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P. Chandra



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    P1.18 - Poster Session 1 - Pathology (ID 175)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Pathology
    • Presentations: 1
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      P1.18-020 - Molecular Alterations in Advanced Lung Cancer: Genomic Sequencing in a Community Profiling Program of the Sarah Cannon Research Institute (SCRI) (ID 3357)

      09:30 - 16:30  |  Author(s): P. Chandra

      • Abstract

      Background
      In October 2012, SCRI launched a genomic sequencing program at a single community clinical research center in middle Tennessee to explore molecular alterations with proven or potential therapeutic significance for patients (pts) with advanced solid and hematologic tumors. Herein we report the findings from the lung cancer cohort tested to date.

      Methods
      Biospecimens from pts with advanced lung cancer (ECOG ≤ 2) who consented to molecular profiling were tested by Next-Generation Sequencing (NGS) with 1000X average coverage in a CLIA/CAP-certified laboratory. Oncogenic hotspot mutations in 35 genes were tested (copy number variation and translocation were not tested). Results were reported to the treating physician within 12 days of receipt of suitable tissue, and were used to inform treatment decisions. Molecular profiling results were stored in a database to enable correlation with clinical outcomes.

      Results
      As of May 31 2013, a total of 594 tumor samples were profiled, 143 (24%) of which were from pts with lung cancer. 23% (33/143) of the lung samples were inadequate for assay. Of the 110 lung samples with sufficient tissue, 47 (43%) were found to have at least 1 identifiable mutation: 30 (27%) single mutations and 17 (16%) multiple mutations. The mutation frequency by histology was adenocarcinoma 63% (34/54 pts), squamous 19% (4/21 pts), large cell 67% (4/6 pts), and small-cell 8% (1/13 pts). The most frequent mutations from this 35-gene panel were KRAS and EGFR (18% and 14%, respectively). Other genetic alterations identified included STK11 6%, MET 5%, RUNX1 4%, FGFR3 3%, BRAF 2%, MEK1 2%, PIK3CA 2%, WT1 1%, SMO 1%, KIT 1%, GNAS 1% and FGFR4 1%.

      Breakdown of KRAS and EGFR Mutations
      Gene Codons Tested Mutation Codons Detected Number of Mutations % of Detected Mutations
      KRAS 12, 13, 61, 146 12 19 95%
      61 1 5%
      EGFR 709-719, exon 19 deletion, 768-790, exon 20 insertion, 833, 858-861 769 2 13%
      796 1 7%
      833 1 7%
      852 1 7%
      858 3 20%
      Deletion 7 40%
      Insertion 1 7%

      Conclusion
      This program confirms the feasibility of molecular profiling in the community setting to assist medical oncologists in treatment decisions for pts with lung cancer, including enrollment in clinical trials.