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Purpose: To prospectively evaluate whether Lung-RADS classification and volumetric nodule assessment were feasible with ultralow-dose (ULD) chest CT scans with deep learning image reconstruction (DLIR)., Methods: The institutional review board approved this prospective study. This study included 40 patients (mean age, 66±12 years; 21 women). Participants sequentially underwent LDCT and ULDCT (CTDIvol, 0.96±0.15 mGy and 0.12±0.01 mGy) scans reconstructed with the adaptive statistical iterative reconstruction-V 50% (ASIR-V50) and DLIR. CT image quality was compared subjectively and objectively. The pulmonary nodules were assessed visually by two readers using the Lung-RADS 1.1 and automatically using a computerized assisted tool., Results: DLIR provided a significantly higher signal-to-noise ratio for LDCT and ULDCT images than ASIR-V50 (all P < .001). In general, DLIR showed superior subjective image quality for ULDCT images (P < .001) and comparable quality for LDCT images compared to ASIR-V50 (P = .01-1). The per-nodule sensitivities of observers for Lung-RADS category 3-4 nodules were 70.6-88.2% and 64.7-82.4% for DLIR-LDCT and DLIR-ULDCT images (P = 1) and categories were mostly concordant within observers. The per-nodule sensitivities of the computer-assisted detection for nodules ≥4 mm were 72.1% and 67.4% on DLIR-LDCT and ULDCT images (P = .50). The 95% limits of agreement for nodule volume differences between DLIR-LDCT and ULDCT images (-85.6 to 78.7 mm3) was similar to the within-scan nodule volume differences between DLIR- and ASIR-V50-LDCT images (-63.9 to 78.5 mm3), with volume differences smaller than 25% in 88.5% and 92.3% of nodules, respectively (P = .65)., Conclusion: DLIR enabled comparable Lung-RADS and volumetric nodule assessments on ULDCT images to LDCT images., Competing Interests: This work was supported by GE Healthcare (Grant number: 06-2020-0300). There are no patents, products in development, or marketed products associated with this research to declare. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2024 Yoo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

BACKGROUND. Changes in lung parenchyma elasticity in usual interstitial pneumonia (UIP) may increase the risk for complications after percutaneous transthoracic needle biopsy (PTNB) of the lung. OBJECTIVE. The purpose of this article was to investigate the association of UIP findings on CT with complications after PTNB, including pneumothorax, pneumothorax requiring chest tube insertion, and hemoptysis. METHODS. This retrospective single-center study included 4187 patients (mean age, 63.8 ± 11.9 [SD] years; 2513 men, 1674 women) who underwent PTNB between January 2010 and December 2015. Patients were categorized into a UIP group and non-UIP group by review of preprocedural CT. In the UIP group, procedural CT images were reviewed to assess for traversal of UIP findings by needle. Multivariable logistic regression analyses were performed to identify associations between the UIP group and needle traversal with postbiopsy complications, controlling for a range of patient, lesion, and procedural characteristics. RESULTS. The UIP and non-UIP groups included 148 and 4039 patients, respectively; in the UIP group, traversal of UIP findings by needle was observed in 53 patients and not observed in 95 patients. The UIP group, in comparison with the non-UIP group, had a higher frequency of pneumothorax (35.1% vs 17.9%, p < .001) and pneumothorax requiring chest tube placement (6.1% vs 1.5%, p = .001) and lower frequency of hemoptysis (2.0% vs 6.1%, p = .03). In multivariable analyses, the UIP group with traversal of UIP findings by needle, relative to the non-UIP group, showed independent associations with pneumothorax (OR, 5.25; 95% CI, 2.94-9.37; p < .001) and pneumothorax requiring chest tube placement (OR, 9.55; 95% CI, 3.74-24.38; p < .001). The UIP group without traversal of UIP findings by needle, relative to the non-UIP group, was not independently associated with pneumothorax (OR, 1.18; 95% CI, 0.71-1.97; p = .51) or pneumothorax requiring chest tube placement (OR, 1.08; 95% CI, 0.25-4.72; p = .92). The UIP group, with or without traversal of UIP findings by needle, was not independently associated with hemoptysis. No patient experienced air embolism or procedure-related death. CONCLUSION. Needle traversal of UIP findings is a risk factor for pneumothorax and pneumothorax requiring chest tube placement after PTNB. CLINICAL IMPACT. When performing PTNB in patients with UIP, radiologists should plan a needle trajectory that does not traverse UIP findings, when possible.

Shared decision-making is imperative for patient-and family-centered care. However, gathering individuals in a single place was challenged by modern life and pandemic restrictions. This study conducted a 1:1 randomized trial to examine the feasibility of a CT-derived 3D virtual explanation module for lung cancer to improve the understanding of patients and third parties in physically separate locations. We prospectively enrolled adults in whom elective surgical resection for lung cancer was planned at a single tertiary hospital in 2020. From presurgical CT scans, deep neural networks automatically segmented lung cancer, airway, pulmonary lobes, skin, and bony thorax. The segmented structures were subsequently transformed into an anonymized interactive 3D module which comprised a standardized scenario with explanatory texts. The intervention group received a link to the module on their smartphone before admission and could repeatedly access the link or transfer it to patients' third parties. A total of 33 and 29 patients were enrolled in the intervention and control arms. The understanding score did not statistically differ between the arms (mean difference, 0.7 [95% CI: -0.2, 1.5]; p = 0.13). However, 76% of patients in the intervention arm accessed the link, and patient median access count was 14. The link recipients of third parties had comparable understanding scores to the patients (mean difference, -0.2 [95% CI: -1.9, 1.5]; p = 1.00), indicating that the understanding could be shared remotely with patients and patients' third parties. In conclusion, it was feasible that people physically separated from patients obtained a comparable understanding of lung cancer surgery using the patient's CT-derived 3D virtual explanation module., (© 2022 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

