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F. Thivolet-Béjui



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    P2.06 - Poster Session 2 - Prognostic and Predictive Biomarkers (ID 165)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Biology
    • Presentations: 1
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      P2.06-031 - Mutational profiling of synchronous bone metastases from lung adenocarcinoma: feasibility and results in a prospective cohort of 46 patients (POUMOS study) (ID 2471)

      09:30 - 09:30  |  Author(s): F. Thivolet-Béjui

      • Abstract

      Background
      Mutational profiling for targetable oncogenic drivers is systematically recommended in the pretherapeutic workup of metastatic lung adenocarcinoma. Pathological and molecular diagnoses may be performed on specimens from metastatic lesions, when the primary pulmonary tumor is not accessible, either because of proximal location increasing the risk of transthoracic procedures, or when the material collected is insufficient in size. The feasibility of performing molecular diagnoses on small specimens from bone metastases has been questioned over time. To prospectively study patients with bone metastases from lung cancer, we set up a multidisciplinary group at the Hospices Civils de Lyon, including rheumatologists, pulmonologists, oncologists, interventional radiologists, pathologists and molecular biologists.

      Methods
      POUMOS was a prospective observational study aiming at evaluating the feasibility of routine percutaneous biopsy of synchronous bone metastases from lung adenocarcinoma, to perform pathological diagnosis and mutational profiling on the bone lesion. Results were correlated with that obtained on specimens from the primary tumor, if available. Technically, bone metastasis specimens, usually multiple, were sent fresh for immediate formalin-fixation, and, if possible, snap-freezing. Decalcification of bone was performed using EDTA for a better preservation of cell morphology and DNA. Mutational profiling of EGFR, KRAS, HER2, BRAF, and PIK3CA, as well as testing for ALK rearrangements, was conducted as recommended by the French National Cancer Institute (INCa) for all adenocarcinoma cases. DNA extraction was performed after laser microdissection of cancer cells; genotyping was based on direct sequencing and/or SNaPshot. Complete description of the process will be presented at the meeting.

      Results
      Starting April 2011, 46 patients with lung adenocarcinoma and synchronous bone metastasis were enrolled. No grade 3-4 adverse effects were reported after the bone biopsy. Mutational profiling was obtained in 45 (98%) cases; one specimen did not provide with sufficiently good quality DNA for the analysis. EGFR mutation was observed in 6 (13%) patients, KRAS mutation in 14 (30%) patients, HER2, BRAF and PIK3CA mutations in 1 (2%) patient each. Updated results, especially correlations between the mutational profiles of primary lung tumors and bone metastases, will be reported at the meeting.

      Conclusion
      Our data demonstrate the feasibility of percutaneous biopsy of synchronous bone metastasis from lung adenocarcinoma to conduct mutational profiling for common oncogenic alterations. The establishment of multidisciplinary teams to ensure the coordination between clinicians, radiologists and pathologists, makes routine pathological and molecular diagnosis on bone metastasis specimens a fast, reliable and safe procedure.