The growth of screening-detected pure ground-glass nodules after 10 years of stability.

BACKGROUND: It remains uncertain how long pure ground-glass nodules (pGGNs) detected on low dose computed tomography (LDCT) should be followed. Further studies with longer follow-up periods are needed to determine the optimal follow-up duration for pGGNs. RESEARCH QUESTION: What is the percentage of enlarging nodules among pGGNs that have remained stable for 10 years? STUDY DESIGN AND METHODS: This was a retrospective cohort study originating from subjects with pGGNs detected on LDCT scans between 1997 and 2006, whose natural courses were reported in 2013. We re-analyzed all the follow-up data until July 2022. The study subjects were followed by our institutional guidelines until they were no longer a candidate for definitive treatment. The growth of the pGGNs was defined as an increase in the diameter of the entire nodule by 2 mm or more or the appearance of new solid portions within the nodules. RESULTS: A total of 89 patients with 135 pGGNs were followed for a median of 193 months. Of 135 pGGNs, 23 (17.0%) increased in size, and the median time to the first detection of a size change was 71 months. Of the 23 growing pGGNs, 122 were detected on the first LDCT, and 13 were newly detected on the follow-up CT scan. An increase in size was observed within 5 years in 8 nodules (34.8%), between 5 and 10 years in 12 nodules (52.2%) and after 10 years in 3 nodules (13.0%). Fifteen nodules were histologically confirmed as adenocarcinoma by surgery. Among the 76 pGGNs stable for 10 years, 3 (3.9%) increased in size. INTERPRETATION: Among pGGNs that remained stable for 10 years, 3.9% eventually grew, indicating that some pGGNs can grow even after a long period of stability. We suggest that pGGNs may need to be followed for more than 10 years to confirm growth.

Repeated rebiopsy for detection of EGFR T790M mutation in patients with advanced-stage lung adenocarcinoma: Associated factors and treatment outcomes of Osimertinib.

OBJECTIVES: This study was performed to investigate the detection rate of EGFR T790M mutation by repeated rebiopsy, to identify the clinical factors related to repeated rebiopsy, and to assess survival outcomes according to the methods and numbers of repeated rebiopsies in patients with lung adenocarcinoma who received sequential osimertinib after failure of previous 1st or 2nd generation EGFR-tyrosine kinase inhibitors. METHODS: This retrospective study included patients with advanced-stage lung adenocarcinoma who were confirmed to have EGFR T790M mutation and to have received osimertinib from January 2020 to February 2021 at Samsung Medical Center. The presence of T790M mutation was assessed based on either plasma circulating tumor DNA (ctDNA) or tissue specimens. Results A total of 443 patients underwent rebiopsy, with 186 (42.0%) testing positive for the T790M mutation by the sixth rebiopsy. The final analysis included 143 eligible patients. Progression-free survival was not significantly different in terms of the methods (tissue: 13.3 months, 95% confidence interval [CI]: [9.4, 23.5] vs plasma: 11.1 months, 95% CI: [8.1, 19.4], p = 0.33) and numbers (one: 13.4 months, 95% CI: [9.4, 23.5] vs two or more: 11.0 months, 95% CI: [8.1, 14.8], p = 0.51) of repeated rebiopsies. Longer overall survival (OS) was found in patients in whom T790M was detected by tissue specimens rather than by plasma ctDNA (2-year OS rate: 81.7% for tissue vs 63.9% for plasma, p = 0.0038). Factors related to the lower numbers of rebiopsies included age and bone metastasis. Factor associated with T790M detection in tissue rather than in plasma was pleural metastasis, while advanced tumor stage was related to T790M confirmation in plasma rather than in tissue. CONCLUSIONS: Repeated rebiopsy for T790M detection in patients with NSCLC can increase the detection rate of the mutation. Detection of T790M by plasma ctDNA might be related to poor survival outcomes.

3D airway geometry analysis of factors in airway navigation failure for lung nodules.

