259 research outputs found

    Motion Recognition and Planning Using Gaussian Process Dynamical Models

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    ํ•™์œ„๋…ผ๋ฌธ (๋ฐ•์‚ฌ)-- ์„œ์šธ๋Œ€ํ•™๊ต ๋Œ€ํ•™์› ๊ณต๊ณผ๋Œ€ํ•™ ๊ธฐ๊ณ„ํ•ญ๊ณต๊ณตํ•™๋ถ€, 2017. 8. ๋ฐ•์ข…์šฐ.๋ณธ ๋…ผ๋ฌธ์—์„œ๋Š” ๋กœ๋ด‡์ด ํ•ด์„์ ์œผ๋กœ ์ •์˜๋˜์ง€ ์•Š์€ ํ™˜๊ฒฝ์— ๋Œ€์‘ํ•˜๋Š” ๋ฌธ์ œ์— ๊ด€ํ•ด ๋‹ค๋ฃฌ๋‹ค. ์ด ํ™˜๊ฒฝ์—๋Š” ๋กœ๋ด‡์ด ํ”ผํ•ด์•ผ ํ•˜๋Š” ์žฅ์• ๋ฌผ๊ณผ ํ•˜์ง€ ์™ธ๊ณจ๊ฒฉ ๋กœ๋ด‡ ์ฐฉ์šฉ์ž์˜ ๋™์ž‘ ์˜๋„์™€ ๋ฐ€์ ‘ํ•˜๊ฒŒ ์—ฐ๊ด€๋œ ์ง€ํ˜•์ง€๋ฌผ์ด ์žˆ๋‹ค. ๊ด€์ ˆ ๊ณต๊ฐ„๊ณผ ๊ทธ ์ €์ฐจ์› ๊ณต๊ฐ„์—์„œ์˜ ๊ฒฝ๋กœ ๊ณ„ํš๋ฒ•์„ ํ†ตํ•ด ์žฅ์• ๋ฌผ์„ ํšŒํ”ผ ํ•˜์˜€๊ณ  ๊ธฐ๊ณ„ํ•™์Šต ๊ธฐ๋ฒ•์„ ํ†ตํ•ด ์ง€ํ˜•์ง€๋ฌผ์— ๊ธฐ์ธํ•œ ์‚ฌ๋žŒ์˜ ๋™์ž‘ ์˜๋„๋ฅผ ์ถ”์ •ํ•˜์˜€๋‹ค. ๋จผ์ € Gaussian process dynamical models (GPDM) ๊ธฐ๋ฐ˜์œผ๋กœ ํ•˜์ง€ ์™ธ๊ณจ๊ฒฉ ๋กœ๋ด‡ ์ฐฉ์šฉ์ž์˜ ์šด๋™ ์˜๋„๋ฅผ ์ถ”์ •ํ•˜๋Š” ์•Œ๊ณ ๋ฆฌ์ฆ˜์„ ์ œ์•ˆํ•˜์˜€๋‹ค. ๊ด€์ธกํ•œ ์งง์€ ์‹œ๊ณ„์—ด ์ž…๋ ฅ ๊ฐ’์— ๋Œ€ํ•˜์—ฌ ์ด์— ์ƒ์‘ํ•˜๋Š” ์ €์ฐจ์› ๊ณต๊ฐ„ ์ขŒํ‘œ๋ฅผ Gaussian process regression ์„ ํ†ตํ•ด ์–ป๋Š”๋‹ค. ๊ฐ ๋ชจ๋ธ์— ๋Œ€ํ•œ ์œ ์‚ฌ๋„๋Š” ํ•™์Šต ๋ฐ์ดํ„ฐ์— ๋Œ€ํ•œ ๊ด€์ธก ๊ฐ’๊ณผ ๊ทธ ์ €์ฐจ์› ๊ณต๊ฐ„ ์ขŒํ‘œ์˜ ๋กœ๊ทธ ์กฐ๊ฑด๋ถ€ ํ™•๋ฅ ๋ถ„ํฌ ํ˜•ํƒœ๋กœ ํ‘œํ˜„๋œ๋‹ค. ์ด ์œ ์‚ฌ๋„๋ฅผ ๋น„๊ตํ•˜์—ฌ ๊ฐ€์žฅ ๊ฐ€๋Šฅ์„ฑ ์žˆ๋Š” ๋™์ž‘์„ ์ถ”์ •ํ•œ๋‹ค. ํ•˜์ง€ ์™ธ๊ณจ๊ฒฉ ๋กœ๋ด‡ ํ”„๋กœํ† ํƒ€์ž… ๋ฐ ๋™์ž‘ ์ถ”์  ์‹œ์Šคํ…œ์„ ์ด์šฉํ•œ ๋ฌผ๋ฆฌ์  ์‹คํ—˜์„ ํ†ตํ•ด ์šฐ๋ฆฌ์˜ ์•Œ๊ณ ๋ฆฌ์ฆ˜์„ ๊ฒ€์ฆํ•˜์˜€๋‹ค. ๋‹ค์Œ์œผ๋กœ๋Š” ์ ์‘์ ์œผ๋กœ ์Šคํ…์‚ฌ์ด์ฆˆ๋ฅผ ๊ฒฐ์ •ํ•˜๋Š” RRT ์•Œ๊ณ ๋ฆฌ์ฆ˜์„ ์ œ์•ˆํ•˜์˜€๋‹ค. ์ง€์ˆ˜ ๊ณฑ(Product of Exponentials, PoE) ํ˜•ํƒœ๋กœ ํ‘œํ˜„๋œ ๋กœ๋ด‡์˜ ์ •๊ธฐ๊ตฌํ•™๊ณผ ํ‘œ์ค€ ์ž‘์šฉ์†Œ ๋…ธ๋ฆ„ ๋ถ€๋“ฑ์‹์œผ๋กœ๋ถ€ํ„ฐ ์ง๋ ฌ ๊ฐœ ์—ฐ์‡„ ๋กœ๋ด‡์˜ ์—”๋“œ์ดํŽ™ํ„ฐ์˜ ์ž‘์—…๊ณต๊ฐ„์—์„œ์˜ ์ตœ๋Œ€ ๋ณ€์œ„์™€ ๊ด€์ ˆ ๊ณต๊ฐ„์—์„œ์˜ ๋ณ€์œ„์— ๋Œ€ํ•œ ๋ถ€๋“ฑ์‹์œผ๋กœ ์œ ๋„ํ•˜์˜€๋‹ค. ์ด ๋ถ€๋“ฑ์‹์„ ์ด์šฉํ•˜์—ฌ ์ฃผ์–ด์ง„ ์žฅ์• ๋ฌผ์˜ ์ตœ์†Œ ํฌ๊ธฐ์— ๋Œ€ํ•˜์—ฌ ์ ์‘์ ์œผ๋กœ ์Šคํ…์‚ฌ์ด์ฆˆ๋ฅผ ๊ฒฐ์ •ํ•˜์˜€๋‹ค. 10 ์ž์œ ๋„ ํ‰๋ฉด ๊ฐœ ์—ฐ์‡„ ๋กœ๋ด‡๊ณผ 7์ถ• ์‚ฐ์—…์šฉ ๋งค๋‹ˆํ“ฐ๋ ˆ์ดํ„ฐ๋ฅผ ์ด์šฉํ•˜์—ฌ ์šฐ๋ฆฌ์˜ ์•Œ๊ณ ๋ฆฌ์ฆ˜์„ ๊ฒ€์ฆํ•˜์˜€๋‹ค. ๋งˆ์ง€๋ง‰์œผ๋กœ ์‚ฌ๋žŒ์˜ ์‹œ์—ฐ ๋™์ž‘์„ GPDM์„ ์ด์šฉํ•ด ์ €์ฐจ์› ๊ณต๊ฐ„์œผ๋กœ ํ•™์Šตํ•˜์—ฌ, ์‚ฌ๋žŒ๊ณผ ์œ ์‚ฌํ•œ ๋™์ž‘์„ ์ƒ์„ฑํ•˜๋Š” ์ €์ฐจ์› ๊ณต๊ฐ„์—์„œ์˜ ๊ฒฝ๋กœ ๊ณ„ํš ๋ฐฉ๋ฒ•์„ ์ œ์•ˆํ•˜์˜€๋‹ค. ์•ž์„œ ์œ ๋„ํ•œ ๋ถ€๋“ฑ์‹์„ ์ €์ฐจ์› ๊ณต๊ฐ„์—์„œ์˜ ๋ณ€์œ„์™€ ์ž‘์—…๊ณต๊ฐ„์—์„œ์˜ ๊ฐ ๋งํฌ์˜ ๋ณ€์œ„์— ๋Œ€ํ•œ ๋ถ€๋“ฑ์‹์œผ๋กœ ํ™•์žฅํ•˜์˜€๋‹ค. ์ด๋ฅผ ์ด์šฉํ•˜์—ฌ ์ž‘์—…๊ณต๊ฐ„์—์„œ ์ •์˜๋œ ์žฅ์• ๋ฌผ์„ ์ƒ˜ํ”Œ๋ง ๊ธฐ๋ฐ˜์œผ๋กœ ์ €์ฐจ์› ๊ณต๊ฐ„์œผ๋กœ ๋งคํ•‘ํ•˜์˜€๋‹ค. ๊ทธ๋ฆฌ๊ณ  ํ•™์Šตํ•œ ๋™์ž‘๊ณผ ์ƒˆ๋กญ๊ฒŒ ์ƒ์„ฑํ•œ ๋™์ž‘ ์‚ฌ์ด์˜ ์œ ์‚ฌ์„ฑ์„ ์ธก์ •ํ•˜๋Š” ์ธก๋„๋ฅผ GPDM ์ปค๋„ํ•จ์ˆ˜๋ฅผ ๊ธฐ๋ฐ˜์œผ๋กœ ์ •์˜ํ•˜์˜€๋‹ค. ์‹œ๋ฎฌ๋ ˆ์ดํ„ฐ์™€ ์‹ค์ œ ๋กœ๋ด‡์— ์ ์šฉํ•ด ๋ด„์œผ๋กœ์จ ์ œ์•ˆํ•œ ๋ฐฉ๋ฒ•์˜ ์œ ํšจ์„ฑ์„ ๊ฒ€์ฆํ•˜์˜€๋‹ค.In this thesis, we deal with the problems that the robot copes with unstructured environments. Examples of such environments are