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J. Matsubayashi



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    P1.01 - Advanced NSCLC (ID 757)

    • Event: WCLC 2017
    • Type: Poster Session with Presenters Present
    • Track: Advanced NSCLC
    • Presentations: 1
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      P1.01-041 - Role of Re-Biopsy During Disease Progression Non-Small Cell Lung Cancer for Acquired Resistance Analysis and Directing Oncology Treatments (ID 10340)

      09:30 - 16:00  |  Author(s): J. Matsubayashi

      • Abstract

      Background:
      It is not possible to properly target treatments in cases of relapse without knowing the nature of new lesions. Third-generation epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKI) can overcome T790M-mediated resistance in non-small-cell lung cancer (NSCLC). But the re-biopsy to confirm T790M status is occasionally difficult. In Japan, transbronchial lung tissue biopsy (TBLB / TBB) is the most common sampling method used for re-biopsy to confirm patients eligible for treatment. We aimed to investigate the success rate of re-biopsy and re-biopsy status of patients with advanced or metastatic NSCLC completing either 1st line chemotherapy or EGFR-TKI therapy.

      Method:
      We initially screened 39 consecutive patients with NSCLC harboring EGFR-sensitive mutations who had experienced PD after any chemotherapy at Tokyo Medical University Hospital January 2014 and December 2016.

      Result:
      38 patients who had experienced PD after EGFR-TKI treatment were eligible. Among 30 patients, tumor progression sites included 3 pleural effusion, 9 thoracic primary/metastatic lesions, 2 hepatic metastases, 15 lymph node metastases. Of the 38 patients, 47.3% underwent rebiopsy sucessfully. Of the 38 biopsied patients, 18 (47.3%) were analyzed for EGFR mutation, using tissue or cytology samples; T790M mutations were identified in 10 (55%) of the 18 patients. Of the 38 biopsied patients, 18 (47.3%) were analyzed for EGFR mutation, using tissue or cytology samples; T790M mutations were identified in 10 (55%) of the 18 patients.

      Conclusion:
      Most re-biopsy samples were diagnosed with malignancy. T790M mutations were identified as much as same in previous studies. However, tissue samples were less available in previous studies. Skill and experience with re-biopsy and noninvasive alternative methods will be increasingly important.

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    P1.07 - Immunology and Immunotherapy (ID 693)

    • Event: WCLC 2017
    • Type: Poster Session with Presenters Present
    • Track: Immunology and Immunotherapy
    • Presentations: 1
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      P1.07-012 - Prediction Sensitivity of PD-1 Checkpoint Blockade Using Pathological Tissues Specimens by Novel Computerized Analysis System (ID 8851)

      09:30 - 16:00  |  Author(s): J. Matsubayashi

      • Abstract
      • Slides

      Background:
      Recent development of immune checkpoint blockade such as anti-PD-1 antibody brought great benefits to non-small cell lung cancer (NSCLC) patients. However, some population of NSCLC showed resistance and pseudo-progressions against anti-PD-1 checkpoint blockade. Thus, it is very important for developing biomarkers which predict of efficacy of PD-1 checkpoint blockade. In this background, we developed novel digital pathology system that predict for response to anti-PD-1 checkpoint blockade using H&E staining sections and technology of AI.

      Method:
      In this study, we extract 361 ROIs(Region of Interest) and 254,205 nuclei were measured from NSCLC cases that treated with anti-PD-1 antibody. We used ilastik for nuclei image segmentation, CellProfiler and our CFLCM tool for features measurement, 992 features are evaluated for each ROI. At first, we analyzed by step-wise discriminant analysis for select the effective features, and using canonical discriminant analysis and SVM (Support vector Machine) RBF kernel model discrimination, we analyzed morphological data based PD-1 blockade response on statistical platform R.

      Result:
      Except undeterminable cases, we got the more than 95% accuracy level discrimination results. The mapping the discriminant scores, SD cases were mapped in the middle of PR and PD. Only using the average and standard deviation of ROIs’ nuclei shape features (size, roundness, perimeter, etc.) and inside nuclei features (mainly chromatin texture) more than 90% discrimination results were obtained. This means the nuclei morphological data is more important than CFLCM (pleomorphism and heterogeneity measurement data). We challenged the prediction for undeterminable cases by using canonical discriminant and SVM.

      Conclusion:
      This time analysis is small number samples, so the results application robustness may be limited. But our results show the possibility for clinical response prediction even on the pre-treatment pathological tissues specimens.