BACKGROUND: This study aimed to quantitatively reveal contributing factors to airway navigation failure during radial probe endobronchial ultrasound (R-EBUS) by using geometric analysis in a three-dimensional (3D) space and to investigate the clinical feasibility of prediction models for airway navigation failure. METHODS: We retrospectively reviewed patients who underwent R-EBUS between January 2017 and December 2018. Geometric quantification was analyzed using in-house software built with open-source python libraries including the Vascular Modeling Toolkit ( http://www.vmtk.org ), simple insight toolkit ( https://sitk.org ), and sci-kit image ( https://scikit-image.org ). We used a machine learning-based approach to explore the utility of these significant factors. RESULTS: Of the 491 patients who were eligible for analysis (mean age, 65 years +/- 11 [standard deviation]; 274 men), the target lesion was reached in 434 and was not reached in 57. Twenty-seven patients in the failure group were matched with 27 patients in the success group based on propensity scores. Bifurcation angle at the target branch, the least diameter of the last section, and the curvature of the last section are the most significant and stable factors for airway navigation failure. The support vector machine can predict airway navigation failure with an average area under the curve of 0.803. CONCLUSIONS: Geometric analysis in 3D space revealed that a large bifurcation angle and a narrow and tortuous structure of the closest bronchus from the lesion are associated with airway navigation failure during R-EBUS. The models developed using quantitative computer tomography scan imaging show the potential to predict airway navigation failure.

Comparative Analysis of Clinical Characteristics and Prognosis Between Primary Lung Cancers Identified as Screening Detected and Incidentally Detected Pulmonary Nodules.

BACKGROUND/AIM: Although the importance of low-dose computed tomography (LDCT) screening is increasingly emphasized and implemented, many lung cancers continue to be incidentally detected during routine medical practices, and data on incidentally detected lung cancer (IDLC) remain scarce. This study aimed to investigate the clinical characteristics and prognosis of IDLCs by comparing them with screening-detected lung cancers (SDLCs). PATIENTS AND METHODS: In this retrospective study, subjects with cT1 (≤3 cm) pulmonary nodules detected on baseline computed tomography (CT), later pathologically confirmed as primary lung cancer in 2015, were included. Patients were categorized into IDLC and SDLC groups based on the setting of the first pulmonary nodule detection. RESULTS: Out of 457 subjects, 129 (28.2%) were IDLCs and 328 (71.8%) were SDLCs. The IDLC group, consisted of older individuals with a higher prevalence of smokers and underlying pulmonary disease, compared to the SDLC group. Adenocarcinomas were more frequently detected in SDLCs (87.5%) than in IDLCs (76.7%, p<0.001). The time to treatment initiation (TTI) and 5-year overall survival (OS) rates were similar. Multivariate analyses revealed underlying interstitial lung disease, DLCO, solidity of nodules and TNM stage as independent risk factors associated with mortality. Less than 30% of study participants would have been eligible for the current lung cancer screening program. CONCLUSION: The IDLC group was associated with older age, higher rate of smokers, underlying pulmonary disease, and non-adenocarcinoma histology. However, prognosis was similar to that of the SDLC group, attributable to the similarity in TNM stage, strict adherence to guidelines, and short TTI. Furthermore, less than 30% of the participants would have been suitable for the existing lung cancer screening program, indicating a potential need to reconsider the scope for screening candidates.

Role of invasive mediastinal nodal staging in survival outcomes of patients with non-small cell lung cancer and without radiologic lymph node metastasis: a retrospective cohort study.

Background: Lung cancer diagnostic guidelines advocate for invasive mediastinal nodal staging (IMNS), but the survival benefits of this approach in patients with non-small cell lung cancer (NSCLC) without radiologic evidence of lymph node metastasis (rN0) remain uncertain. We aimed to investigate the impact of IMNS in patients with rN0 NSCLC by comparing the long-term survival between patients who underwent IMNS and those who did not (non-IMNS). Methods: In this retrospective cohort study, we included patients with NSCLC but without radiologic evidence of lymph node metastasis from the Registry for Thoracic Cancer Surgery and the clinical data warehouse at the Samsung Medical Centre, Republic of Korea between January 2, 2008 and December 31, 2016. We compared the 5-year overall survival (OS) rate as the primary outcome after propensity score matching between the IMNS and non-IMNS groups. The age, sex, performance statue, tumor size, centrality, solidity, lung function, FDG uptake in PET-CT, and histological examination of the tumor before surgery were matched. Findings: A total of 4545 patients (887 in the IMNS group and 3658 in the non-IMNS group) who received curative treatment for NSCLC were included in this study. By the mediastinal node dissection, the overall incidence of unforeseen mediastinal node metastasis (N2) was 7.2% (317/4378 patients). Despite the IMNS, 67% of pathological N2 was missed (61/91 patients with unforeseen N2). Based on propensity score matching, 866 patients each for the IMNS and non-IMNS groups were assigned. There was no significant difference in 5-year OS and recurrence-free survival (RFS) between two groups: 5-year OS was 73.9% (95% confidence interval, CI: 71%-77%) for IMNS and 71.7% (95% CI: 68.6%-74.9%; p = 0.23), for non-IMNS (hazard ratio, HR 0.90, 95% CI: 0.77-1.07), while 5-year RFS was 64.7% (95% CI: 61.5%-68.2%) and 67.5% (95% CI: 64.3%-70.9%; p = 0.35 (HR 1.08, 95% CI: 0.92-1.27), respectively. Moreover, the timing and locations of recurrence were similar in both groups. Interpretation: IMNS might not be required before surgery for patients with NSCLC without LN suspicious of metastasis. Further randomised trials are required to validate the findings of the present study. Funding: None.