Objectives: A recent meta-analysis of individual patient data revealed that preoperative percutaneous transthoracic needle lung biopsy (PTNB) was associated with an increased risk of ipsilateral pleural recurrence in stage I lung cancer. This study aimed to examine whether particular PTNB techniques reduced the risk of pleural recurrence., Methods: We retrospectively included 415 consecutive patients with stage I lung cancer who underwent preoperative PTNB and curative resection from 2009 through 2016. Detailed information was collected, including clinical, PTNB technique, radiologic, and pathologic characteristics of lung cancer. Cox regression analyses were performed to identify risk factors for pleural recurrence before and after propensity score matching., Results: The overall follow-up period after PTNB was 62.1 ± 23.0 months, and ipsilateral pleural recurrence occurred in 40 patients. Before propensity score matching, age (p = 0.063), microscopic pleural invasion (p = 0.065), and pathologic tumor size (p = 0.016) tended to be associated with pleural recurrence in univariate analyses and subsequently were matched using a propensity score. After propensity score matching, multivariate analysis revealed that ipsilateral pleural recurrence was associated with a larger target size on computed tomography (hazard ratio [HR] = 1.498; 95% CI, 1.506-2.125; p = 0.023) and microscopic lymphatic invasion (HR = 3.526; 95% CI, 1.491-8.341; p = 0.004). However, no PTNB techniques such as needle gauge, biopsy, or pleural passage numbers were associated with a reduced risk of recurrence., Conclusions: No particular PTNB techniques were associated with reduced pleural seeding after PTNB in stage I lung cancer. Regardless of the technique, PTNB needs to be cautiously applied when early lung cancer is suspected, followed by curative treatment., Key Points: • Age, microscopic pleural invasion, and pathologic tumor size tended to be associated with pleural recurrence in stage I lung cancer before propensity matching. • After propensity matching, pre-biopsy CT target size and microscopic lymphatic invasion were associated with pleural recurrence. • No particular PTNB techniques were associated with reduced pleural seeding in stage I lung cancer before and after propensity matching., (© 2021. The Author(s), under exclusive licence to European Society of Radiology.)

Background Body mass index (BMI) and sarcopenia status are well-established prognostic factors in patients with lung cancer. However, the relationship between the amount of adipose tissue and survival remains unclear. Purpose To investigate the association between baseline adipopenia and outcomes in patients with early-stage non-small cell lung cancer (NSCLC). Materials and Methods Consecutive patients who underwent surgical resection for stage I NSCLC between 2011 and 2015 at a single tertiary care center were retrospectively identified. The primary outcome was the 5-year overall survival (OS) rate, and secondary outcomes were the 5-year disease-free survival (DFS) rate and the major postoperative complication rate. The abdominal total fat volume at the waist and the skeletal muscle area at the L3 level were obtained from preoperative PET/CT data and were normalized by the height squared to calculate the fat volume index (FVI) and skeletal muscle index. Adipopenia was defined as the sex-specific lowest quartile of the FVI for the study sample, and sarcopenia was determined using the skeletal muscle index reference value (men, <55 cm 2 /m 2 ; women, <39 cm 2 /m 2 ). The association between body composition and outcomes was evaluated using Cox regression analysis. Results A total of 440 patients (median age, 65 years [interquartile range, 58-72 years]; 243 men) were evaluated. Most underweight patients (<20 kg/m 2 ) had adipopenia (97%, 36 of 37 patients), but overweight patients (25-30 kg/m 2 , n = 138) and obese patients (>30 kg/m 2 , n = 14) did not have adipopenia (3%, four of 152 patients). In the group with a normal BMI (20-25 kg/m 2 ), 28% (70 of 251 patients) had adipopenia and 67% (168 of 251 patients) had sarcopenia. After adjusting for age, sex, smoking history, surgical procedure, stage, histologic type, BMI, and sarcopenia, adipopenia was associated with reduced 5-year OS (hazard ratio [HR] = 2.2; 95% CI: 1.1, 3.8; P = .02) and 5-year non-cancer-specific OS rates (HR = 3.2; 95% CI: 1.2, 8.7; P = .02). There was no association between adipopenia and postoperative complications ( P = .45) or between adipopenia and the 5-year DFS rate ( P = .18). Conclusion Baseline adipopenia was associated with a reduced 5-year overall survival rate in patients with early-stage non-small cell lung cancer and may indicate risk for non-cancer-related death. © RSNA, 2021 Online supplemental material is available for this article.

Objective: We conducted a systematic review and meta-analysis of the tissue adequacy and complication rates of percutaneous transthoracic needle biopsy (PTNB) for molecular analysis in patients with non-small cell lung cancer (NSCLC)., Materials and Methods: We performed a literature search of the OVID-MEDLINE and Embase databases to identify original studies on the tissue adequacy and complication rates of PTNB for molecular analysis in patients with NSCLC published between January 2005 and January 2020. Inverse variance and random-effects models were used to evaluate and acquire meta-analytic estimates of the outcomes. To explore heterogeneity across the studies, univariable and multivariable meta-regression analyses were performed., Results: A total of 21 studies with 2232 biopsies (initial biopsy, 8 studies; rebiopsy after therapy, 13 studies) were included. The pooled rates of tissue adequacy and complications were 89.3% (95% confidence interval [CI]: 85.6%-92.6%; I² = 0.81) and 17.3% (95% CI: 12.1%-23.1%; I² = 0.89), respectively. These rates were 93.5% and 22.2% for the initial biopsies and 86.2% and 16.8% for the rebiopsies, respectively. Severe complications, including pneumothorax requiring chest tube placement and massive hemoptysis, occurred in 0.7% of the cases (95% CI: 0%-2.2%; I² = 0.67). Multivariable meta-regression analysis showed that the tissue adequacy rate was not significantly lower in studies on rebiopsies ( p = 0.058). The complication rate was significantly higher in studies that preferentially included older adults ( p = 0.001)., Conclusion: PTNB demonstrated an average tissue adequacy rate of 89.3% for molecular analysis in patients with NSCLC, with a complication rate of 17.3%. PTNB is a generally safe and effective diagnostic procedure for obtaining tissue samples for molecular analysis in NSCLC. Rebiopsy may be performed actively with an acceptable risk of complications if clinically required., Competing Interests: Soon Ho Yoon works as a chief medical officer in MEDICALIP since Nov 2020, outside this work. Other authors report no conflicts of interest relevant to this article., (Copyright © 2021 The Korean Society of Radiology.)

