31 results on '"Nakashima, Taku"'
Search Results
2. Hypoxia-inducible factor 1α modulates interstitial pneumonia-mediated lung cancer progression.
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Shimoji K, Nakashima T, Masuda T, Namba M, Sakamoto S, Yamaguchi K, Horimasu Y, Mimae T, Miyamoto S, Iwamoto H, Fujitaka K, Hamada H, Okada M, and Hattori N
- Subjects
- Animals, Humans, Mice, Ascorbic Acid, Hypoxia pathology, Lung pathology, Tumor Microenvironment, Hypoxia-Inducible Factor 1, alpha Subunit metabolism, Lung Diseases, Interstitial complications, Lung Diseases, Interstitial metabolism, Lung Diseases, Interstitial pathology, Lung Neoplasms genetics, Pneumonia, Pulmonary Fibrosis pathology
- Abstract
Background: The prognosis of patients with lung cancer accompanied by interstitial pneumonia is poorer than that of patients with lung cancer but without interstitial pneumonia. Moreover, the available therapeutic interventions for lung cancer patients with interstitial pneumonia are limited. Therefore, a new treatment strategy for these patients is required. The aim of the present study was to investigate the pathophysiological relationship between interstitial pneumonia and lung cancer and explore potential therapeutic agents., Methods: A novel hybrid murine model of lung cancer with interstitial pneumonia was established via bleomycin-induced pulmonary fibrosis followed by orthotopic lung cancer cell transplantation into the lungs. Changes in tumor progression, lung fibrosis, RNA expression, cytokine levels, and tumor microenvironment in the lung cancer with interstitial pneumonia model were investigated, and therapeutic agents were examined. Additionally, clinical data and samples from patients with lung cancer accompanied by interstitial pneumonia were analyzed to explore the potential clinical significance of the findings., Results: In the lung cancer with interstitial pneumonia model, accelerated tumor growth was observed based on an altered tumor microenvironment. RNA sequencing analysis revealed upregulation of the hypoxia-inducible factor 1 signaling pathway. These findings were consistent with those obtained for human samples. Moreover, we explored whether ascorbic acid could be an alternative treatment for lung cancer with interstitial pneumonia to avoid the disadvantages of hypoxia-inducible factor 1 inhibitors. Ascorbic acid successfully downregulated the hypoxia-inducible factor 1 signaling pathway and inhibited tumor progression and lung fibrosis., Conclusions: The hypoxia-inducible factor 1 pathway is critical in lung cancer with interstitial pneumonia and could be a therapeutic target for mitigating interstitial pneumonia-mediated lung cancer progression., (© 2023. The Author(s).)
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- 2023
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3. Predictive value of serum high-mobility group box 1 levels for checkpoint inhibitor pneumonitis.
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Tanahashi H, Yamaguchi K, Kurose K, Nakao S, Sakamoto S, Horimasu Y, Masuda T, Miyamoto S, Nakashima T, Iwamoto H, Fujitaka K, Hamada H, Oga T, Oka M, and Hattori N
- Subjects
- Humans, B7-H1 Antigen, Retrospective Studies, Carcinoma, Non-Small-Cell Lung drug therapy, Lung Neoplasms drug therapy, Lung Neoplasms complications, HMGB1 Protein, Antineoplastic Agents, Immunological adverse effects, Pneumonia chemically induced
- Abstract
Background and Objective: Checkpoint inhibitor pneumonitis (CIP), caused by the anti-programmed cell death-1 (PD-1)/programmed cell death ligand-1 (PD-L1) antibody, can be a fatal adverse event in cancer patients. However, no predictive biomarkers for CIP have been identified. Because high-mobility group box 1 (HMGB1) can aggravate lung injury and potentially increase the immune response, it was investigated as a predictive blood marker., Methods: Blood samples, prospectively stored before anti-PD-1/PD-L1 monotherapy between December 2015 and October 2020, were obtained at two university hospitals from 87 and 43 non-small cell lung cancer (NSCLC) patients (discovery and validation cohorts, respectively). We retrospectively evaluated the association of serum HMGB1 levels with the incidence of CIP developed within 3 months of initiating anti-PD-1/PD-L1 therapy., Results: CIP was observed in 9 (10.3%) and 6 (14.0%) patients in the discovery and validation cohorts, respectively. In each cohort, serum HMGB1 levels were significantly and reproducibly higher in patients with CIP. In the discovery cohort, an HMGB1 cut-off level of 11.24 ng/ml was identified by receiver operating characteristic analysis. CIP incidence in the HMGB1
high subgroup was significantly higher than that in the HMGB1low subgroup in the discovery (41.2% vs. 2.9%) and validation cohorts (36.4% vs. 6.3%). In an exploratory pooled analysis, three patients died of grade 5 CIP; a 19.29 ng/ml HMGB1 cut-off level detected grade 5 CIP with 100% sensitivity and 96.85% specificity., Conclusion: Our results suggest that HMGB1 may be a potential blood marker to predict the development and severity of CIP in NSCLC patients., (© 2022 Asian Pacific Society of Respirology.)- Published
- 2023
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4. Predictive role of circulatory levels of high-mobility group box 1 for radiation pneumonitis in patients with non-small cell lung cancer treated with definitive thoracic radiotherapy.
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Isoyama S, Yamaguchi K, Imano N, Sakamoto S, Horimasu Y, Masuda T, Miyamoto S, Nakashima T, Iwamoto H, Fujitaka K, Hamada H, Nagata Y, and Hattori N
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- Humans, Retrospective Studies, Radiation Pneumonitis etiology, Radiation Pneumonitis pathology, Carcinoma, Non-Small-Cell Lung radiotherapy, Lung Neoplasms pathology, HMGB1 Protein
- Abstract
Background: High-mobility group box 1 (HMGB1) is a pro-inflammatory protein associated with the pathophysiology of lung injury and lung tumorigenesis. Here, we investigated the predictive potential of serum HMGB1 levels for radiation pneumonitis in patients with lung cancer., Methods: This was a retrospective biomarker study of 73 patients with non-small cell lung cancer treated with definitive thoracic radiotherapy between August 2007 and January 2021. We measured HMGB1 levels in serum stored before treatment, and analyzed its association with the development of grade ≥ 2 or grade ≥ 3 radiation pneumonitis. Additionally, baseline characteristics affecting HMGB1 levels were identified., Results: Of the 73 patients, 21 (28.8%) and 6 (8.2%) patients experienced grade 2 and ≥ 3 radiation pneumonitis, respectively. Univariate and multivariate logistic regression analyses revealed that higher baseline levels of serum HMGB1 were significantly associated with a higher risk of grade ≥ 3, but not grade ≥ 2, radiation pneumonitis. The incidence of grade ≥ 3 radiation pneumonitis was higher in patients with HMGB1 levels ≥ 6.2 ng/mL than in those with levels < 6.2 ng/mL (25.0% vs. 3.5%, p = 0.019). Baseline serum levels of HMGB1 were independently and positively associated with gross tumor volume., Conclusions: Higher serum HMGB1 levels were significantly associated with the risk of grade ≥ 3 radiation pneumonitis in patients with lung cancer, and therefore, HMGB1 could be a potential blood biomarker for predicting severe radiation pneumonitis., (© 2022. The Author(s) under exclusive licence to Japan Society of Clinical Oncology.)
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- 2022
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5. Association of the RAGE/RAGE-ligand axis with interstitial lung disease and its acute exacerbation.