obstacles that robots should avoid and terrain features that are closely related to the intentions of the wearer of an exoskeleton robot. We make robots to avoid obstacles through path planning algorithms in joint space and its low-dimensional space. We also estimate human motion intentions caused by terrain features using machine learning techniques. First, we propose an algorithm based on Gaussian process dynamical models (GPDM) to estimate motion intention of the wearer of exoskeleton robot. For the observed short time series input values, the corresponding low dimensional space coordinates are obtained via Gaussian process regression. The similarity for each model is expressed in the form of the logarithm of the conditional probability distribution of observed values and its low-dimensional coordinates given the training data. This similarity is compared to estimate the most likely motion. We validate our algorithm through physical experiments using an exoskeleton robot prototype and motion tracking system. Next, we propose a rapidly-exploring random tree (RRT) algorithm that adaptively determines an appropriate stepsize. Using a standard operator norm inequality and the forward kinematics equations expressed as the product of exponentials, we derive an approximate bound on the Cartesian displacement of the open chain tip for a given joint space displacement. Using this inequality bound, we adaptively determine the stepsize for a given minimum obstacle size. We verify our algorithm by numerical experiments using a ten-dof planar open chain robot and a seven-axis industrial manipulator. Finally, we propose a path planning method in a low-dimensional space that generates a human-like motion by learning the human demonstration motion using GPDM. We extend the above inequality to the inequality between displacement in the low-dimensional space and displacement of each links in the workspace. We use this to map the obstacles defined in the workspace to the low-dimensional space based on the uniform sampling. In addition, we define a measure based on the GPDM kernel function to measure the similarity between the learned motion and the newly generated motion. We validate the proposed method by applying it to a simulator and an actual robot.Abstract iii List of Tables xi List of Figures xiii 1 Introduction 1 1.1 Contributions of This Thesis . . . . . . . . . . . . . . . . . . . . . . 4 1.1.1 GPDM-Based Human Motion Intention Recognition for Lower-Limb Exoskeleton . . . . . . . . . . . . . . . . . . . . . . . . 4 1.1.2 An Adaptive Stepsize RRT Planning Algorithm for Open Chain Robots . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5 1.1.3 A Gaussian Process Dynamical Model-Based Planning Method 8 1.2 Organization . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9 2 Preliminaries 11 2.