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    • Education: 2006 M.D. St. Marianna University School of Medicine 2012 Ph.D. St. Marianna University School of Medicine... moreedit
    Flexible bronchoscopy (FB) is a common modality for the diagnosis of lung cancer. Recently, the number of older patients with lung cancer is increasing, and FB is being utilized more for these patients. FB carried out in patients aged... more
    Flexible bronchoscopy (FB) is a common modality for the diagnosis of lung cancer. Recently, the number of older patients with lung cancer is increasing, and FB is being utilized more for these patients. FB carried out in patients aged ≥85 years at St. Marianna University Hospital, Kawasaki, Japan, were reviewed. The indication of FB was decided on a case-by-case basis, taking into consideration the condition of the patient, which included mental status and accessibility of the lesion. Outcomes included complications, diagnostic yields, treatment options and survival after FB evaluation. From April 2015 to March 2019, 1604 diagnostic FBs were carried out. A total of 28 were carried out for the diagnosis of lung cancer (19 transbronchial lung biopsy, 9 transbronchial needle aspiration) in patients aged ≥85 years. Although there were three complications reported (pneumonia, fever, asthma exacerbation), they were successfully treated. A total of 19 cases were diagnosed with malignancy; five were treated with stereotactic body radiation therapy, five were prescribed targeted therapy, two underwent surgery and one was treated by cytotoxic monotherapy. Six patients were not included for active treatment. A total of 12 patients who received active treatment for lung cancer reported a 2-year survival rate of >60%. FB for lung cancer diagnosis in patients aged ≥85 years were carried out with acceptable safety and diagnostic yield. Considering the development of less invasive therapeutic measures for lung cancer, FB is safe and valuable in individuals aged ≥85 years suspected of lung cancer with therapeutic indications. Geriatr Gerontol Int 2021; ••: ••-••.
    Dear Editor, Nivolumab, a monoclonal antibody against programmed cell death 1 (PD-1), induces antitumor immune reactions and is increasingly used for treating malignant melanoma, lung cancer and other malignancies. With increasing... more
    Dear Editor, Nivolumab, a monoclonal antibody against programmed cell death 1 (PD-1), induces antitumor immune reactions and is increasingly used for treating malignant melanoma, lung cancer and other malignancies. With increasing frequency of nivolumab use, the incidences of immune-related adverse events (irAE) are also increasing. The reported cutaneous irAE include vitiligo, maculopapular rash, lichenoid dermatitis, erythematous, psoriasiform eruption, bullous reaction, pruritus, perivascular dermatitis and eczema. Here, we report a rare and distinctive cutaneous irAE seen in a patient receiving nivolumab therapy. A 70-year old Japanese man with lung cancer was treated with nivolumab (3 mg/kg per dose) every 2 weeks. After 18 courses, the patient developed disseminated faint erythema with pruritus on his trunk and upper extremities (Fig. 1a) and erythematous-to-violaceous papules with peripheral desquamative scales on the dorsa of his hands (Fig. 1b). He had no history of skin di...
    Next‐generation sequencing (NGS) enables the diagnosis of large numbers of gene aberrations during one examination, and precision medicine has been developed for patients with advanced non–small cell lung cancer (NSCLC). However,... more
    Next‐generation sequencing (NGS) enables the diagnosis of large numbers of gene aberrations during one examination, and precision medicine has been developed for patients with advanced non–small cell lung cancer (NSCLC). However, peripheral lung lesions account for the majority of advanced lung cancers, especially lung adenocarcinoma. In these cases, it is difficult to obtain tissue samples which contain sufficient tumor cells by transbronchial biopsy (TBB) with forceps. Even when the target lesions are quite small, bronchial brushing can obtain enough tumor cells by endobronchial ultrasonography using guide sheath (EBUS‐GS). In this study, we investigate the suitability of bronchial brushing cytology specimens obtained by EBUS‐GS‐TBB to evaluate the correlation between the success rate of NGS and extracted DNA/RNA yields according to biopsy method. We prospectively collected 222 tumor samples obtained from patients with advanced lung cancer. All patients were enrolled in a prospective nationwide genomic screening project for lung cancer (LC‐SCRUM‐Japan/Asia). Genomic data were obtained from the clinico‐genomic database of LC‐SCRUM‐Japan/Asia. The extraction yields of DNA/RNA from samples obtained by EBUS‐GS‐TBB were relatively low compared with tissue samples. The success rate of DNA sequencing for EBUS‐GS‐TBB was 97.9%, with no significant differences between biopsy methods. The success rate of RNA sequencing for EBUS‐GS‐TBB was 80.4%, which was relatively low compared with surgical biopsy samples (P = 0.069). However, some rare oncogenic driver aberrations were detected from these specimens. This study demonstrated that cytology samples obtained by transbronchial brushing with EBUS‐GS‐TBB were suitable for NGS analysis.
