Non-small cell lung cancer with tumor proportion score > 90% could increase the risk of severe immune-related adverse events in first-line treatments with immune checkpoint inhibitors: A retrospective single-center study.

BACKGROUND: Since 2015, immune checkpoint inhibitors have been a clinical treatment strategy for patients with advanced or recurrent non-small cell lung cancer (NSCLC). However, the relationship between immune-related adverse event (irAE) risk factors and patient clinical characteristics is unclear. This study aimed to evaluate the relationship between irAE risk and the clinical characteristics of patients with NSCLC. METHODS: We included patients with advanced or recurrent NSCLC with known programmed death-ligand 1 expression levels treated with immune checkpoint inhibitors. We retrospectively examined the medical records of 260 patients with NSCLC (March 2016-November 2020) and analyzed the relationship between the patient clinical characteristics and irAEs. RESULTS: Our retrospective analysis revealed that tumor proportion score (TPS) ≥ 90% and adenocarcinoma histology were independent risk factors for irAEs (odds ratio: 3.750 95% confidence interval [CI]: 1.58-8.89 and 0.424 95% CI: 0.19-0.97, respectively) in first-line treatment. However, in patients receiving second- or later-line treatments, no clinical characteristics were identified as risk factors for irAEs. Furthermore, no difference was observed in the response rates to first-line treatments between the TPS ≥ 90% and TPS < 90% groups (74% vs. 71%, p = 0.83). In later-line treatments, the TPS ≥ 90% group had a better response rate than the TPS < 90% group (55% vs. 17%, p < 0.05). However, no significant differences in overall survival were observed in either of the groups. CONCLUSIONS: TPS ≥ 90% and adenocarcinoma histology were independent risk factors for irAEs in previously untreated patients with advanced or recurrent NSCLC. Therefore, patients at high risk of irAEs require additional monitoring.

Expectoration of tonsillar metastasis of pulmonary pleomorphic carcinoma after pseudoprogression: A case report.

Pulmonary pleomorphic carcinoma is a rare malignant tumor that grows rapidly and has a poor prognosis. Although no effective treatments have so far been established, immune checkpoint inhibitors (ICIs) have shown clinical improvement in some cases of pleomorphic carcinoma. However, pseudoprogression is a major concern for treatment of this carcinoma using ICIs. Here, we report the case of a 61-year-old man who was diagnosed with large cell carcinoma of the lung with brain metastases. Systemic chemotherapy comprising carboplatin and pemetrexed was administered as a first-line therapy; however, disease progression was observed. A tonsillar lesion grew rapidly after the administration of nivolumab as a second-line therapy. Tracheostomy was planned to avoid suffocation, but the patient naturally expectorated the tumor. Pathological examination revealed that it was a palatine tonsillar metastasis of pulmonary pleomorphic carcinoma with infiltration of CD8+/CD4- lymphocytes and necrosis. The primary lesion expanded after nivolumab administration and shrank with no additional nivolumab administration. We therefore concluded that pseudoprogression caused expectoration of the tonsillar metastasis. Hence, ICIs can cause serious adverse events due to pseudoprogression.

EGFR-mutant lung adenocarcinoma associated with antisynthetase syndrome successfully treated with osimertinib.

Here, we report a rare case involving a 66-year-old man with epidermal growth factor receptor (EGFR)-mutant lung adenocarcinoma and antisynthetase syndrome (ASS) treated with osimertinib. The patient presented with respiratory failure and bilateral pulmonary opacities; he was diagnosed with ASS accompanied by interstitial lung disease (ILD), consistent with paraneoplastic syndrome. After steroid pulse therapy, osimertinib was administered for lung adenocarcinoma without ILD exacerbation. Osimertinib could therefore be a treatment option for EGFR-mutant lung cancer with paraneoplastic ILD.

Safety and effectiveness of pirfenidone combined with carboplatin-based chemotherapy in patients with idiopathic pulmonary fibrosis and non-small cell lung cancer: A retrospective cohort study.