Association between commuting time and work-related low back pain with respect to sports and leisure activities in Korean workers.

Long commuting times can induce work-related low back pain (LBP), which can be exacerbated by reduced sports and leisure activities. However, there is a lack of empirical research on commuting time and work-related LBP in Korea. In this study, we aimed to investigate the relationship between commuting time and work-related LBP as well as the effect of sports and leisure activities on Korean workers. We utilized data from the sixth Korean Working Conditions Survey to analyze the relationship between commuting time and work-related LBP using multivariable logistic regression. The total number of included workers was 28,202. Workers without sports and leisure activities, and long commuting times (40-59, 60-79, and ≥80 min) showed significantly higher odds ratios for work-related LBP (1.29 [95% Confidence intervals=1.12-1.49], 1.42 [1.22-1.65], and 1.96 [1.68-2.28], respectively). However, in workers with sports and leisure activities, the results were significant only for commuting times of 60-79 and ≥80 min (1.41 [1.13-1.75], 1.60 [1.28-1.99], respectively). Long commuting times were associated with work-related LBP, and engagement in sports and leisure activities was found to play a role in mitigating the impact among Korean wage workers.

Clinical Effect of Endosonography on Overall Survival in Patients with Radiological N1 Non-Small Cell Lung Cancer.

PURPOSE: It is unclear whether performing endosonography first in non-small cell lung cancer (NSCLC) patients with radiological N1 (rN1) has any advantages over surgery without nodal staging. We aimed to compare surgery without endosonography to performing endosonography first in rN1 on the overall survival (OS) of patients with NSCLC. MATERIALS AND METHODS: This is a retrospective analysis of patients with rN1 NSCLC between 2013 and 2019. Patients were divided into 'no endosonography' and 'endosonography first' groups. We investigated the effect of nodal staging through endosonography on OS using propensity score matching (PSM) and multivariable Cox proportional hazard regression analysis. RESULTS: In the no endosonography group, pathologic N2 occurred in 23.0% of patients. In the endosonography first group, endosonographic N2 and N3 occurred in 8.6% and 1.6% of patients, respectively. Additionally, 51 patients were pathologic N2 among 249 patients who underwent surgery and mediastinal lymph node dissection (MLND) in endosonography first group. After PSM, the 5-year OSs were 68.1% and 70.6% in the no endosonography and endosonography first groups, respectively. However, the 5-year OS was 80.2% in the subgroup who underwent surgery and MLND of the endosonography first group. Moreover, in patients receiving surgical resection with MLND, the endosonography first group tended to have a better OS than the no endosonography group in adjusted analysis using various models. CONCLUSION: In rN1 NSCLC, preoperative endosonography shows better OS than surgery without endosonography. For patients with rN1 NSCLC who are candidates for surgery, preoperative endosonography may help improve survival through patient selection.

Clinical Course of Patients With Mediastinal Lymph Node Tuberculosis and Risk Factors for Paradoxical Responses.

