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K. Kerr

Moderator of

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    SC21 - Predictive Biomarkers for Outcome of Systemic Therapy in NSCLC (ID 345)

    • Event: WCLC 2016
    • Type: Science Session
    • Track: Biology/Pathology
    • Presentations: 5
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      SC21.01 - Predictive Biomarkers in NSCLC: The Impact of Tumor Heterogeneity (ID 6685)

      16:00 - 17:30  |  Author(s): Y. Yatabe

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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      SC21.02 - Predictive Biomarkers for Chemotherapy of NSCLC (ID 6686)

      16:00 - 17:30  |  Author(s): M. Filipits

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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      SC21.03 - Predictive Biomarkers for Immune Checkpoint Inhibitors in Lung Cancer (ID 6687)

      16:00 - 17:30  |  Author(s): F.R. Hirsch

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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      SC21.04 - Patient-Derived Xenografts for Guiding Therapy of Lung Cancer (ID 6688)

      16:00 - 17:30  |  Author(s): B.C. Cho

      • Abstract
      • Presentation
      • Slides

      Abstract:
      Preclinical drug screening and biomarker discovery in the NCI-60 cancer cell line panel as well as the xenograft developed by growing these cell lines subcutaneously in immunodeficient mice have repeatedly failed to predict clinical responses. In an attempt to circumvent the limited predictive values of conventional preclinical models, there has been increasing attention in the development and characterization of Patient-derived tumor xenograft (PDX) models. The PDX models, which were created by direct implantation of patient’s tumor in immunodeficient mice, have shown to reflect principal histologic and genetic characteristics of original patient tumors and retain tumor heterogeneity better than any other preclinical model. These models have been shown to be predictive of clinical outcomes and are being used for translational research, preclinical drug screening and biomarker identification and validation. The PDX model may also be used in the application of ‘co-clinical trial’ approach, in which it is developed from a patient enrolled in a clinical trial and treated with the same experimental agents to emulate clinical response. This strategy permits the assessment of drug response simultaneously in the patient and mouse model, providing an interesting platform to investigate resistance mechanism, predictive biomarkers and novel combination strategies in a real-time manner. I will present the utility of PDX models, which faithfully replicated the histologic, genomic and pharmacologic features observed in the original patients, and ‘co-clinical trial’ that mirror a phase II trial of agents targeting fibroblast growth factor receptor (FGFR) in non-small cell lung cancer.

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      SC21.05 - Emerging Role of Liquid Biopsies in NSCLC (ID 6689)

      16:00 - 17:30  |  Author(s): P. Mack

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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Author of

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    ISS12 - Immuno–Oncology: A Renaissance in the Treatment of Lung Cancer – MSD Oncology (ID 448)

    • Event: WCLC 2016
    • Type: Industry Supported Symposium
    • Track:
    • Presentations: 1
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      ISS12.03 - The Value of OD-L1 Expression in NSCLC (ID 6904)

      12:45 - 14:15  |  Author(s): K. Kerr

      • Abstract

      Abstract not provided

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    P1.02 - Poster Session with Presenters Present (ID 454)

    • Event: WCLC 2016
    • Type: Poster Presenters Present
    • Track: Biology/Pathology
    • Presentations: 1
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      P1.02-025 - Evaluation of NGS and RT-PCR Methods for ALK Assessment in European NSCLC Patients: Results from the ETOP Lungscape Project (ID 5001)

      14:30 - 15:45  |  Author(s): K. Kerr

      • Abstract

      Background:
      The reported prevalence of ALK rearrangement in NSCLC ranges from 2%-7%, depending on population and detection method. The primary standard diagnostic method is fluorescence in situ hybridization (FISH). Recently, immunohistochemistry (IHC) has also proven to be a reproducible and sensitive technique. Reverse transcriptase-polymerase chain reaction (RT-PCR) has been advocated and most recently the advent of targeted Next-Generation Sequencing (NGS) for ALK and other fusions has become possible. This is one of the first studies comparing all 4 techniques in resected NSCLC from the large ETOP Lungscape cohort.

      Methods:
      96 cases from the ETOP Lungscape iBiobank (N=2709) selected based on any degree of IHC staining (clone 5A4 antibody, Novocastra, UK) were examined by FISH (Abbott Molecular, Inc.; Blackhall, JCO 2014), central RT-PCR and NGS. H-score 120 is used as cutoff for IHC+. For both RT-PCR and NGS, RNA was extracted from the same formalin-fixed, paraffin-embedded tissues. For RT-PCR, primers were used covering the most frequent ALK translocations. For NGS, the Oncomine™ Solid Tumour Fusion Transcript Kit was used, allowing simultaneous sequencing of 70 ALK, RET and ROS1 specific fusion transcripts associated with NSCLC, as well as novel ALK translocations using 5’-3’ ALK gene expression ‘Imbalance Assay’.