BACKGROUND: Pirfenidone is an antifibrotic agent that is potentially effective for the treatment of idiopathic pulmonary fibrosis (IPF). However, no study has reported on its prophylactic value against chemotherapy-associated acute IPF exacerbations when combined with chemotherapy for non-small cell lung cancer (NSCLC). The present study assessed the safety and effectiveness of pirfenidone combined with carboplatin-based chemotherapy or immune checkpoint inhibitors (ICIs) in patients with IPF and NSCLC. METHODS: A total of 14 patients with IPF and NSCLC who received treatment from 2013 to 2019 were included. Patients were treated with pirfenidone combined with carboplatin and nanoparticle albumin-bound paclitaxel or S-1 as first-line chemotherapy. After confirming disease progression, patients received cytotoxic agents or ICIs, including nivolumab and pembrolizumab. Pirfenidone was continued regardless of chemotherapy changes. Overall survival (OS) and progression-free survival (PFS) for lung cancer and IPF were calculated. Moreover, the cumulative incidence of acute exacerbation of IPF (AE-IPF) within one year was evaluated. RESULTS: Median PFS for lung cancer was 110 days (95% confidence interval [CI]: 57-199 days), while the median OS was 362 days (95% CI: 220-526 days). Moreover, PFS for IPF was 447 days (95% CI: 286-indeterminate days), and the cumulative incidence of AE-IPF within one year was 18%. Notably, none of the patients developed AE-IPF associated with first-line chemotherapy. Among the included patients, four received ICIs, none of whom developed ICI-associated AE-IPF. CONCLUSIONS: The present study found that pirfenidone combined with carboplatin-based regimens or ICIs might be safe first-line chemotherapy for patients with IPF and NSCLC. KEY POINTS: SIGNIFICANT FINDINGS OF THE STUDY: No patients with IPF and NSCLC who received pirfenidone in combination with first-line carboplatin-based chemotherapy or late-line ICIs developed acute IPF exacerbations. What this study adds Pirfenidone might have a prophylactic effect against chemotherapy-associated AE-IPF.

Hyperprogressive disease in patients with non-small cell lung cancer treated with nivolumab: A case series.

BACKGROUND: Nivolumab is an anti-PD-1 blocking monoclonal antibody approved for the treatment of non-small cell lung cancer (NSCLC). However, some patients on immunotherapy may experience rapid progression and worsening clinical status, known as hyperprogressive disease. We retrospectively reviewed the clinical records of patients with NSCLC administered nivolumab therapy at Toneyama National Hospital, Japan, from January 2016 to January 2018. Of the 87 patients administered nivolumab therapy, five experienced rapid progression during one cycle of nivolumab therapy. Four patients were treated with corticosteroids to overcome their symptomatic events. Nivolumab exhibited efficacy after temporal progression, so-called "pseudoprogression", in three patients, and their symptoms and laboratory results improved. In the other patient, pleural and pericardial effusions increased after nivolumab therapy, and drainage was required, with no subsequent recurrence. The clinical courses of our case series indicate that alternative treatment, namely high-dose corticosteroids, antibiotics, and drainage, effectively treated the symptoms of rapid tumor progression. Of note, corticosteroids suppressed the temporary inflammatory reaction to nivolumab. Although hyperprogressive disease is thought to be associated with poor quality of life and survival, these treatment strategies may be useful in patients with expected responses to immunotherapy.

Post-progression survival after cessation of treatment with nivolumab for advanced non-small cell lung cancer: A retrospective study.

OBJECTIVES: The effectiveness of treatment after cessation of nivolumab in patients with advanced non-small cell lung cancer (NSCLC) has not been well investigated. The aim of the present study was to clarify the clinical benefit of post-nivolumab treatment in such patients. MATERIALS AND METHODS: A retrospective review was conducted on patients who received treatment after cessation of nivolumab due to disease progression or adverse events at the Toneyama National Hospital between January 2016 and April 2017. RESULTS: Among 64 patients treated with nivolumab, 26 patients received treatment after cessation of nivolumab due to disease progression (n = 21) or adverse events (n = 5). The median age of the patients was 68 years and 19 patients were male. Nineteen patients had performance status (PS) 1 or less at initiation of post-nivolumab treatment. Four, 20, and 2 patients were treated with platinum doublets, a single agent, and molecular targeting agents, respectively. Response rate, disease control rate, and median progression-free survival of first-line post-nivolumab treatment were 34.6% (9 patients), 73.1% (19 patients), and 2.8 months (95% confidence interval [CI]: 1.7-5.2), respectively. Adverse events (≥ grade 3) and treatment cessation were observed in 57.7% (15 patients) and 19.2% (5 patients), respectively. There were no statistically significant differences for the majority of patient characteristics between the groups with (n = 26) and without post-nivolumab treatment. However, PS at cessation of nivolumab and post-progression survival (PPS) after cessation of nivolumab (median PPS: 12.6 vs. 1.4 months, 95% CI: 3.8-14.7 vs. 0.4-2.2) were significantly different between the groups. A multivariate Cox regression analysis showed significant correlation of PS at cessation of nivolumab (hazard ratio [HR]: 0.34, 95% CI: 0.13-0.87) and post-nivolumab treatment (HR: 0.19, 95% CI: 0.08-0.43) with prolonged PPS after nivolumab. CONCLUSION: Median post-progression survival in patients with advanced NSCLC who received post-nivolumab treatment was approximately 1 year.