    OBJECTIVES Immune checkpoint inhibitors (ICIs) have proven to be effective treatment for lung cancer. However, a precise predictive immuno-oncology biomarker is still under development. We investigated the associations among PD-L1... more
    OBJECTIVES Immune checkpoint inhibitors (ICIs) have proven to be effective treatment for lung cancer. However, a precise predictive immuno-oncology biomarker is still under development. We investigated the associations among PD-L1 expression, tumor mutational burden (TMB), and oncogenic driver alterations in advanced non-small cell lung cancer (NSCLC) patients treated with ICIs. MATERIALS AND METHODS This multicenter cohort study included 1017 lung cancer patients. PD-L1 expression using four IHC assays (22C3, 28-8, SP263, SP142), TMB by whole-exome sequencing and oncogenic driver alterations were analyzed comprehensively. Clinical characteristics, treatment and survival data were collected. RESULTS The results of 22C3 and 28-8 for PD-L1 expression showed acceptable concordance (k = 0.89; 95% confidence interval [CI], 0.87-0.92), and the clinical outcomes of ICIs classified according to PD-L1 expression by both assays were also approximately the same. There was slight concordance (k = 0.16; 95% CI, 0.11-0.22) between 22C3 and SP142, and high PD-L1 expression by SP142 was correspond to very high PD-L1 expressions by other assays. Patients with both high PD-L1 expression and high TMB showed a good response to ICIs with the response rate of 64% and median progression-free survival of 9.0 months despite of small population. Common EGFR or STK11 mutations showed a lower rate of high PD-L1 expression and a worse efficacy of ICIs and KRAS mutations had no negative impact on response to ICIs. CONCLUSION Comprehensive assessment of PD-L1 expression, TMB, and oncogenic driver alterations would help to better predict the clinical outcomes of ICIs in NSCLC patients.
    BACKGROUND Bevacizumab is a promising candidate for combination treatment with epidermal growth factor receptor tyrosine-kinase inhibitors (eg, erlotinib), which could improve outcomes for patients with metastatic EGFR-mutant... more
    BACKGROUND Bevacizumab is a promising candidate for combination treatment with epidermal growth factor receptor tyrosine-kinase inhibitors (eg, erlotinib), which could improve outcomes for patients with metastatic EGFR-mutant non-small-cell lung cancer (NSCLC). We have previously shown in NEJ026, a phase 3 trial, that the combination of bevacizumab plus erlotinib significantly prolonged progression-free survival compared with erlotinib alone in these patients. In further analyses, we aimed to examine the effects of bevacizumab-erlotinib on overall survival, time from enrolment to progressive disease during second-line treatment or death, and quality of life. METHODS This open-label, randomised, multicentre, phase 3 trial (NEJ026) was done in 69 hospitals and medical, community-based centres across Japan. Eligible patients had stage IIIB, stage IV, or postoperative recurrent, EGFR-mutant (exon 19 deletion or exon 21 Leu858Arg point mutation) NSCLC, had not previously received systemic chemotherapy, and were randomly assigned (1:1) by a computer-generated randomisation sequence and minimisation to receive either 150 mg oral erlotinib once daily plus 15 mg/kg intravenous bevacizumab once every 21 days, or 150 mg oral erlotinib once daily, until disease progression or intolerable toxicity. Randomisation was stratified according to sex, smoking status, EGFR mutation subtype, and clinical disease stage. All participants, investigators, and study personnel (including those assessing outcomes) were unmasked to treatment allocation. We report the secondary outcomes of overall survival and quality of life (the period from enrolment to confirmation of a minimally important difference on the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire [EORTC QLQ]-C30), and the exploratory outcome of time from enrolment to progressive disease during second-line treatment or death. Overall survival and the exploratory outcome were analysed in the modified intention-to-treat population, which comprised all randomly assigned patients who received at least one dose of the study drug and had response evaluations. Quality of life was analysed in patients in the modified intention-to-treat population who had completed the quality of life questionnaires. The trial is registered with the University Hospital Medical Information Network Clinical Trials Registry, UMIN000017069, and the Japan Registry of Clinical Trials, jRCTs031180056, and is currently closed. FINDINGS Between June 3, 2015, and Aug 31, 2016, 228 patients were enrolled. 