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Yamaguchi K, Iwamoto H, Sakamoto S, Horimasu Y, Masuda T, Miyamoto S, Nakashima T, Fujitaka K, Hamada H, and Hattori N
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- Animals, Disease Progression, Glycation End Products, Advanced therapeutic use, Ligands, Mice, Prognosis, Receptor for Advanced Glycation End Products, Idiopathic Pulmonary Fibrosis, Lung Diseases, Interstitial pathology, Lung Neoplasms drug therapy
- Abstract
The receptor for advanced glycation end product (RAGE) is a transmembrane receptor highly expressed in type 1 pneumocytes of healthy lungs. RAGE is considered to play a homeostatic role in the lung, as RAGE knockout mice develop lung fibrosis as they age. In contrast, RAGE can bind numerous ligands, including high-mobility group box 1 (HMGB1). These interactions initiate pro-inflammatory signaling associated with the pathogenesis of lung injury and interstitial lung disease (ILD), including idiopathic pulmonary fibrosis (IPF). ILD is a broad category of diffuse parenchymal lung disease characterized by various extents of lung fibrosis and inflammation, and IPF is a common and progressive ILD of unknown cause. The prognosis of patients with IPF is poor, and acute exacerbation of IPF (AE-IPF) is one of the main causes of death. Recent reports indicate that acute exacerbations can occur in other ILDs (AE-ILD). Notably, ILD is frequently observed in patients with lung cancer, and AE-ILD after surgical procedures or the initiation of chemotherapy for concomitant lung cancer are clinically important due to their association with increased mortality. In this review, we summarize the associations of RAGE/soluble RAGE (sRAGE)/RAGE ligands with the pathogenesis and clinical course of ILD, including IPF and AE-IPF. Additionally, the potential use of sRAGE and RAGE ligands as predictive markers of AE-IPF and cancer treatment-triggered AE-ILD is also discussed., Competing Interests: Conflict of Interest The authors have no conflicts of interest., (Copyright © 2022 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.)
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- 2022
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6. Characteristic computed tomography features in mesenchymal-epithelial transition exon14 skipping-positive non-small cell lung cancer.
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Watari N, Yamaguchi K, Terada H, Hamai K, Masuda K, Nishimura Y, Sakamoto S, Masuda T, Horimasu Y, Miyamoto S, Nakashima T, Iwamoto H, Shoda H, Ishikawa N, Fujitaka K, Miyazaki K, Miyata Y, Hamada H, Awai K, and Hattori N
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- Aged, Exons, Female, Humans, Male, Mutation, Proto-Oncogene Proteins c-met genetics, Retrospective Studies, Tomography, X-Ray Computed, Carcinoma, Non-Small-Cell Lung diagnostic imaging, Carcinoma, Non-Small-Cell Lung drug therapy, Carcinoma, Non-Small-Cell Lung genetics, Lung Neoplasms diagnostic imaging, Lung Neoplasms drug therapy, Lung Neoplasms genetics
- Abstract
Background: Mesenchymal-epithelial transition exon14 (METex14) skipping is one of the therapeutic driver oncogene mutations in non-small cell lung cancer (NSCLC), and can be treated with tepotinib and capmatinib. There is only one report on computed tomography (CT) findings of METex14 skipping-positive NSCLC, which shows that the primary tumor tends to have a large mass in the upper lobe, and extrathoracic metastases are common. This study examined the CT findings of METex14 skipping-positive NSCLC, focusing on the features of the margins and internal structures., Methods: We consecutively included patients with METex14 skipping-positive NSCLC who were diagnosed between January 2018 and December 2020 at four independent institutions. We retrospectively reviewed the patient demographics and CT findings for tumor margins (invasion into surrounding tissue, lobulation, pleural indentation, spicula, and ground-glass opacity) and internal structures (air bronchograms, cavitation and internal low-density area)., Results: Fifteen patients with METex14 skipping-positive NSCLC were identified. Almost half of the patients were men (7/15; 46.7%), and their median age was 75.0 years. More than half were either current or former smokers (9/15; 60.0%). A vast majority of histological subtypes were adenocarcinoma (10/15; 66.7%), followed by pleomorphic carcinoma (3/15; 20.0%) and squamous cell carcinoma (2/15; 13.3%). With regard to CT findings, most primary tumors presented as masses larger than 30 mm (12/15; 80.0%) and were located in the upper lobes (12/15; 80.0%). Invasion into surrounding tissue and presence of internal low-density areas were observed in 60.0% (9/15) and 66.7% (10/15) of the primary tumors, respectively. Additionally, their frequencies increased to 72.7% (8/11) and 90.9% (10/11) in stage III/IV cases, respectively. In lymph node metastasis, internal low-density areas were observed in 8/10 cases (80.0%). Although these two CT features were rarely observed in distant metastases at diagnosis, they became apparent with progression of the metastatic tumor size., Conclusions: METex14 skipping-positive NSCLC tumors tend to invade surrounding tissue and possess internal low-density areas. These CT findings might be characteristic of METex14 skipping-positive NSCLC., (© 2022. The Author(s).)
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- 2022
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7. First-line osimertinib treatment in a patient with lung adenocarcinoma with coexisting epidermal growth factor receptor G719S and de novo T790M mutations.
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Ito N, Masuda T, Ooka I, Hosoya T, Yamaguchi K, Sakamoto S, Horimasu Y, Nakashima T, Miyamoto S, Iwamoto H, Fujitaka K, Hamada H, and Hattori N
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- Acrylamides, Aged, Aniline Compounds, ErbB Receptors genetics, Female, Humans, Mutation, Protein Kinase Inhibitors, Adenocarcinoma of Lung drug therapy, Adenocarcinoma of Lung genetics, Adenocarcinoma of Lung pathology, Carcinoma, Non-Small-Cell Lung complications, Carcinoma, Non-Small-Cell Lung drug therapy, Carcinoma, Non-Small-Cell Lung genetics, Lung Neoplasms complications, Lung Neoplasms drug therapy, Lung Neoplasms genetics
- Abstract
Osimertinib is the standard treatment for non-small cell lung cancer (NSCLC) with an active epidermal growth factor receptor (EGFR) mutation and a T790M mutation-present in cases of acquired resistance. However, there have been no reports on the efficacy of osimertinib in patients with EGFR G719S and de novo T790M mutations. Here, we present the case of a 71-year-old woman who received first-line osimertinib for lung adenocarcinoma with G719S and de novo T790M mutations. A partial response was observed after osimertinib initiation; however, the disease progressed 5 months after. Next-generation sequencing using a rebiopsy sample from the brain metastases revealed no newly acquired resistance mutations, including EGFR C797S. From experience, the efficacy of osimertinib in NSCLC with G719S and T790M compound mutations may be poor. Therefore, optimal treatment for these cases should be determined., (© 2021 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)
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- 2022
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8. Association between glucose intolerance and chemotherapy-induced lung injury in patients with lung cancer and interstitial lung disease.
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Otani T, Yamaguchi K, Nakao S, Sakamoto S, Horimasu Y, Masuda T, Miyamoto S, Nakashima T, Iwamoto H, Fujitaka K, Hamada H, and Hattori N
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- Aged, Female, Glycated Hemoglobin analysis, Glycation End Products, Advanced blood, Humans, Hyperglycemia chemically induced, Hyperglycemia physiopathology, Lung Diseases, Interstitial complications, Lung Diseases, Interstitial physiopathology, Lung Neoplasms physiopathology, Male, Retrospective Studies, Vital Capacity, Antineoplastic Agents adverse effects, Glucose Intolerance chemically induced, Lung Diseases, Interstitial drug therapy, Lung Injury chemically induced, Lung Neoplasms drug therapy
- Abstract
Purpose: Cytotoxic chemotherapy-induced lung injury is a fatal complication in patients with lung cancer and interstitial lung disease (ILD). We aimed to evaluate the association between hyperglycemia and this form of lung injury in patients with lung cancer concomitant with ILD., Methods: From 1147 patients with advanced lung cancer, we retrospectively enrolled 98 patients with ILD whose hemoglobin A1c (HbA1c) levels were measured, and investigated the association between HbA1c levels and cytotoxic chemotherapy-induced lung injury. In 73 patients whose serum samples were retained, we measured serum levels of advanced glycation end products (AGE) and assessed the association of AGE levels with HbA1c levels and cytotoxic chemotherapy-induced lung injury., Results: The incidence of cytotoxic chemotherapy-induced lung injury was significantly higher in patients with HbA1c levels ≥ 5.8% than in those with HbA1c levels < 5.8%, but not in those with HbA1c levels ≥ 6.5% than in those with HbA1c levels < 6.5%. The multivariate logistic regression model revealed that HbA1c level ≥ 5.8% was a significant risk factor for this complication [odds ratio 3.178 (95% confidence interval 1.057-9.556), P = 0.040]. In addition, serum AGE levels were significantly higher in patients with HbA1c levels ≥ 5.8% than in those with HbA1c levels < 5.8% [median (interquartile range); 0.129 (0.023-0.290) and 0.474 (0.213-1.109) μg/mL, P = 0.001]., Conclusion: Glucose intolerance (e.g., HbA1c level ≥ 5.8%) may be a risk factor of cytotoxic chemotherapy-induced lung injury, which might be associated with elevated AGE production due to hyperglycemia., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
- Published
- 2021
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9. Tolerability and efficacy of IMpower133 regimen modified for dialysis patients with extensive-stage small cell lung cancer: Two case reports.