Two cases of response to pembrolizumab in epidermal growth factor receptor mutated lung adenocarcinoma patients with programmed death-ligand 1 overexpression.

Recently, the immune checkpoint inhibitor (ICI) pembrolizumab was demonstrated to be superior to platinum doublet chemotherapy in the first-line setting in patients with tumor programmed death-ligand 1 (PD-L1) expression of at least 50%. However, because patients with epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK) rearrangements were not included in that study, the efficacy of pembrolizumab in lung cancers carrying EGFR mutations could not be determined. Here we describe two cases of response to pembrolizumab in EGFR mutated lung adenocarcinoma patients with PD-L1 overexpression. These cases indicate that ICI is an effective treatment for EGFR mutated lung adenocarcinoma patients with PD-L1 overexpression.

Radiation Pneumonitis with Eosinophilic Alveolitis in a Lung Cancer Patient.

A 59-year-old woman suffering from dry cough and dyspnea was admitted to our hospital. She had undergone concurrent chemo-radiotherapy five months earlier. Chest computed tomography revealed bilateral ground-glass opacities extending outside the irradiated lung field. Her eosinophil numbers were increased in both the peripheral blood and the bronchoalveolar lavage fluid; therefore, she was diagnosed with radiation pneumonitis accompanied by eosinophilic alveolitis. Steroid therapy promptly improved the pneumonitis. Radiation pneumonitis accompanied by eosinophilic alveolitis extending outside the irradiated field is rare. Bronchoalveolar lavage is useful for a diagnosis, and steroid therapy is effective for treatment.

Case series of pleomorphic carcinomas of the lung treated with nivolumab.

Pleomorphic carcinoma (PC) of the lung is a rare type of non-small cell lung cancer, exhibiting aggressive behavior and resistance to chemotherapy and radiotherapy. A previous study reported that PCs expressed high levels of PD-L1, suggesting the potential efficacy of immune checkpoint inhibitors in these tumors. We retrospectively reviewed the clinical records of three patients with PC of the lung treated with nivolumab: a 59-year-old woman (Case 1), a 66-year-old man (Case 2), and an 83-year-old man (Case 3). PD-L1 was highly expressed in their tumor cells. Two cases showed a partial response with long progression-free survival. However, in Case 2, brain and bone metastases progressed during nivolumab treatment in spite of high PD-L1 expression. This case series indicates that nivolumab is effective to some extent for PC of the lung. However, the clinical course of patients treated with nivolumab should be carefully observed, even when PD-L1 is highly expressed.

Vitiligo in a patient with lung adenocarcinoma treated with nivolumab: A case report.

Nivolumab, an anti-programmed cell death-1 protein monoclonal antibody, is effective for treating patients with late-stage non-small-cell lung cancer. Immune checkpoint inhibitors such as nivolumab induce various kinds of immune-related adverse events, including vitiligo. Vitiligo has been reported in patients with melanoma but not lung cancer. We describe a 75-year-old man with lung adenocarcinoma, stage 4 with pleural and pericardial effusion, that progressed after first-line chemotherapy. Subsequently, he was treated with nivolumab as second-line therapy. After 6days of administering nivolumab, he developed vitiligo suddenly on the trunk of his body. Except for vitiligo, his physical examination was normal, and treatment with nivolumab was well tolerated. Therefore, this treatment was continued without further development or expansion of vitiligo. A computed tomography scan showed a reduction in the size of the lung nodule and stabilization of the pleural and pericardial effusion. This is the first case of vitiligo associated with the use of nivolumab in a patient with lung adenocarcinoma.

Survivin expression in lung cancer: Association with smoking, histological types and pathological stages.