112 patients who received bevacizumab-erlotinib and 112 who received erlotinib only were included in the modified intention-to-treat population. At data cutoff (Nov 30, 2019) and a median follow-up of 39·2 months (IQR 23·9-43·5), the median overall survival was 50·7 months (95% CI 37·3-not estimable [NE]) in the bevacizumab-erlotinib group and 46·2 months (38·2-NE) in the erlotinib-only group (hazard ratio [HR] 1·007, 95% CI 0·681-1·490; p=0·97). In analysis of the exploratory outcome, after a median follow-up of 23·9 months (IQR 14·2-39·1), the median time from enrolment to progressive disease during second-line treatment or death was 28·6 months (95% CI 22·1-35·9) in the bevacizumab-erlotinib group and 24·3 months (20·4-29·1) in the erlotinib-only group (HR 0·773, 95% CI 0·562-1·065). The median time between enrolment and confirmation of a minimally important difference on the EORTC QLQ-C30 was 6·0 months (95% CI 5·2-11·3) in the bevacizumab-erlotinib group and 8·3 months (5·7-13·9) in the erlotinib-only group (p=0·47). INTERPRETATION The addition of bevacizumab to erlotinib did not prolong survival in patients with metastatic EGFR-mutant NSCLC, but both treatment groups had relatively long survival durations. Why the addition of bevacizumab to erlotinib did not affect overall survival is unclear, but it is possible that the beneficial effects of combination therapy were not seen because overall survival was influenced by treatment regimens used after disease progression. FUNDING Chugai Pharmaceutical.
    The tumourigenesis of early lung adenocarcinomas, including adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA), and lepidic predominant invasive adenocarcinoma (LPA), remains unclear. This study aimed to capture... more
    The tumourigenesis of early lung adenocarcinomas, including adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA), and lepidic predominant invasive adenocarcinoma (LPA), remains unclear. This study aimed to capture disease-related molecular networks characterising each subtype and tumorigenesis by assessing 14 lung adenocarcinomas (AIS, five; MIA, five; LPA, four). Protein–protein interaction networks significant to the three subtypes were elucidated by weighted gene co-expression network analysis and pairwise G-statistics based analysis. Pathway enrichment analysis for AIS involved extracellular matrix proteoglycans and neutrophil degranulation pathway relating to tumour growth and angiogenesis. Whereas no direct networks were found for MIA, proteins significant to MIA were involved in oncogenic transformation, epithelial-mesenchymal transition, and detoxification in the lung. LPA was associated with pathways of HSF1-mediated heat shock response regulation, DNA dama...
    9605 Background: A rapidly increasing number of oncogenic drivers have been identified in non-small cell lung cancer (NSCLC), and most of them occur in less than 5% of patients. Large-scale genomic screening to identify patients with rare... more
    9605 Background: A rapidly increasing number of oncogenic drivers have been identified in non-small cell lung cancer (NSCLC), and most of them occur in less than 5% of patients. Large-scale genomic screening to identify patients with rare driver alterations is thus necessary to enable precision medicine and to support the development of novel targeted therapies and companion diagnostics (CDx). Methods: A lung cancer genomic screening project (LC-SCRUM-Asia) capturing clinical outcome was established in 2013 with 206 institutions in Japan and 5 in Taiwan currently participating. A separate genomic screening project with similar structure was established in China (LC-IRICA-China) in collaboration with LC-SCRUM-Asia in 2019 (3 institutions enrolling, 17 about to open, 63 undergoing review). Samples are analyzed by a multi-gene PCR panel and targeted next-generation sequencing. The target is to enroll 70000 NSCLC patients (20000 from LC-SCRUM-Asia and 50000 from LC-IRICA-China) by 2022....
