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M. Fang



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    P1.01 - Advanced NSCLC (ID 757)

    • Event: WCLC 2017
    • Type: Poster Session with Presenters Present
    • Track: Advanced NSCLC
    • Presentations: 1
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      P1.01-003 - Patients Harboring a Novel PIK3CA Point Mutation after Acquired Resistance to Crizotinib in ROS1 Rearrangement Adenocarcinoma: A Case Report (ID 8245)

      09:30 - 16:00  |  Author(s): M. Fang

      • Abstract
      • Slides

      Background:
      The c-ros oncogene 1 receptor tyrosine kinase (ROS1) rearrangement has been identified in 1%-2% of non-small cell lung cancer (NSCLC) cases, these patients would benefit from the inhibitor of anaplastic lymphoma kinase (ALK), crizotinib. But the resistance to crizotinib inevitably developed in the patients with ROS1 rearrangement NSCLC and shown a response to crizotinib initially. The mechanism of acquired resistance to crizotinib for the patients with ROS1 rearrangement NSCLC is not identified completely now.

      Method:
      A 66-year-old female diagnosed with adenocarcinoma, who shown EGFR wild and ALK negative detected by Polymerase Chain Reaction(PCR). According to the detection of ROS1 rearrangement by the next generation sequencing (NGS) in blood after the patient received chemotherapy twice (pemetrexed and carboplatin), the addition of bevacizumab to chemotherapy 4 times (pemetrexed, carboplatin and bevacizumab) and maintenance therapy 3 times (pemetrexed and bevacizumab), crizotinib was used. Disease progressed explosively 6 months later, although the patient shown a response to crizotinib initially. Then NGS was carried out on blood again, a novel point mutation (p.L531P)of the PIK3CA gene was detected.

      Result:
      This case was the second report for bypass activation conferred crizotinib resistance to the patient with ROS1 rearrangement NSCLC. And it also was the first report that confirmed mTOR signaling pathways activation would lead to acquired resistance to crizotinib in the clinical. And everolimus, the mTOR signaling pathway inhibitor, was used. However, the disease of the patient was too serious, and she still died of circulatory failure. In conclusion, progression-free survival was 5.0 months and overall survival was 16.0 months.

      Conclusion:
      Bypass activation is one of potential resistance mechanisms to ROS1 rearrangement NSCLC conferred crizotinib and regimen for mTOR signaling pathway inhibitor may be one of the treatment options.

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    P1.02 - Biology/Pathology (ID 614)

    • Event: WCLC 2017
    • Type: Poster Session with Presenters Present
    • Track: Biology/Pathology
    • Presentations: 1
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      P1.02-043 - A Comparison of Consistency of Detecting BRAF Gene Mutations in Peripheral Blood and Tumor Tissue of Non-Small-Cell Lung Cancer Patients (ID 8248)

      09:30 - 16:00  |  Author(s): M. Fang

      • Abstract
      • Slides

      Background:
      BRAF, one of the three members of the RAF kinase family, belongs to the group of serine-threonine kinases and plays a vital role in mitogen-activated protein kinase (MAPK) pathways. Mutations of BRAF have been found in 0.5-3% of non-small-cell lung cancer (NSCLC). Among the different mutations occurring in the BRAF gene, BRAF V600E is the most common. A number of BRAF inhibitors, including sorafenib, vemurafenib and dabrafenib, are under clinical development. Thus, the detection of genetic driver mutation in lung cancer patients has become the most important tool in clinical practice. The aim is to detect the consistency of the BRAF gene mutation in peripheral blood and tumor tissue of patients with NSCLC and discuss the clinical application value of BRAF gene mutation in peripheral blood.

      Method:
      Real-time fluorescent quantitative polymerase chain reaction (RT-PCR) was used to detect the tissues in 257 patients of NSCLC and the peripheral blood samples in 318 patients of NSCLC, of which 185 cases of peripheral blood specimens could match the tissue samples, and detected the BRAF gene mutation in them by comparison of mutations consistency in blood and tissue samples, and analyzed the correlation between BRAF gene mutations and clinical characteristics of patients.

      Result:
      The BRAF gene mutation rate was 7.23% in peripheral blood of 23 patients with NSCLC, and was 5.45% in 14 cancer tissues, the mutation consistency was 80.00% in peripheral blood tumor tissue matched samples. The consistency was statistically significant (κ=0.710, P<0.001).

      Conclusion:
      The consistency of the BRAF gene mutation in peripheral blood and tissue is high. BRAF gene mutations of peripheral blood could be used for clinical diagnosis and treatment in cases when tissue specimen is hard to get.

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