Survivin is expressed in the nucleus and/or cytoplasm of various malignant cells. Nuclear survivin is critical for the completion of mitosis, while cytoplasmic survivin functions as an inhibitor of apoptosis. The expression of survivin has been reported to be associated with the aggressiveness of certain types of cancer. The present study examined the association between cigarette smoking history and the expression of survivin and Ki-67 in lung adenocarcinomas of pathological (p) stages I, II and III. The expression of survivin and Ki-67 in adenocarcinomas was also compared with that of other p-stage I lung cancers, including squamous cell carcinoma (SqCC), large cell neuroendocrine carcinoma (LCNEC) and small cell carcinoma (SmCCs), of patients with a smoking history. In adenocarcinomas at p-stage I, labeling indices (LIs) of nuclear survivin and Ki-67 were significantly higher in tissue samples from smokers than those from non-smokers; however, the nuclear survivin and Ki-67 LIs in p-stage II and III adenocarcinomas from non-smokers and smokers were similar to those in p-stage I adenocarcinomas of smokers. The nuclear survivin and Ki-67 LIs in adenocarcinomas of smokers at p-stage I were lower than those in SqCCs, LCNECs and SmCCs of smokers at the same stage. Smokers with adenocarcinoma also exhibited a higher survival rate compared with that of smokers with SqCCs, LCNECs and SmCCs. The present results indicated that a history of smoking is associated with increased nuclear survivin and Ki-67 expression in lung adenocarcinomas of p-stage I, but not p-stages II or III. In addition it was revealed that, in smokers, the nuclear survivin and Ki-67 expression in p-stage I adenocarcinomas was lower than that of other p-stage I lung cancer types, and was associated with an enhanced survival rate. In conclusion, smoking is associated with the histogenesis of lung adenocarcinoma but not with the development of lung adenocarcinoma, based on the nuclear expression levels of Ki-67 and survivin.

Nuclear survivin expression in small cell lung cancer.

BACKGROUND/AIM: Little evidence exists regarding a relationship between survivin expression and prognosis in small cell lung cancer (SCLC). We investigated the relationship between survivin expression, clinical characteristics and prognosis in SCLC patients. MATERIALS AND METHODS: We retrospectively reviewed medical records of study patients and analyzed their tumor sections using nuclear survivin labeling index (LI). RESULTS: A significant correlation between nuclear survivin LI and clinical stage was found (p=0.012). In multivariate analysis, a significant association was found between survival and clinical stage (hazard ratio (HR)=2.09; 95 % confidence interval (CI)=1.08-4.31; p=0.027) but not between survival and nuclear survivin LI (HR=0.96; 95 % CI=0.91-1.02; p=0.2). CONCLUSION: We did not find any positive relationship between nuclear survivin expression and survival in SCLC patients. Conversely, we found a positive relationship between clinical stage and nuclear survivin LI, which is considered to be useful in deciding treatment strategies.

[Safe treatment of lung squamous cell carcinoma with nanoparticle albumin-bound Paclitaxel in a patient with a previous hypersensitivity reaction after docetaxel administration].

A 61-year-old man was diagnosed with lung squamous cell carcinoma in the lower lobe of the right lung. He had received first-line chemotherapy consisting of cisplatin and docetaxel (DTX); however, an allergic/hypersensitivity reaction occurred shortly after administration of the second course of DTX. Thirty-nine months later, he received nanoparticle albumin-bound paclitaxel (nab-PTX) as sixth-line chemotherapy, which did not produce a hypersensitivity reaction. Hypersensitivity after DTX administration may have been due to the DTX vehicle. Therefore, nab-PTX administered under close supervision is a valid therapeutic option in similar cases.

Lymphatic invasion of micropapillary cancer cells is associated with a poor prognosis of pathological stage IA lung adenocarcinomas.

The cancer cells of lung adenocarcinoma with a micropapillary pattern (MPP) have been found to frequently invade lymphatic vessels, and the prognosis of patients with lung adenocarcinoma with an MPP is poor. In the present study, the cancer cells of lung adenocarcinomas containing an MPP were found to express vimentin more extensively than those in lung adenocarcinoma without an MPP. The contribution of cancer cells in the MPP component to adenocarcinoma lymphatic invasion was assessed using vimentin as a marker. Vimentin expression was analyzed in the cancer cells present in each lymphatic vessel and compared with the expression of vimentin in the cancer cells in the adenocarcinomas without an MPP component. The results showed that the cancer cells in the lymphatic vessels expressed vimentin more extensively than those in the adenocarcinoma components without an MPP, suggesting that cancer cells derived from an MPP component are present in the lymphatic vessels. By contrast, the area of the MPP component in each adenocarcinoma was <25%. These findings suggest that cancer cells in MPP components have a high capacity to invade lymphatic vessels and that their high invasive capacity may be associated with a poor prognosis in patients with adenocarcinoma with an MPP component.