    Background Although anti-PD-1 antibodies are the most promising agents in advanced non-small cell lung cancer (NSCLC), no definitive biomarkers of efficacy exist. We developed a novel assay for peripheral blood mononuclear cell (PBMC)... more
    Background Although anti-PD-1 antibodies are the most promising agents in advanced non-small cell lung cancer (NSCLC), no definitive biomarkers of efficacy exist. We developed a novel assay for peripheral blood mononuclear cell (PBMC) biomarker using the prediction formula consisting of CD62L-downregulated (CD62Llow) CD4+T cells and CD25+Foxp3+CD4+T cells. This study aimed to validate it. Methods This prospective multicenter phase II study included patients with treated advanced or metastatic NSCLC. After registration and PBMC biomarker analysis, they were classified into responder (RT) or non-responder (NRT) type. Nivolumab was administered every two weeks. The primary endpoint was disease control rate (DCR) at nine weeks after nivolumab treatment in RT patients. Desired and threshold DCR were set at 80% and 60%, respectively. Secondary endpoints were objective response rate (ORR), time to treatment failure, progression-free survival (PFS), overall survival, safety and tolerability...
    TPS9120 Background: Vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR) pathways are shown to be interrelated in several preclinical studies. Furthermore, recent clinical studies have shown the adding... more
    TPS9120 Background: Vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR) pathways are shown to be interrelated in several preclinical studies. Furthermore, recent clinical studies have shown the adding effect of an anti VEGF monoclonal antibody with an epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) for the non-small-cell lung cancer (NSCLC) patients with EGFR mutation. Thus, osimertinib plus ramucirumab would be the promising candidate for the new standard treatment in EGFR mutation positive NSCLC. Methods: This study is an investigator initiated trial. Previously untreated EGFR mutation positive advanced non squamous NSCLC patients aged 20 years or older with a performance status of 0 or 1 are randomized at a 1:1 ratio to receive osimertinib (80mg) every day either without or with ramucirumab (10mg/kg) every 2 weeks until evidence of disease progression or development of unacceptable toxicity. The primary endpoint of the study...
    Background: In central airway stenosis, stenting leads to an increase in bronchial patency and to the active distribution of ventilation. However, an improvement in blood flow and gas exchange has not yet been understood. The purpose of... more
    Background: In central airway stenosis, stenting leads to an increase in bronchial patency and to the active distribution of ventilation. However, an improvement in blood flow and gas exchange has not yet been understood. The purpose of this study is to evaluate the distribution of pulmonary blood flow using computed tomography (CT) and perfusion scintigraphy. Methods: We assessed lung perfusion in 8 patients with bronchial stenosis. CT and perfusion scintigraphy were performed before and after interventional bronchoscopy. We measured the cross-sectional area (CSA) of less than 5 mm 2 (CSAl5), 10 mm 2 (CSAl10), and 100 mm 2 (CSAl100) by computed tomography. The scintigraphic lung image was divided into the right and left lung. The distribution of lung perfusion was calculated to express the mean counts for the respective lungs as a percentage of the total counts in both lungs. Results: In patients with bronchial stenosis, perfusion was reduced at the obstructed area. After intervention, two different findings were obtained depending on the duration of obstruction. When airway obstruction occurred for less than 1 month, perfusion immediately improved due to better ventilation. In patients with long-term lung collapse, perfusion was still severely reduced at the obstructed area. Three month later, CT and perfusion scintigraphy showed an improvement in blood flow. CSAl5, CSAl10 and CSAl100 were significantly correlated with the distribution of lung perfusion (r=-0.67, Pl0.01; r=-0.71, Pl0.01; r=-0.66, Pl0.01, respectively). Conclusions: Interventional bronchoscopy improved blood flow and gas exchange. CT and perfusion scintigraphy were useful in the assessment of regional blood flow.
    Background This study aimed to determine the relationship of programmed death-ligand 1 (PD-L1) expression and standardized uptake values in fluorodeoxyglucose–positron emission tomography/computed tomography (FDG-PET/CT) with prognosis in... more
    Background This study aimed to determine the relationship of programmed death-ligand 1 (PD-L1) expression and standardized uptake values in fluorodeoxyglucose–positron emission tomography/computed tomography (FDG-PET/CT) with prognosis in non–small-cell lung cancer (NSCLC). Methods We retrospectively analyzed 328 NSCLC patients who underwent lobectomy/segmentectomy with lymph node dissection. PD-L1 expression was detected by immunohistochemically stained using the murine monoclonal antibody clone 22C3. The preoperative maximum standardized uptake value (SUVmax) of FDG-PET/CT at the primary lesion; pathological factors including histological type, microscopic lymphatic, venous, and pleural invasion; and lymph node metastases in resected specimens was determined. Significant prognostic clinicopathologic factors were analyzed by univariate and multivariate analyses. Results PD-L1 expression was higher in men, smokers, squamous cell carcinoma, advanced pathologic stages, positive venous...