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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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      P2.05-012 - Prognostic Factors for Surgically Resected Non-Small Cell Lung Cancer with Cavity Formation  (ID 8763)

      09:30 - 16:00  |  Author(s): J. Matsubayashi

      • Abstract

      Background:
      Small pulmonary nodules have been detected frequently by computed tomography (CT). Lung cancers with cavity formation are also easily detected. There are a few reports focused on the cavity wall, although cancer cells exist along the cavity wall, not inside. We evaluated the impact of cavity wall thickness on prognosis and assessed the clinicopathological features in non-small cell lung cancer (NSCLC) with cavity formation.

      Method:
      Between 2005 and 2011, 1313 patients underwent complete resection for NSCLC. Of these cases, we reviewed 65 patients (5.0%) diagnosed with NSCLC with cavity formation by chest CT. We classified the patients into three groups based on the maximum cavity wall thickness, namely, ≤ 4 mm (Group 1, 8 patients), > 4 mm and ≤ 15 mm (Group 2, 33 patients), and > 15 mm (Group 3, 24 patients).

      Result:
      The number of patients with pathological whole tumor size > 3 cm was 2 (25%) in Group 1, 17 (52%) in Group 2, and 23 (96%) in Group 3 (p < 0.001). Cases with lymph node metastasis were 0 (0%) in Group 1, 5 (15%) in Group 2, and 10 (42%) in Group 3 (p = 0.016). The 5-year overall survival (OS) rates were 100% in Group 1, 84.0% in Group 2, and 52.0% in Group 3, with significant differences between Group 1 and Group 3 (p = 0.044) and between Group 2 and Group 3 (p = 0.034). In univariate analysis, neither whole tumor size nor lymph node metastasis was a prognostic factor for OS (p = 0.505, p = 0.274). Only cavity wall thickness was a significant prognostic factor by multivariate analysis (p = 0.009).Figure 1



      Conclusion:
      Maximum cavity wall thickness was an important prognostic factor in NSCLCs with cavity formation, comparable with other established prognostic factors.

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    P3.02 - Biology/Pathology (ID 620)

    • Event: WCLC 2017
    • Type: Poster Session with Presenters Present
    • Track: Biology/Pathology
    • Presentations: 1
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      P3.02-012 - Liquid Based Cytology (LBC) Specimens Were Useful for EGFR Mutation Test (ID 10305)

      09:30 - 16:00  |  Author(s): J. Matsubayashi

      • Abstract
      • Slides

      Background:
      Reliable EGFR mutation testing techniques are required to identify eligible patients for EGFR-TKI treatment. Nowadays, surgically resected tissues or biopsy specimens are mainly used for the molecular testing. However, the biopsy samples sometimes have a certain limitation and so the cytology specimens are chosen for EGFR testing instead. Plasma sample has also become an option in EGFR-TKI resistant cases in which often have difficulties to obtain the inadequate tumor yield. In this study, we evaluated the feasibilities of using cytology samples and plasma specimens the EGFR molecular testing.

      Method:
      Cytology samples were obtained from biopsy and cells were suspended into liquid-based cytology (LBC) media. Tumor contents in the samples were confirmed with Papanicolaou stained slides. Plasma samples were also collected from patients shortly before the tissue biopsy. EGFR mutations in these samples were analyzed by cobas EGFR Mutation Test v2. Also, EGFR testing result of tissue specimens of the patients corresponded were collected from the medical records measured by cobas EGFR Mutation Test v2 as references.The feasibilities of both cytology and plasma specimen were evaluated comparing the results with the tissue samples.

      Result:

      EGFR mutation rate of tissue, plasma and LBC
      Tissue Plasma LBC
      EGFR mutation + 18 9 14
      EGFR mutation - 42 51 43
      Invalid 0 0 3
      Total 60 60 60
      Positive rate (%) 30.0 15.0 23.3
      One-hundred seven patients were registered to this study. 60 patients were enrolled to this study. EGFR mutation rates in tissue, cytology, and plasma were 30.0, 23.3 and 15.0 %, respectively. Concordance analysis was performed comparing cytology specimens and plasma specimens to the tissue samples. Overall concordance EGFR mutation status was 85.0 and 81.7%, respectively. A total 7 cytology specimens had discordances and 3 were invalid results. For plasma samples, discordants were found in11 samples but no invalids.

      Conclusion:
      Plasma was easy to obtain sample, but rate of detection was low. If a cancer cell is detected enough, LBC is useful for the examination for EGFR. Preservation of sample is easy, and re-useful for the examination, repeatedly.

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