Association of cigarette smoking with the expression of nuclear survivin in pathological Stage IA lung adenocarcinomas.

Survivin is expressed in the cytoplasm and/or nucleus of various types of malignant tumor cells. Cytoplasmic survivin functions as an apoptosis inhibitor, while nuclear survivin is indispensable for complete mitosis completion. To investigate the effect of cigarette smoking on the survivin expression in lung adenocarcinomas at the early developmental stage, we examined the expression of nuclear and cytoplasmic survivin in pathological Stage IA lung adenocarcinomas resected from 38 non-smokers and 44 smokers (current smokers and ex-smokers) using an immunohistochemical method. Labeling indices of nuclear survivin in tumors of smokers were significantly greater than those of non-smokers. The labeling index of nuclear survivin was above 3 % in only 1 (2.6 %) of the 38 tumors of the non-smokers, while the labeling indices in 19 (43.2 %) of 44 tumors of the smokers were above 3 % with a significantly greater frequency. There was no significant difference in the labeling index of nuclear survivin between current smokers and ex-smokers. There was no significant difference in the labeling index of cytoplasmic survivin between tumors of the non-smokers and the smokers. The present results show that cigarette smoking is associated with the higher nuclear surviving expression in lung adenocarcinomas at the early stage, suggesting that cigarette smoking affects the nuclear survivin expression in lung adenocarcinomas at the early developmental stage.

CXCL12 as a biological marker for the diagnosis of tuberculous pleurisy.

Although a chemokine CXCL12 is implicated in some infectious diseases, especially those in which T cell-mediated immunity plays critical roles, the relevance of CXCL12 to tuberculosis has never been elucidated. To determine the clinical efficacy of CXCL12 as a diagnostic marker for tuberculous (TB) pleurisy, we measured CXCL12 concentration in pleural fluid and serum from patients with various etiologies. Of 60 patients with pleural fluid, the median age of TB patients was 52 which was significantly lower than 71 of non-TB patients (P < 0.01). CXCL12 level in TB effusion (4456 ± 1013 pg/mL, n = 15) was significantly higher than non-TB effusion (2851 ± 1229 pg/mL, n = 45) (P < 0.01). On the other hand, serum CXCL12 level showed no significant differences among TB pleurisy, non-TB pleurisy, and normal healthy subjects. The sensitivity and specificity of CXCL12 in pleural fluid for the diagnosis of TB pleurisy was 60.0% and 93.2% (cut-off value = 4600 pg/mL), respectively. Area under the receiver operating characteristic (ROC) curve (AUC) for CXCL12 was 0.84. As the source of CXCL12, pleural mesothelium, endothelium of pulmonary vessels, bronchial epithelium, multinucleated giant epithelioid cells, and macrophages were positive for CXCL12 staining. Increased CXCL12 level in pleural fluid could be an informative diagnostic marker for differentiating TB pleurisy from other etiologies.

Treatment of Non-Small-Cell Lung Cancer with Erlotinib following Gefitinib-Induced Hepatotoxicity: Review of 8 Clinical Cases.

Objective. Gefitinib often induces liver damage. A few reports have described that the subsequent administration of erlotinib was associated with less hepatotoxicity, but the safety and efficacy of this treatment are still not fully investigated. Therefore, we evaluated retrospectively the patients with erlotinib following gefitinib-induced hepatotoxicity. Methods and Patients. We retrospectively reviewed the medical records between December 2007 and March 2010. The patients were evaluated including the following information: age, gender, histology of lung cancer, performance status, smoking status, epidermal growth factor receptor (EGFR) mutation status, liver metastasis, viral hepatitis, alcoholic liver injury, clinical response, and hepatotoxicity due to EGFR tyrosine kinase inhibitors. Results. We identified 8 patients with erlotinib following gefitinib-induced hepatotoxicity. All achieved disease control by gefitinib. Hepatotoxicity was grades 2 and 3 in 3 and 5 patients, respectively. The median duration of treatment with gefitinib was 112.5 days and the median time to gefitinib-induced hepatotoxicity was 51.5 days. The median duration of treatment with erlotinib was 171.5 days. Grade 1 and 2 erlotinib-induced hepatotoxicity was observed in 2 and 1 patient, respectively. Conclusions. Erlotinib administration with careful monitoring is thought to be a good alternative strategy for patients who respond well to gefitinib treatment but experience hepatotoxicity.

