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P. Mitchell



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    ORAL 13 - Immunotherapy Biomarkers (ID 104)

    • Event: WCLC 2015
    • Type: Oral Session
    • Track: Biology, Pathology, and Molecular Testing
    • Presentations: 1
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      ORAL13.06 - Programmed Death Ligand-1 (PDL-1) Expression in Non-Small Cell Lung Cancer (NSCLC): Analysis of a Large Early Stage Cohort; and Concordance of Expression in Paired Primary-Nodal and Primary-Metastasis Tumour Samples (ID 3226)

      16:45 - 18:15  |  Author(s): P. Mitchell

      • Abstract
      • Presentation
      • Slides

      Background:
      PDL-1 expression in NSCLC is frequently associated with response to PD-1 pathway inhibitor therapy. However, it is unclear whether PDL-1 expression status is maintained in nodes and distant metastases and further information is needed on the relationship between expression and patient and tumour characteristics and prognosis

      Methods:
      TMAs were constructed using 1mm cores (triplicate) of FFPE primary tumour from patients undergoing surgery with curative intent, from N2 nodal tumour (triplicate) and from metastatic NSCLC tumour (duplicate cores or single small sections). PDL-1 protein expression was measured using a validated, automated immuno-histochemical assay using the 28-8 monoclonal antibody (Dako, Carpinteria, CA), with samples categorised as positive when tumour cell membranes were stained to any intensity in 5% of assessable tumour in any core.

      Results:
      57 paired primary–metastasis cases were analysed: median age 64 years (33-56); 30 male (53%); adenocarcinoma 27 (47%) and squamous cell 15 (26%). Metastatic sites were: brain 27; trachea/bronchus/lung/pleura 17; chest wall/skin 5; lymph nodes 6. Seven cases were synchronous (6 brain) while the median interval between primary and metastasis for other cases was 1.3 years (range 0.2-8.5). Primary and metastatic tumour samples were PDL1 positive for 13 (23%) and 14 (25%) cases respectively and for 44 cases (77%) expression was concordant. Discordance with negative primary and positive metastasis was seen in 7 cases (12%), while 6 cases (11%) were positive in primary and negative in metastasis. Using assay cut offs of 1% and 50%, concordance was 63% and 89% respectively. Eight cases had more than one metastasis analysed and the primary and all metastases were concordant for 6 cases while 2 cases were positive in primary but negative in one of the metastases. TMAs from 518 primary cases were also analysed and data on 123 cases are currently available. Histology was adenocarcinoma 58 (47%) and squamous 38 (31%). Thirty seven cases (30%) were PDL1+. Of the 13 never or light (≤10 PY) smokers, only 2 (9%) were positive. Further data on all cases and matched primary-nodes will be presented.

      Conclusion:
      PDL1 expression in ≥5% tumour cell was seen in 30% of cases. Concordance of expression in matched primary and metastasis was seen in 77% of cases. These data suggest that if PDL-1 expression status is critical in the decision to treat metastatic NSCLC with a PD-1 pathway inhibitor, then re-biopsy of a metastasis may be warranted.

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    P1.04 - Poster Session/ Biology, Pathology, and Molecular Testing (ID 233)

    • Event: WCLC 2015
    • Type: Poster
    • Track: Biology, Pathology, and Molecular Testing
    • Presentations: 1
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      P1.04-061 - Comparison of MET Expression in Primary and Corresponding Nodal and Distant Metastases in Non-Small Cell Lung Cancer (NSCLC) (ID 2430)

      09:30 - 17:00  |  Author(s): P. Mitchell

      • Abstract

      Background:
      Hepatocyte Growth Factor and its corresponding receptor MET are potential therapeutic targets for NSCLC. In NSCLC MET is over expressed, activated and mutated and is involved in resistance to tyrosine kinase inhibitors. A high proportion of primary NSCLC cases show elevated MET expression on immunohistochemistry (IHC), however, it is not clear whether expression changes during the metastatic process. We investigated paired NSCLC tumour samples to determine whether MET receptor expression differs in the primary and its corresponding lymph node and distant metastases.

      Methods:
      Tissue Microarrays (TMAs) were constructed using 1mm cores of primary and metastatic matched NSCLC archival paraffin tissues in triplicate. For IHC, TMAs were stained with the SP44 clone (Ventana) and an H-score calculated based on the percentage of cells stained and their intensity with a minimum of 0 and maximum of 300. The mean of values from multiple cores was calculated. Two independent scorers assessed the tissues. Discordance was defined as an H-score difference of greater than 100 between the primary tumour and its metastasis.