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Watari N, Yamaguchi K, Masuda T, Ito N, Sakamoto S, Horimasu Y, Miyamoto S, Nakashima T, Iwamoto H, Fujitaka K, Hamada H, and Hattori N
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- Aged, Antineoplastic Agents administration & dosage, Antineoplastic Combined Chemotherapy Protocols administration & dosage, Humans, Male, Renal Insufficiency therapy, Antibodies, Monoclonal, Humanized administration & dosage, Carboplatin administration & dosage, Etoposide administration & dosage, Lung Neoplasms drug therapy, Renal Dialysis, Small Cell Lung Carcinoma drug therapy
- Abstract
The IMpower133 regimen, composed of atezolizumab/etoposide (VP-16)/carboplatin (CBDCA), is the standard first-line treatment for extensive-stage small cell lung cancer (ES-SCLC). However, the safety and efficacy of triplet therapy in patients receiving dialysis have not been sufficiently evaluated. Here, we report two cases of dialysis patients with ES-SCLC who received the modified IMpower133 regimen. Patient 1 was a 69-year-old man, and patient 2 was a 73-year-old man who received dialysis because of end-stage renal failure caused by diabetic nephropathy. Both patients received a modified IMpower133 regimen in the following order: atezolizumab (1200 mg/body) on day 1, VP-16 (50 mg/m
2 ) on days 1 and 3, and CBDCA (300 mg/m2 ) on day 1. Four hours of dialysis was performed 1 hour after completing the administration of CBDCA on Day 1 and 2 hours after completing the administration of VP-16 on Day 3. Both patients achieved a partial response and received atezolizumab maintenance therapy after four cycles of triplet therapy without uncontrollable adverse events. By modifying the dosage, the order of drugs, and the timing of dialysis, the IMpower133 regimen may be tolerable and effective for patients receiving dialysis., (© 2021 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)- Published
- 2021
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10. Analysis of microRNA Expression in Liquid-Based Cytology Samples May Be Useful for Primary Lung Cancer Diagnosis.
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Araki Y, Arihiro K, Yamaguchi K, Sakamoto S, Horimasu Y, Masuda T, Miyamoto S, Nakashima T, Iwamoto H, Fujitaka K, Hamada H, and Hattori N
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- Adult, Aged, Aged, 80 and over, Bronchoscopy, Cell Biology, Female, Humans, Male, Middle Aged, Young Adult, Biomarkers, Tumor genetics, Lung Neoplasms diagnosis, MicroRNAs genetics
- Abstract
Objectives: Bronchoscopy is frequently performed for patients suspected of having lung cancer; however, we sometimes fail to make a definitive diagnosis, resulting in additional invasive testing. Many studies indicate that microRNAs (miRs) are abnormally expressed in cancers. We examined the diagnostic value of 4 miRs (miR-21, miR-31, miR-182, and miR-183) extracted from liquid-based cytology (LBC) samples and validated whether they were diagnostically useful., Methods: We collected 18 surgically resected tissue samples and 136 LBC specimens obtained during bronchoscopic examination at Hiroshima University Hospital. We extracted RNA from these samples and compared the expression of 4 miRs by reverse transcription-quantitative polymerase chain reaction., Results: We confirmed that expression of the 4 miRs was significantly higher in cancer tissues than in tumor-adjacent normal tissues. We examined the expression of these miRs in 125 (cancer cases, 83; noncancer cases, 42) of 136 cytologic samples. Expression of all 4 miRs was significantly higher in patients with lung cancer than in those without lung cancer. Among samples judged as benign or indeterminate, levels of these miRs were also significantly higher in patients with lung cancer than in those without lung cancer., Conclusions: The analysis of miR expression in LBC samples might be helpful for primary lung cancer diagnosis., (© American Society for Clinical Pathology, 2021. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
- Published
- 2021
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11. Prediction of radiation pneumonitis after definitive radiotherapy for locally advanced non-small cell lung cancer using multi-region radiomics analysis.
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Kawahara D, Imano N, Nishioka R, Ogawa K, Kimura T, Nakashima T, Iwamoto H, Fujitaka K, Hattori N, and Nagata Y
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- Area Under Curve, Carcinoma, Non-Small-Cell Lung pathology, Humans, Lung Neoplasms pathology, Radiation Pneumonitis etiology, Carcinoma, Non-Small-Cell Lung radiotherapy, Lung Neoplasms radiotherapy, Radiation Pneumonitis diagnosis, Radiometry methods, Radiotherapy adverse effects
- Abstract
To predict grade ≥ 2 radiation pneumonitis (RP) in patients with locally advanced non-small cell lung cancer (NSCLC) using multi-region radiomics analysis. Data from 77 patients with NSCLC who underwent definitive radiotherapy between 2008 and 2018 were analyzed. Radiomic feature extraction from the whole lung (whole-lung radiomics analysis) and imaging- and dosimetric-based segmentation (multi-region radiomics analysis) were performed. Patients with RP grade ≥ 2 or < 2 were classified. Predictors were selected with least absolute shrinkage and selection operator logistic regression and the model was built with neural network classifiers. A total of 49,383 radiomics features per patient image were extracted from the radiotherapy planning computed tomography. We identified 4 features and 13 radiomics features in the whole-lung and multi-region radiomics analysis for classification, respectively. The accuracy and area under the curve (AUC) without the synthetic minority over-sampling technique (SMOTE) were 60.8%, and 0.62 for whole-lung and 80.1%, and 0.84 for multi-region radiomics analysis. These were improved 1.7% for whole-lung and 2.1% for multi-region radiomics analysis with the SMOTE. The developed multi-region radiomics analysis can help predict grade ≥ 2 RP. The radiomics features in the median- and high-dose regions, and the local intensity roughness and variation were important factors in predicting grade ≥ 2 RP., (© 2021. The Author(s).)
- Published
- 2021
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12. Predictive role of circulatory HMGB1 in postoperative acute exacerbation of interstitial lung disease in lung cancer patients.
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Yamaguchi K, Nakao S, Iwamoto H, Kagimoto A, Handa Y, Sakamoto S, Horimasu Y, Masuda T, Mimae T, Miyamoto S, Nakashima T, Tsutani Y, Fujitaka K, Miyata Y, Hamada H, Okada M, and Hattori N
- Subjects
- Aged, Aged, 80 and over, Biomarkers blood, Disease Progression, Female, Humans, Lung Neoplasms blood, Lung Neoplasms complications, Male, Middle Aged, Postoperative Period, Retrospective Studies, HMGB1 Protein blood, Lung Diseases, Interstitial blood, Lung Neoplasms surgery
- Abstract
Postoperative acute exacerbation of interstitial lung disease (AE-ILD) can be fatal in patients with lung cancer concomitant with ILD. We aimed to elucidate the predictive potential of high-mobility group box 1 (HMGB1), which is associated with the development and severity of lung injury, for evaluating the risk of this complication. We included 152 patients with lung cancer and ILD who underwent radical surgery between January 2011 and August 2019. We evaluated the preoperative levels of serum HMGB1 and its predictive potential for postoperative AE-ILD. Postoperative AE-ILD developed in 17 patients. Serum levels of HMGB1 were significantly higher in patients with postoperative AE-ILD than in those without (median [interquartile range]: 5.39 [3.29-11.70] ng/mL vs. 3.55 [2.07-5.62] ng/mL). Univariate and multivariate logistic regression analyses revealed that higher HMGB1 levels were significantly associated with the development of postoperative AE-ILD in entire studied patients (n = 152). In the subgroup analysis, higher HMGB1 levels were associated with a significantly increased risk of this complication in patients who underwent lobectomy (n = 77) than in those who underwent sublobar resection (n = 75). Serum HMGB1 could be a promising marker for evaluating the risk of postoperative AE-ILD, specifically in patients who underwent lobectomy.