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11 2.2 Gaussian Process . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12 2.2.1 Gaussian Process Regression . . . . . . . . . . . . . . . . . . 12 2.2.2 Gaussian Process Latent Variable models . . . . . . . . . . . 16 2.2.3 Gaussian Process Dynamical Models . . . . . . . . . . . . . . 19 2.3 Forward Kinematics of Open Chains . . . . . . . . . . . . . . . . . . 23 3 GPDM-Based Human Motion Intention Recognition for Lower-Limb Exoskeleton 27 3.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27 3.2 Human Motion Intention Recognition using GPDM . . . . . . . . . 29 3.3 Data Description . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 30 3.3.1 Human Motion Capture Data . . . . . . . . . . . . . . . . . 30 3.3.2 Sensor Mock-up Data . . . . . . . . . . . . . . . . . . . . . . 33 3.4 Experiments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 35 3.4.1 Previous Research . . . . . . . . . . . . . . . . . . . . . . . . 35 3.4.2 Human Motion Capture Data . . . . . . . . . . . . . . . . . 40 3.4.3 Sensor Mock-up Data . . . . . . . . . . . . . . . . . . . . . . 44 3.5 Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 45 3.5.1 Comparison both Data Sets . . . . . . . . . . . . . . . . . . . 45 3.5.2 Sensitivity Analysis . . . . . . . . . . . . . . . . . . . . . . . 49 3.6 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 51 4 An Adaptive Stepsize RRT Planning Algorithm for Open Chain Robots 53 4.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 53 4.2 A Cartesian Displacement Bound for Open Chains . . . . . . . . . 54 4.3 Adaptive Stepsize RRT . . . . . . . . . . . . . . . . . . . . . . . . . 58 4.4 Experiments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 63 4.4.1 Ten-Dof Planar Robot . . . . . . . . . . . . . . . . . . . . . . 65 4.4.2 Ten-Dof Planar Robot Case II: Latent Space RRT . . . . . 70 4.4.3 Seven-DoF Industrial Robot Arm . . . . . . . . . . . . . . . 77 4.5 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 82 5 A Gaussian Process Dynamical Model-Based Planning Method 85 5.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 85 5.2 Learning from Demonstration Framework . . . . . . . . . . . . . . . 88 5.2.1 Learning a New Pose in the Latent Space . . . . . . . . . . 90 5.2.2 Constraints in Latent Space . . . . . . . . . . . . . . . . . . 91 5.2.3 Mapping Obstacle into Latent Space . . . . . . . . . . . . . 92 5.2.4 Motion Planning in Latent Space . . . . . . . . . . . . . . . 102 5.3 Experiments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 108 5.3.1 Grasping Experiments . . . . . . . . . . . . . . . . . . . . . . 108 5.4 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 114 6 Conclusion 117 Bibliography 121 Abstract 128Docto