    Many studies demonstrating lung repair by means of stem/progenitor cells or growth factors have been reported in animal emphysema models. We focused on adipose tissue-derived stromal/stem cells (ASCs) for regenerative medicine, since it... more
    Many studies demonstrating lung repair by means of stem/progenitor cells or growth factors have been reported in animal emphysema models. We focused on adipose tissue-derived stromal/stem cells (ASCs) for regenerative medicine, since it has a high potential to secrete multiple angiogenic factors and differentiate various kinds of cells. To demonstrate the therapeutic impact of ASCs transplantation and to elucidate mechanisms of the effects in rat emphysema models. ASCs were isolated from Wistar rat inguinal subcutaneous adipose tissue. Emphysema was induced by intratracheal instillation of porcine pancreatic elastase (PPE). One week after induction of PPE, cell transplantation was performed intravenously. At 1 and 2 weeks after transplantation, we assessed arterial blood analysis and histopathological changes and measurement of chemokine levels. After PPE induction, arterial oxygen pressure (PaO 2 ) was reduced. After ASCs transplantation, PaO 2 significantly improved. In addition, ...
    9054 Background: RAS ( KRAS, NRAS and HRAS) is a targetable oncogene family in several cancers, including NSCLC, and the clinical development of various RAS-targeted therapies are ongoing. However, the clinical relevance of uncommon RAS... more
    9054 Background: RAS ( KRAS, NRAS and HRAS) is a targetable oncogene family in several cancers, including NSCLC, and the clinical development of various RAS-targeted therapies are ongoing. However, the clinical relevance of uncommon RAS mutations, such as NRAS and HRAS mutations, in NSCLC patients (pts) remains unclear. Methods: In a large-scale genomic screening project (LC-SCRUM-Asia), we have prospectively analyzed lung cancer pts for genomic alterations by a targeted next-generation sequencing (NGS) system, Oncomine Comprehensive Assay. We evaluated clinico-pathological and genomic characteristics in NRAS- or HRAS-mutated NSCLC pts comparing with those in KRAS-mutated pts based on the LC-SCRUM-Asia database. Results: Since March 2015 to December 2020, 9131 NSCLC pts were enrolled in the LC-SCRUM-Asia, and 8374 of them (92%) were successfully analyzed by NGS. The RAS mutation frequencies were 1134 KRAS (14%), 50 NRAS (0.6%), and 15 HRAS (0.2%). The most frequent variant of NRAS a...
    OBJECTIVES This phase I/II study assessed the efficacy and safety of combination therapy with carboplatin (CBDCA) and nab-paclitaxel (nab-PTX) in advanced elderly patients (aged ≥75 years) with advanced squamous cell lung cancer (SqCLC).... more
    OBJECTIVES This phase I/II study assessed the efficacy and safety of combination therapy with carboplatin (CBDCA) and nab-paclitaxel (nab-PTX) in advanced elderly patients (aged ≥75 years) with advanced squamous cell lung cancer (SqCLC). MATERIALS AND METHODS In this phase I study, the doses of carboplatin at an area under the curve (AUC) of 5 or 6 mg/mL/min on day 1 (levels 1 and 2, respectively) were administered along with weekly nab-PTX (100 mg/m2) on days 1, 8, and 15 every 4 weeks for up to 6 cycles using a modified 3 + 3 design. The primary endpoint for the phase II study was the 6-month progression-free survival (6 m PFS) rate. RESULTS A total of 46 patients were enrolled in this study. Ten patients were enrolled in the phase I part. At dose level 1, 2/7 patients showed dose-limiting toxicities (DLTs) of grade 3 diarrhea and febrile neutropenia; at dose level 2, 1/3 patient exhibited grade 3 anorexia as a DLT. The recommended dose was determined to be level 2. Efficacy was t...