      Results:
      NGS provided results for 90 cases, while RT-PCR for 77. Overall, 70 cases have results for all 4 methods, with fully concordant 60 (85.7%) cases (49 ALK-, 11 ALK+). Before employing the ‘Imbalance Assay', in 5 of the remaining 10 cases, NGS differs from the other methods (3 NGS-, 2 NGS+), while in the other 5, NGS agrees with RT-PCR in all, IHC in 2, and FISH in 1. Using the concordant result of at least two of the three methods as true negative/positive, the specificity and sensitivity of the fourth is 96/94/100/96% and 94/94/89/72% for IHC/FISH/RT-PCR/NGS, respectively (incorporating imbalance: NGS sensitivity=83%). Imbalance scores are presented here for 18 NGS- cases: 9 ‘NGS-/FISH+/IHC+’, 9 ‘NGS-/FISH-/IHC-‘. Among the ‘NGS-/FISH+/IHC+’, there is strong evidence of imbalance in 4 cases (score’s range: 0.0144-0.0555), uncertain in 5 (range: 0.0030-0.0087), and no evidence (scores≤0.0004) in the 9 negative cases.

      Conclusion:
      NGS is a useful screening tool for ALK rearrangement status, superior to RT-PCR when RNA yield is limited. When using NGS, it is critically important to integrate the 5’-3’ imbalance assay and to confirm with one or more additional methods in the ‘imbalance’ cases. Data further highlight the possibility of missing actionable rearrangements when only one screening methodology is available.

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    P3.01 - Poster Session with Presenters Present (ID 469)

    • Event: WCLC 2016
    • Type: Poster Presenters Present
    • Track: Biology/Pathology
    • Presentations: 1
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      P3.01-021 - Reproducibility of Comprehensive Histologic Assessment and Refining Histologic Criteria in P Staging of Multiple Tumour Nodules (ID 5365)

      14:30 - 15:45  |  Author(s): K. Kerr

      • Abstract
      • Slides

      Background:
      Multiple tumor nodules (MTNs) are being encountered, with increasing frequency with the 8[th] TNM staging system recommending classification as separate primary lung cancers (SPLC) or intrapulmonary metastases (IM). Pathological staging requires assessment of morphological features, with criteria of Martini and Melamed supplanted by comprehensive histologic assessment of tumour type, predominant pattern, other histologic patterns and cytologic features. With publication of the 2015 WHO classification of lung tumours, we assessed the reproducibility of comprehensive histologic assessment and also sought to identify the most useful histological features.

      Methods:
      We conducted an online survey in which pathologists reviewed a sequential cohort of resected multifocal tumours to determine whether they were SPLC, IM, or a combination. Specific histological features for each nodule were entered into the database by the observing pathologist (tumour type, predominant adenocarcinoma pattern, and histological features including presence of lepidic growth, intra-alveolar cell clusters, cell size, mitotic rate, nuclear pleomorphism, nucleolar size and pleomorphism, nuclear inclusions, necrosis pattern, vascular invasion, mucin content, keratinization, clear cell change, cytoplasmic granules¸ lymphocytosis, macrophage response, acute inflammation and emperipolesis). Results were statistically analyzed for concordance with submitting diagnosis (gold standard) and among pathologists. Consistency of each feature was correlated with final determination of SPLC vs. IM status (p staging) by chi square analysis and Fisher exact test.

      Results:
      Seventeen pathologists evaluated 126 tumors from 48 patients. Kappa score on overall assessment of primary v. metastatic status was 0.60. There was good agreement as measured by Cohen’s Kappa (0.64, p<0.0001) between WHO histological patterns in individual cases with SPLC or IM status but proportions for histology and SPT or IM status were not identical (McNemar's test, p<0.0001) and additional histological features were assessed. There was marked variation in p values among the specific histological features. The strongest correlations (<0.05) between p staging status and histological features were with nuclear pleomorphism, cell size, acinus formation, nucleolar size, mitotic rate, nuclear inclusions, intra-alveolar clusters and necrosis pattern. Correlation between lymphocytosis, mucin content, lepidic growth, vascular invasion, macrophage response, clear cell change, acute inflammation keratinization and emperipolesis did not reach a p value of 0.05.

      Conclusion:
      Comprehensive histologic assessment shows good reproducibility between practicing lung pathologists. In addition to main tumour type and predominant patterns, nuclear pleomorphism, cell size, acinus formation, nucleolar size, and mitotic rate appear to be useful in distinguishing between SPLC and IM.

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    SC24 - Management of Indeterminate Pulmonary Nodules (ID 348)

    • Event: WCLC 2016
    • Type: Science Session
    • Track: Pulmonology
    • Presentations: 1
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      SC24.04 - The Role of the Pathologist in the Management of Indeterminate Pulmonary Nodules (ID 6703)

      11:00 - 12:30  |  Author(s): K. Kerr

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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    SH01 - WCLC 2016 Scientific Highlights - Prevention, Biology, Pathology (ID 483)

    • Event: WCLC 2016
    • Type: Scientific Highlights
    • Track: Epidemiology/Tobacco Control and Cessation/Prevention
    • Presentations: 1
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      SH01.03 - Pathology (ID 7119)

      07:30 - 08:30  |  Author(s): K. Kerr

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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