    Incorporation of SKI-G-801, a Novel AXL Inhibitor, With Anti-PD-1 Plus Chemotherapy Improves Anti-Tumor Activity and Survival by Enhancing T Cell Immunity

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    A recently developed treatment strategy for lung cancer that combines immune checkpoint inhibitors with chemotherapy has been applied as a standard treatment for lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC), and it has improved the outcomes of chemotherapy. Maintenance treatment with anti-PD-1 antibody (aPD-1) enhances the effect of immunochemical combination therapy and improves therapeutic efficacy, which contributes toward a significant improvement in patient survival rates. The AXL receptor tyrosine kinase (AXL), which is expressed in tumor cells, plays an essential role in the resistance of cancers to chemotherapy and immunotherapy, and stimulates signaling associated with epithelial-mesenchymal transition (EMT) in metastatic cancer. AXL is thus an attractive target for controlling resistance to anti-tumor therapies. In this study, we examined the effect of AXL inhibitors on immune activation and tumor growth in TC1 and C3PQ mouse tumor models, in the context of clinical immunotherapy/chemotherapy and maintenance treatment, using an aPD-1 with/without pemetrexed. To determine the optimal timing for administration of SKI-G-801, an AXL inhibitor, we investigated its anti-tumor effects based on inclusion at the immunochemotherapy and maintenance therapy stages. We also performed flow cytometry-based immune profiling of myeloid cells and lymphoid cells at different points in the treatment schedule, to investigate the immune activation and anti-tumor effects of the AXL inhibitor. The addition of SKI-G-801 to the immune checkpoint inhibitor and chemotherapy stage, as well as the maintenance therapy stage, produced the best anti-tumor results, and significant tumor growth inhibition was observed in both the TC1 and C3PQ models. Both models also exhibited increased proportion of effector memory helper T cells and increased expression of CD86+ macrophages. Especially, regulatory T cells were significantly reduced in the TC1 tumor model and there was an increase in central memory cytotoxic T cell infiltration and an increased proportion of macrophages with high CD80 expression in the C3PQ tumor model. These results suggest increased infiltration of T cells, consistent with previous studies using AXL inhibitors. It is expected that the results from this study will serve as a stepping stone for clinical research to improve the existing standard of care.ope

    Patient-Derived Cells to Guide Targeted Therapy for Advanced Lung Adenocarcinoma

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    Adequate preclinical model and model establishment procedure are required to accelerate translational research in lung cancer. We streamlined a protocol for establishing patient-derived cells (PDC) and identified effective targeted therapies and novel resistance mechanisms using PDCs. We generated 23 PDCs from 96 malignant effusions of 77 patients with advanced lung adenocarcinoma. Clinical and experimental factors were reviewed to identify determinants for PDC establishment. PDCs were characterized by driver mutations and in vitro sensitivity to targeted therapies. Seven PDCs were analyzed by whole-exome sequencing. PDCs were established at a success rate of 24.0%. Utilizing cytological diagnosis and tumor colony formation can improve the success rate upto 48.8%. In vitro response to a tyrosine kinase inhibitor (TKI) in PDC reflected patient treatment response and contributed to identifying effective therapies. Combination of dabrafenib and trametinib was potent against a rare BRAF K601E mutation. Afatinib was the most potent EGFR-TKI against uncommon EGFR mutations including L861Q, G719C/S768I, and D770_N771insG. Aurora kinase A (AURKA) was identified as a novel resistance mechanism to olmutinib, a mutant-selective, third-generation EGFR-TKI, and inhibition of AURKA overcame the resistance. We presented an efficient protocol for establishing PDCs. PDCs empowered precision medicine with promising translational values.ope

    SKI-G-801, an AXL kinase inhibitor, blocks metastasis through inducing anti-tumor immune responses and potentiates anti-PD-1 therapy in mouse cancer models

