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Steven G Gray

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    IBS06 - Multimodality Treatment - Realtime Data from National Registries (Ticketed Session) (ID 37)

    • Event: WCLC 2019
    • Type: Interactive Breakfast Session
    • Track: Mesothelioma
    • Presentations: 1
    • Now Available
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      IBS06.01 - Realtime Data from Europe ETOP / ESTS Database (Now Available) (ID 3331)

      07:00 - 08:00  |  Author(s): Steven G Gray

      • Abstract
      • Presentation
      • Slides


      Title: Mesothelioma Realtime Data from Europe - ETOP Mesoscape / ESTS Database


      Malignant pleural mesothelioma (MPM) is an aggressive malignancy with increasing prevalence and poor prognosis. Despite a still increase in incidence, it remains an orphan disease and studying limited numbers of MPM cases hampers the derivation of solid conclusions.

      The combination of two databases including clinical as well as pathological information will allow researchers to improve the knowledge and facilitate decision-making in patients with MPM.

      The European Thoracic Oncology Platform (ETOP) Mesoscape project and the European Society of Thoracic Surgeons’ (ESTS) database are designed to address clinical, pathological, and molecular characteristics of mesothelioma patients and their impact on outcome. The joined analysis of both databases is a unique approach to real-time data reflecting the reality of mesothelioma characteristics, treatment and prognosis in Europe.

      Materials and Methods:

      A decentralized biobank with fully annotated tissue samples is established for ETOP Mesoscape. Selection criteria for participating centers included sufficient number of cases, and documented ethical approval. Patient selection is based on availability of comprehensive clinical data with adequate follow-up, and adequate quantity and quality of formalin-fixed tissue.
      The ESTS database is a clinical database with pre-operative, intra-operative and post-operative data. A minimum set of data is captured, including demographic, histology, treatment, staging and follow up data.

      The characteristics between the two databases are compared using the Fisher’s exact test (for categorical variables) and Mann-Whitney test (for continuous variables), while Kaplan-Meier method (with log-rank test).


      Up to 29 May 2019, the ETOP Mesoscape included information on 497 patients from 10 centers, diagnosed between 1999-2018. In the ESTS database, as of April 2019, 2269 patients are included, diagnosed between 1989-2019.

      Patients in both databases are primarily men (84% in the ETOP, 71% in the ESTS), of 0/1 ECOG Performance status (46/46% and 59/29% in ETOP and ESTS respectively), with known previous exposure to asbestos (75% and 93%) and median ages 64 and 67 years old.

      Significant differences are detected between the two data sources with respect to gender, exposure to asbestos and age (p-value <0.001).

      The primary histology of patients is epithelioid (72% in ETOP and 70% in ESTS), followed by biphasic (22%; 17%) and sarcomatoid (6%; 9%) (not significantly different between the two databases).

      Clinical staging is available for 77% of the patients in ETOP, but only for the 28% in the ESTS database. The stage distribution (I/II/III/IV) is 14/29/42/15% in the ETOP and 23/21/41/16% in the ESTS (significantly difference p<0.001).

      Among the biomarkers common in both data sources, Calretinin and WT1 are detected in the vast majority of patients tested (Calretinin: 97% in both cases; WT1: 89% and 87% in the ETOP and ESTS database respectively).

      For the ETOP cases 90% (of those tested) are CK5/6 positive, 91% D2-40 positive and 97% Pan-CK positive.

      Palliative treatment has been administered in 41% of the ETOP cases. Among them, 84% received palliative chemotherapy (with the vast majority 92%, using multiple agents). Palliative surgery was undertaken in 32% (62 of 194 patients with available information) and palliative radiotherapy for 13% of the patients.

      Complete resection has been performed in 59% of the ETOP Mesoscape patients. This was combined with induction chemotherapy (81%), while adjuvant chemotherapy and radiotherapy was administered in 4% and 37% respectively.