Objective: To investigate the diagnostic accuracy and complications of cone-beam CT-guided percutaneous transthoracic needle biopsy (PTNB) of juxtaphrenic lesions and identify the risk factors for diagnostic failure and complications., Materials and Methods: In total, 336 PTNB procedures for lung lesions (mean size ± standard deviation [SD], 4.3 ± 2.3 cm) abutting the diaphragm in 326 patients (189 male and 137 female; mean age ± SD, 65.2 ± 11.4 years) performed between January 2010 and December 2014 were included. The accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the PTNB procedures for the diagnosis of malignancy were measured based on the intention-to-diagnose principle. The risk factors for diagnostic failures and complications were evaluated using logistic regression analysis., Results: The accuracy, sensitivity, specificity, PPV, and NPV were 92.7% (293/316), 91.3% (219/240), 91.4% (74/81), 96.9% (219/226), and 77.9% (74/95), respectively. There were 23 diagnostic failures (7.3%), and lesion sizes ≤ 2 cm ( p = 0.045) were the only significant risk factors for diagnostic failure. Complications occurred in 98 cases (29.2%), including 89 cases of pneumothorax (26.5%) and 7 cases of hemoptysis (2.1%). The multivariable analysis showed that old age (> 65 years) ( p = 0.002), lesion size of ≤ 2 cm ( p = 0.003), emphysema ( p = 0.006), and distance from the pleura to the target lesion (> 2 cm) ( p = 0.010) were significant risk factors for complications., Conclusion: The diagnostic accuracy of cone-beam CT-guided PTNB of juxtaphrenic lesions for malignancy was fairly high, and the target lesion size was the only significant predictor of diagnostic failure. Complications of cone-beam CT-guided PTNB of juxtaphrenic lesions occurred at a reasonable rate., Competing Interests: The authors have no potential conflicts of interest to disclose., (Copyright © 2021 The Korean Society of Radiology.)

Introduction: Conflicting results exist regarding whether preoperative transthoracic biopsy increases the risk of pleural recurrence in early lung cancer. We conducted a systematic, patient-level meta-analysis to evaluate the risk of pleural recurrence in stage I lung cancer after percutaneous transthoracic lung biopsy., Methods: A systematic search of OVID-MEDLINE, Embase and the Cochrane Database of Systematic Reviews was performed through October 2018. Eligible studies were original articles on the risk of pleural recurrence in stage I lung cancer after transthoracic biopsy. We contacted the corresponding authors of eligible studies to obtain individual patient-level data. We used the Fine-Gray model for time to recurrence and lung cancer-specific survival and a Cox proportional hazards model for overall survival., Results: We analysed 2394 individual patient data from 6 out of 10 eligible studies. Compared with other diagnostic procedures, transthoracic biopsy was associated with a higher risk for ipsilateral pleural recurrence, which manifested solely (subdistribution HR (sHR), 2.58; 95% CI 1.15 to 5.78) and concomitantly with other metastases (sHR 1.99; 95% CI 1.14 to 3.48). In the analysis of secondary outcomes considering a significant interaction between diagnostic procedures and age groups, reductions of time to recurrence (sHR, 2.01; 95% CI 1.11 to 3.64), lung cancer-specific survival (sHR 2.53; 95% CI 1.06 to 6.05) and overall survival (HR 2.08; 95% CI 1.12 to 3.87) were observed in patients younger than 55 years, whereas such associations were not observed in other age groups., Discussion: Preoperative transthoracic lung biopsy was associated with increased pleural recurrence in stage I lung cancer and reduced survival in patients younger than 55 years., Competing Interests: Competing interests: SHY works a chief medical officer in MEDICALIP since November 2020 outside this work. CMP received a research grant from Lunit outside this work., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: To evaluate the degree of variability in computer-assisted interpretation of low-dose chest CTs (LDCTs) among radiologists in a nationwide lung cancer screening (LCS) program, through comparison with a retrospective interpretation from a central laboratory., Materials and Methods: Consecutive baseline LDCTs (n = 3353) from a nationwide LCS program were investigated. In the institutional reading, 20 radiologists in 14 institutions interpreted LDCTs using computer-aided detection and semi-automated segmentation systems for lung nodules. In the retrospective central review, a single radiologist re-interpreted all LDCTs using the same system, recording any non-calcified nodules ≥ 3 mm without arbitrary rejection of semi-automated segmentation to minimize the intervention of radiologist's discretion. Positive results (requiring additional follow-up LDCTs or diagnostic procedures) were initially classified by the lung CT screening reporting and data system (Lung-RADS) during the interpretation, while the classifications based on the volumetric criteria from the Dutch-Belgian lung cancer screening trial (NELSON) were retrospectively applied. Variabilities in positive rates were assessed with coefficients of variation (CVs)., Results: In the institutional reading, positive rates by the Lung-RADS ranged from 7.5 to 43.3%, and those by the NELSON ranged from 11.4 to 45.0% across radiologists. The central review exhibited higher positive rates by Lung-RADS (20.0% vs. 27.3%; p < .001) and the NELSON (23.1% vs. 37.0%; p < .001), and lower inter-institution variability (CV, 0.30 vs. 0.12, p = .003 by Lung-RADS; CV, 0.25 vs. 0.12, p = .014 by the NELSON) compared to the institutional reading., Conclusion: Considerable inter-institution variability in the interpretation of LCS results is caused by different usage of the computer-assisted system., Key Points: • Considerable variability existed in the interpretation of screening LDCT among radiologists partly from the different usage of the computerized system. • A retrospective reading of low-dose chest CTs in the central laboratory resulted in reduced variability but an increased positive rate.