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    Objectives: AXL-mediated activation of aberrant tyrosine kinase drives various oncogenic processes and facilitates an immunosuppressive microenvironment. We evaluated the anti-tumor and anti-metastatic activities of SKI-G-801, a small-molecule inhibitor of AXL, alone and in combination with anti-PD-1 therapy. Methods: In vitro pAXL inhibition by SKI-G-801 was performed in both human and mouse cancer cell lines. Immunocompetent mouse models of tumor were established to measure anti-metastatic potential of SKI-G-801. Furthermore, SKI-G-801, anti-PD-1 or their combination was administered as an adjuvant or neoadjuvant in the 4T1 tumor model to assess their potential for clinical application. Results: SKI-G-801 robustly inhibited pAXL expression in various cell lines. SKI-G-801 alone or in combination with anti-PD-1 potently inhibited metastasis in B16F10 melanoma, CT26 colon and 4T1 breast models. SKI-G-801 inhibited the growth of B16F10 and 4T1 tumor-bearing mice but not immune-deficient mice. An antibody depletion assay revealed that CD8+ T cells significantly contributed to SKI-G-801-mediated survival. Anti-PD-1 and combination group were observed the increased CD8+Ki67+ and effector T cells and M1 macrophage and decreased M2 macrophage, and granulocytic myeloid-derived suppressor cell (G-MDSC) compared to the control group. The neoadjuvant combination of SKI-G-801 and anti-PD-1 therapy achieved superior survival benefits by inducing more profound T-cell responses in the 4T1 syngeneic mouse model. Conclusion: SKI-G-801 significantly suppressed tumor metastasis and growth by enhancing anti-tumor immune responses. Our results suggest that SKI-G-801 has the potential to overcome anti-PD-1 therapy resistance and allow more patients to benefit from anti-PD-1 therapy.ope