BACKGROUND: Paradoxical responses (PR) occur more frequently in lymph node tuberculosis (LNTB) than in pulmonary tuberculosis and present difficulties in differential diagnosis of drug resistance, new infection, poor patient compliance, and adverse drug reactions. Although diagnosis of mediastinal LNTB has become much easier with the development of endosonography, limited information is available. The aim of this study was to investigate the clinical course of mediastinal LNTB and the risk factors associated with PR. METHODS: Patients diagnosed with mediastinal LNTB via endosonography were evaluated retrospectively between October 2009 and December 2019. Multivariable logistic regression was applied to evaluate the risk factors associated with PR. RESULTS: Of 9,052 patients who underwent endosonography during the study period, 158 were diagnosed with mediastinal LNTB. Of these, 55 (35%) and 41 (26%) concurrently had pulmonary tuberculosis and extrapulmonary tuberculosis other than mediastinal LNTB, respectively. Of 125 patients who completed anti-tuberculosis treatment, 21 (17%) developed PR at a median of 4.4 months after initiation of anti-tuberculosis treatment. The median duration of anti-tuberculosis treatment was 6.3 and 10.4 months in patients without and with PR, respectively. Development of PR was independently associated with age < 55 years (adjusted odds ratio [aOR], 5.72; 95% confidence interval [CI], 1.81-18.14; P = 0.003), lymphocyte count < 800/µL (aOR, 8.59; 95% CI, 1.60-46.20; P = 0.012), and short axis diameter of the largest lymph node (LN) ≥ 16 mm (aOR, 5.22; 95% CI, 1.70-16.00; P = 0.004) at the time of diagnosis of mediastinal LNTB. CONCLUSION: As PR occurred in one of six patients with mediastinal LNTB during anti-tuberculosis treatment, physicians should pay attention to patients with risk factors (younger age, lymphocytopenia, and larger LN) at the time of diagnosis.

Combined effect of work from home and work during nonwork time on sleep disturbance.

Background: Owing to the coronavirus disease 2019 pandemic, being exposed to work from home and work during nonwork time simultaneously can lead to sleep disturbance; however, their combined effect is unclear. We aimed to investigate the combined effect of work from home and work during nonwork time on sleep disturbance. Methods: This study used data from the Sixth Korean Working Condition Survey and included 27,473 paid workers. Logistic regression analysis was conducted to investigate the relationship between work from home, work during nonwork time, and sleep disturbance according to sex. We re-classified participants into 4 groups based on their working from home (No/Yes) and working during nonwork time (No/Yes). The relative excess risk due to interaction was calculated to examine the effect of exposure to both telecommuting and non-regular work hours on sleep disturbance. Results: Workers exposed to work from home and work during nonwork time had significantly higher risks of sleep disturbance for all, men, and women workers (OR [95% CI]: 1.71 [1.46-2.02], 1.79 [1.43-2.23], and 1.64 [1.29-2.08] for work from home and 3.04 [2.70-3.42], 3.61 [3.09-4.22], and 2.41 [2.01-2.90] for work during nonwork time, respectively). Compared to those who were not exposed to both factors, when workers had both job factors, the ORs (95% CI) of sleep disturbance for all, men, and women were 3.93 (2.80-5.53), 5.08 (3.21-8.03), and 2.91 (1.74-4.87), respectively. The relative excess risk due to interaction of work from home and work during nonwork time was not significant for sleep disturbance. Conclusions: Work from home and work during nonwork time were each associated with sleep disturbance, but the interaction between the two factors on sleep disturbance was not observed in both men and women.

Advances in methylation analysis of liquid biopsy in early cancer detection of colorectal and lung cancer.

Methylation patterns in cell-free DNA (cfDNA) have emerged as a promising genomic feature for detecting the presence of cancer and determining its origin. The purpose of this study was to evaluate the diagnostic performance of methylation-sensitive restriction enzyme digestion followed by sequencing (MRE-Seq) using cfDNA, and to investigate the cancer signal origin (CSO) of the cancer using a deep neural network (DNN) analyses for liquid biopsy of colorectal and lung cancer. We developed a selective MRE-Seq method with DNN learning-based prediction model using demethylated-sequence-depth patterns from 63,266 CpG sites using SacII enzyme digestion. A total of 191 patients with stage I-IV cancers (95 lung cancers and 96 colorectal cancers) and 126 noncancer participants were enrolled in this study. Our study showed an area under the receiver operating characteristic curve (AUC) of 0.978 with a sensitivity of 78.1% for colorectal cancer, and an AUC of 0.956 with a sensitivity of 66.3% for lung cancer, both at a specificity of 99.2%. For colorectal cancer, sensitivities for stages I-IV ranged from 76.2 to 83.3% while for lung cancer, sensitivities for stages I-IV ranged from 44.4 to 78.9%, both again at a specificity of 99.2%. The CSO model's true-positive rates were 94.4% and 89.9% for colorectal and lung cancers, respectively. The MRE-Seq was found to be a useful method for detecting global hypomethylation patterns in liquid biopsy samples and accurately diagnosing colorectal and lung cancers, as well as determining CSO of the cancer using DNN analysis.Trial registration: This trial was registered at ClinicalTrials.gov (registration number: NCT04253509) for lung cancer on 5 February 2020, https://clinicaltrials.gov/ct2/show/NCT04253509 . Colorectal cancer samples were retrospectively registered at CRIS (Clinical Research Information Service, registration number: KCT0008037) on 23 December 2022, https://cris.nih.go.kr , https://who.init/ictrp . Healthy control samples were retrospectively registered.