Objective: This study aimed to evaluate the tumor doubling time of invasive lung adenocarcinoma according to the International Association of the Study for Lung Cancer (IASLC)/American Thoracic Society (ATS)/European Respiratory Society (ERS) histologic classification., Materials and Methods: Among the 2905 patients with surgically resected lung adenocarcinoma, we retrospectively included 172 patients (mean age, 65.6 ± 9.0 years) who had paired thin-section non-contrast chest computed tomography (CT) scans at least 84 days apart with the same CT parameters, along with 10 patients with squamous cell carcinoma (mean age, 70.9 ± 7.4 years) for comparison. Three-dimensional semiautomatic segmentation of nodules was performed to calculate the volume doubling time (VDT), mass doubling time (MDT), and specific growth rate (SGR) of volume and mass. Multivariate linear regression, one-way analysis of variance, and receiver operating characteristic curve analyses were performed., Results: The median VDT and MDT of lung cancers were as follows: acinar, 603.2 and 639.5 days; lepidic, 1140.6 and 970.1 days; solid/micropapillary, 232.7 and 221.8 days; papillary, 599.0 and 624.3 days; invasive mucinous, 440.7 and 438.2 days; and squamous cell carcinoma, 149.1 and 146.1 days, respectively. The adjusted SGR of volume and mass of the solid-/micropapillary-predominant subtypes were significantly shorter than those of the acinar-, lepidic-, and papillary-predominant subtypes. The histologic subtype was independently associated with tumor doubling time. A VDT of 465.2 days and an MDT of 437.5 days yielded areas under the curve of 0.791 and 0.795, respectively, for distinguishing solid-/micropapillary-predominant subtypes from other subtypes of lung adenocarcinoma., Conclusion: The tumor doubling time of invasive lung adenocarcinoma differed according to the IASCL/ATS/ERS histologic classification., Competing Interests: The authors have no potential conflicts of interest to disclose., (Copyright © 2021 The Korean Society of Radiology.)

Percutaneous transthoracic needle biopsy (PTNB) is one of the essential diagnostic procedures for pulmonary lesions. Its role is increasing in the era of CT screening for lung cancer and precision medicine. The Korean Society of Thoracic Radiology developed the first evidence-based clinical guideline for PTNB in Korea by adapting pre-existing guidelines. The guideline provides 39 recommendations for the following four main domains of 12 key questions: the indications for PTNB, pre-procedural evaluation, procedural technique of PTNB and its accuracy, and management of post-biopsy complications. We hope that these recommendations can improve the diagnostic accuracy and safety of PTNB in clinical practice and promote standardization of the procedure nationwide., Competing Interests: The authors have no potential conflicts of interest to disclose., (Copyright © 2021 The Korean Society of Radiology.)

Objectives: We aimed to compare the CT interpretation before and after the implementation of a computerized system for lung nodule detection and measurements in a nationwide lung cancer screening program., Methods: Our screening program started in April 2017, with 14 participating institutions. Initially, all CTs were interpreted using interpretation systems in each institution and manual nodule measurement (conventional system). A cloud-based CT interpretation system, equipped with semi-automated measurement and CAD (computer-aided detection) for lung nodules (cloud-based system), was implemented during the project. Positive rates and performances for lung cancer diagnosis based on the Lung-RADS version 1.0 were compared between the conventional and cloud-based systems., Results: A total of 1821 (M:F = 1782:39, mean age 62.7 years, 16 confirmed lung cancers) and 4666 participants (M:F = 4560:106, mean age 62.8 years, 31 confirmed lung cancers) were included in the conventional and cloud-based systems, respectively. Significantly more nodules were detected in the cloud-based system (0.76 vs. 1.07 nodule/participant, p < .001). Positive rate did not differ significantly between the two systems (9.9% vs. 11.0%, p = .211), while their variability across institutions was significantly lower in the cloud-based system (coefficients of variability, 0.519 vs. 0.311, p = .018). The Lung-RADS-based sensitivity (93.8% vs. 93.5%, p = .979) and specificity (90.9% vs. 89.6%, p = .132) did not differ significantly between the two systems., Conclusion: Implementation of CAD and semi-automated measurement for lung nodules in a nationwide lung cancer screening program resulted in increased number of detected nodules and reduced variability in positive rates across institutions., Key Points: • Computer-aided CT reading detected more lung nodules than radiologists alone in lung cancer screening. • Positive rate in lung cancer screening did not change with computer-aided reading. • Computer-aided CT reading reduced inter-institutional variability in lung cancer screening.

The global coronavirus disease 2019 pandemic continues to escalate at a rapid pace inundating medical facilities and creating substantial challenges globally. The risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in patients with cancer seems to be higher, especially as they are more likely to present with an immunocompromised condition, either from cancer itself or from the treatments they receive. A major consideration in the delivery of cancer care during the pandemic is to balance the risk of patient exposure and infection with the need to provide effective cancer treatment. Many aspects of the SARS-CoV-2 infection currently remain poorly characterized and even less is known about the course of infection in the context of a patient with cancer. As SARS-CoV-2 is highly contagious, the risk of infection directly affects the cancer patient being treated, other cancer patients in close proximity, and health care providers. Infection at any level for patients or providers can cause considerable disruption to even the most effective treatment plans. Lung cancer patients, especially those with reduced lung function and cardiopulmonary comorbidities are more likely to have increased risk and mortality from coronavirus disease 2019 as one of its common manifestations is as an acute respiratory illness. The purpose of this manuscript is to present a practical multidisciplinary and international overview to assist in treatment for lung cancer patients during this pandemic, with the caveat that evidence is lacking in many areas. It is expected that firmer recommendations can be developed as more evidence becomes available., (Copyright © 2020 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

