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J. Su



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    JCES01 - Joint IASLC - Chinese Society for Clinical Oncology - Chinese Alliance Against Lung Cancer Session (ID 413)

    • Event: WCLC 2016
    • Type: Joint Chinese / English Session
    • Track:
    • Presentations: 1
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      JCES01.24 - Molecular Mechanism of Transformation from Adenocarcinoma to Small-Cell Lung Cancer after EGFR-TKI (ID 7066)

      J. Su

      • Abstract
      • Slides

      Background:
      In patients with advanced non–small-cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) activating mutations, EGFR-tyrosine kinase inhibitors (TKIs) are recommended as first-line treatment due to favorable clinical efficacy. However, acquired resistance inevitably develops after median progression-free survival (PFS) of 9-14 months. Among the mechanisms of acquired resistance, small-cell lung cancer (SCLC) transformation was reported to account for nearly 5%. However, the molecular details underlying this histological change and resistance to EGFR-TKI therapy remain unclear.

      Methods:
      15 out of 233 (6.4%) patients were confirmed to develop SCLC transformation after failure to EGFR-TKI. We analyzed the clinical parameters of these patients by using chi-square test and Kaplan-Meier analysis. To explore gene alterations that might contribute to SCLC transformation, next generation sequencing (NGS) was performed on four pairs of matched pre- and post-transformation tumor tissue samples. We further performed NGS on 11 matched circulating tumor DNA (ctDNA) to explore the potential mechanism of resistance to EGFR-TKI.

      Results:
      The median age of SCLC transformed patients was 53 years. 93.3% (14/15) patients harbored EGFR exon19 deletion. The median PFS and overall survival (OS) of SCLC-transformed patients treated with EGFR-TKI compared to those without transformation were 11.7 versus 11.9 months (P=0.473) and 29.4 versus 24.3 months (P=0.664), respectively. All 4 patients developed loss of heterozygosity of TP53/RB1 after transformation. Besides, increased copy number of five proto-oncogenes were identified in post-transformation tissue samples. Three patients developed EGFR T790M mutation in the post-transformation ctDNA rather than their tissue samples.

      Conclusion:
      SCLC transformation was commonly seen in patients harboring EGFR exon 19 deletion. The clinical outcomes of TKI and OS in SCLC transformed patients were similar to non-transformed patients. The loss of heterozygosity of TP53 and RB1along with increased copy number of proto-oncogenes may lead to the SCLC transformation. The mechanisms of acquired resistance to TKI during SCLC transformation might be the emergence of classic drug resistance mutations, which was undetectable due to the intra-tumor heterogeneity.

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    P2.03b - Poster Session with Presenters Present (ID 465)

    • Event: WCLC 2016
    • Type: Poster Presenters Present
    • Track: Advanced NSCLC
    • Presentations: 1
    • Now Available
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      P2.03b-041 - Cerebrospinal Fluid Tumor Cells for Diagnosis of Leptomeningeal Metastases in Non-Small Cell Lung Cancer (Now Available) (ID 4479)

      J. Su

      • Abstract
      • Slides

      Background:
      The diagnosis of leptomeningeal metastases (LM) relied on tumor cells found in cerebrospinal fluid (CSF) and/or typical magnetic resonance imaging (MRI) findings, but both lack sensitivity. The CellSearch Assay™ had been validated to detect CTCs for follow-ups of cancer patients, and we adapted it to identify CSF tumor cells (CSFTCs) in non-small cell lung cancer (NSCLC) with suspected LM, and moreover detected their gene statuses of epidermal growth factor receptor (EGFR).

      Methods:
      Twenty-one NSCLC patients with suspicious LM had CSF analyzed through both traditional Thinprep cytologic test (TCT) and CellSearch, and peripheral blood were detected for circulating tumor cells (CTCs) in fourteen patients. The statuses of EGFR were tested in primary tissues of all twenty-one patients and in CSFTCs of eight patients.

      Results:
      All twenty-one patients were identified as LM, CSFTCs were captured by CellSearch in twenty patients (median 969 CSFTCs/ 7.5 mL, range: 27-14888), while CTCs were captured in only five patients (median 2 CTCs/7.5 mL, range: 2-4), which were much lower than CSFTCs. The sensitivity of CellSearch was 95.2%, while that of TCT from the same CSF puncture was 57.1%, and that of MRI was 52.4%, and that of combined MRI and TCT was 90.5%. Moreover, the specificity of CSFTCs was 100%. Among eight patients with EGFR tested in CSFTCs, six patients matched with primary tissues and resistant gene T790M was identified in two cases.Figure 1



      Conclusion:
      Cerebrospinal fluid tumor cells could be more sensitive and effective to diagnose LM, and may serve as the potential way of liquid biopsy for EGFR mutation in NSCLC with LM.

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