近藤 征史

Despite innovative advances in molecular targeted therapy, treatment strategies using immune checkpoint inhibitors (ICIs) for epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) have not progressed significantly. Accumulating evidence suggests that ICI chemotherapy is inadequate in this population. Biomarkers of ICI therapy, such as programmed cell death ligand 1 (PD-L1) and tumor-infiltrating lymphocytes (TILs), are not biomarkers in patients with EGFR mutations, and the specificity of the tumor microenvironment has been suggested as the reason for this. Combination therapy with PD-L1 and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitors is a concern because of its severe toxicity and limited efficacy. However, early-stage NSCLC may differ from advanced-stage NSCLC. In this review, we comprehensively review the current evidence and summarize the potential of ICI therapy in patients with EGFR mutations after acquiring resistance to treatment with EGFR-tyrosine kinase inhibitors (TKIs) with no T790M mutation or whose disease has progressed on osimertinib.

mRNA vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have played a key role in reducing morbidity and mortality from coronavirus disease 2019 (COVID-19). We conducted a double-blind, placebo-controlled phase I/II trial to evaluate the safety, tolerability, and immunogenicity of EXG-5003, a two-dose, controllable self-replicating RNA vaccine against SARS-CoV-2. EXG-5003 encodes the receptor binding domain (RBD) of SARS-CoV-2 and was administered intradermally without lipid nanoparticles (LNPs). The participants were followed for 12 months. Forty healthy participants were enrolled in Cohort 1 (5 µg per dose, n = 16; placebo, n = 4) and Cohort 2 (25 µg per dose, n = 16; placebo, n = 4). No safety concerns were observed with EXG-5003 administration. SARS-CoV-2 RBD antibody titers and neutralizing antibody titers were not elevated in either cohort. Elicitation of antigen-specific cellular immunity was observed in the EXG-5003 recipients in Cohort 2. At the 12-month follow-up, participants who had received an approved mRNA vaccine (BNT162b2 or mRNA-1273) >1 month after receiving the second dose of EXG-5003 showed higher cellular responses compared with equivalently vaccinated participants in the placebo group. The findings suggest a priming effect of EXG-5003 on the long-term cellular immunity of approved SARS-CoV-2 mRNA vaccines.

Naldemedine is structurally designed to prevent passage across the blood–brain barrier (BBB), resulting in the attenuation of opioid-induced constipation without interfering with the analgesic effects of opioids. However, the influence of brain metastasis (BM), as one indicator of BBB disruption, on the analgesic effects of opioids in patients treated with naldemedine remains unclear. To examine whether the analgesic effects of opioids following naldemedine treatment are lower in patients with BM than in those without BM, we surveyed inpatients with lung and breast cancers treated with naldemedine at Fujita Health University Hospital between April 2017 and March 2022. Changes in the numeric rating scale (NRS) scores, morphine milligram equivalents (MMEs), and the number of rescues were assessed as analgesia-related outcomes during the first 7 days of naldemedine treatment in patients with or without BM, matched by the propensity score. In total, 172 patients were enrolled. After propensity-score matching, 30 patients with BM and 60 patients without BM were included in the analysis. Changes in NRS scores, MMEs, and the number of rescues did not differ between patients with and without BM. In the linear mixed-effects model, the coefficient of interaction between patients with or without BM and the days for each outcome was not statistically significant. BM does not influence the analgesic effect of opioids in patients with lung and breast cancers treated with naldemedine. Naldemedine may be useful for treating BM.

BACKGROUND: The Cockcroft-Gault formula is commonly used as a substitute for glomerular filtration rate (GFR) in Calvert's formula for carboplatin dosing, where adjusting serum creatinine measured using the enzymatic method with 0.2 mg/dL has been suggested in Japan. However, the effects of these adjustments on efficacy in patients with non-small-cell lung cancer remain unknown. METHODS: We conducted a post hoc analysis of the PREDICT1 study (CJLSG1201), a multicenter prospective observational trial of carboplatin-pemetrexed. Glomerular filtration rate values in Calvert's formula were back-calculated from the administered dosages of carboplatin and the reported value of the target area under the curve. We estimated the serum creatinine adjustments and divided the patients into crude and adjusted groups. RESULTS: Patients in the crude group (N = 169) demonstrated similar efficacy to those in the adjusted group (N = 104) in progression-free survival (PFS) and overall survival (OS) (hazard ratio [HR], 1.02; 95% confidence interval [CI], 0.76-1.35; p = 0.916 vs. HR, 0.87; 95% CI, 0.65-1.17; p = 0.363), with higher grade 3-4 hematologic toxicity. Among patients aged ≥75 years, the crude group (N = 47) showed superior efficacy compared with the adjusted group (N = 17) in PFS and OS (HR, 0.37; 95% CI, 0.20-0.69; p = 0.002 vs. HR, 0.43; 95% CI, 0.23-0.82; p = 0.010). CONCLUSIONS: Serum creatinine adjustment may be associated with similar efficacy compared to the crude serum creatinine value. In older patients, the adjustment should be cautiously applied owing to the potential for reduced efficacy.