    A study on Risk Premium in Ship Finance: Focused on Collateral vlaue of ships

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    2008๋…„ 9์›” ๊ธˆ์œต์œ„๊ธฐ ๋ฐœ์ƒ ์ดํ›„ ์„ ๋ฐ•๊ธˆ์œต ์‹œ์žฅ์€ ์ปค๋‹ค๋ž€ ๋ณ€ํ™”๋ฅผ ๊ฒช๊ณ  ์žˆ๋‹ค. ํ•ด์šด์‚ฐ์—…์ด ์žฅ๊ธฐ์นจ์ฒด๋ฅผ ๋ฒ—์–ด๋‚˜์ง€ ๋ชปํ•˜๋ฉด์„œ ์„ ๋ฐ•์˜ ํ˜„๊ธˆํ๋ฆ„ ์ฐฝ์ถœ๋Šฅ๋ ฅ์ด ์ €ํ•˜๋˜์–ด ์„ ๋ฐ•์˜ ๋‹ด๋ณด๊ฐ€์น˜์— ๋Œ€ํ•œ ๊ทผ๋ณธ์ ์ธ ์˜๋ฌธ์ด ์ œ๊ธฐ๋˜๊ณ  ์žˆ๋‹ค. ์„ ๋ฐ•๊ธˆ์œต์€ ํ•ญ๊ณต๊ธฐ๊ธˆ์œต๊ณผ ๋”๋ถˆ์–ด ๋Œ€ํ‘œ์ ์ธ ์ž์‚ฐ๋‹ด๋ณด๋ถ€๊ธˆ์œต์˜ ํ•˜๋‚˜๋กœ ์ธ์‹๋˜์–ด์™”๋‹ค. ์„ ๋ฐ•๊ธˆ์œต์˜ ๋ฐœ๋‹ฌ๊ณผ์ •์„ ์‚ดํŽด๋ณด๋ฉด ์„ ๋ฐ•์ด ์•ˆ์ •์  ๋‹ด๋ณด๊ฐ€์น˜๋ฅผ ๊ฐ€์ง„ ์ž์‚ฐ์œผ๋กœ ์ธ์‹๋˜๋ฉด์„œ ๊ธˆ์œต๊ธฐ๊ด€์€ ์„ ๋ฐ•์„ ์ธํ”Œ๋ ˆ ๋ฐฉ์–ด์ˆ˜๋‹จ์œผ๋กœ ์—ฌ๊ฒจ ์„ ๋ฐ•๊ธˆ์œต์„ ์ž์‚ฐ๋‹ด๋ณด๋ถ€๊ธˆ์œต์œผ๋กœ ๋ฐœ์ „์‹œ์ผฐ๋‹ค. ๊ทธ๋Ÿฌ๋‚˜ 2008๋…„ ์ดํ›„ ์šด์ž„์‹œ์žฅ์˜ ์žฅ๊ธฐ ๋ถˆํ™ฉ์€ ์„ ๋ฐ•์˜ ๋‹ด๋ณด๊ฐ€์น˜์— ๋Œ€ํ•œ ๊ทผ๋ณธ์ ์ธ ๋ณ€ํ™”๋ฅผ ์•ผ๊ธฐ ์‹œ์ผฐ๋‹ค. ๋ณธ ์—ฐ๊ตฌ๋Š” ์„ ๋ฐ•๊ธˆ์œต์˜ ๋ฆฌ์Šคํฌ ํ”„๋ฆฌ๋ฏธ์—„์— ์„ ๋ฐ•์˜ ๋‹ด๋ณด๊ฐ€์น˜์ด์™ธ์— ์–ด๋– ํ•œ ์š”์†Œ๋“ค์ด ์˜ํ–ฅ์„ ๋ฏธ์น˜๋Š”์ง€ ๋น„์žฌ๋ฌด์  ์š”์†Œ๋“ค์ธ ์„ ๊ฐ€, ๋Œ€์ถœ๊ทœ๋ชจ, ๋Œ€์ถœ์‹œ๊ธฐ, ์„ ์ข…, ๋Œ€์ถœ์—ฐ๋„๋ฅผ ์ค‘์‹ฌ์œผ๋กœ ๋ถ„์„ํ•˜์˜€๋‹ค. ๋ถ„์„๊ฒฐ๊ณผ ์„ ๊ฐ€, ๋Œ€์ถœ๊ทœ๋ชจ, ๋Œ€์ถœ์‹œ๊ธฐ, ์„ ์ข…์€ ๋ฆฌ์Šคํฌ ํ”„๋ฆฌ๋ฏธ์—„์— ์˜ํ–ฅ์„ ๋ฏธ์น˜์ง€ ๋ชปํ•˜๊ณ  ๋Œ€์ถœ์‹œ๊ธฐ(2008๋…„ ์ดํ›„ ๋Œ€์ถœ๋ถ„)๋งŒ ์˜ํ–ฅ์„ ๋ฏธ์น˜๋Š” ๊ฒƒ์œผ๋กœ ๋‚˜ํƒ€๋‚ฌ๋‹ค. ์ด๋Š” ๊ธฐ์กด์˜ ์„ ๋ฐ•๊ธˆ์œต์—์„œ ์ค‘์š”ํ•˜๊ฒŒ ๋‹ค๋ค„์ง€๋˜ ์š”์†Œ๋“ค์ด ์‹œ์žฅ๋ณ€ํ™”์— ๋”ฐ๋ผ ๋ฐ”๋€Œ๊ณ  ์žˆ์Œ์„ ์‹œ์‚ฌํ•œ๋‹ค. ์ฃผ์ œ์–ด : ์„ ๋ฐ•์˜ ๋‹ด๋ณด๊ฐ€์น˜, ๋ฆฌ์Šคํฌ ํ”„๋ฆฌ๋ฏธ์—„, ์‹œ์žฅ์ƒํ™ฉ์ œ1์žฅ ์„œ๋ก  1 1.1 ์—ฐ๊ตฌ ๋ฐฐ๊ฒฝ๊ณผ ์—ฐ๊ตฌ ๋ชฉ์  1 1.2 ์—ฐ๊ตฌ ๋ฐฉ๋ฒ•๊ณผ ์—ฐ๊ตฌ ๋ฒ”์œ„ 3 1.3 ๋…ผ๋ฌธ์˜ ๊ตฌ์„ฑ 4 ์ œ2์žฅ ์„ ํ–‰์—ฐ๊ตฌ 5 ์ œ3์žฅ ์„ ๋ฐ•๊ธˆ์œต 9 3.1 ์„ ๋ฐ•๊ธˆ์œต๊ฐœ์š” 9 3.2 ์„ ๋ฐ•๊ธˆ์œต์‹œ์žฅ ๋™ํ–ฅ 10 3.3 ์„ ๋ฐ•๊ธˆ์œต์˜ ์ข…๋ฅ˜ 11 3.4 ๋ณธ ์—ฐ๊ตฌ์˜ ๋Œ€์ƒ 14 ์ œ4์žฅ ์ž์‚ฐ๋‹ด๋ณด๋ถ€๊ธˆ์œต ๋ฐ ๋ฆฌ์Šคํฌ ํ”„๋ฆฌ๋ฏธ์—„ 15 4.1 ์ž์‚ฐ๋‹ด๋ณด๋ถ€๊ธˆ์œต์˜ ์˜์˜ 15 4.2 ์ฐจ์ฃผ์˜ ์„ฑ๊ฒฉ์— ๋”ฐ๋ฅธ ๋‹ด๋ณด๊ฐ€์น˜์˜ ๋ณ€ํ™” 16 4.3 DSCR, LTV ๋“ฑ์— ๋”ฐ๋ฅธ ๋‹ด๋ณด๊ฐ€์น˜์˜ ๋ณ€ํ™” 17 4.4 ๋ฆฌ์Šคํฌ ํ”„๋ฆฌ๋ฏธ์—„ 18 4.5 ์œ„ํ—˜๊ณผ ์ˆ˜์ต์˜ ๊ตํ™˜๊ด€๊ณ„ 18 ์ œ5์žฅ ์—ฐ๊ตฌ๋ฐฉ๋ฒ• 20 5.1 ๋ถ„์„๋ฐฉ๋ฒ• 20 5.2 ๋ณ€์ˆ˜์˜ ์„ ์ • 21 5.2.1 ์„ ๊ฐ€์ง€์ˆ˜ 22 5.2.2 ๋Œ€์ถœ๊ทœ๋ชจ 23 5.2.3 ๋Œ€์ถœ๊ธฐ๊ฐ„ 23 5.2.4 ์„ ์ข… 24 5.2.5 ๋Œ€์ถœ์—ฐ๋„ 25 5.3 ๋ฆฌ์Šคํฌ ํ”„๋ฆฌ๋ฏธ์—„ 26 ์ œ6์žฅ ๋ถ„์„๊ฒฐ๊ณผ 28 6.1 ์„ ๊ฐ€์ง€์ˆ˜ 29 6.2 ๋Œ€์ถœ๊ทœ๋ชจ 33 6.3 ๋Œ€์ถœ๊ธฐ๊ฐ„ 34 6.4 ์„ ์ข… 34 6.5 ๋Œ€์ถœ์‹œ๊ธฐ 34 ์ œ7์žฅ ๊ฒฐ๋ก  36 7.1 ์—ฐ๊ตฌ๊ฒฐ๊ณผ ์š”์•ฝ 36 7.2 ์‹œ์‚ฌ์  ๋ฐ ํ•œ๊ณ„ 37 ์ฐธ๊ณ ๋ฌธํ—Œ 39Maste

