Author of

• 14723

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  MINI 13 - Genetic Alterations and Testing (ID 120)

  • Event: WCLC 2015
  • Type: Mini Oral
  • Track: Biology, Pathology, and Molecular Testing
  • Presentations: 1
  • Moderators:Y. Koh, R.K. Thomas
  • Coordinates: 9/08/2015, 10:45 - 12:15, 205+207

  • 14734

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    MINI13.11 - Detection of Rare Clinically Actionable Mutations in NSCLC Metastatic to the Brain by Targeted Next Generation Sequencing (ID 1004)

    11:45 - 11:50  |  Author(s): S.J. Weinstein
    • Abstract
    • Presentation
    • Slides

    Background:
    Genotyping of non-small cell lung cancers (NSCLC) is important for directing patient care, particularly in adenocarcinomas (ADC) where targeted therapeutics are available. There is emerging evidence of efficacy of targeted therapy in the treatment and prevention of brain metastases. With recent adoption of next-generation sequencing technologies it is possible to test individual tumors simultaneously for somatic mutations in multiple genes. Here, we present the mutational spectrum of NSCLC brain metastases in our institution over a three year period.
    
    Methods:
    The department of pathology archives was searched to identify cases of NSCLC metastatic to brain that underwent surgical resections during 2012-2014. Clinicopathologic information was recorded from the pathology reports and the medical records. Molecular genotyping analysis was performed for EGFR/KRAS mutations using single gene analysis (prior to 2013) or by next generation sequencing (NGS) using the AmpliSeq Cancer Hotspot Panel v2. FISH was used to test for ALK rearrangements.
    
    Results:
    During 2012-2014, 31 NSCLC patients underwent surgical resection for brain metastases. Eighteen patients were female (58%) and 13 were male. The median age was 70 years (range 51-89). Tumor histology included 24 ADC and 7 squamous cell carcinomas (SCC). Twenty-three cases had molecular genotyping studies performed on the metastatic disease or the primary lung cancer. These included 3 SCC and 20 ADC. Of the ADC, 12 were tested with the NGS panel; 8 had been tested prior to 2013. The most frequently mutated genes were KRAS (8/20; 40%) and TP53 (7/12; 58%). Of the patients with KRAS mutations 7/8 were female (p = 0.085). The NGS assay detected clinically actionable mutations that would have not been detected with prior single gene assays including an EGFR exon 20 insertion, an ERBB2 exon 20 insertion, and two PIK3CA mutations. Additional mutations were detected in JAK3, FLT3, FBXW7, ATM, STK11, VHL and RB1.
    
    Conclusion:
    We found that 40% of the genotyped ADC metastases harbored KRAS mutations more frequently in females (although not significant), similar to prior reports. In addition, with NGS we were able to detect additional clinically significant targetable mutations. In summary, NSCLC genotyping can potentially help guide treatment and prevention of brain metastases.
    
    

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