Clinical characteristics of miliary pulmonary metastases in non-small cell lung cancer.

BACKGROUND: The prognosis of miliary pulmonary metastases (MPM), which are characterized as randomly disseminated, innumerable, and small metastatic nodules, has been considered as being poor. The purpose of this study was to evaluate the clinical characteristics and survival of MPM in patients with non-small cell lung cancer (NSCLC). METHODS: This retrospective study included NSCLC patients with MPM and nonmiliary pulmonary metastases (NMPM) detected during staging evaluation between 2000 and 2020. MPM was defined as >50 bilaterally distributed metastatic pulmonary nodules (<1 cm in diameter), and NMPM was defined as the presence of ≤15 metastatic pulmonary nodules regardless of size. Baseline characteristics, genetic alterations and overall survival (OS) rates were compared between the two groups. RESULTS: Twenty-six patients with MPM and 78 patients with NMPM were analyzed. The median number of patients who smoked was significantly lower in the MPM group than in the NMPM group (0 vs. 8 pack years, p = 0.030). The frequency of EGFR mutation was significantly higher in the MPM group (58%) than in the NMPM group (24%; p = 0.006). There was no significant difference in 5-year OS between the MPM and the NMPM group by the log-rank test (p = 0.900). CONCLUSION: MPM in NSCLC were significantly related to EGFR mutation. The OS rate of the MPM group was not inferior to that of the NMPM group. The presence of EGFR mutations should be thoroughly evaluated for NSCLC patients with initial presentation of MPM.

Association Between Commuting Time and Subjective Well-Being in Relation to Regional Differences in Korea.

BACKGROUND: Long commuting times have a negative impact on mental health. However, few studies have explored the relationship between commuting time and well-being based on urbanization by region. Our study examines this relationship as well as the effect of regional differences on Korean workers. METHODS: We used data from the sixth Korean Working Conditions Survey. Commuting time and occupational factors were assessed using a questionnaire, and subjective well-being was assessed using the World Health Organization-5 Well-Being Index. Regions were divided into the cities and the provinces based on Korea's administrative divisions. Logistic regression analysis was performed to investigate the association between commuting time and well-being. Adjusted odds ratios (aORs) with 95% confidence intervals (CIs) for well-being were estimated, using participants commuting time of < 20 minutes as a reference group. RESULTS: The total number of workers was 29,458 (13,855 men, 15,603 women). We found higher aORs for low well-being among workers with long commuting times (aOR, 1.23; 95% CI, 1.11-1.36 and aOR, 1.28; 95% CI, 1.16-1.42 for 60-79 and ≥ 80 minutes, respectively). When stratified by sex and region, higher aORs for low well-being were found only in the workers who lived in cities. CONCLUSION: Long commuting time was negatively associated with well-being in Korean wage workers living in the cities. Policies for reducing commuting time should be discussed to address the mental health of workers, especially those living in metropolitan cities.

Prediction Models for Mediastinal Metastasis and Its Detection by Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration in Potentially Operable Non-Small Cell Lung Cancer: A Prospective Study.