Purpose: To perform a systematic review and meta-analysis evaluating usefulness of high-risk CT features (HRFs) on follow-up CT in detecting local recurrence after stereotactic body radiation therapy (SBRT) in lung cancer patients., Methods: Pubmed and EMBASE were searched up to January 11th, 2019. We included studies that differentiated local recurrence from post-SBRT changes after SBRT on follow-up CT in lung cancer patients. Methodological quality was assessed using QUADAS-2. The association between HRFs and local recurrence were pooled in the form of odds ratio (OR) using the random effects model. Heterogeneity was examined by the Inconsistency index (I 2 )., Results: Eight studies were included, consisting of 356 lung cancer patients. The overall prevalence of patients with local recurrence was 18.8 % (67/356). Compared with post-SBRT changes, local recurrence after SBRT more frequently demonstrated air-bronchogram disappearance (OR = 7.15), bulging margin (OR = 24.12), craniocaudal growth (OR = 26.07), enlargement after 12 months (OR = 28.11), enlarging opacity (OR = 7.92), linear margin disappearance (OR = 29.24), and sequential enlargement (OR = 83.23) (p ≤ 0.02). Pleural effusion appearance was not related with local recurrence (p = 0.82). Heterogeneity varied among HRFs (I 2  = 0-91 %). The quality of the studies was considered moderate., Conclusions: Several HRFs on follow-up CT after SBRT were useful in suggesting local recurrence. These HRFs may help raise clinical suspicion of local recurrence, initiate prompt additional test for confirmation and perform subsequent proper personalized salvage treatment., Competing Interests: Declaration of Competing Interest Otherwise, all authors of this manuscript declare no relationships with any companies, whose products or services may be related to the subject matter of the article., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Introduction: Differentiating between multiple primary lung cancer (MPLC) and intrapulmonary metastasis (IPM) is critical for developing a therapeutic strategy to treat multiple lung cancers with multiple pulmonary sites of involvement., Methods: We retrospectively included 252 lesions (126 pairs) from 126 patients with surgically resected multiple lung adenocarcinomas. Each pair was classified as MPLC or IPM based on histopathologic findings as the reference standard. A novel algorithm was established with four sequential decision steps based on the combination of computed tomography (CT) lesion types (step 1), CT lesion morphology (step 2), difference of maximal standardized uptake values on positron-emission tomography/CT (step 3), and presence of N2/3 lymph node metastasis or distant metastasis (step 4). The diagnostic accuracy of the algorithm was analyzed. Performances of 11 observers were assessed without and with knowledge of algorithm., Results: Among 126 pairs, 90 (71.4%) were classified as MPLCs and 36 (28.6%) as IPMs. On applying the diagnostic algorithm, the overall accuracy for diagnosis of IPM among conclusive cases up to step 4 was 88.9%, and 65 and 44 pairs were correctly diagnosed based on step 1 and step 2, respectively. Specificity and positive predictive value for diagnosis of IPM increased significantly in all observers compared with reading rounds without the algorithm., Conclusions: Application of the algorithm based on comprehensive information on clinical and imaging variables can allow differentiation between MPLCs and IPMs. When both of two suspected malignant lesions appear as solid predominant lesions without spiculation or air-bronchogram on CT, IPM should be considered., (Copyright © 2019 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

OBJECTIVE. The purpose of this study was to perform a systematic review and meta-analysis regarding CT features of non-small cell lung cancer (NSCLC) with anaplastic lymphoma kinase (ALK) rearrangement. MATERIALS AND METHODS. The PubMed and Embase databases were searched up to February 20, 2019. Studies that evaluated CT features of NSCLC with and without ALK rearrangement was included. Methodologic quality was assessed using Quality Assessment of Diagnostic Accuracy Studies-2. The association between CT features and ALK rearrangement was pooled in the form of the odds ratio (OR) or the mean difference (MD) using the random-effects model. Heterogeneity was examined using the inconsistency index ( I 2 ). Publication bias was examined using funnel plots and Egger tests. RESULTS. Sixteen studies were included, consisting of 3113 patients with NSCLC. The overall prevalence of patients with ALK rearrangement was 17% (528/3113). Compared with NSCLC without ALK rearrangement, on CT images those with ALK rearrangement were more frequently solid (OR = 2.86), central in location (OR = 2.72), and 3 cm or smaller (OR = 0.57); had lower contrast-enhanced CT attenuation (MD = -4.79 HU); more frequently had N2 or N3 disease (OR = 5.63), lymphangitic carcinomatosis (OR = 3.46), pleural effusion (OR = 1.91), or pleural metastasis (OR = 1.81); and less frequently had lung metastasis (OR = 0.66). Heterogeneity varied among CT features ( I 2 = 0-80%). No significant publication bias was seen ( p = 0.15). CONCLUSION. NSCLC with ALK rearrangement had several distinctive CT features compared with that without ALK rearrangement. These CT biomarkers may help identify patients likely to have ALK rearrangement.

OBJECTIVE. The purpose of this study was to investigate the CT features predictive of resectability in sleeve lobectomy (SL) for patients with non-small cell lung cancers (NSCLCs) and the outcomes of this procedure. MATERIALS AND METHODS. The study included 45 patients with NSCLCs who planned to undergo SL as a first-line surgical option and underwent SL or pneumonectomy between February 2014 and July 2017. The patients were dichotomized according to whether SL was achieved without residual disease. ROC curve and logistic regression analyses were performed to identify CT features predictive of resectability in SL without residual disease. For outcome analysis, postoperative complications and survival were compared between the two patient groups. RESULTS. SL was successfully performed in 25 patients (55.6%), whereas eight patients underwent SL but had a positive resection margin and 12 required pneumonectomy. The AUC value of the tumor-involved length of the salvage bronchus for SL without residual disease was 0.802, with 5 mm considered the optimal cutoff for this tumor-involved length. A tumor-involved length of 5 mm or less for the salvage bronchus representing the distal anastomosis end in SL was the sole significant predictor for resectability in SL without residual disease in logistic regression analysis (odds ratio, 16.0; 95% CI, 3.7-69.6; p < 0.001). The group of patients who underwent SL without residual disease tended to have a more favorable survival outcome than patients who underwent SL but had residual disease or those who underwent pneumonectomy ( p = 0.110), but postoperative complication rates were similar between the two patient groups (20.0% vs 25.0%, respectively). CONCLUSION. A tumor-involved salvage bronchus length of 5 mm or less was a CT feature predictive of resectability in SL without residual disease, which may improve the survival of patients with NSCLCs.

