.30, P = .01)., Conclusion: Patients with resected cN0 lung adenocarcinoma who have even a small GGO component have markedly better survival than patients with PS tumors, which may have implications for both treatment and surveillance strategies., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Everolimus (ERL), a mammalian target of rapamycin (mTOR) inhibitor, has been used for the management of several advanced cancers. ERL frequently causes lung injury, although the clinical and radiographic features have not been clarified. The aim of this study was to assess the clinical features of ERL-induced lung injury and determine the associated risk factors., Methods: This single-center, retrospective study included 45 patients (29 men, 16 women; age, 12-78 years) who had received ERL at our hospital between August 2010 and March 2016. Drug-induced lung injury (DILI) was diagnosed using the Japanese Respiratory Society criteria. We obtained information regarding the clinical course, symptoms, clinical findings, blood test findings, and chest computed tomography findings from the patients' medical records. Risk factors for DILI onset were investigated using the Wilcoxon rank sum test., Results: Fifteen patients (33%) were diagnosed with DILI. The median time from ERL administration to DILI onset was 64 days. High Serum Krebs von den Lungen-6 (KL-6) levels and a low estimated glomerular filtration rate (eGFR) before ERL administration were found to be significant risk factors for DILI. KL-6 and lactate dehydrogenase (LDH) were significantly elevated at the onset of DILI. All 15 patients recovered; 11 were without steroids., Conclusions: Our results suggest that patients with high KL-6 levels and a low eGFR at baseline are at increased risk of ERL-induced lung injury. In addition, KL-6 and LDH may be useful biomarkers of ERL-induced lung injury., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Introduction: Osimertinib is an EGFR inhibitor licensed for the treatment of EGFR-mutant, T790M-positive NSCLC. Previously unreported, frequent transient asymptomatic pulmonary opacities were noted in patients during osimertinib therapy at the University of Colorado., Methods: Computed tomography imaging and clinical notes on patients with NSCLC who had been treated with osimertinib at the University of Colorado were retrospectively reviewed., Results: Transient asymptomatic pulmonary opacities developed in seven of 20 patients (35%) while they were receiving osimertinib. The radiological patterns seen included ground-glass opacities with or without nodular consolidation. The median time to development of the first lesion was 8.7 weeks (range 1.6-43 weeks), the median time to resolution during continued osimertinib was 6 weeks (range 1-11 weeks)., Conclusions: Transient asymptomatic pulmonary opacities may be a previously unrecognized, benign feature associated with osimertinib therapy that may be mistaken for isolated pulmonary progression or the beginning of more severe pneumonitis. If new-onset pulmonary lesions, especially those associated with ground-glass appearances, are asymptomatic and localized and there is no evidence of disease progression elsewhere, it may be reasonable to continue treatment with osimertinib and monitor the lesions for resolution., (Copyright © 2016 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

Background: Pulmonary ground-glass nodules (GGNs) include both malignant and benign lesions. Some GGNs become larger, whereas others remain unchanged for years. We have previously reported that smoking history and large diameters are predictors for growth. However, the genetic differences among GGNs remain unclear., Patients and Methods: GGNs with ground-glass component of ≥50% on a thin-section computed tomography scan that were resected between 2012 and 2014 were evaluated for clinicopathological features and the presence of EGFR/KRAS/ALK/HER2 mutations. 'Incidence of 2-mm growth' and 'Time to 2-mm growth' were analyzed according to the mutational status., Results: Among 104 GGNs in 96 patients, this study included 3 atypical adenomatous hyperplasia (AAH), 19 adenocarcinoma in situ (AIS), 27 minimally invasive adenocarcinoma (MIA), and 55 invasive adenocarcinoma (IA). Among the 71 lesions evaluable for growth, 30 GGNs exhibited growth and 5 lesions remained unchanged for ≥2 years before surgery was carried out. We identified mutations or rearrangements in 75% of GGNs (78/104). EGFR mutations were noted in 64% of samples, KRAS in 4%, ALK in 3%, and HER2 in 4%. The remaining 26 quadruple-negative tumors were significantly associated with AAH/AIS (P < 0.01) and no-growth (P < 0.01) compared with driver mutation-positive tumors, whereas EGFR mutation-positive tumors were correlated with MIA/IA (P < 0.01) and growth (P < 0.01) compared with EGFR-negative tumors., Conclusions: Three fourths of resected GGNs were positive for EGFR, KRAS, ALK, or HER2 mutations. Quadruple-negative tumors were associated with a lack of GGN growth, whereas EGFR mutation-positive tumors displayed a correlation with growth., (© The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: This multicenter study aimed to validate the ability of (18)F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) plus high-resolution computed tomography (HR-CT) to predict the malignant behavior and prognosis of early adenocarcinomas of the lung., Methods: We calculated maximum standardized uptake values (maxSUV) from PET/CT images and ground-glass opacity (GGO) ratios on HR-CT images before complete surgical intervention in 610 patients with clinical stage IA lung adenocarcinoma. Pathologic invasiveness and survival were compared with clinical factors and radiographic findings including the maxSUV, which was revised to correct for interinstitutional discrepancies that confer limitations upon multicenter PET studies., Results: Analyses of receiver-operating characteristic curves revealed optimal maxSUV and GGO ratio cutoffs to predict recurrence of 2.9 and 25%, respectively. Both the maxSUV and GGO ratio reflected tumor invasiveness, nodal metastasis, recurrence, and patient survivals, and were significant prognostic factors for recurrence-free and cancer-specific survivals on multivariate Cox analysis (all, p < 0.001). The combination of maxSUV and GGO ratio is a better predictor of malignant tumor grade than either alone., Conclusions: The combination of maxSUV and GGO ratio as well as each alone are important predictors of prognosis in patients with clinical stage IA adenocarcinoma of the lung and should be considered before selecting therapeutic strategies., (Copyright © 2013 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)