BACKGROUND: Prediction models for mediastinal metastasis and its detection by endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) have not been developed using a prospective cohort of potentially operable patients with non-small cell lung cancer (NSCLC). RESEARCH QUESTION: Can mediastinal metastasis and its detection by EBUS-TBNA be predicted with prediction models in NSCLC? STUDY DESIGN AND METHODS: For the prospective development cohort, 589 potentially operable patients with NSCLC were evaluated (July 2016-June 2019) from five Korean teaching hospitals. Mediastinal staging was performed using EBUS-TBNA (with or without the transesophageal approach). Surgery was performed for patients without clinical N (cN) 2-3 disease by endoscopic staging. The prediction model for lung cancer staging-mediastinal metastasis (PLUS-M) and a model for mediastinal metastasis detection by EBUS-TBNA (PLUS-E) were developed using multivariable logistic regression analyses. Validation was performed using a retrospective cohort (n = 309) from a different period (June 2019-August 2021). RESULTS: The prevalence of mediastinal metastasis diagnosed by EBUS-TBNA or surgery and the sensitivity of EBUS-TBNA in the development cohort were 35.3% and 87.0%, respectively. In PLUS-M, younger age (< 60 years and 60-70 years compared with ≥ 70 years), nonsquamous histology (adenocarcinoma and others), central tumor location, tumor size (> 3-5 cm), cN1 or cN2-3 stage by CT, and cN1 or cN2-3 stage by PET-CT were significant risk factors for N2-3 disease. Areas under the receiver operating characteristic curve (AUCs) for PLUS-M and PLUS-E were 0.876 (95% CI, 0.845-0.906) and 0.889 (95% CI, 0.859-0.918), respectively. Model fit was good (PLUS-M: Hosmer-Lemeshow P = .658, Brier score = 0.129; PLUS-E: Hosmer-Lemeshow P = .569, Brier score = 0.118). In the validation cohort, PLUS-M (AUC, 0.859 [95% CI, 0.817-0.902], Hosmer-Lemeshow P = .609, Brier score = 0.144) and PLUS-E (AUC, 0.900 [95% CI, 0.865-0.936], Hosmer-Lemeshow P = .361, Brier score = 0.112) showed good discrimination ability and calibration. INTERPRETATION: PLUS-M and PLUS-E can be used effectively for decision-making for invasive mediastinal staging in NSCLC. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT02991924; URL: www. CLINICALTRIALS: gov.

Diagnostic Performance of Endosonography to Detect Mediastinal Lymph Node Metastasis in Patients with Radiological N1 Non-Small Cell Lung Cancer.

PURPOSE: Guidelines recommend that non-small cell lung cancer (NSCLC) patients with suspected hilar lymph node (LN) metastases should undergo invasive mediastinal LN staging prior to surgical treatment via endosonography. We evaluated the diagnostic performance of endosonography for detecting occult mediastinal metastases (OMM) and determined the factors associated with OMM in NSCLC patients with radiological N1. Materials and Methods: Patients with confirmed primary NSCLC with radiological N1 who underwent endosonography for nodal staging assessment from January 2013 to December 2019 were retrospectively analyzed. RESULTS: The prevalence of OMM was found to be 83/279 (29.7%) and only 38.6% (32/83) were diagnosed via endosonography. However, five of them were confirmed as N3 by endosonography. The overall diagnostic sensitivity, negative predictive value, accuracy, and area under the curve of endosonography were 38.6%, 79.4%, 81.7%, and 0.69, respectively. In multivariable analysis, central tumor (adjusted odds ratio [aOR], 2.05; 95% confidence interval [CI], 1.15 to 3.68; p=0.016), solid tumor (aOR, 10.24; 95% CI, 1.32 to 79.49; p=0.026), and adenocarcinoma (aOR, 3.01; 95% CI, 1.63 to 5.55; p < 0.001) were related to OMM in radiological N1 NSCLC patients. CONCLUSION: Although the sensitivity of endosonography for detecting OMM was only 40%, the prevalence of OMM was not low (30%) and some cases even turned out to be N3 diseases. Clinicians should be aware that OMM may be more likely in patients with central, solid, and adenocarcinomatous tumor when performing nodal staging in radiological N1 NSCLC via endosonography.

The Incidence and Risk Factors of Chronic Pulmonary Infection after Radiotherapy in Patients with Lung Cancer.

PURPOSE: This study aimed to investigate cumulative incidence and risk factors associated with chronic pulmonary infection (CPI) development after radiotherapy for lung cancer. Materials and Methods: We retrospectively analyzed 1,872 patients with lung cancer who received radiotherapy for lung cancer from 2010-2014, had a follow-up period of ≥ 3 months after radiotherapy, and did not have CPI at the time of radiotherapy. CPI was defined as pulmonary tuberculosis, non-tuberculous mycobacterial pulmonary disease, chronic pulmonary aspergillosis, or pulmonary actinomycosis. The cumulative incidence of CPI and overall survival (OS) were estimated using the Kaplan-Meier method, and a multivariable Cox proportional hazards analysis was performed to identify risk factors associated with CPI development. RESULTS: The median follow-up period was 2.3 years with OS rates of 55.6% and 37.6% at 2 and 5 years, respectively. CPI developed in 59 patients at a median of 1.8 years after radiotherapy, with cumulative incidence rates of 1.1%, 3.4%, 5.0%, and 6.8% at 1, 3, 5, and 7 years, respectively. A lower body mass index, interstitial lung disease, prior pulmonary tuberculosis, larger clinical target volume, history of lung cancer surgery or radiation pneumonitis, and use of inhaled corticosteroids were independent risk factors for CPI development. CONCLUSION: The long-term survival rate of lung cancer patients receiving radiotherapy was not low, but the cumulative incidence of CPI gradually increased to 6.8% at 7 years after radiotherapy. Therefore, close monitoring of CPI development is required in surviving patients with risk factors.