Non-diagnostic results can affect the diagnostic performance of percutaneous transthoracic needle biopsy (PTNB) but have not been critically meta-analyzed yet. To meta-analyze the incidence and malignancy rate of non-diagnostic results, 3-by-2 table approaches rather than the conventional 2-by-2 approaches are needed to know its impact on the diagnostic performance of PTNB. A systematic literature search identified studies evaluating the diagnostic performance of PTNB with extractable outcomes. A total of 143 studies with 35,059 biopsies were included. The pooled incidence of non-diagnostic results was 6.8% (95% CI, 6.0-7.6%; I 2  = 0.91). The pooled malignancy rate of non-diagnostic results was 59.3% (95% CI, 51.7-66.8%; I 2  = 0.80), and was correlated with the prevalence of malignancy (correlation coefficient, 0.66; 95% CI, 0.42-0.91). Pooled percentage decrease of sensitivity and specificity due to non-diagnostic results were 4.5% (95% CI, 3.2-5.7%; I 2  = 0.64) and 10.7% (95% CI, 7.7-13.7%; I 2  = 0.70), respectively, and the pooled incidence of non-diagnostic results was 4.4% (95% CI, 3.2-5.8%; I 2  = 0.83) in lesions ultimately diagnosed as malignancies and 10.4% (95% CI, 7.5-13.8%; I 2  = 0.74) in benign disease. In conclusion, non-diagnostic results averagely occurred in 6.8% of PTNB and more than half of the results were malignancies. The non-diagnostic results decreased specificity and sensitivity by 10.7% and 4.5%, respectively, demanding efforts to minimize the non-diagnostic results in PTNB.

We conducted a preliminary evaluation of the usefulness of personalized 3D-printed models for improving patient comprehension in informed consent for surgical resection of stage I lung cancer. From January through March 2018, we enrolled a total of 20 adult patients who were suspected to have stage I lung cancer on a preoperative multidetector chest computed tomography and decided to undergo elective surgical resection. The patients were randomly assigned to 3D printing and control arms. Informed consent was obtained before surgery with or without a half-life-size patient-specific 3D-printed model depending on the assigned arm. The patients evaluated the quality of the informed consent process in a 5-point scale using a questionnaire regarding patient knowledge, benefit, risk, alternative treatments, and satisfaction. The patient knowledge score was significantly higher in the 3D-printing group than in the control group (13.6 ± 1.5 vs 11.8 ± 1.6; P = 0.02), while the total score and the scores of the other 4 categories did not significantly differ between the groups: total score, 61.3 ± 7.8 vs 55.4 ± 7.3 (P = 0.12); benefit, 13.1 ± 0.9 vs 11.6 ± 2.1 (P = 0.10); risk, 11.3 ± 2.1 vs 11.7 ± 1.7 (P = 0.73); alternative treatment, 10.3 ± 3.1 vs 9.0 ± 2.7 (P = 0.40); and satisfaction, 13.0 ± 2.2 vs 11.3 ± 2.5 (P = 0.10). Personalized 3D printing was technically implementable and had the potential to improve patient comprehension in informed consent for surgical resection in patients suspected of having stage I lung cancer., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Purpose To evaluate the malignancy risk of lung lesions that show nondiagnostic results at transthoracic needle biopsy (PTNB) of the lung and to identify any malignancy-associated risk factors in each nondiagnostic category. Materials and Methods In this retrospective study, 9384 initial PTNBs (9239 patients [mean age, 65 years; age range, 20-99 years] consisting of 5729 men [mean age, 66 years; age range, 20-99 years] and 3510 women [mean age, 63 years; age range, 20-94 years]) were performed in eight institutions between January 2010 and December 2014. PTNB results were categorized as diagnostic (malignant or specifically benign) or nondiagnostic (nonspecific benign pathologic findings, atypical cells, or insufficient specimen), and the proportion of final malignant diagnoses per nondiagnostic category was obtained. Malignancy-associated factors were determined by using multivariable analyses. Results Nondiagnostic results were present in 27.6% (2590 of 9384) of PTNBs. Proportions of final malignant diagnoses were 21.3% (339 of 1592) for nonspecific benignities, 90.1% (503 of 558) for atypical cells, and 46.6% (205 of 440) for insufficient specimens. In the nonspecific benign category, granulomatous inflammation (odds ratio [OR], 0.04; 95% confidence interval [CI]: 0.02, 0.12; P < .001), abscess (OR, 0.04; 95% CI: 0.01, 0.28; P = .001), and organizing pneumonia (OR, 0.05; 95% CI: 0.01, 0.23; P < .001) were demonstrated to be important factors negating malignancy. Atypical cells suspicious for malignancy were more associated with malignancy (OR, 6.3; 95% CI: 1.9, 21.0; P = .003) than were atypical cells of indeterminate malignancy. All 130 lesions with atypical cells suggestive of malignancy were finally malignant. Conclusion After nondiagnostic lung biopsies, lesions categorized as atypical cell lesions have a high likelihood of malignancy, with somewhat lower likelihood for lesions with insufficient specimens and nonspecific benign categories. © RSNA, 2018 Online supplemental material is available for this article. See also the editorial by Elicker in this issue.

