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Yuichi Ishikawa

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    MS 18 - Biomarker for Anti-PD-L1 Therapy (ID 540)

    • Event: WCLC 2017
    • Type: Mini Symposium
    • Track: Immunology and Immunotherapy
    • Presentations: 5
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      MS 18.02 - An Update on the BLUEPRINT and Related Projects (ID 8123)

      15:45 - 17:30  |  Presenting Author(s): Fred R. Hirsch

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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      MS 18.03 - Potential Application of Molecular Genomic for Immunotherapy (ID 7645)

      15:45 - 17:30  |  Presenting Author(s): Rolf A Stahel

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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      MS 18.04 - PD-L1 Expression in Early Stage Lung Cancer (ID 7646)

      15:45 - 17:30  |  Presenting Author(s): Jin-Haeng Chung

      • Abstract
      • Presentation
      • Slides

      Abstract:
      The significant activity of programmed cell death 1 (PD-1)/PD-1 ligand 1 (PD-L1) checkpoint inhibitors in heavily pre-treated patients with advanced non–small-cell lung cancer (NSCLC) marked the beginning of a new era of immunotherapy. Recently published randomised clinical trials’ data have led to the approval of 3 PD-1/PD-L1 inhibitors—nivolumab (Opdivo; Bristol-Myers Squibb Company), pembrolizumab (Keytruda; Merck Sharp & Dohme Corp), and atezolizumab (Tecentriq, Genentech/Roche)—for the treatment of advanced NSCLC after first-line therapy. Furthermore, pembrolizumab was recently approved by the FDA as a first-line therapy for patients with advanced NSCLC. However, the overall response rates to these agents in an unselected population are reportedly low, thus emphasising the need for predictive biomarkers that identify beneficial candidates. The recently approved tests for anti-PD-1/PD-L1 therapy in NSCLC include the assessment of PD-L1 expression using immunohistochemistry (IHC) as a companion diagnostic test (22C3 for pembrolizumab) and 2 complementary diagnostic tests (28-8 for nivolumab and SP142 for atezolizumab). Another PD-L1 assay is being currently tested in clinical trials (e.g. SP263). In addition to commercial assays, laboratories and research institutions may establish their own laboratory-developed tests (LDTs) using various antibodies available, most notably the E1L3N clone. Hence, the PD-L1 expression status, as well as its predictive and prognostic value, differ considerably based on the antibody clones, platforms, and interpretation criteria used. However, the current assays evaluating the predictive role of tumour PD-L1 expression remain without harmonization in terms of the staining analysis and scoring system. The intratumoural heterogeneity in PD-L1 expression is another important issue. At present, PD-L1 testing is mainly conducted on biopsy specimens, which may not represent the tumour as a whole, and it may lead to false results, particularly in cases where testing is conducted using small tissue specimens, such as bronchial or transthoracic biopsy specimens. The resulting false-negative results could lead to the under-treatment of patients. In this presentation, I’d like to introduce 1) the results of comparison study between 4 different PD-L1 IHC and scoring systems in the surgically resected early stage lung cancer specimen 2) the correlation of PD-L1 expression between TMA specimens and the corresponding resected specimen to better understand the intratumoral heterogeneity.

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      MS 18.05 - Liquid Biopsy Biomarkers in IO: Is There Room? (ID 7647)

      15:45 - 17:30  |  Presenting Author(s): Christian Rolfo

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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      MS 18.06 - Future Perspectives of Biomarkers for Anti PD-1/PD-L1 Therapy (ID 8124)

      15:45 - 17:30  |  Presenting Author(s): Julie R Brahmer

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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Author of

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    MTE 17 - Neuroendocrine Tumor (Sign Up Required) (ID 566)

    • Event: WCLC 2017
    • Type: Meet the Expert
    • Track: SCLC/Neuroendocrine Tumors
    • Presentations: 1
    • Moderators:
    • Coordinates: 10/17/2017, 07:00 - 08:00, Room 418
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      MTE 17.01 - Pathological Features of Neuroendocrine Tumors (ID 7798)

      07:00 - 08:00  |  Presenting Author(s): Yuichi Ishikawa

      • Abstract
      • Presentation
      • Slides

      Abstract:
      In the WHO 2015 classification, neuroendocrine tumors (NETs) have become one of the 4 major histological types of lung cancer. NET includes typical carcinoid (TC), atypical carcinoid (AC), small cell lung carcinoma (SCLC) and large cell neuroendocrine carcinoma (LCNEC). In this presentation, I’ll talk about problems of diagnosis of SCLC, and challenge “common knowledges” of NETs as follows: 1. SCLC is highly malignant and only very rarely the patients survive after 5 years. What are pathological characteristics of tumors with longer survival? 2. There are no subtypes of SCLC, only combined SCLC is described in the WHO 2015. Isn’t subtyping of pure SCLC needed? Also, is SCLC a hilar-type cancer? 3. Diagnosis of SCLC doesn’t require immunohistochemistry (IHC) although IHC is used to diagnose even adenocarcinoma and squamous cell carcinoma. Isnt’ IHC useful for SCLC? 4. NET includes TC, AC, SCLC and LCNEC. Is this a spectrum of NET, showing progression of NET? In other words, does AC progress to LCNEC? 5. For adenocarcinoma diagnosis, transcription factor TTF-1 is useful even when the tumor doesn’t express glandular phenotypes such as mucin and CEA. In case of NET, we usually pay attention to NE phenotypes such as synaptophysin and NCAM, not to transcription factors. Aren’t transcription factors such as ASCL1 and INSM 1 useful for SCLC diagnosis? 6. Is the Kulchitsky an origin of SCLC? I’d like to answer these questions, mainly based on our own experiences.