    Prognostic implications of PD-L1 expression in patients with angiosarcoma

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    Aim: There are limited data on the feasibility of programmed death ligand-1 (PD-L1) expression as a prognostic biomarker in metastatic angiosarcoma. Patients & methods: We retrospectively collected and analyzed the data on PD-L1 expression in 70 angiosarcoma patients who were diagnosed at our center between 2005 and 2019. Results: Thirteen (19%) patients had PD-L1 expression. Metastatic angiosarcoma patients who were PD-L1-negative (n = 24) showed longer median progression-free survival (4.9 vs 1.6 months; p = 0.04) and median overall survival (OS; 10.9 vs 5.4 months; p = 0.01) than those who were PD-L1-positive (n = 4). PD-L1 status proved to be a significant factor for OS. Conclusion: Metastatic angiosarcoma patients with PD-L1 expression showed shorter survival. PD-L1 status is an independent prognostic factor for OS in metastatic angiosarcoma patients.ope

    A phase II study of poziotinib in patients with recurrent and/or metastatic head and neck squamous cell carcinoma

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    Background: In phase I studies, poziotinib has shown meaningful efficacy against various types of cancers. This phase 2 study aimed to investigate the efficacy and safety of poziotinib in recurrent and/or metastatic head and neck squamous cell carcinoma (R/M-HNSCC). Methods: Overall, 49 patients were enrolled (median age, 62 years; age range, 21-78 years). Patients received a median of two prior treatments including chemotherapy and others and received 12 mg poziotinib orally once daily as part of a 28-day cycle. The primary endpoint was objective response rate (ORR), and the secondary endpoints were progression-free survival (PFS) and overall survival (OS). Targeted capture sequencing was performed using available tissues to identify translational biomarkers related to clinical response. Results: ORR was 22.4%, median PFS was 4.0 months (95% confidence interval [CI], 1.8-6.2 months), and median OS was 7.6 months (95% CI, 4.4-10.8 months). The most common treatment-related adverse events were acneiform rash (85%) and mucositis (77%). A grade 3 or higher adverse event was acneiform rash (3%). Targeted capture sequencing was performed in 30 tissue samples. TP53 and PIK3CA were the most frequently mutated genes (43%), followed by CCND1 (33%) and EGFR (30%). Mutations in ERBB2, ERBB3, and ERBB4, which are HER family genes, were observed in 17%, 13%, and 10% samples, respectively. There was no difference in the frequency of somatic mutations in the HER family genes between the clinically benefitted and non-benefitted groups. Conclusion: Compared to other pan-HER inhibitors, poziotinib showed clinically meaningful efficacy in heavily treated R/M-HNSCC. Clinical trial registration number: NCT02216916.ope

    Analyses of CNS Response to Osimertinib in Patients with T790M-Positive Advanced NSCLC from ASTRIS Korean Subset, Open-Label Real-World Study