- Published
- 2021
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13. Pulmonary lymphangitic carcinomatosis from recurrent gastric cancer 19 years after primary resection: a case report.
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Shioya S, Masuda T, Iwamoto H, Yamaguchi K, Sakamoto S, Horimasu Y, Miyamoto S, Nakashima T, Fujitaka K, Hamada H, and Hattori N
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- Humans, Neoplasm Recurrence, Local surgery, Carcinoma, Lung Neoplasms surgery, Peritoneal Neoplasms, Stomach Neoplasms surgery
- Abstract
Pulmonary lymphangitic carcinomatosis is one rare pattern of pulmonary metastases in advanced cancers. Gastric cancer is one of the most common forms of cancer that causes pulmonary lymphangitic carcinomatosis. However, recurrent gastric cancer presenting as pulmonary lymphangitic carcinomatosis after surgery is extremely rare. Furthermore, recurrence is usually observed within 5 years. We present the first case of pulmonary lymphangitic carcinomatosis in a patient with recurrent gastric cancer, 19 years after resection. In patients with a history of gastric cancer and the presence of interstitial shadow, pulmonary lymphangitic carcinomatosis should be considered in the differential diagnosis even if several years have passed since surgery.
- Published
- 2021
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14. Autoantibody Positivity Is a Risk Factor for Chemotherapy-induced Exacerbation of Interstitial Pneumonia in Lung Cancer.
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Ito N, Masuda T, Nakashima T, Nakao S, Yamaguchi K, Sakamoto S, Horimasu Y, Miyamoto S, Iwamoto H, Fujitaka K, Hamada H, and Hattori N
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- Aged, Aged, 80 and over, Disease Progression, Female, Humans, Induction Chemotherapy methods, Kaplan-Meier Estimate, Lung Diseases, Interstitial etiology, Lung Diseases, Interstitial immunology, Lung Neoplasms pathology, Male, Middle Aged, Prognosis, Retrospective Studies, Risk Factors, Autoantibodies immunology, Induction Chemotherapy adverse effects, Lung Diseases, Interstitial diagnosis, Lung Neoplasms drug therapy
- Abstract
Background: No study has yet investigated the incidence of chemotherapy-induced acute exacerbation of interstitial pneumonia (AE-IP) in patients with autoantibody-positive IP and lung cancer. Herein, we retrospectively compared the incidence of chemotherapy-induced AE-IP in patients with lung cancer between those with autoantibody-positive and -negative IP., Patients and Methods: Between October 2003 and December 2018, patients with lung cancer who received chemotherapy, underwent serological test of antinuclear antibody or rheumatoid factor, and were diagnosed with IP were enrolled., Results: A total of 81 patients were enrolled; autoantibody-positive cases were observed in 23.5%. Autoantibody positivity was an independent risk factor for chemotherapy-induced AE-IP at 6 months after initiation of chemotherapy for lung cancer. The time to onset of AE-IP was significantly shorter in autoantibody-positive patients than in the seronegative patients., Conclusion: Chemotherapy-induced AE-IP developed earlier in patients with autoantibody than in those without. Therefore, the potential development of AE-IP in autoantibody-positive patients warrants monitoring., (Copyright © 2021 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)
- Published
- 2021
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15. Alectinib-induced Immune Hemolytic Anemia in a Patient with Lung Adenocarcinoma.
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Okumoto J, Sakamoto S, Masuda T, Yamaguchi K, Horimasu Y, Miyamoto S, Nakashima T, Iwamoto H, Fukushima N, Fujitaka K, Hamada H, and Hattori N
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- Aged, 80 and over, Carbazoles adverse effects, Female, Humans, Piperidines, Adenocarcinoma of Lung drug therapy, Anemia, Hemolytic, Lung Neoplasms drug therapy
- Abstract
Drug-induced immune hemolytic anemia (DIIHA) is a rare condition with an increasing incidence associated with the frequent use of certain drugs. An 85-year-old woman with lung adenocarcinoma prescribed alectinib complained of dyspnea on exertion at our hospital. Based on her laboratory tests results on admission, we focused on the clinical course of anemia and hemolysis progression after alectinib administration. The patient's anemia and hemolysis gradually improved after discontinuation of alectinib, leading to a diagnosis of alectinib-induced IHA, presented here as the first case encountered in a patient with lung adenocarcinoma. Furthermore, we discuss the importance of correlating clinical laboratory findings in DIIHA.
- Published
- 2021
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16. Clinical significance of BIM deletion polymorphism in chemoradiotherapy for non-small cell lung cancer.
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Wakabayashi Y, Masuda T, Fujitaka K, Nakashima T, Okumoto J, Shimoji K, Nishimura Y, Yamaguchi K, Sakamoto S, Horimasu Y, Miyamoto S, Iwamoto H, Ohshimo S, Hamada H, and Hattori N
- Subjects
- Adult, Aged, Aged, 80 and over, Carcinoma, Non-Small-Cell Lung mortality, Chemoradiotherapy methods, Consolidation Chemotherapy methods, Disease-Free Survival, Female, Humans, Immune Checkpoint Inhibitors therapeutic use, Lung Neoplasms mortality, Male, Middle Aged, Polymorphism, Genetic, Retrospective Studies, Bcl-2-Like Protein 11 genetics, Carcinoma, Non-Small-Cell Lung genetics, Carcinoma, Non-Small-Cell Lung therapy, Lung Neoplasms genetics, Lung Neoplasms therapy
- Abstract
The standard treatment for locally advanced non-small cell lung cancer (NSCLC) is chemoradiotherapy (CRT) followed by anti-programmed cell death-ligand 1 (anti-PD-L1) treatment. BIM deletion polymorphism induces the suppression of apoptosis resulting from epidermal growth factor (EGFR)-tyrosine kinase inhibitors in EGFR-mutated NSCLC patients. We aimed to examine the effects of BIM polymorphism on CRT and anti-PD-L1/PD-1 treatment in NSCLC patients. In this retrospective study of 1312 patients with unresectable NSCLC treated at Higashi-Hiroshima Medical Center and Hiroshima University Hospital between April 1994 and October 2019, we enrolled those who underwent CRT or chemotherapy using carboplatin + paclitaxel or cisplatin + vinorelbine, or anti-PD-L1/PD-1 treatment. Of 1312 patients, 88, 80, and 74 underwent CRT, chemotherapy, and anti-PD-L1/PD-1 treatment, respectively, and 17.0%, 15.2% and 17.6% of these patients showed BIM polymorphism. Among patients receiving CRT, the progression-free survival was significantly shorter in those with BIM deletion than in those without. In the multivariate analyses, BIM polymorphism was an independent factor of poor anti-tumor effects. These results were not observed in the chemotherapy and anti-PD-L1/PD-1 treatment groups. In in vitro experiments, BIM expression suppression using small interfering RNA in NSCLC cell lines showed a significantly suppressed anti-tumor effect and apoptosis after irradiation but not chemotherapy. In conclusion, we showed that BIM polymorphism was a poor-predictive factor for anti-tumor effects in NSCLC patients who underwent CRT, specifically radiotherapy. In the implementation of CRT in patients with BIM polymorphism, we should consider subsequent treatment, keeping in mind that CRT may be insufficient., (© 2020 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)
- Published
- 2021
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17. Coexisting TIF1γ-positive Primary Pulmonary Lymphoepithelioma-like Carcinoma and Anti-TIF1γ Antibody-positive Dermatomyositis.