INTRODUCTION: Favipiravir, an antiviral agent with activity against SARS-CoV-2, was made available to hospitals in Japan for off-label use among COVID-19 patients between 2020 and 2021. METHODS: A nationwide observational cohort study was conducted on patients who received favipiravir as part of clinical care between February 2020 and December 2021. Information was collected on demographics, comorbidities, severity of illness, use of favipiravir and other medications targeting COVID-19, adverse events, clinical status at 7 and 14 days and clinical outcome one month after admission to the hospital. RESULTS: A total of 17,508 hospitalized patients who received favipiravir were registered from 884 hospitals. In terms of demographics, 55.9% were age ≥60 years, and 62.3% were male. At least one of the four surveyed comorbidities was present in 45.5% of the patients. The rates of clinical improvement at 7 and 14 days were 72.4％ and 87.5%, 61.4% and 76.6%, and 45.4% and 59.5% for mild, moderate, and severe diseases, respectively. The case fatality rates within a month from hospitalization were 3.3%, 12.6%, and 29.1% for mild, moderate, and severe diseases, respectively. Significant correlations were observed between death and advanced age, male sex, moderate or severe disease, diabetes, cardiovascular diseases, and immunosuppression. Commonly reported adverse events included uric acid level increase or hyperuricemia (16.8%), liver function abnormalities (6.9%), and rash (1.0%). CONCLUSIONS: Favipiravir was well tolerated among COVID-19 patients. The study provides insights into the use of this agent at hospitals across Japan in the early phase of the pandemic.

BACKGROUND/AIM: The systemic administration of anticancer drugs may cause ocular adverse reactions (OARs). However, such adverse events are generally rare and occur with an unknown frequency. This study aimed to investigate the tendency of occurrence of OARs induced by systemic anticancer drugs using a large spontaneous pharmacovigilance database in Japan. PATIENTS AND METHODS: The safety signals for eight OARs (periorbital and eyelid, conjunctival, corneal, scleral, lacrimal, lens, retinal, and optic nerve disorders) and their associations with anticancer drugs were evaluated by analyzing reporting odds ratios (RORs) and information components (ICs) based on data from the Japanese Adverse Drug Event Report (JADER). RESULTS: Safety signals associated with anticancer drugs were detected for periorbital and eyelid disorders (imatinib), conjunctival disorders (imatinib and lapatinib), corneal disorders (S-1, erlotinib, capecitabine, cetuximab, gefitinib, vandetanib, trastuzumab emtansine, lapatinib), lacrimal disorders (S-1, pembrolizumab), lens disorders (lenalidomide, pomalidomide, elotuzumab, tamoxifen, bexarotene, venetoclax), retinal disorders (encorafenib, binimetinib, tamoxifen, nab-paclitaxel, trametinib, dabrafenib), and optic nerve disorders (tamoxifen and blinatumomab). Some anticancer drugs showed differences in safety signals based on sex and age. CONCLUSION: Safety signals indicative of the risk of occurrence of OARs were observed for several anticancer drugs, and several hitherto unreported ocular adverse events requiring caution were also detected. Our results will help predict the occurrence of OARs by oncologists, ophthalmologists, pharmacists, and other healthcare professionals.

Abstract Artificial intelligence (AI) applications in medical imaging continue facing the difficulty in collecting and using large datasets. One method proposed for solving this problem is data augmentation using fictitious images generated by generative adversarial networks (GANs). However, applying a GAN as a data augmentation technique has not been explored, owing to the quality and diversity of the generated images. To promote such applications by generating diverse images, this study aims to generate free-form lesion images from tumor sketches using a pix2pix-based model, which is an image-to-image translation model derived from GAN. As pix2pix, which assumes one-to-one image generation, is unsuitable for data augmentation, we propose StylePix2pix, which is independently improved to allow one-to-many image generation. The proposed model introduces a mapping network and style blocks from StyleGAN. Image generation results based on 20 tumor sketches created by a physician demonstrated that the proposed method can reproduce tumors with complex shapes. Additionally, the one-to-many image generation of StylePix2pix suggests effectiveness in data-augmentation applications.