    9097 Background: TMB estimation using targeted NGS panels is widely performed in clinical practice. The objective of this study was to determine the optimal NGS panel for estimating TMB and to evaluate its clinical implications for NSCLC.... more
    9097 Background: TMB estimation using targeted NGS panels is widely performed in clinical practice. The objective of this study was to determine the optimal NGS panel for estimating TMB and to evaluate its clinical implications for NSCLC. Methods: Two NGS panels, Oncomine Tumor Mutation Load Assay (OMLA) and FoundationOne (F1), were compared to select the most accurate TMB prediction panel. From February 2017 to May 2018, 350 lung cancer patients were analyzed by whole-exome sequencing (WES), and the concordance rate of OMLA and F1 to WES was examined. In addition, its clinical utility as a biomarker for immune checkpoint inhibitors (ICIs) was evaluated in our international genome screening network (LC-SCRUM-Asia). From June 2019 to December 2020, 3141 patients with NSCLC from 185 institutions were enrolled, and genomic analysis was successful. The clinico-genomic database of LC-SCRUM-Asia was used for this analysis. Results: The linear correlation with WES was 0.80 for OMLA and 0.7...
    BACKGROUND The current study aimed to evaluate the significance of clinicopathological factors, particularly the immunohistochemistry of programed cell death ligand-1 (PD-L1), in eight cases each of pulmonary sarcomatoid carcinoma (PSC)... more
    BACKGROUND The current study aimed to evaluate the significance of clinicopathological factors, particularly the immunohistochemistry of programed cell death ligand-1 (PD-L1), in eight cases each of pulmonary sarcomatoid carcinoma (PSC) and malignant pleural mesothelioma (MPM) at our hospital. METHODS From January 2004 to December 2020, a total of 16 consecutive patients (eight with PSC and eight with MPM diagnosed via surgical resection or biopsy) were included in this study. After retrospectively reviewing the patient characteristics, the associations between PD-L1 status and age, sex, stage, histological type, and prognosis were investigated. RESULTS PD-L1-positive staining was observed in four (50%) PSC cases and one (12.5%) MPM case. Among the four PD-L1-positive PSC cases, two showed high PD-L1 expression in the vimentin-positive sarcomatoid compartment. Moreover, among those with PSC, two survived for about 10 years, whereas the others died within 5 years. No clear correlation was found between PD-L1 expression and prognosis. Among the patients with MPM, four survived for more than 2 years, with the longest being 9 years. Among MPM cases who received nivolumab, one patient with positive PD-L1 staining in the sarcomatoid survived, whereas the other with negative PD-L1 staining did not. CONCLUSION The present study showed that sarcomatoid carcinoma had a higher PD-L1 expression compared to non-small-cell lung cancer and that both PSC and MPM tended to exhibit PD-L1 positivity in the sarcomatoid compartment. Moreover, while immune checkpoint inhibitors may somewhat prolong the prognosis of both tumors, further studies with a larger cohort are necessary to confirm our results.
    No therapeutic targets have been identified for lung squamous cell cancer (SqCC) which is the second most prevalent lung cancer because its molecular profiles remain unclear. This study aimed to unveil disease-related protein networks by... more
    No therapeutic targets have been identified for lung squamous cell cancer (SqCC) which is the second most prevalent lung cancer because its molecular profiles remain unclear. This study aimed to unveil disease-related protein networks by proteomic and bioinformatic assessment of laser-microdissected cancerous cells from seven SqCCs compared with eight representative lung adenocarcinomas. We identified three network modules significant to lung SqCC using weighted gene co-expression network analysis. One module was intrinsically annotated to keratinization and cell proliferation of SqCC, accompanied by hypoxia-induced aerobic glycolysis, in which key regulators were activated (HIF1A, ROCK2, EFNA1-5) and highly suppressed (KMT2D). The other two modules were significant for translational initiation, nonsense-mediated mRNA decay, inhibited cell death, and interestingly, eIF2 signaling, in which key regulators, MYC and MLXIPL, were highly activated. Another key regulator LARP1, the master...
    Abstract Background Consolidation therapy with durvalumab after concurrent chemoradiotherapy has been reported to significantly prolong progression‐free survival and overall survival in patients with stage III unresectable non‐small cell... more
    Abstract Background Consolidation therapy with durvalumab after concurrent chemoradiotherapy has been reported to significantly prolong progression‐free survival and overall survival in patients with stage III unresectable non‐small cell lung cancer (NSCLC). However, which chemotherapy regimen should be selected for consolidation therapy with durvalumab is currently unknown. Methods We retrospectively reviewed consecutive patients with unresectable stage III NSCLC who received concurrent definitive chemoradiotherapy with platinum‐based chemotherapy. We reviewed the timing and severity of radiation pneumonitis by assessing chemotherapy regimens and histology. Results A total of 103 patients were identified. Fourteen patients (13.6%) developed grade 2 or greater radiation pneumonitis within 42 days after chemoradiotherapy. No adenocarcinoma patients treated with a regimen of cisplatin plus pemetrexed developed grade 2 or greater radiation pneumonitis within 42 days; however, 20% of patients who were treated with carboplatin plus paclitaxel developed grade 2 or greater radiation pneumonitis. Furthermore, the objective response rates and disease control rates of cisplatin plus pemetrexed were equal to or greater than those of carboplatin plus paclitaxel in adenocarcinoma patients. Conclusion Cisplatin plus pemetrexed regimen may be a preferable option to consider for subsequent consolidation therapy with durvalumab in patients with unresectable stage III adenocarcinoma.