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Nakanishi Y, Yamaguchi K, Yoshida Y, Sakamoto S, Horimasu Y, Masuda T, Nakashima T, Miyamoto S, Iwamoto H, Hirata S, Fujitaka K, Hamada H, Sugiyama E, and Hattori N
- Subjects
- Aged, 80 and over, Autoantibodies, Biopsy, Female, Humans, Carcinoma complications, Dermatomyositis complications, Lung Neoplasms complications, Transcription Factors immunology
- Abstract
Anti-transcriptional intermediary factor 1γ (anti-TIF1γ) antibody-positive dermatomyositis (DM) is strongly associated with cancer, although the mechanism of action is still unclear. We herein describe the first known case of an 80-year-old woman diagnosed with TIF1γ-positive primary pulmonary lymphoepithelioma-like carcinoma (LELC) coexisting with anti-TIF1γ antibody-positive DM. The diagnosis of LELC can only be made by a surgical lung biopsy, and not by a computed tomography-guided biopsy, because of heavy lymphocytic infiltration. This instructive case reaffirmed the importance of active screening for malignancy in patients with anti-TIF1γ antibody-positive DM. Interestingly, the results also suggested that the strong relationship which exists between anti-TIF1γ antibody-positive DM and cancer is potentially caused by tumor-derived TIF1γ.
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- 2020
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18. Serum high-mobility group box 1 as a predictive marker for cytotoxic chemotherapy-induced lung injury in patients with lung cancer and interstitial lung disease.
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Nakao S, Yamaguchi K, Iwamoto H, Sakamoto S, Horimasu Y, Masuda T, Miyamoto S, Nakashima T, Ohshimo S, Fujitaka K, Hamada H, and Hattori N
- Subjects
- Acute Lung Injury etiology, Aged, Biomarkers blood, Female, Humans, Lung Diseases, Interstitial complications, Lung Neoplasms complications, Male, Middle Aged, Predictive Value of Tests, Acute Lung Injury chemically induced, Acute Lung Injury diagnosis, Antineoplastic Agents adverse effects, Cytotoxins adverse effects, High Mobility Group Proteins blood, Lung Diseases, Interstitial drug therapy, Lung Neoplasms drug therapy
- Abstract
Background: High-mobility group box 1 (HMGB1) is a pro-inflammatory protein, that is associated with tumorigenesis, interstitial lung disease (ILD), and acute lung injury. Chemotherapy-induced lung injury is a common and serious adverse event in patients with lung cancer and ILD, but its pathogenesis and predictive biomarkers are not known. This study aimed to investigate the predictive potential of serum HMGB1 levels for cytotoxic chemotherapy-induced lung injury in these patients., Methods: From 743 patients with advanced lung cancer, we enrolled 83 consecutive patients with ILD and background-matched 83 patients without ILD. Additionally, 83 healthy subjects were included. After measuring baseline levels of serum HMGB1 in three groups, we evaluated the predictive values of baseline HMGB1 levels for cytotoxic chemotherapy-induced lung injury in patients with lung cancer and ILD., Results: Higher levels of serum HMGB1 were independently associated with higher tumor burden, as assessed by total tumor size, and the presence of ILD. Twenty-five (30.1%) of patients with lung cancer and ILD experienced cytotoxic chemotherapy-induced lung injury within one year. Univariate Cox proportional hazards model showed that higher levels of HMGB1 and higher tumor burden were associated with disease onset. Moreover, multivariate analysis revealed that only HMGB1 was independently associated with this severe complication in patients with lung cancer and ILD., Conclusions: HMGB1 is a potential predictive blood biomarker for cytotoxic chemotherapy-induced lung injury in patients with lung cancer and ILD. This study also suggests a potential pathogenesis of this serious adverse event that tumor- and ILD-derived HMGB1 accelerates lung injury., (Copyright © 2020 Elsevier Ltd. All rights reserved.)
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- 2020
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19. Albumin-globulin ratio is a predictive biomarker of antitumor effect of anti-PD-1 antibody in patients with non-small cell lung cancer.
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Nakanishi Y, Masuda T, Yamaguchi K, Sakamoto S, Horimasu Y, Mimae T, Nakashima T, Miyamoto S, Tsutani Y, Iwamoto H, Fujitaka K, Miyata Y, Hamada H, Okada M, and Hattori N
- Subjects
- Adult, Aged, Aged, 80 and over, Biomarkers, Tumor blood, Carcinoma, Non-Small-Cell Lung drug therapy, Carcinoma, Non-Small-Cell Lung metabolism, Carcinoma, Non-Small-Cell Lung pathology, Female, Humans, Lung Neoplasms drug therapy, Lung Neoplasms metabolism, Lung Neoplasms pathology, Male, Middle Aged, Prognosis, Retrospective Studies, Survival Analysis, Antineoplastic Agents, Immunological therapeutic use, Carcinoma, Non-Small-Cell Lung blood, Lung Neoplasms blood, Programmed Cell Death 1 Receptor agonists, Serum Albumin analysis, Serum Globulins analysis
- Abstract
Background: Anti-programmed cell death receptor (PD)-1 antibody treatment results in better prognosis than standard chemotherapy in patients with non-small cell lung cancer (NSCLC), especially those with high PD-ligand 1 (PD-L1) expression. However, several studies have reported a lack of antitumor effect of PD-1 antibody, even in patients with high PD-L1 expression. Therefore, reliable predictors of treatment response are urgently needed. The albumin-globulin ratio (AGR) is associated with prognosis in several cancers. We aimed to determine whether AGR is a predictive biomarker of anti-PD-1 antibody response in patients with NSCLC., Patients and Methods: Seventy-four NSCLC patients treated with anti-PD-1 antibody were retrospectively enrolled. Patients with driver mutations were excluded., Results: The mean AGR was significantly higher in the disease control (DC) group than in the progressive disease (PD) group (p < 0.001). Receiver operating characteristic curve analysis revealed an AGR cutoff value for dividing patients into the DC or PD groups of 1.17. Multivariate logistic regression analysis showed that a high AGR (≥1.17, cutoff value) was an independent predictor of DC (p = 0.001). Progression-free survival (PFS) and overall survival (OS) were significantly longer in the high-AGR group than in the low-AGR group (p = 0.008, p = 0.002, respectively). Multivariate Cox regression analysis of PFS and OS showed that high AGR was an independent prognostic factor (p = 0.020, p < 0.001, respectively)., Conclusion: Pretreatment serum AGR may be a useful predictor for DC and prognostic factor of anti-PD-1 antibody in patients with NSCLC. The clinical utility of AGR still needs to be confirmed in a prospective analysis.
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- 2020
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20. Non-small Cell Lung Cancer Treated by an Anti-programmed Cell Death-1 Antibody without a Flare-up of Preexisting Granulomatosis with Polyangiitis.
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Yamada T, Masuda T, Yamaguchi K, Sakamoto S, Horimasu Y, Miyamoto S, Nakashima T, Iwamoto H, Hirata S, Fujitaka K, Hamada H, Sugiyama E, and Hattori N
- Subjects
- Aged, Carcinoma, Non-Small-Cell Lung complications, Carcinoma, Non-Small-Cell Lung diagnostic imaging, Carcinoma, Non-Small-Cell Lung secondary, Glucocorticoids therapeutic use, Granulomatosis with Polyangiitis drug therapy, Humans, Lung Neoplasms complications, Lung Neoplasms pathology, Male, Neoplasm Recurrence, Local drug therapy, Positron-Emission Tomography, Prednisolone therapeutic use, Thoracic Wall diagnostic imaging, Tomography, X-Ray Computed, Antibodies, Monoclonal, Humanized therapeutic use, B7-H1 Antigen antagonists & inhibitors, Carcinoma, Non-Small-Cell Lung drug therapy, Granulomatosis with Polyangiitis complications, Lung Neoplasms drug therapy
- Abstract
The safety and efficacy of anti-programmed cell death-1 (PD-1) antibodies in patients with granulomatosis with polyangiitis (GPA) still remain unclear. An 83-year-old man with GPA that was well controlled with immunosuppressive therapy was diagnosed with a postoperative recurrence of non-small cell lung cancer (NSCLC). Because the programmed cell death ligand 1 (PD-L1) tumor proportion score was 90%, pembrolizumab was administered. After 10 cycles, immune-related adverse events or GPA flare was not observed, and the patient showed an antitumor response. Anti-PD-1 antibody should therefore be considered a treatment option for PD-L1-high-expressing NSCLC patients with well-controlled GPA.