OBJECTIVES: To evaluate the effectiveness of remdesivir in the early stage of nonsevere COVID-19. Although several randomized controlled trials have compared the effectiveness of remdesivir with that of a placebo, there is limited evidence regarding its effect in the early stage of nonsevere COVID-19 cases. METHODS: We evaluated the effectiveness of remdesivir in the early stage of nonsevere COVID-19 using the COVID-19 Registry Japan, a nationwide registry of hospitalized patients with COVID-19 in Japan. Two regimens ("start remdesivir" therapy within 4 days from admission versus no remdesivir during hospitalization) among patients without the need for supplementary oxygen therapy were compared by a 3-step processing (cloning, censoring, and weighting) method. The primary outcome was a supplementary oxygen requirement during hospitalization. Secondary outcomes were 30-day in-hospital mortality and the risk of invasive mechanical ventilation or extracorporeal membrane oxygenation (IMV/ECMO). The data of 12,487 cases met our inclusion criteria. The "start remdesivir" regimen showed a lower risk of supplementary oxygen requirement (hazard ratio [HR]: 0.850, 95% confidence interval [CI]: 0.798-0.906, p value < 0.001). Both 30-day in-hospital mortality and risk of IMV/ECMO introduction were not significantly different between the 2 regimens (HRs: 1.04 and 0.983, 95% CI: 0.980-1.09 and 0.906-1.07, p values: 0.210 and 0.678, respectively). CONCLUSIONS: Remdesivir might reduce the risk of oxygen requirement during hospitalization in the early stage of COVID-19; however, it had no positive effect on the clinical outcome and reduction in IMV/ECMO requirement.

Background: Before widespread coronavirus disease (COVID-19) vaccinations, Japan experienced three COVID-19 epidemic waves. This study aimed to evaluate the characteristics of hospitalised COVID-19 patients and reveal temporal changes. Methods: This study included 33,554 hospitalised patients with COVID-19 from 553 healthcare facilities. Data were analysed by age group and epidemic wave (first wave, 01/01/2020-05/31/2020; second wave, 06/01/2020-10/31/2020; and third wave, 11/01/2020-03/31/2021). Findings: By age group, 3% (under 18), 22% (young), 34% (middle-aged), and 41% (older patients) were aged 0-17, 18-39, 40-64, and >65 years; while 16%, 35%, and 49% were in the first, second, and third wave, respectively. The patients' overall median age (58 years; interquartile range, 39-74) was lowest and highest during the second and third waves, respectively. The frequency of any comorbidity was lowest and highest during the second (44·5%) and third (63·6%) waves, respectively. The symptoms at admission and exposure history differed considerably with age. The overall case fatality rate (5%) was highest among older patients (11·4%). Case fatality rate was highest and lowest during the first (7·3%) and second (2·8%) waves, respectively. Medication use changed over time. Interpretation: Although the overall case fatality rate remained relatively low, it was more than twice as high among older patients. After adjusting for age and comorbidities, the risk of death was highest in the first wave. Funding: This work was supported by the Ministry of Health, Labour and Welfare "Research on Emerging and Re-emerging Infectious Diseases and Immunization" 19HA1003].

PURPOSE: Using CT findings from a prospective, randomized, open-label multicenter trial of favipiravir treatment of COVID-19 patients, the purpose of this study was to compare the utility of machine learning (ML)-based algorithm with that of CT-determined disease severity score and time from disease onset to CT (i.e., time until CT) in this setting. MATERIALS AND METHODS: From March to May 2020, 32 COVID-19 patients underwent initial chest CT before enrollment were evaluated in this study. Eighteen patients were randomized to start favipiravir on day 1 (early treatment group), and 14 patients on day 6 of study participation (late treatment group). In this study, percentages of ground-glass opacity (GGO), reticulation, consolidation, emphysema, honeycomb, and nodular lesion volumes were calculated as quantitative indexes by means of the software, while CT-determined disease severity was also visually scored. Next, univariate and stepwise regression analyses were performed to determine relationships between quantitative indexes and time until CT. Moreover, patient outcomes determined as viral clearance in the first 6 days and duration of fever were compared for those who started therapy within 4, 5, or 6 days as time until CT and those who started later by means of the Kaplan-Meier method followed by Wilcoxon's signed-rank test. RESULTS: % GGO and % consolidation showed significant correlations with time until CT (p < 0.05), and stepwise regression analyses identified both indexes as significant descriptors for time until CT (p < 0.05). When divided all patients between time until CT of 4 days and that of more than 4 days, accuracy of the combined quantitative method (87.5%) was significantly higher than that of the CT disease severity score (62.5%, p = 0.008). CONCLUSION: ML-based CT texture analysis is equally or more useful for predicting time until CT for favipiravir treatment on COVID-19 patients than CT disease severity score.