    9038 Background: The clinical significance of genetic alterations in stage II/III non-small cell lung cancer (NSCLC) patients has not yet been clarified. We have prospectively analyzed NSCLC patients for cancer-related gene alterations... more
    9038 Background: The clinical significance of genetic alterations in stage II/III non-small cell lung cancer (NSCLC) patients has not yet been clarified. We have prospectively analyzed NSCLC patients for cancer-related gene alterations and have followed up clinical course of the patients, establishing a large-scale clinico-genomic database in our nationwide genome screening project (LC-SCRUM-Japan). Methods: Submitted tumor samples were subjected to a targeted next-generation sequencing (NGS) system, Oncomine™ Comprehensive Assay. Therapeutic and prognostic data were collected and updated every year. Results: Since March 2015 to May 2019, 5166 non-squamous NSCLC patients from 263 institutions had been enrolled in the LC-SCRUM-Japan, and 754 of them were diagnosed as stage II/III. The median age of the 754 patients was 67 years (range, 21-92), and 503 (67%) were male, 595 (79%) smokers and 631 (84%) stage III. Of 640 available samples, 258 (40%) had targetable gene alterations, compr...
    9097Background: Potentially targetable genes have been identified in squamous cell lung cancer (SqLC), but effective molecular-targeted therapies against SqLC have not yet been established. To select appropriate patients for clinical... more
    9097Background: Potentially targetable genes have been identified in squamous cell lung cancer (SqLC), but effective molecular-targeted therapies against SqLC have not yet been established. To select appropriate patients for clinical trials of targeted therapies, we have analyzed advanced SqLCs for genetic alterations in our nationwide genomic screening system (LC-SCRUM-Japan). Methods: LC-SCRUM-Japan was established in February 2013, and a genomic screening of advanced SqLCs has been operated since March 2015. As of December 2015, 155 institutions across Japan were participating and 105 SqLCs patients had been enrolled in this study. Submitted tumor samples were analyzed for genetic alterations using a next-generation sequencing system, Oncomin Comprehensive Assay, enabling the simultaneous analysis of 143 cancer-related genes. Results: The median age of the 105 patients was 69 years (range, 27-84 years). Eighty-eight (84%) were male and most patients (95%) were smokers. Among 88 available samples, poten...
    printing supported by . Visit Chiesi at Stand D.30 SUNDAY, SEPTEMBER 25TH 2011 (r=0.805, p<0.0001), and for 130 normal (r=0.758, p<0.0001) and 82 abnormal sites (r=0.654, p<0.0001). For malignant cases, there was significant... more
    printing supported by . Visit Chiesi at Stand D.30 SUNDAY, SEPTEMBER 25TH 2011 (r=0.805, p<0.0001), and for 130 normal (r=0.758, p<0.0001) and 82 abnormal sites (r=0.654, p<0.0001). For malignant cases, there was significant correlation in the total 160 sites (r=0.810, p<0.0001), 112 normal (r=0.782, p<0.0001) and 48 abnormal (r=0.564, p<0.0001). Benign cases showed significant correlations in the total 52 sites (r=0.780, p<0.0001), 18 normal (r=0.778, p<0.0001) and 34 abnormal sites (r=0.731, p<0.0001). Conclusions: This EBUS technique was successful in establishing accurate airway measurements for suitable airway stent sizes in interventional procedures, especially in cases with tracheobrochial malacia. P611 Bronchoscopic application of mitomycin-C as adjuvant treatment of postintubation tracheal stenosis Filipa Viveiros, Joana Gomes, Ana Oliveira, Sofia Neves, José Almeida, João Moura e Sá. Pulmonology Service, Centro Hospitalar de Gaia/Espinho, Vila No...

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