A case of acute and severe thrombocytopenia due to readministration of rifampicin.

A 49-year-old-woman was diagnosed with tuberculosis of the left humerus. She had received treatment, including rifampicin, for tuberculosis 17 years previously. Treatment was begun with isoniazid, rifampicin, ethambutol, and pyrazinamide, but these were discontinued because of mild neutropenia and thrombocytopenia 2 weeks posttreatment. Rifampicin and ethambutol were readministered after a 4-day interruption; however, generalized purpura appeared several hours later. By the next day, her platelet count was reduced from 160 × 10(3) to 3 × 10(3)/µl. The patient improved rapidly after platelet transfusion and steroid treatment. Readministration of drugs other than rifampicin did not induce thrombocytopenia; therefore, thrombocytopenia was likely due to rifampicin.

Results of pulmonary resection following neoadjuvant therapy for locally advanced (IIIA-IIIB) lung cancer.

OBJECTIVE: We performed this study to determine the role and prognostic factors of neoadjuvant therapy followed by surgery for locally advanced non-small cell cancer. METHODS: One hundred patients with clinical stage III non-small cell lung cancer (79 IIIA, 21 IIIB; 78 males, 22 females; average age 60.5 years) received neoadjuvant therapy, of whom 84 received two cycles of platinum chemotherapy combined with an average radiation dose of 41.5Gy, and 16 patients underwent chemotherapy alone. The mean follow-up duration was 80.9 months. Survival rate was estimated by the Kaplan-Meier method, and a Cox proportional hazards model was applied to determine the prognostic factors. RESULTS: The operative procedures included 74 lobectomies, 7 bi-lobectomies, and 19 pneumonectomies. Two patients died within 30 days due to adult respiratory distress syndrome and acute pulmonary embolism, respectively. The overall 5-year survival rate was 39.7% with a median survival time (MST) of 39.6 months. The 5-year survival rate for downstaged (pN1,2) patients was 53.5% while it was 16.3% for patients with residual N2. There was no difference in survival between lobectomy and pneumonectomy (MST 38 months vs 42 months). Univariate and multivariate analyses revealed that nodal status and tumor size after neoadjuvant therapy were independent prognostic factors. CONCLUSIONS: Neoadjuvant therapy was shown to deliver the optimal effect for surgery for cIIIA/IIIB NSCLC with acceptable mortality. Re-staging to exclude the residual multiple nodal metastasis can lead to the proper patient selection. A pneumonectomy, as a last option, following neoadjuvant therapy did not affect the mortality.

Diagnosis of solitary pulmonary nodule: optimal strategy based on nodal size.

We attempted to determine the smallest size of nodule that could be accurately diagnosed by fluoroscopic fiberoptic bronchoscopy (FFB) and computed tomography (CT) guided trans-corporeal biopsy (CTGB) procedures. Parenchymal lesions (n=1483) detected using chest roentgenography were investigated in the present study, and the diagnostic capabilities of FFB and CTGB were determined based on receiver-operating characteristic curves. A total of 990 nodules (67%) were diagnosed using FFB, while 58 (4%) were diagnosed with CTGB, 339 (23%) by surgery, and 100 (6%) by other methods. The area under the curve (AUC) was 0.74 (0.72<95% CI <0.77) in FFB cases and 0.95 (0.92<95% CI <0.98) in CTGB cases. FFB was found capable of diagnosing nodules with sizes between 0 and 1.0 cm, 1.0 and 1.5 cm, 1.5 and 2.0 cm, and more than 2.0 cm at ratios of 0/58 (0%), 19/115 (16%), 59/141 (35%), and 1072/1173 (97%), respectively (P<0.0001). The diagnostic ability of CTGB for nodules categorized in the same manner was 0/25 (0%), 2/29 (7%), 5/24 (21%), and 53/63 (84%), respectively (P<0.0001). For SPNs smaller than 1.5 cm in diameter, both FFB and CTGB showed a low diagnostic sensitivity.