INTRODUCTION: Several randomized controlled trials have compared the effectiveness of favipiravir with that of placebo. However, evidence regarding its effect on nonsevere, early-stage coronavirus disease 2019 (COVID-19) remains insufficient. METHODS: We used the COVID-19 Registry Japan, a nationwide registry of inpatients with COVID-19, for evaluating the effectiveness of favipiravir on patients with nonsevere, early-stage COVID-19. Eligible patients, who did not need supplementary oxygen therapy at admission, were classified according to two regimens (starting favipiravir therapy within 4 days from admission vs. no favipiravir during hospitalization) and were then compared using a three-step method (cloning, censoring, and weighting). The primary outcome was supplementary oxygen requirement during hospitalization, and the secondary outcomes were the need for invasive mechanical ventilation or extracorporeal membrane oxygenation (IMV/ECMO) and overall mortality at 30 days. RESULTS: A total of 7654 cases were analyzed. The "start favipiravir" regimen did not show substantial differences in the primary outcome [hazard ratio 0.825, 95% confidence interval (CI) 0.657-1.04, p = 0.098] and both of the secondary outcomes [need for IMV/ECMO and overall 30-day mortality, hazard ratio 1.02 (95% CI 0.649-1.60) and 0.869 (95% CI 0.519-1.46), p = 0.929 and 0.594, respectively]. CONCLUSIONS: In this large cohort from a COVID-19 registry, favipiravir was not associated with a positive effect on the clinical outcome on patients with nonsevere, early-stage COVID-19, suggesting that it is not an essential drug for COVID-19 treatment.

To fight severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), mass vaccination has begun in many countries. To investigate the usefulness of a serological assay to predict vaccine efficacy, we analyzed the levels of IgG, IgM, and IgA against the receptor-binding domain (RBD) of SARS-CoV-2 in the sera from BNT162b2 vaccinated individuals in Japan. This study included 219 individuals who received two doses of BNT162b2. The levels of IgG, IgM, and IgA against RBD were measured by enzyme-linked immunosorbent assay before and after the first and second vaccination, respectively. The relationship between antibody levels and several factors, including age, gender, and hypertension were analyzed. Virus-neutralizing activity in sera was measured to determine the correlation with the levels of antibodies. A chemiluminescent enzyme immunoassay (CLEIA) method to measure IgG against RBD was developed and validated for the clinical setting. The levels of all antibody isotypes were increased after vaccination. Among them, RBD-IgG was dramatically increased after the second vaccination. The IgG levels in females were significantly higher than in males. There was a negative correlation between age and IgG levels in males. The IgG levels significantly correlated with the neutralizing activity. The CLEIA assay measuring IgG against RBD showed a reliable performance and a high correlation with neutralizing activity. Monitoring of IgG against RBD is a powerful tool to predict the efficacy of SARS-CoV-2 vaccination and provides useful information in considering a personalized vaccination strategy for COVID-19. IMPORTANCE Mass vaccination campaigns using mRNA vaccines against SARS-CoV-2 have begun in many countries. Serological assays to detect antibody production may be a useful tool to monitor the efficacy of SARS-CoV-2 vaccination in individuals. Here, we reported the induction of antibody isotype responses after the first and second dose of the BNT162b2 vaccine in a well-defined cohort of employees in Japan. We also reported that age, gender, and hypertension are associated with differences in antibody response after vaccination. This study not only provides valuable information with respect to antibody responses after BNT162b2 vaccination in the Japanese population but also the usefulness of serological assays for monitoring vaccine efficacy in clinical laboratories to determine a personalized vaccination strategy for COVID-19.