Nondiagnostic, radial-probe endobronchial ultrasound-guided biopsy for peripheral lung lesions: The added value of radiomics from ultrasound imaging for predicting malignancy.

OBJECTIVES: This study investigated whether radiomic features extracted from radial-probe endobronchial ultrasound (radial EBUS) images can assist in decision-making for subsequent clinical management in cases with indeterminate pathologic results. METHODS: A total of 494 patients who underwent radial EBUS biopsy for lung nodules between January 2017 and December 2018 were allocated to our training set. For the validation set, 229 patients with radial EBUS biopsy results from January 2019 to April 2020 were used. A multivariate logistic regression analysis was used for feature selection and prediction modeling. RESULTS: In the training set, 157 (67 benign and 90 malignant) of 212 patients pathologically diagnosed as indeterminate were analyzed. In the validation set, 213 patients were diagnosed as indeterminate, and 158 patients (63 benign and 95 malignant) were included in the analysis. The performance of the radiomics-added model, which considered satellite nodules, linear arc, shape, patency of vessels and bronchi, echogenicity, spiculation, C-reactive protein, and minimum histogram, was 0.929 for the training set and 0.877 for the validation set, whereas the performance of the model without radiomics was 0.910 and 0.891, respectively. CONCLUSION: Although the next diagnostic step for indeterminate lung biopsy results remains controversial, integrating various factors, including radiomic features from radial EBUS, might facilitate decision-making for subsequent clinical management.

Efficacy of Combining Multiple Electromagnetic Navigation Bronchoscopy Modalities for Diagnosing Lung Nodules.

Electromagnetic navigation bronchoscopy (ENB) is one of the non-invasive methods used for lung nodule biopsy. We evaluated the efficacy of combining radial endobronchial ultrasound (R-EBUS)-guided transbronchial lung biopsy (TBLB) with ENB-guided TBLB or transbronchial needle aspiration (TBNA) for diagnosing lung nodules. Forty patients with a lung nodule underwent ENB-TBLB or TBNA, followed by R-EBUS-TBLB if available. The final diagnosis was benign or malignant, depending on the surgical pathology or 24-month follow-up computed tomography (CT). We compared the sensitivity, negative predictive value, and accuracy between combinations of procedures. The mean nodule size was 21.65 mm, and 60.0% of the nodules were solid. The bronchus was within the nodule in 67.5% and 65.0% of cases examined using CT and R-EBUS, respectively. The accuracies of ENB-TBLB alone, ENB-TBLB/TBNA, and R-EBUS-TBLB plus ENB-TBLB/TBNA were 74.4%, 82.5%, and 90.0%, respectively. The sensitivity levels of the aforementioned procedures were 69.8%, 78.8%, and 87.9%, respectively. Among 21 patients who underwent both ENB-TBLB and R-EBUS-TBLB, the latter revealed malignant cells in three of nine patients (33.3%) with benign ENB-TBLB results. Combined ENB-TBLB/TBNA and R-EBUS-TBLB had increased sensitivity and diagnostic accuracy for lung nodules. ENB and R-EBUS are complementary; using both modalities improves the sensitivity and accuracy of lung nodule diagnoses.

Mortality and lung function decline in patients who develop chronic pulmonary aspergillosis after lung cancer surgery.