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    Up to 40% of patients with epidermal growth factor receptor (EGFR) mutation-positive non-small-cell lung cancer (NSCLC) may develop central nervous system (CNS) metastases throughout their disease. Moreover, the first- and second-generation EGFR-tyrosine kinase inhibitors have limited efficacy because of their poor bloodโ€“brain barrier permeability. Therefore, we conducted preplanned analyses of ASTRIS, a clinical study of the third-generation EGFR-TKI osimertinib to demonstrate its potential role in intracranial response efficacies. We retrospectively examined 89 NSCLC patients with brain evaluation who were not amenable to curative surgery or radiotherapy and received osimertinib upon confirmation of the presence of the T790M mutation. We collected the information regarding patientsโ€™ baseline characteristics, baseline intracranial status, including leptomeningeal metastases (LM), and intracranial responses measured by Response Evaluation Criteria in Solid Tumors version 1.1, using independent central review. The median age was 60 years, and 69.7% of the patients were female. Sixty-five patients (73.0%) had brain metastases (BM) at baseline and nineteen patients (23.5%) had additional LM. Among patients with brain metastases, 24 (36.9%) had โ‰ฅ1 measurable brain metastases and 16 were evaluated for the objective response. In the CNS evaluable for response set, the intracranial objective response rate (cORR) and disease control rate (cDCR) were 62.5% (95% confidence interval (CI), 38.3โ€“82.6%) and 93.8% (95% CI, 74.3โ€“99.3%), respectively. The median intracranial progression-free survival (cPFS) was 13.0 (95% CI, 7.21โ€“18.8) months, including patients with measurable and non-measurable BM or LM. Our cORR, cDCR, and cPFS were comparable to those observed in previous clinical trials. The outcome of this study helps to demonstrate the potential role of intracranial efficacies of osimertinib 80 mg administration in T790M-positive advanced NSCLC with/without BM or LM. View Full-ope

    Real World Characteristics and Clinical Outcomes of HER2-Mutant Non-Small Cell Lung Cancer Patients Detected by Next-Generation Sequencing

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    Purpose This study was conducted to investigate the clinical characteristics of patients with advanced nonโ€“small cell lung cancer (NSCLC) harboring human epidermal growth factor receptor 2 (HER2) mutations and to evaluate response to standard treatment and HER2-targeted agents. Materials and Methods Using tissue and/or blood next-generation sequencing, we identified 44 patients with NSCLC harboring HER2 mutations who were treated at Severance Hospital between December 2016 and February 2021. Clinical data, including patient characteristics, mutation status, incidence of metastasis for distant lesions, and response to chemotherapy, were retrospectively analyzed. Results The median age was 58 years, and 61% of the patients were female. Most patients (64%) were never-smokers. Adenocarcinoma was the most predominant subtype (98%). A total of 66% of the patients had extrathoracic metastatic lesions, and 32% had intracranial lesions at initial presentation. The median time to the development of brain metastasis was 15.6 months (range, 2.4 to 43.7). The most common type of HER2 mutation was 12 base pair in-frame insertion in exon 20, A775_G776insYVMA. Of the 44 patients, two had concomitant driver mutations, one with epidermal growth factor receptor (EGFR) mutation (V769M), and one with BRAF mutation (V600E). Patients treated with pemetrexed-based chemotherapy (75%) had an overall response rate (ORR) and progression-free survival (PFS) of 30% and 8.3 months (95% confidence interval [CI], 3.9 to 12.7), respectively. The ORR and PFS of HER2-targeted agent treated patients (14%) were 0.0% and 1.9 months (95% CI, 0.1 to 2.8), respectively. Conclusion Given its distinct characteristics and treatment responses, novel treatment strategies for HER2-mutant NSCLC should be developed promptly to improve survival outcomes of patients.ope

    Clinical utility of a plasma-based comprehensive genomic profiling test in patients with non-small cell lung cancer in Korea

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    Objectives: Plasma-based comprehensive circulating cell-free DNA (cfDNA) next generation sequencing (NGS) has shown utility in advanced non-small cell lung cancer (aNSCLC). The aim of this study was to determine the feasibility of cfDNA-based NGS to identify actionable gene alterations in patients with aNSCLC. Patients and methods: This single-center non-interventional retrospective study evaluated Korean patients with biopsy-confirmed stage III/IV non-squamous aNSCLC. Tissue biopsy samples were collected at baseline, and/or at progression and analysed with Standard of Care (SOC) testing; cfDNA was analyzed by NGS in some patients concurrently. Results: aNSCLC patients with cfDNA test results (n = 405) were categorized into three groups: treatment naรฏve (n = 182), progressive aNSCLC after chemotherapy and/or immunotherapy (n = 157), and progressive aNSCLC after tyrosine kinase inhibitors (TKIs) (n = 66). Clinically informative driver mutations were identified for 63.5% of patients which were classified as OncoKB Tiers 1 (44.2%), 2 (3.4%), tier 3 (18.9%), and 4 (33.5%). Concordance between cfDNA NGS and tissue SOC methods for concurrently collected tissue samples (n = 221) with common EGFR mutations or ALK/ROS1 fusions was 96.9%. cfDNA analysis identified tumor genomic alterations in 13 patients that were unidentified with tissue testing, enabling initiation of targeted treatment. Conclusions: In clinical practice, results of cfDNA NGS are highly concordant with those of tissue SOC testing in aNSCLC patients. Plasma analysis identified actionable alterations that were missed or not evaluated by tissue testing, enabling the initiation of targeted therapy. Results from this study add to the body of evidence in the support routine use of cfDNA NGS for patients with aNSCLC. ยฉ 2023 The Author(s)ope
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