OBJECTIVES: To determine whether anticoagulation therapy improves outcomes in patients with coronavirus disease 2019 (COVID-19) in Japan given their lower risk of thrombosis compared with Western cohorts. METHODS: The efficacy of anticoagulation therapy in hospitalized patients with COVID-19 was evaluated using a nationwide registry: the COVID-19 Registry Japan. The inverse probability of weight treatment method was used to adjust for baseline confounders in the anticoagulation and non-anticoagulation groups. RESULTS: Of the 1748 patients included, anticoagulants were used in 367 patients (treatment group). The patients in the anticoagulant group were older, predominantly male, and often presented with obesity, hyperlipidaemia, hypertension, diabetes and elevated D-dimer levels. Twenty-nine-day mortality was 7.6% in the whole cohort (treatment group, 11.2%; no treatment group, 6.6%), 6% in patients who were not treated with steroids (treatment group, 12.3%; no treatment group, 5.2%), and 11.2% in patients treated with steroids (treatment group, 10.5%; no treatment group, 11.8%). Mortality in the whole cohort was similar between the treatment and no treatment groups (P=0.99), and an insignificant decreasing trend in mortality was observed in patients treated with steroids (P=0.075). CONCLUSIONS: Anticoagulants may be beneficial in Asians, in whom comorbidities and risk of thrombosis may differ from other ethnic groups.

INTRODUCTION: We aimed to evaluate the efficacy and safety of nanoparticle albumin-bound (nab-) paclitaxel for previously treated patients with advanced NSCLC. METHODS: In this randomized, open-label, noninferiority phase 3 trial, we enrolled patients with advanced NSCLC previously treated with cytotoxic chemotherapy. Patients were randomly allocated (1:1) to receive docetaxel (60 mg/m2) on day 1 or nab-paclitaxel (100 mg/m2) on days 1, 8, and 15 of a 21-day cycle. The primary end point was overall survival (OS) analyzed on an intention-to-treat basis. RESULTS: Between May 22, 2015, and March 12, 2018, a total of 503 patients were randomly allocated to the treatment. Median OS was 16.2 months (95% confidence interval [CI]: 14.4-19.0) for the 252 patients allocated to nab-paclitaxel and 13.6 months (95% CI: 10.9-16.5) for the 251 patients allocated to docetaxel (hazard ratio = 0.85, 95.2% CI: 0.68-1.07). Median progression-free survival was 4.2 months (95% CI: 3.9-5.0) for the nab-paclitaxel group versus 3.4 months (95% CI: 2.9-4.1) for the docetaxel group (hazard ratio = 0.76, 95% CI: 0.63-0.92, p = 0.0042). The objective response rate was 29.9% (95% CI: 24.0-36.2) for the nab-paclitaxel group and 15.4% (95% CI: 10.9-20.7) for the docetaxel group (p = 0.0002). Adverse events of grade greater than or equal to 3 included febrile neutropenia (5 of 245 patients [2%] in the nab-paclitaxel group versus 55 of 249 patients [22%] in the docetaxel group) and peripheral sensory neuropathy (24 [10%] versus 2 [1%], respectively). CONCLUSIONS: Nab-paclitaxel was noninferior to docetaxel in terms of OS. It should, thus, be considered a standard treatment option for previously treated patients with advanced NSCLC.

The incidence rate of post-cataract surgery posterior capsule opacification (PCO) and lens turbidity is about 20% in 5 years. Soemmering's ring, which is a type of PCO also called a regenerated lens with similar tissue structure to that of a human lens, is an important proxy for elucidating the mechanism of lens regeneration and maintenance of transparency. The authors created new human immortalized crystalline lens epithelial cells (iHLEC-NY1s) with excellent differentiation potential, and as a result of culturing the cells by static and rotation-floating methods, succeeded in producing a three-dimensional cell structure model (3D-iHLEC-NY1s) which is similar to Soemmering's ring in tissue structure and expression characteristics of αA-crystalline, βB2-crystalline, vimentin proteins. 3D-iHLEC-NY1s is expected to be a proxy in vitro experimental model of Soemmering's ring to enable evaluation of drug effects on suppression of cell aggregate formation and transparency. By further improving the culture conditions, we aim to control the cell sequence and elucidate the mechanism underlying the maintenance of lens transparency.