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- 2019
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21. Chemotherapy-associated Acute Exacerbation of Interstitial Lung Disease Shortens Survival Especially in Small Cell Lung Cancer.
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Nakao S, Yamaguchi K, Sakamoto S, Horimasu Y, Masuda T, Miyamoto S, Nakashima T, Iwamoto H, Fujitaka K, Hamada H, and Hattori N
- Subjects
- Aged, Carcinoma, Non-Small-Cell Lung drug therapy, Carcinoma, Non-Small-Cell Lung mortality, Carcinoma, Non-Small-Cell Lung pathology, Female, Humans, Lung Diseases, Interstitial mortality, Lung Diseases, Interstitial pathology, Male, Prognosis, Retrospective Studies, Small Cell Lung Carcinoma pathology, Antineoplastic Agents adverse effects, Antineoplastic Agents therapeutic use, Lung Diseases, Interstitial chemically induced, Lung Neoplasms drug therapy, Lung Neoplasms mortality, Small Cell Lung Carcinoma drug therapy, Small Cell Lung Carcinoma mortality
- Abstract
Background/aim: In lung cancer (LC) patients, pre-existing interstitial lung disease (ILD) is a risk of chemotherapy-associated acute exacerbation of ILD (AE-ILD). AE-ILD shows a diverse clinical course varying from fatal respiratory failure to asymptomatic event, and the prognostic impact is still unclear., Materials and Methods: We retrospectively evaluated the association between the prognosis and AE-ILD in 86 LC patients with pre-existing ILD who were treated with cytotoxic chemotherapy, especially focusing on histological types of LC., Results: Thirty (34.9%) patients had AE-ILD, that was significantly associated with a poor prognosis in LC patients with ILD. When analyzed by histological types, a significant association of AE-ILD with shorter survival was observed only in the small cell LC (SCLC) group, but not in the non-small cell LC group., Conclusion: The development of AE-ILD by cytotoxic chemotherapy is associated with poor prognosis in LC patients with ILD, especially in patients with SCLC., (Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)
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- 2019
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22. Pre-existing interstitial lung abnormalities are risk factors for immune checkpoint inhibitor-induced interstitial lung disease in non-small cell lung cancer.
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Nakanishi Y, Masuda T, Yamaguchi K, Sakamoto S, Horimasu Y, Nakashima T, Miyamoto S, Tsutani Y, Iwamoto H, Fujitaka K, Miyata Y, Hamada H, Okada M, and Hattori N
- Subjects
- Adult, Aged, Aged, 80 and over, Antibodies, Monoclonal therapeutic use, Antibodies, Monoclonal, Humanized adverse effects, Antibodies, Monoclonal, Humanized therapeutic use, Carcinoma, Non-Small-Cell Lung drug therapy, Female, Humans, Lung diagnostic imaging, Lung pathology, Lung Diseases, Interstitial diagnostic imaging, Lung Diseases, Interstitial pathology, Lung Neoplasms drug therapy, Male, Middle Aged, Nivolumab adverse effects, Nivolumab therapeutic use, Retrospective Studies, Risk Factors, Tomography, X-Ray Computed, Antibodies, Monoclonal adverse effects, Carcinoma, Non-Small-Cell Lung complications, Lung Diseases, Interstitial chemically induced, Lung Diseases, Interstitial etiology, Lung Neoplasms complications, Programmed Cell Death 1 Receptor immunology
- Abstract
Background: Approximately 5% of non-small cell lung cancer (NSCLC) patients develop immune checkpoint inhibitor (ICI)-induced interstitial lung disease (ICI-ILD), 10% of whom die. However, there are no established risk factors for its occurrence. Interstitial lung abnormalities (ILA) are areas of increased lung density on lung computed tomography (CT) in individuals with no known ILD. This study retrospectively investigated whether any patient characteristics, including ILA, were risk factors for ICI-ILD in patients with NSCLC., Methods: NSCLC patients who received anti-programmed death (PD)-1 antibody treatment at our hospital between September 2015 and December 2017 were enrolled. Information on patient characteristics before anti-PD-1 antibody administration, including chest CT findings and laboratory data, were obtained., Results: Among 83 enrolled patients, the incidence of ICI-ILD was 16.9% (14/83). All ICI-ILD cases developed by the third line of treatment. The incidence of ICI-ILD was significantly higher in patients with pre-existing ILA than that in those without (p = 0.007). Furthermore, patients with ground glass attenuation (GGA) in ILA had a higher incidence of ICI-ILD than that in those without (p < 0.001). In univariate logistic analysis, ILA were significant risk factors for ICI-ILD (p = 0.005). Multivariate logistic analysis revealed that only GGA in ILA was a significant risk factor for ICI-ILD (p < 0.001)., Conclusions: Pre-existing ILA are risk factors for ICI-ILD and GGA in ILA is an independent risk factor for ICI-ILD. Therefore, we should be more aware of the development of ICI-ILD in patients with ILA, especially those with GGA., (Copyright © 2019 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.)
- Published
- 2019
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23. Inhibition of PAI-1 limits chemotherapy resistance in lung cancer through suppressing myofibroblast characteristics of cancer-associated fibroblasts.
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Masuda T, Nakashima T, Namba M, Yamaguchi K, Sakamoto S, Horimasu Y, Miyamoto S, Iwamoto H, Fujitaka K, Miyata Y, Hamada H, Okada M, and Hattori N
- Subjects
- Aged, Aged, 80 and over, Animals, Apoptosis, Cancer-Associated Fibroblasts metabolism, Cancer-Associated Fibroblasts pathology, Cell Cycle, Cell Proliferation, Female, Follow-Up Studies, Gene Expression Regulation, Neoplastic, Humans, Lung Neoplasms metabolism, Lung Neoplasms pathology, Male, Mice, Mice, Inbred C57BL, Middle Aged, Myofibroblasts metabolism, Myofibroblasts pathology, Plasminogen Activator Inhibitor 1 metabolism, Prognosis, Retrospective Studies, Tumor Cells, Cultured, Antineoplastic Agents pharmacology, Biomarkers, Tumor analysis, Cancer-Associated Fibroblasts drug effects, Drug Resistance, Neoplasm, Lung Neoplasms drug therapy, Myofibroblasts drug effects, Plasminogen Activator Inhibitor 1 chemistry
- Abstract
Plasminogen activator inhibitor-1 (PAI-1) promotes pulmonary fibrosis through increasing myofibroblast (MF) characteristics, expressing alpha-smooth muscle actin (α-SMA) in fibroblasts. Fibroblasts in the tumour stroma are called cancer-associated fibroblasts (CAFs). Some CAFs have MF characteristics and substantially promote tumour progression and chemotherapy resistance. This study determined whether inhibition of PAI-1 suppressed MF characteristics of CAFs and limited chemotherapy resistance in lung cancer. To investigate cellular PAI-1 expression and its correlation with α-SMA expression of CAFs, 34 patients' paraffin-embedded lung adenocarcinoma tissue sections were immunohistochemically stained for PAI-1 and α-SMA. Immunohistochemical analysis of lung adenocarcinoma tissues showed that PAI-1 expression was correlated with that of α-SMA (r = 0.71, p < 0.001). Furthermore, in vitro, α-SMA expression of CAFs was limited by PAI-1 inhibition, and apoptosis of CAFs was increased. In addition, the effectiveness of cisplatin on lung cancer cells co-cultured with CAFs was increased by suppressing α-SMA expression using PAI-1 inhibitor. In lung adenocarcinoma tissues, PAI-1 expression was associated with T factor and TNM stage. Our data suggest that inhibition of PAI-1 increased the chemotherapeutic effect on lung cancer through suppressing the MF characteristics of CAFs. Hence, PAI-1 might be a promising therapeutic target for patients with chemotherapeutic-resistant lung cancer with CAFs., (© 2019 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.)
