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R. Penzel



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    P1.06 - Poster Session 1 - Prognostic and Predictive Biomarkers (ID 161)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Biology
    • Presentations: 1
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      P1.06-023 - Anaplastic Lymphoma Kinase (ALK)-detection in Non-small Cell Lung Cancer: results of the first European IHC-based (D5F3-Optiview) panel test within 16 institutes (ID 1825)

      09:30 - 09:30  |  Author(s): R. Penzel

      • Abstract

      Background
      The study was supported by Ventana Medical Systems, Inc., a Member of the Roche Group Background: The reliable identification of NSCLC patients with anaplastic lymphoma kinase (ALK) gene rearrangement is crucial for the prescription of ALK tyrosine kinase inhibitors (e.g. crizotinib). Whereas the US FDA-approval (2011) is based upon FISH-testing, the European EMA-approval (2012) refers to the definition of “ALK-positive” NSCLCs without mandating a particular test. Therefore a reliable ALK-immunohistochemistry (IHC) could be a promising option in daily routine practice.

      Methods
      Material and methods: To test the reliability of ALK-IHC-diagnosis in a multi-centre environment (17 European institutes from Belgium, Denmark, France, Germany, Scotland, Spain, Sweden and Switzerland) two tissue microarrays (TMA) consisting of 15 NSCLC cases (all adenocarcinomas; 3 cores for each case) were independently tested for ALK-expression by each laboratory using Ventana Medical System’s ALK (D5F3) primary antibody combined with OptiView DAB IHC detection and OptiView Amplification kits. Cases included in the study were unequivocal ALK-break positive or negative (by FISH), as well as so called “ALK-borderline” cases (low percentage of ALK-break positive cells by FISH, around the cut-off of 15%, therefore challenging in diagnosis, but PCR-confirmed as harbouring EML-4-ALK-fusion variants and thus eligible for therapy). Prior to the TMA-based case testing, each participating instrument was qualified using the VENTANA ALK 2 in 1 Control Slides. To provide a uniform baseline interpretation, a webinar-based training was given to all observers. This training included an overview of the ALK Interpretation Guide, a guided review of 50 patient cases using digital whole slide images, and a proficiency exam certifying each observer.

      Results
      Results: Detailed data analysis was only partly accomplished at the time of abstract submission and will be presented in detail at the “World Conference on LUNG Cancer” in Sydney. Besides the binary evaluation of the cases (ALK-negative vs. ALK-positive) observers were asked to estimate the staining intensity (0-3) within positive cases in correlation to the number of tumor cells and to generate the H-score.

      Conclusion
      Conclusion: Referring to the EMA-approval text our multi-centre study may contribute to validation and accuracy of IHC-based ALK-testing. Such a validated and reliable IHC-assay could be used: (a) as a good pre-screening method reducing time consuming and costly FISH analysis (shorten turn-around time for test results) and (b) as a final predictive approach in cases with reduced interpretability of FISH results (e.g. minimal tumor cell content in small biopsies, decalcified or artificial altered tissue, FISH in doubt/”borderline”).

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    P2.24 - Poster Session 2 - Supportive Care (ID 157)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Supportive Care
    • Presentations: 1
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      P2.24-053 - 11-Year Survival of a Patient with Untreated, EGFR Positive, Pulmonary Adenocarcinoma (ID 3229)

      09:30 - 09:30  |  Author(s): R. Penzel

      • Abstract

      Background
      Lung cancer is the most common cancer related death and the fourth most common cause of death in Germany. The five-year survival rate in European and North American countries is in between 5,5% and 15,7%. In the last couple of years though, significant progress has been made concerning personalized medicine in this disease entity. Novell targeted therapies with tyrosin kinase inhibitors (TKI) for patients with a mutation in the EGFR gene offer a new treatment option.

      Methods
      A 78-year old male patient was referred to the Thoraxklinik Heidelberg with atypical thoracic pain after cardiologic assessment. In 2001 he was given the diagnosis of pulmonary adenocarcinoma of the right upper lobe in the Asklepios Hospital Munich-Gauting. Because of his overall good clinical condition the patient had declined any treatment to this point. A new PET- CT was conducted and compared to the computer tomography of 2001 revealed a significantly grown lesion in the right upper lobe as well as new, small bipulmonar lesions suspicious of lung metastasis.

      Results
      A new histological assessment was performed on an endobronchial forceps biopsy of the now occluded right upper lobe. The diagnosis of a partial lepidic differentiated adeno-carcinoma was consistent with the diagnosis as well as the preserved specimens of 2001. We were able to perform an EGFR mutation analysis of the 2001,- as well as of the new tumor specimens through PCR-amplification and bidirectional sequencing of exons 18, 19 and 21. In each of the probes we detected a deletion combined with an insertion c.2127_29del (p.E709_T710delinsD) in exon 18.

      Conclusion
      The above mentioned mutation has already been described in the literature but there is no information concerning the responsiveness of tyrosine kinase inhibitors in this particular mutation. Now that the cancer had spread we decided to start treatment with erlotinib. Due to cutaneous side effects the patient decided to discontinue this therapy. Since then he has been in regular follow-up showing a stable disease and good general state of health.