BACKGROUND: Lung cancer surgery is reported as a risk factor for chronic pulmonary aspergillosis (CPA). However, limited data are available on its clinical impact. We aimed to determine the effect of developed CPA after lung cancer surgery on mortality and lung function decline. METHODS: We retrospectively identified the development of CPA after lung cancer surgery between 2010 and 2016. The effect of CPA on mortality was evaluated using multivariable Cox proportional hazard analyses. The effect of CPA on lung function decline was evaluated using multiple linear regression analyses. RESULTS: During a median follow-up duration of 5.01 (IQR, 3.41-6.70) years in 6777 patients, 93 developed CPA at a median of 3.01 (IQR, 1.60-4.64) years. The development of CPA did not affect mortality in multivariable analysis. However, the decline in forced vital capacity (FVC) and forced expiratory volume in 1 second (FEV1) were greater in patients with CPA than in those without (FVC, - 71.0 [- 272.9 to - 19.4] vs. - 10.9 [- 82.6 to 57.9] mL/year, p < 0.001; FEV1, - 52.9 [- 192.2 to 3.9] vs. - 20.0 [- 72.6 to 28.6] mL/year, p = 0.010). After adjusting for confounding factors, patients with CPA had greater FVC decline (ß coefficient, - 103.6; 95% CI - 179.2 to - 27.9; p = 0.007) than those without CPA. However, the FEV1 decline (ß coefficient, - 14.4; 95% CI - 72.1 to 43.4; p = 0.626) was not significantly different. CONCLUSION: Although the development of CPA after lung cancer surgery did not increase mortality, the impact on restrictive lung function deterioration was profound.

Comparison of clinical outcomes of pulmonary sequestration in adults between surgery and non-surgery groups.

Background: Pulmonary sequestration (PS) is a rare congenital lung malformation that can be incidentally diagnosed in adulthood. The natural course of PS in adults is scarcely known. Methods: In this retrospective cohort study, medical records and imaging results of adult patients diagnosed with PS between 1994 and 2019 were reviewed. Diagnoses of PS were confirmed by histopathological findings in resected cases, while non-resected cases were diagnosed based on the presence of anomalous systemic arterial supply and abnormal lung parenchyma on enhanced chest computed tomography (CT). Results: Among 104 patients with PS, the median age at diagnosis was 40.5 years, and 69 (66.3%) patients were asymptomatic. Patients in the surgery group were significantly younger (38.6 vs. 45.3 years, respectively, P=0.016), were more likely to be symptomatic initially (51.6% vs. 28.6%, respectively, P=0.015), and had larger PS (90.0 vs. 66.3 mm, respectively, P<0.001) than the non-surgery group. Of the patients in the surgery group, 29.0% (18/62) experienced postoperative complications. In the surgically resected cases, infections were only detected in intralobar PS, not in extralobar PS. Among 25 subjects without initial symptoms in the non-surgery group, 24 (96.0%) remained asymptomatic at the last follow-up. Conclusions: Adults with PS tended to undergo resection if they were young, symptomatic, and had large PS (a median diameter of 90.0 mm). Almost all subjects who were initially asymptomatic and did not undergo surgery remained asymptomatic at the last follow-up. Therefore, considering the indolent course of PS, initially asymptomatic adults with PS could be followed up without surgery.

Clinical utility of EBUS-TBNA of hilar, interlobar, and lobar lymph nodes in patients with primary lung cancer.

BACKGROUND: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is used to evaluate hilar/interlobar/lobar lymph nodes. This study aimed to assess the clinical utility of EBUS-TBNA for station 10/11/12 lymph nodes (LNs) in patients with primary lung cancer. METHODS: This was a retrospective analysis of a prospectively collected database of patients with primary lung cancer who underwent EBUS-TBNA for station 10/11/12 LNs from January 2015 to December 2019. Patients with benign results from EBUS-TBNA who did not undergo surgical sampling/clinical follow-up or who received radiotherapy/chemotherapy were excluded. RESULTS: The analyses were conducted on 889 LNs from 797 patients. The overall diagnostic sensitivity, specificity, accuracy, negative predictive value (NPV), and positive predictive value of EBUS-TBNA were 95.7, 100, 97.3, 93.2, and 100%, respectively. Diagnostic sensitivity was significantly lower for LNs <10 mm than ≥10 mm in size (90.1% vs. 97.8%; p < 0.001). There was no significant difference in diagnostic performance according to the nodal station (10 vs. 11/12) and left- versus right-sided LNs. The diagnostic sensitivity (100 vs. 95.5%; p = 0.221) and specificity (100 vs. 100%) of N3 LNs was not significantly different from those of N1 LNs. In this study, eight (8/91, 8.8%) patients with cN1 NSCLC received neoadjuvant treatment based on the results of EBUS-TBNA. CONCLUSION: EBUS-TBNA accurately evaluates station 10/11/12 LNs of both N1 and N3 disease. The diagnostic performances of EBUS-TBNA for station 10/11/12 LNs seem to be comparable to those of EBUS-TBNA for mediastinal LNs.