      Results:
      61 patients with primary and matched distant metastasis were included in the main analysis with 38 (62%) male and brain the most common site of metastasis (27/61, 44%). The histology was adenocarcinoma in 26 patients, squamous cell in 21 and large cell, undifferentiated or mixed in 14. The median H-score was 100 in primary tissue and 120 in metastatic tissue. Brain secondaries showed the highest median H-score (140) compared with other metastatic sites (105). MET concordance was present in 50/61 cases (82%). MET discordance was found in 11/61 tumours including 6/26 (23%) of adenocarcinomas, 2/21 (10%) of squamous carcinomas and 3/14 (21%) of mixed or large cell tumours. Discordant elevation in metastases was present in 6/61 (10 %) and reduction in 5/61 (8%). MET FISH data was available for 54/61 of primary tissues and 60/61 of metastasis. MET was amplified only in 2/61(3%) cases, seen in both primary and secondary tissues, associated with strong positivity on IHC. An additional 75 patients had matched primary and lymph node metastasis MET IHC and FISH data available. High rate of concordance, 66/75 (88%) also was present in this nodal cohort. The median H-score was 100 in primary tissue and 117 in nodal metastatic, similar to the main primary and distant metastatic group. MET discordance between primary and nodal secondary was found only in 9/75 (12%) with discordant elevation in 4/75 (5%) and discordant reduction in 5/75 (7%). MET FISH true amplification was seen in 2 paired specimens and one primary with clonal amplification which was non-amplified in the lymph node metastasis.

      Conclusion:
      In this cohort of paired biopsies, increased MET expression in the primary was retained in a high proportion of distant and lymph node metastases. These data indicate that MET expression in metastases can be predicted by expression in the primary and further suggests that treatment decisions in the metastatic setting can be based on MET IHC results of archival primary or lymph node tumour.

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    P2.01 - Poster Session/ Treatment of Advanced Diseases – NSCLC (ID 207)

    • Event: WCLC 2015
    • Type: Poster
    • Track: Treatment of Advanced Diseases - NSCLC
    • Presentations: 1
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      P2.01-067 - Quality in Lung Cancer Care: The Victorian Lung Cancer Registry Pilot Initial Report (ID 1296)

      09:30 - 17:00  |  Author(s): P. Mitchell

      • Abstract

      Background:
      The Victorian Lung Cancer Registry is a clinical quality registry designed with the aim of improving the quality of care delivered to Victorians with lung cancer by collecting and assessing management, treatment and outcome data on all new cases of lung cancer.

      Methods:
      The establishment of the Victorian Lung Cancer Registry Pilot Project commenced with the appointment of a Steering Committee to provide project governance. Review of current literature and evidence-based national and international clinical practice guidelines was undertaken by an expert working group. Included data items were epidemiologically sound, reproducible and valid. The data set enables the capture of identified quality indicators designed to describe the structural quality, process quality and indicators of outcome in lung cancer management. Case ascertainment is derived from institutional ICD-10 coding and participant consent occurs via an “opt-off” system. Follow up and outcome measures are collected at baseline, 6 and 12 months after diagnosis capturing survival, treatment and quality of life. Institutional recruitment was designed to sample from metropolitan public, metropolitan private and regional hospitals.

      Results:
      Data was collected on 690 patients from 1 July 2012 to 31 June 2013 from 8 Victorian Hospitals (3 public and 3 private metropolitan and 2 regional). Evidence of distress screening was available for 27% of subjects. Diagnosis was confirmed < 28 days from referral in 66% of cases across institutions. A statement of ECOG status was available in 45% of cases and clinical TNM staging in 49% prior to treatment. A record of multidisciplinary team meeting presentation was available in 59% of cases. First treatment was initiated < 42 days from diagnosis in 76% of cases. Curative surgery was provided for 28% of subjects, curative chemotherapy <5% and curative radiotherapy < 5%.

      Conclusion:
      The evaluation of registry outcomes at governance, administrative and clinical levels may identify targets for quality and service improvement and further define safety measures. The comparison of performance outcomes across institutions and sectors may drive competitive recruitment to improve measures on a longitudinal basis.