Objectives: To determine whether percutaneous transthoracic needle biopsy (PTNB) increased the risk of pleural recurrence in stage I non-small-cell lung cancer (NSCLC)., Methods: In this retrospective study, we reviewed 830 consecutive patients with stage I NSCLC who underwent curative resection between 2004 and 2010. Cox regression analyses with propensity score matching were performed to identify risk factors for pleural recurrence., Results: Of 830 patients, 540 (65.1%) underwent PTNB before surgery, while 290 (34.9%) underwent preoperative bronchoscopic biopsy or intraoperative wedge resection for a pathological diagnosis. Concomitant pleural recurrence occurred in 42 patients (5.1% [95% CI, 3.8-6.8]; 34 [6.3%] PTNB patients and eight [2.8%] non-PTNB patients) and isolated pleural recurrence took place in 26 patients (3.1% [95% CI, 2.1-4.6]; 20 [3.7%] PTNB patients and 6 [2.1%] non-PTNB patients). On multivariate analysis after matching, only visceral pleural invasion was associated with concomitant pleural recurrence (hazard ratio [HR]=3.367; 95% CI, 1.262-8.986; p=0.015) and isolated pleural recurrence (HR=3.216; 95% CI, 1.037-9.978; p=0.043), while PTNB was associated with neither concomitant nor isolated pleural recurrence (p=0.605 and p=0.963, respectively). Among 540 patients undergoing PTNB, the transfissural approach did not have a significant association with pleural recurrence (p=0.539 and p=0.313, respectively); instead, visceral pleural invasion and microscopic lymphatic invasion were significantly associated with concomitant pleural recurrence, and microscopic lymphatic invasion was associated with isolated pleural recurrence (p<0.05)., Conclusion: PTNB did not significantly increase the risk of pleural recurrence in stage I NSCLC, whereas visceral pleural invasion was responsible for pleural recurrence., Key Points: • PTNB did not significantly increase the risk of pleural recurrence in stage I NSCLC, whereas visceral pleural invasion was responsible for pleural recurrence. • The transfissural approach in PTNB did not increase the risk of pleural recurrence. • PTNB can be performed for the confirmatory diagnosis of peripheral stage I lung cancer without concern for the risk of pleural recurrence.

Objective: To evaluate the impact of nodule visibility during real-time fluoroscopy and other biopsy-related variables on the diagnostic accuracy and complication rates of cone beam CT (CBCT) virtual navigation (VN)-guided percutaneous transthoracic needle biopsies (PTNBs) of small (≤1 cm) pulmonary nodules., Methods: Patients (99 males and 114 females; age, 62.1 ± 11.1 years) who underwent CBCT VN-guided biopsies for lung nodules ≤ 1 cm were retrospectively reviewed. The visibility of target nodules was assessed on the captured fluoroscopy images. Diagnostic accuracies were calculated and logistic regression analyses were performed to determine independent influencing factors for the correct diagnosis and complications (pneumothoraxes and hemoptysis) in CBCT VN-guided PTNBs, respectively., Results: Among 213 nodules, 63 (29.6%) were invisible on real-time fluoroscopy during VN. The diagnostic accuracy of CBCT VN-guided PTNBs for the invisible nodules was 76.7%, while for the visible nodules was 89.1% (p = 0.042). In the logistic regression analysis, the visibility of a target nodule (odds ratio = 2.49, p = 0.047) was the only independent influencing factor for a correct diagnosis. As regards complication rates, nodule visibility was not a significant factor for the occurrence of a pneumothorax or hemoptysis., Conclusion: Although nodule visibility on real-time fluoroscopy was an affecting factor for the correct diagnosis, CBCT VN-guided PTNB was feasible for the invisible nodules with diagnostic accuracy of 76.7%. Advance in knowledge: CBCT VN-guided PTNB can be tried safely for the subcentimeter-sized pulmonary nodules regardless of their fluoroscopic visibility.

Objectives: To find predictors of non-diagnostic repeat biopsy specimen acquisition for mutational analysis and detection of epidermal growth factor receptor (EGFR) T790M mutation., Methods: We retrospectively reviewed 90 non-small cell lung cancer patients harbouring EGFR mutations who underwent repeat cone-beam CT-guided transthoracic needle biopsy. Clinical characteristics as well as biopsy-related factors were compared between patients with and without diagnostic specimen acquisition and between patients with and without T790M mutation. After univariate analysis, multivariate logistic regression analysis was performed to reveal independent predictors., Results: Diagnostic biopsy specimens for mutational test were obtained in 90% (81/90) of patients, of which 62% (50/81) possessed T790M mutation. None of the analysed variables were significantly associated with non-diagnostic specimen acquisition. For T790M detection, duration of EGFR tyrosine kinase inhibitor treatment (p = 0.066), duration of total chemotherapy (p = 0.026), tumour size (p = 0.066), and metastatic lung lesion as a biopsy target (p = 0.029) showed p values less than 0.10. Multivariate analysis revealed that target tumour size (odds ratio, 0.765; p = 0.031) was an independent predictor of T790M mutation. Metastatic lesions as biopsy targets (odds ratio, 4.194; p = 0.050) showed marginal statistical significance., Conclusions: Non-diagnostic repeat biopsy specimen acquisition was not related to the clinical or technical factors. However, detection of T790M at repeat biopsy might be associated with smaller target tumour size and selection of metastatic lesions as biopsy targets., Key Points: • Cone-beam CT-guided repeat biopsy yielded high diagnostic specimen acquisition rate. • Biopsy-related features were associated with the detection of T790M mutation. • Target tumour size was an independent predictor of the T790M detection. • Biopsy targeting metastatic lung nodules might help detect the T790M mutation.