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- 2019
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24. Performance Status Is a Risk Factor for Depression before the Diagnosis of Lung Cancer Patients.
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Miwata K, Masuda T, Yamaguchi K, Sakamoto S, Horimasu Y, Miyamoto S, Nakashima T, Iwamoto H, Fujitaka K, Hamada H, and Hattori N
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- Adult, Aged, Aged, 80 and over, Female, Humans, Lung Neoplasms pathology, Lung Neoplasms therapy, Male, Middle Aged, Multivariate Analysis, Neoplasm Staging, Prospective Studies, Psychiatric Status Rating Scales, Risk Factors, Self Report, Severity of Illness Index, Surveys and Questionnaires, Depression etiology, Lung Neoplasms psychology
- Abstract
Objective Previous studies have shown that lung cancer patients experience depression before their diagnosis. However, the patient characteristics that are risk factors for depression before the diagnosis of lung cancer are unclear. We therefore performed this study to identify the characteristics that are risk factors for depression in lung cancer patients. Methods We performed a prospective observational study that included 183 patients who visited our department for suspected lung cancer between August 2014 and March 2017. These patients completed a Quick Inventory of Depressive Symptomatology-Self Report questionnaire. Ten patients with a history of depression were excluded. Results Among the remaining 173 patients, 110 were diagnosed with lung cancer. Among these 110 patients, 57 had depression. A poor performance status (PS) was significantly more prevalent in patients with depression than in those without. Furthermore, a multivariate analysis revealed that a poor PS was the only independent risk factor for depression before the diagnosis of lung cancer. Conclusion Physicians can use this information to evaluate whether patients have depression before the diagnosis of lung cancer.
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- 2019
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25. Cerebral embolism during edoxaban administration for venous thromboembolism in a patient with lung adenocarcinoma: A case report.
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Nakao S, Masuda T, Sakamoto S, Yamaguchi K, Horimasu Y, Miyamoto S, Nakashima T, Iwamoto H, Fujitaka K, Hamada H, and Hattori N
- Subjects
- Adenocarcinoma drug therapy, Antineoplastic Agents therapeutic use, Disease Progression, Factor Xa Inhibitors administration & dosage, Female, Fibrinolytic Agents therapeutic use, Heparin therapeutic use, Humans, Intracranial Embolism drug therapy, Middle Aged, Pyridines administration & dosage, Thiazoles administration & dosage, Venous Thromboembolism prevention & control, Adenocarcinoma complications, Factor Xa Inhibitors adverse effects, Intracranial Embolism chemically induced, Lung Neoplasms complications, Pyridines adverse effects, Thiazoles adverse effects, Venous Thromboembolism complications
- Abstract
Rationale: The efficacy of direct oral anticoagulants (DOACs) in the treatment and prophylaxis of cancer-related venous thromboembolism (VTE) is reportedly similar to that of heparin. However, the effect of DOACs on the prophylaxis of cancer-related arterial thromboembolism (ATE) remains unclear. To our knowledge, we present the 1st case where cerebral ATE was encountered during edoxaban administration for VTE in a patient with lung adenocarcinoma., Patient Concerns: In March 2017, a 63-year-old female was diagnosed with lung adenocarcinoma (cT2aN3M1b stage IVa) along with having asymptomatic VTE; thus, 60 mg/day edoxaban administration was initiated. In addition, 1st-line chemotherapy generated a partial antitumoral response. However, owing to lung cancer progression, a secondary treatment with pembrolizumab administration was initiated. The patient suddenly experienced aphasia 11 days after pembrolizumab administration., Diagnosis: The patient was diagnosed as multiple cerebral ATE using brain magnetic resonance imaging. However, VTE recurrence was not observed. Based on the findings of lung cancer progression and increased coagulation, cerebral ATE was diagnosed as Trousseau syndrome., Interventions: DOAC administration was switched to heparin administration., Outcomes: Coagulation profile normalized and aphasia improved without any further disease symptoms., Lessons: We considered that DOACs are effective for the treatment and prophylaxis of VTE but may be insufficient for ATE prevention. Therefore, DOACs should be replaced with heparin to prevent ATE when cancer and coagulation become uncontrollable with DOAC.
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- 2019
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26. Bevacizumab with Single-agent Chemotherapy in Previously Treated Non-squamous Non-small-cell Lung Cancer: Phase II Study.
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Yamaguchi K, Masuda T, Fujitaka K, Miwata K, Sakamoto S, Horimasu Y, Hamai K, Miyamoto S, Nakashima T, Okamoto Y, Iwamoto H, Ishikawa N, Miyata Y, Okada M, Hamada H, and Hattori N
- Subjects
- Bevacizumab administration & dosage, Carcinoma, Non-Small-Cell Lung mortality, Carcinoma, Non-Small-Cell Lung pathology, Female, Humans, Kaplan-Meier Estimate, Lung Neoplasms mortality, Lung Neoplasms pathology, Male, Neoplasm Staging, Recurrence, Retreatment, Salvage Therapy, Treatment Outcome, Tubulin Modulators administration & dosage, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Carcinoma, Non-Small-Cell Lung drug therapy, Lung Neoplasms drug therapy
- Abstract
Aim: This study was designed to evaluate the efficacy and tolerability of bevacizumab with docetaxel or pemetrexed in previously treated patients with non-squamous non-small cell lung cancer., Patients and Methods: This study enrolled patients who had received at least one chemotherapy regimen, regardless of prior use of bevacizumab. Combinations of docetaxel or pemetrexed were chosen by attending physicians. The primary endpoint was progression-free survival, and secondary endpoints were safety, disease control rate, and overall survival., Results: Thirty patients from two institutions were eligible. The median progression-free and overall survival were 5.0 months (95% confidence interval=3.2-8.8 months) and 15.8 months (95% confidence interval=10.5-19.6 months), respectively. The disease control rate was 66.7%. Treatments were well tolerated, but the development rate of osteonecrosis of the jaw was 10%., Conclusion: Addition of bevacizumab in a salvage setting might be effective, but the development of osteonecrosis of the jaw needs to be monitored., (Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)
- Published
- 2018
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27. Nivolumab-induced severe pancytopenia in a patient with lung adenocarcinoma.
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Tokumo K, Masuda T, Miyama T, Miura S, Yamaguchi K, Sakamoto S, Horimasu Y, Nakashima T, Miyamoto S, Yoshida T, Iwamoto H, Fujitaka K, Hamada H, and Hattori N
- Subjects
- Adenocarcinoma drug therapy, Adenocarcinoma pathology, Antineoplastic Agents, Immunological adverse effects, Drug-Related Side Effects and Adverse Reactions pathology, Fatal Outcome, Humans, Lung Neoplasms drug therapy, Lung Neoplasms pathology, Male, Middle Aged, Nivolumab adverse effects, Pancytopenia etiology, Pancytopenia pathology, Remission Induction, Adenocarcinoma diagnosis, Antineoplastic Agents, Immunological therapeutic use, Bone Marrow pathology, Drug-Related Side Effects and Adverse Reactions diagnosis, Lung Neoplasms diagnosis, Nivolumab therapeutic use, Pancytopenia diagnosis
- Abstract
Severe leukopenia, thrombocytopenia, and bi-cytopenia due to nivolumab have been reported. In this report, we present the first case of nivolumab-induced severe pancytopenia in a patient with lung adenocarcinoma. A 56-year-old Japanese man with lung adenocarcinoma received nivolumab therapy as second-line treatment. After 3 cycles of this therapy, although computed tomography (CT) showed a reduced tumor size, laboratory findings revealed pancytopenia and a bone marrow biopsy showed a severely hypoplastic marrow. The pancytopenia was diagnosed as an adverse effect of nivolumab; filgrastim (75 μg/day), steroid-pulse therapy (intravenous methylprednisolone: 500 mg/day), and subsequently intravenous prednisolone (50 mg/day) were administered. Furthermore, intravenous administration of immunoglobulins was also performed. However, these treatments were ineffective. He was further diagnosed with fungal pneumonia and a catheter-related bloodstream infection. Anti-bacterial chemotherapy was administered. Two months after hospitalization, the neutrophil count improved to 1000/μL, but multiple red blood cell and platelet transfusions were needed. Therefore, further chemotherapy for lung adenocarcinoma could not be initiated, and the patient died due to progression of lung cancer 118 days after the onset of pancytopenia. The possibility of severe pancytopenia as an immune-related adverse event should be considered as a mandatory prerequisite for nivolumab therapy., (Copyright © 2018 Elsevier B.V. All rights reserved.)