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    P2.05 - Early Stage NSCLC (ID 706)

    • Event: WCLC 2017
    • Type: Poster Session with Presenters Present
    • Track: Early Stage NSCLC
    • Presentations: 1
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      P2.05-016 - Clinical Importance and Application of New T Descriptors in the 8th TNM Classification for Pathological T0-1 Lung Adenocarcinoma (ID 9341)

      09:30 - 16:00  |  Author(s): Yuichi Ishikawa

      • Abstract
      • Slides

      Background:
      In the new TNM classification (8th), significant revision was made for pathological (p) T descriptors. Tumors, 3 cm or less in size, measuring invasive size, were subclassified into five categories, Tis, T1mi, T1a, T1b and T1c, termed T0-1 tumors here. Purpose of this study was to examine clinical importance of new pT descriptors and apply to indication criteria of limited surgery for pT0-1 lung adenocarcinoma.

      Method:
      We retrospectively reviewed pathological data of lung adenocarcinomas surgically resected between 2011 and 2016 at our institute, and reclassified them according to the new TNM classification. We found 874 tumors classified as pT0-1. We compared invasion-related factors such as lymph node (LN) metastasis, lymphatic and /or vascular invasion (LVI) and existence of lepidic component among the five T categories.

      Result:
      There were 154, 196, 195, 255 and 74 cases in the pTis, T1mi, T1a, T1b and T1c category, respectively. LN metastasis was found in 50 of 874 (6%) cases. LN metastasis rates were 0%, 2%, 10% and 27% in T1mi, T1a, T1b and T1c, respectively. In 108 of 874 cases, invasive size was equal to whole tumor size, meaning that they contain less of lepidic component. LN metastasis rates of the 108 cases were 13%, 13% and 27% in T1a, T1b and T1c, respectively, implying that LN metastasis of T1a diseases were much often with less lepidic component. In the 824 cases without LN metastases, LVI was observed in 156 (19%) cases. LVI rates were 1%, 21%, 39 and 46% in T1mi, T1a, T1b and T1c, respectively. In 89 of 824 cases, invasive size was equal to whole tumor size. LVI rates of the 89 cases were 31%, 54% and 54% in T1a, T1b and T1c, respectively, meaning that LVI rates were more frequent in T1a-c diseases with less lepidic component.

      Conclusion:
      LN metastasis was rare (2%) in T1a diseases, and they may be good candidates for limited surgery such as segmentectomy. However, T1a diseases with less lepidic component, showing 13% of LN metastasis, may be difficult to cure by limited surgery. On the other hand, in T1b and T1c diseases, LN metastasis rates did not significantly differ between cases with and without lepidic component. T1mi diseases, rarely showing LVI, can be managed same as Tis and cured by partial resection. Taken together, it is the most important to predict pathological T descriptors preoperatively accurately by imaging analysis for T0-1 lung adenocarcinoma.

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    P3.13 - Radiology/Staging/Screening (ID 729)

    • Event: WCLC 2017
    • Type: Poster Session with Presenters Present
    • Track: Radiology/Staging/Screening
    • Presentations: 1
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      P3.13-009 - Rapid Detection of Lung Cancer by Fluorescent Imaging using a γ-Glutamyltranspeptidase-activatable Fluorescent Probe (ID 8326)

      09:30 - 16:00  |  Author(s): Yuichi Ishikawa

      • Abstract
      • Slides

      Background:
      Visualizing the spread of cancer cells in lung cancer surgery is sometimes difficult. γ-Glutamyl-transpeptidase (GGT) is a cell surface-associated enzyme that is overexpressed in various type of human cancers. γ-Glutamyl hydroxymethyl rhodamine green (gGlu-HMRG), an activatable fluorescent probe, is non-fluorescent under a neutral pH and normal cellular environment. However, it becomes highly fluorescent upon reaction with GGT. We evaluated ex vivo fluorescent imaging of lung cancers using the GGT-activatable fluorescent probe.

      Method:
      Between April 2011 to November 2014, 116 resected cancer cells (91 primary lung cancers, 21 pulmonary metastases, and 4 pleural disseminations) were prospectively included in this study. Each tumor was analyzed by first taking a baseline image before gGlu-HMRG was sprayed onto the freshly resected specimen (termed N0; fluorescent intensity of normal lung, T0; that of lung cancer), and then by taking fluorescent images 30 min after spraying (N30 and T30) with the Maestro In-vivo imaging system (PerkinElmer Inc.). Positive fluorescent activity was defined as follows: in cases where fluorescence was observed only in tumor tissues, ΔN(=N30-N0) < 0 and ΔT(=T30-T0) < 0, in cases where fluorescence was observed in both normal and tumor tissues, ΔN > 0 and ΔT/ΔN > 1.

      Result:
      Figure 1In primary lung cancer, 61 of 91 (67%) cases rapidly developed fluorescent activity. In cases with pulmonary metastases, 15 of 21 (71.4%) cases showed positive fluorescent activity. Four disseminated pleural nodules all showed positive fluorescent activity (100%). Age, gender, tumor size, tumor marker, histology (adenocarcinoma (Ad) vs. non-Ad, squamous cell carcinoma (Sq) vs. non-Sq), pleural invasion, and angio-lymphatic invasion were not significant factors influencing fluorescent intensity.



      Conclusion:
      Fluorescence imaging with gGlu-HMRG may become one of the most powerful tools for accurate staging by rapidly detecting cancer cells and thus become highly useful for cancer resection.

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