      The surgical approach adopted for the ESTS patients was either video-assisted thoracoscopic surgery (VATS) (59%) or thoracotomy (41%) based on a subset of 887 patients with available information. Post-operation treatment information is available for 620 ESTS patients. Among them, 71% received chemotherapy, 54% underwent surgery and 15% radiotherapy.


      We present the combined results from the ETOP Mesoscape and the ESTS database, one of the largest databases. These two series allow us to report on mesothelioma epidemiology and treatment.

      Up to now, the comparison of the baseline characteristics of the patients of the two data sources revealed some statistically significant differences with respect to gender, age, exposure to asbestos and clinical stage.

      As tissue from all ETOP Mesoscape patients is preserved locally and is available for detailed molecular investigations, Mesoscape provides an excellent basis to evaluate the influence of molecular parameters on the disease outcome, besides providing an overview of the molecular landscape.

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    P2.09 - Pathology (ID 174)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Pathology
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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      P2.09-16 - Assessment of PD-L1 and CD8 Expression in Lung Cancer Using RNA in Situ Hybridisation (ID 2693)

      10:15 - 18:15  |  Author(s): Steven G Gray

      • Abstract


      PD-L1 is routinely assessed using immunohistochemistry (IHC) as a companion-diagnostic test. However, patients may be missing out on therapy as issues exist in determining PD-L1 positivity. This is partly due to the use of different antibodies, staining platforms and positivity cut-offs. The use of RNA in-situ hybridisation (RISH) for the detection of PD-L1 levels may be a way to address this; particularly as PD-L1 mRNA expression levels are associated with better overall survival in NSCLC. It is well established that PD-L1 expression is associated with increased numbers of Tumour Infiltrating Lymphocytes (TILs) including those which are CD8+. Therefore, it may also be worthwhile to combine PD-L1 testing with additional marker testing such as CD8. The aim of this study is to investigate the expression of PD-L1 and CD8 by RISH in a cohort of NSCLC samples and correlate with clinical outcome.


      RISH protocols (RNAScope® 2.5 HD assay, Advanced Cell Diagnostics, Inc.) were initially optimised on a well annotated cell line TMA (low, moderate and high expression) and compared with standard IHC (DAKO - clone 22C3). Following successful optimisation of the technique, a test cohort of 35 full-face FFPE NSCLC samples were examined for PD-L1 expression by both RISH and IHC. All slides were scored independently by a pathologist. RISH slides were scored as per ACD guidelines (0-4; based on number of positive dots per cell and number of dot clusters). IHC was scored using the standard tumour proportion score system. Image analysis (IA) was subsequently performed by Visiopharm®. Currently, a further cohort of 200 FFPE samples is being assessed, in addition to 50 FFPE samples from patients who received an anti-PD-1 therapy. Optimisation is on-going for dual CD8/PD-L1 RISH staining.


      In the initial 35 samples, PD-L1 was detected in 20% of cases by IHC (≥50% positivity) with mRNA expression identified in 14% of cases by RISH (≥2). In contrast with other recently published studies, issues were identified between IHC and RISH. There were 3 cases which scored positive by IHC, which were negative by RISH. Additionally, 1 case was positive by RISH but negative by IHC. The comparison between both assays produced a ‘moderate agreement’ as assessed using Cohen’s kappa coefficient (ĸ=0.528, p=0.002). IA undertaken on both assays could not be statistically compared using Cohen’s kappa coefficient due to the use of a composite scoring matrix to quantify RISH mRNA signals. However, IHC stained sections scored by IA showed similarity to IHC scored by a pathologist. Further optimisation is required on the RISH IA scoring algorithm. A comparison of PD-L1 IHC with RISH, combined with dual CD8/PD-L1 staining in a larger cohort of clinical samples is on-going, which will further determine the clinical utility of this technique.


      Data from our test cohort of samples have shown that PD-L1 detection by RISH is feasible and compares well to IHC. Preliminary data would also suggest that IA may be better than a pathologist alone, particularly in borderline cases. RISH may be a suitable method for improved detection of PD-L1 in NSCLC.