Objectives: To compare interobserver agreements among multiple readers and accuracy for the assessment of solid components in subsolid nodules between the lung and mediastinal window settings., Methods: Seventy-seven surgically resected nodules with solid components smaller than 8 mm were included in this study. In both lung and mediastinal windows, five readers independently assessed the presence and size of solid component. Bootstrapping was used to compare the interobserver agreement between the two window settings. Imaging-pathology correlation was performed to evaluate the accuracy., Results: There were no significant differences in the interobserver agreements between the two windows for both identification (lung windows, k = 0.51; mediastinal windows, k = 0.57) and measurements (lung windows, ICC = 0.70; mediastinal windows, ICC = 0.69) of solid components. The incidence of false negative results for the presence of invasive components and the median absolute difference between the solid component size and the invasive component size were significantly higher on mediastinal windows than on lung windows (P < 0.001 and P < 0.001, respectively)., Conclusions: The lung window setting had a comparable reproducibility but a higher accuracy than the mediastinal window setting for nodule classifications and solid component measurements in subsolid nodules., Key Points: • Reproducibility was similar between the two windows in nodule classifications. • Reproducibility was similar between the two windows in solid component measurements. • Accuracy for solid component assessment was higher on lung windows.

Objectives: To prospectively compare the accuracies of PET/MR and PET/CT in the preoperative staging of non-small cell lung cancer (NSCLC)., Methods: Institutional review board approval and patients' informed consents were obtained. 45 patients with proven or radiologically suspected lung cancer which appeared to be resectable on CT were enrolled. PET/MR was performed for the preoperative staging of NSCLC followed by PET/CT without contrast enhancement on the same day. Dedicated MR images including diffusion weighted images were obtained. Readers assessed PET/MR and PET/CT with contrast-enhanced CT. Accuracies of PET/MR and PET/CT for NSCLC staging were compared., Results: Primary tumour stages (n = 40) were correctly diagnosed in 32 patients (80.0 %) on PET/MR and in 32 patients (80.0 %) on PET/CT (P = 1.0). Node stages (n = 42) were correctly determined in 24 patients (57.1 %) on PET/MR and in 22 patients (52.4 %) on PET/CT (P = 0.683). Metastatic lesions in the brain, bone, liver, and pleura were detected in 6 patients (13.3 %). PET/MR missed one patient with pleural metastasis while PET/CT missed one patient with solitary brain metastasis and two patients with pleural metastases (P = 0.480)., Conclusions: This study demonstrated that PET/MR in combination with contrast-enhanced CT was comparable to PET/CT in the preoperative staging of NSCLC while reducing radiation exposure., Key Points: • PET/MR can be comparable to PET/CT for preoperative NSCLC staging. • PET/MR and PET/CT show excellent correlation in measuring SUVmax of primary lesions. • Using PET/MR, estimated radiation dose can decrease by 31.1 % compared with PET/CT.

Purpose To evaluate histogram and texture parameters on pretreatment dynamic contrast material-enhanced (DCE) magnetic resonance (MR) images in lung cancer in terms of temporal change, optimal time for analysis, and prognostic potential. Materials and Methods This retrospective study was approved by the institutional review board, and the requirement to obtain informed consent was waived. Thirty-eight patients with pathologically proved lung cancer undergoing standard pretreatment DCE MR imaging were included. A fat-suppressed, T1-weighted, volume-interpolated breath-hold MR sequence was performed every 30 seconds for 300 and 480 seconds after contrast material administration. A region of interest was manually drawn in the largest cross-sectional area of the tumor on DCE MR images to extract semiquantitative perfusion, histogram, and texture parameters. Predictability of 2-year progression-free survival (PFS) was analyzed by using the Kaplan-Meier method and Cox regression analysis. Results MR histogram and texture parameters increased rapidly 30-60 seconds after contrast material administration. Standard deviation and entropy then plateaued, whereas skewness and kurtosis rapidly decreased. Univariate Cox regression analysis revealed that standard deviation and entropy were significant predictors of survival; their statistical significance was preserved from 60 to 300 seconds, with the smallest P values (P ≤ .001) occurring from 120 to 180 seconds. At multivariate Cox regression analysis, entropy was the sole significant predictor of 2-year PFS (hazard ratio at 180 seconds, 10.098 [95% confidence interval: 1.579, 64.577], P = .015; hazard ratio at 120 seconds: 11.202 [95% confidence interval: 1.761, 71.260], P = .010). Conclusion Histogram and texture parameter changes varied after contrast material injection. The 120-180-second window after contrast material injection was optimal for MR imaging-derived texture parameter and entropy at DCE MR imaging. (©) RSNA, 2016 Online supplemental material is available for this article.

PET/MR imaging, a new hybrid modality, is thought to have great potential in oncologic imaging because it provides advantages of both PET, which allows functional imaging capability, and MR imaging, which allows high spatial resolution imaging without radiation exposure. Despite the inherent weakness of MR imaging in lung imaging, initial studies on lung cancer revealed that PET/MR imaging showed highly correlated standardized uptake values of lesions and equivalent performance in terms of lesion detection and staging compared with PET/computed tomography (CT). Thus, to affirm the actual clinical benefits of dedicated PET/MR imaging over PET/CT, prospective studies with more patients are warranted., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Various designs of positron emission tomography/magnetic resonance imaging (PET/MRI) systems have been recently introduced to clinical practice, which have overcome preexisting technical challenges concerning the fusion of PET and MRI systems. Although further improvements are still necessary especially for bony lesions, quantification using current MRI-based attenuation correction techniques has been shown to be comparable to that of PET/computed tomography (CT) systems. On the basis of the results of previous whole-body MRI studies, PET/MRI is expected to show even better performance than PET/CT in M-staging especially for brain and liver metastases. Another advantage of PET/MRI over PET/CT, in addition to good soft tissue contrast, is the potential reduction in radiation dose. The next important hurdle to overcome for its clinical application is the development of time-efficient protocols for lung cancer evaluation and interpretation of discordant results from both modalities. Multiparametric imaging through PET/MRI will help radiologists better understand tumor biology and better evaluate treatment response.