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M. Reiser

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    MO18 - NSCLC - Targeted Therapies IV (ID 116)

    • Event: WCLC 2013
    • Type: Mini Oral Abstract Session
    • Track: Medical Oncology
    • Presentations: 1
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      MO18.07 - The Network Genomic Medicine: A prospective comprehensive molecular screening network for NSCLC (ID 2898)

      16:15 - 17:45  |  Author(s): M. Reiser

      • Abstract
      • Presentation
      • Slides

      The potential of personalized medicine for improvement of lung cancer patient outcome has been paradigmatically shown by the treatment of advanced EGFR mutation- and ALK translocation positive NSCLC patients with the respective tyrosine kinase inhibitors. Furthermore numerous targeted drugs for molecular defined subgroups of NSCLC (e.g. ROS1- rearrangements) are in clinical development with the potential to improve outcome. Therefore one of the major challenges today is the implementation of comprehensive high-quality real time molecular diagnostics and personalized therapy for all NSCLC patients regardless of where they are treated.

      To increase the availability of molecular testing and subsequently personalized treatment options for NSCLC patients in the catchment area of our cancer center, we established the Network Genomic Medicine (NGM) in January 2010. NGM is a collaborative network currently encompassing more than 40 different health care providers representing the full spectrum of lung cancer care in Germany including university hospitals, large non-university lung clinics and office based oncologists. NGM is based at the Center for Integrated Oncology (CIO), i.e. the joint comprehensive cancer center of the University Hospitals of Cologne and Bonn. At the NGM - headquarter genetic and clinical data are analysed and patients without approved targeted treatment options are screened for recruitment into NGM-linked personalized trials offered by the Lung Cancer Group Cologne (LCGC). Before the introduction of routine Next Generation Sequencing (NGS) within NGM in 06/2013 we screened lung adenocarcinomas (AD) via single gene assays for mutations in EGFR, KRAS, BRAF and PIK3CA, for amplifications in HER2 and translocations in ALK, ROS1 and RET. Squamous cell lung cancer (SCC) patients were screened for amplifications in FGFR1 and mutations in DDR2.

      We screened 5,145 lung cancer patients from January 2010 till April 2013. Genomic testing was feasible in 3,863 tumor samples (75%). 63% of the patients were male and 65% of samples were AD. In AD the following frequencies of genetic lesions were detected: EGFR 13.8% (288/2078); ALK 3.3% (54/1618); KRAS 33.8% (831/2457); BRAF 3.5% (76/2123); PIK3CA 3.1% (70/2190); HER2 amplified 3.6% (62/1717); RET 4.7% (4/85) and ROS1 5.1% (7/135). In SCC we found a frequency of 21% (279/1333) for FGFR1 amplification and 2.1% (11/505) for DDR2 mutations. Further we saw 18 KRAS/PIK3CA, 5 EGFR/PIK3CA, 5 BRAF/PIK3CA double mutant samples and 3 samples where a FGFR amplification was co-occurring with a DDR2 mutation. Overall 40% of NSCLC patients harboured a potentially targetable molecular alteration. In addition we could allocate more than 40 patients to early personalized clinical trials via the close collaboration of the partners within NGM and LCGC. *The frequencies of RET and ROS1 are biased, because of a preselection of pan negative patients.

      NGM is one of the largest prospective molecular screening efforts for NSCLC worldwide, with currently more than 3000 samples analysed per year. Our experiences so far underline that central comprehensive high-quality real time molecular diagnostics is feasible in a large health care provider network and allows implementation of personalized medicine in routine clinical care of lung cancer patients.

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