- Published
- 2018
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28. The extent of ground-glass attenuation is a risk factor of chemotherapy-related exacerbation of interstitial lung disease in patients with non-small cell lung cancer.
- Author
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Masuda T, Hirano C, Horimasu Y, Nakashima T, Miyamoto S, Iwamoto H, Ohshimo S, Fujitaka K, Hamada H, and Hattori N
- Subjects
- Aged, Aged, 80 and over, Carcinoma, Non-Small-Cell Lung complications, Disease Progression, Female, Humans, Lung Diseases, Interstitial complications, Lung Neoplasms complications, Male, Middle Aged, Prognosis, Retrospective Studies, Risk Factors, Tomography, X-Ray Computed methods, Antineoplastic Agents adverse effects, Antineoplastic Agents therapeutic use, Carcinoma, Non-Small-Cell Lung diagnostic imaging, Carcinoma, Non-Small-Cell Lung drug therapy, Lung Diseases, Interstitial chemically induced, Lung Diseases, Interstitial diagnostic imaging, Lung Neoplasms diagnostic imaging, Lung Neoplasms drug therapy
- Abstract
Objectives: Chemotherapy-related acute exacerbation (AE) of interstitial lung disease (ILD) is observed in certain patients with non-small cell lung cancer (NSCLC) who have ILD. Although the prognosis of AE-ILD is extremely poor, there are no established risk factors for its occurrence. Therefore, we retrospectively investigated whether high-resolution computed tomography (HRCT) findings could identify risk factors for AE-ILD., Materials and Methods: Between January 2005 and December 2016, 35 patients with NSCLC who received chemotherapy at Hiroshima University Hospital and were diagnosed with ILD on HRCT were enrolled. The extent of ground-glass attenuation (GGA), reticulation, honeycomb appearance, and emphysema, as well as the presence of micronodules, traction bronchiectasis, and consolidation were evaluated in five levels of the lung bilaterally. The HRCT scores of GGA, reticulation, honeycomb appearance, and emphysema were determined by the following formula: 100 × sum of the extent of the HRCT findings/lung area., Results: Thirty-five patients underwent various first- to fifth-line chemotherapy regimens. Nine patients (25.7%) developed AE-ILD. The median HRCT scores of GGA and reticulation were significantly higher in patients with AE-ILD than in those without. On univariate analysis, a GGA area score ≥ 24.8, reticulation area score ≥ 19.5, and KL-6 level ≥ 946 U/mL were significant risk factors. Multivariate logistic analysis revealed that only a GGA area score ≥ 24.8 was an independent risk factor of AE-ILD., Conclusions: The GGA area on HRCT is a risk factor for chemotherapy-related AE-ILD. Therefore, this parameter can be used to predict the risk of AE-ILD before administering chemotherapy.
- Published
- 2018
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29. Chronic Intestinal Pseudo-obstruction and Orthostatic Hypotension Associated with Small Cell Lung Cancer that Improved with Tumor Reduction after Chemoradiotherapy.
- Author
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Izumi Y, Masuda T, Horimasu Y, Nakashima T, Miyamoto S, Iwamoto H, Fujitaka K, Hamada H, and Hattori N
- Subjects
- Asian People, Chemoradiotherapy, Chronic Disease, Humans, Hypotension, Orthostatic diagnostic imaging, Intestinal Pseudo-Obstruction diagnostic imaging, Lung Neoplasms pathology, Male, Middle Aged, Paraneoplastic Syndromes diagnostic imaging, Paraneoplastic Syndromes radiotherapy, Small Cell Lung Carcinoma diagnostic imaging, Treatment Outcome, Hypotension, Orthostatic etiology, Hypotension, Orthostatic therapy, Intestinal Pseudo-Obstruction etiology, Intestinal Pseudo-Obstruction therapy, Lung Neoplasms complications, Small Cell Lung Carcinoma complications
- Abstract
Chronic intestinal pseudo-obstruction (CIPO) is a rare disease with symptoms of ileus without obstruction. Most cases of CIPO are idiopathic, and CIPO as a paraneoplastic neurological syndrome (PNS) associated with small cell lung cancer (SCLC) is rare. A 63-year-old man was diagnosed with functional ileus and confined to bed due to orthostatic hypotension. Chest computed tomography revealed a right hilar mass suspected of being lung cancer. Based on detailed examinations, he was diagnosed with limited-stage SCLC. His symptoms were confirmed as PNS because his serum anti-Hu antibody was positive. His PNS was improved with complete tumor reduction by chemoradiotherapy.
- Published
- 2017
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30. [A Case of Central Diabetes Insipidus That Was Caused by Pituitary Metastasis of Lung Adenocarcinoma and Was Controlled by Radiation Therapy].
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Izumi Y, Masuda T, Nabeshima S, Horimasu Y, Nakashima T, Miyamoto S, Iwamoto H, Fujitaka K, Murakami Y, Hamada H, Nagata Y, and Hattori N
- Subjects
- Adenocarcinoma of Lung, Aged, Humans, Magnetic Resonance Imaging, Male, Pituitary Neoplasms diagnostic imaging, Pituitary Neoplasms secondary, Adenocarcinoma radiotherapy, Diabetes Insipidus, Neurogenic etiology, Lung Neoplasms radiotherapy, Pituitary Neoplasms radiotherapy
- Abstract
Background: Pituitary metastasis of lung cancer is rare; however, it often causes diabetes insipidus. Although the majority of such patients are treated with radiation therapy, it remains unclear whether diabetes insipidus can be controlled by radiation therapy., Case: A 72-year-old man was admitted to our hospital for hemosputum, headache, and polyuria. A chest CT scan showed a 3.0 cm mass in the left upper lobe of his lung. Bronchofiberscopy results confirmed the pathological diagnosis of lung adenocarcinoma. Based on the findings from PET-CT, head MRI, and endocrine tests, the diagnosis of lung adenocarcinoma( cT1bN0M1b, stage IV)accompanied with central diabetes insipidus caused by pituitary metastasis was made. Oral administration of desmopressin reduced urine volumes; however, chemotherapy for achieving stable disease in the primary tumor was ineffective in controlling the symptoms of diabetes insipidus. Chemotherapy was discontinued after 4 months because of severe hematological toxicity. During 2 months after the cessation of chemotherapy, polyuria worsened and, therefore, radiation therapy for pituitary metastasis was started. Following the radiation therapy, an apparent reduction in urine volume was observed., Conclusion: Our experience of this case suggests that radiation therapy for pituitary metastasis should be considered at the time when diabetes insipidus becomes clinically overt.
- Published
- 2017
31. Metastatic breast cancer presenting as air-space consolidation on chest computed tomography.
- Author
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Ohnishi H, Haruta Y, Yokoyama A, Nakashima T, Hattori N, and Kohno N
- Subjects
- Air, Diagnosis, Differential, Female, Humans, Lung Neoplasms secondary, Middle Aged, Breast Neoplasms diagnostic imaging, Lung Neoplasms diagnostic imaging, Tomography, X-Ray Computed
- Abstract
A 56-year-old woman suffered from hepatic and bone metastases of breast cancer. Two months after starting combination chemotherapy with trastuzumab and docetaxel, air-space consolidation was observed in the right lower lung lobe on a chest computed tomography (CT) and a high serum KL-6 level was detected. Drug-induced pneumonitis with organizing pneumonia type was suspected, however, a transbronchial lung biopsy and cytological examination of the bronchoalveolar lavage fluid provided evidence of metastatic breast cancer. While the lung is a frequently affected site from metastasis of breast cancer, we report a rare case presenting as air-space consolidation on a chest CT.
- Published
- 2009
- Full Text
- View/download PDF
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