Although concurrent chemoradiotherapy is the standard therapy for unresectable stage III non-small cell lung cancer (NSCLC), no optimal concurrent chemoradiotherapy regimen has been identified in non-squamous NSCLC. We conducted an open-label, multicenter phase I trial to assess the safety of carboplatin (CBDCA) plus pemetrexed (PEM) with concurrent thoracic radiotherapy (TRT) of 60 Gy. The primary endpoint was determination of the maximum tolerated dose. In total, 6 patients were registered during the period from February 2012 through January 2014. Dose-limiting toxicities (DLTs) were observed in 2 patients (one case each of prolonged neutropenia and pneumonitis). The overall response rate was 83.3%, and median progression-free survival was 20.1 months. Since only two DLTs were observed in the phase I cohort, we concluded that CBDCA plus PEM with concurrent TRT was feasible in Japanese patients with unresectable stage III non-squamous NSCLCs. We will recommend the dose of CBDCA area under the curve 5 plus PEM 500 mg/m2 for the next phase II trial.

Aims: Malignant pleural mesothelioma (MPM) is an aggressive malignancy with poor prognosis and limited treatment options. Cisplatin plus pemetrexed is the only approved first-line treatment for patients with unresectable MPM. Recently, promising outcomes were observed with first-line bevacizumab combined with cisplatin/pemetrexed, leading to the recommendation of this regimen as a first-line treatment option for patients with MPM. Bevacizumab plus cisplatin/pemetrexed has been shown to be safe and effective in non–small cell lung cancer, however, there are no efficacy or safety data in Japanese patients with MPM treated with this regimen. We conducted a multicenter study to evaluate tolerability and safety for Japanese patients with chemotherapy-naïve, unresectable MPM. Methods: Eligible patients (n = 7) received bevacizumab plus cisplatin/pemetrexed (up to six cycles), then single-agent bevacizumab until disease progression or onset of unacceptable adverse events (AEs), according to the 3+3 design analogy. Results: One patient (14.3%) reported an AE (gastric ulcer) meeting tolerability criteria. All patients experienced gastrointestinal disorders, including nausea (grade 1/2 only, n = 6, 85.7%) and constipation (grade 1/2 only, n = 5, 71.4%). Five patients (71.4%) had grade 3 hypertension. Two patients discontinued treatment due to gastric ulcer (n = 1) and proteinuria (n = 1). At data cut-off, four patients had stable disease, two had partial response and one had non-complete response/non-progressive disease due to the absence of target lesions. Conclusions: Bevacizumab plus cisplatin/pemetrexed then bevacizumab was well tolerated in Japanese patients with MPM.

BACKGROUND: Pneumothorax is one complication of transbronchial biopsy (TBB) using endobronchial ultrasonography with a guide sheath (EBUS-GS-TBB). We sought to clarify the risk factors for pneumothorax after EBUS-GS-TBB under fluoroscopic guidance. METHODS: We retrospectively reviewed data from 916 patients who underwent EBUS-GS-TBB at Fujita Health University Hospital. We evaluated the following risk factors for pneumothorax after EBUS-GS-TBB: patient characteristics (sex, age, and pulmonary comorbidities); lesion data (location, size, existence of ground-glass opacities [GGOs], pleural involvement, computed tomography [CT] bronchus sign, visibility on fluoroscopy, and EBUS findings); final diagnosis; years of bronchoscopist experience; and guide sheath size. Univariate and multivariate logistic regression analyses were performed. RESULTS: Among the 916 patients, 30 (3.28%) presented with pneumothorax. With a univariate analysis, factors that independently predisposed to pneumothorax included lesions containing GGOs, lesions in sagittal lung segments on fluoroscopy, lesions that were not visible on fluoroscopy, and infectious lesions. A univariate analysis also showed that lesions in the right upper lobe or left upper division, as well as malignant lesions, were less likely to lead to pneumothorax. Age, underlying pulmonary disease, CT bronchus sign, EBUS findings, bronchoscopist experience, and guide sheath size did not influence the incidence of pneumothorax. A multivariate analysis revealed that only lesions containing GGOs (odds ratio [OR] 6.47; 95% confidence interval [CI] 2.13-19.6, P = 0.001) and lesions in lung segments with a sagittal orientation on fluoroscopy (OR 2.47; 95% CI 1.09-5.58, P = 0.029) were significant risk factors for EBUS-GS-TBB-related pneumothorax. CONCLUSIONS: EBUS-GS-TBB of lesions containing GGOs or lesions located in sagittal lung segments on fluoroscopy correlate with a higher pneumothorax risk.