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Ying Chen



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    JCSE01 - Perspectives for Lung Cancer Early Detection (ID 779)

    • Event: WCLC 2018
    • Type: Joint IASLC/CSCO/CAALC Session
    • Track: Screening and Early Detection
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/23/2018, 07:30 - 11:15, Room 202 BD
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      JCSE01.22 - Differential Molecular Mechanisms Associated with Dramatic and Gradual Progression in NSCLC Patients with Intrathoracic Dissemination (ID 14713)

      11:15 - 11:15  |  Presenting Author(s): Ying Chen

      • Abstract
      • Slides

      Background
      Lung cancer is a highly heterogeneous disease with diverse clinical outcomes. The pleural cavity is a frequent metastasis site of proximal lung cancer. Better understanding of its underlining molecular mechanisms associated with dramatic and gradual progression of pleural metastasis in patients with non-small cell lung cancer (NSCLC) is essential for prognosis, intervention and new therapy development.We performed whole-exome sequencing (WES) of matched primary lung adenocarcinoma and pleural metastatic tumors from 26 lung cancer patients with dramatic progression (DP, n=13) or gradual progression (GP, n=13). Somatic alterations at both genome-wide level and gene level were detected. Kaplan-Meier survival analysis and multivariate Cox regression models were applied to analyze the association between different somatic alterations and clinical parameters.We first analyzed the differences in somatic alterations between AP and RP group in the primary tumors, and identified higher somatic copy number alteration (SCNA) level in DP group compared to GP group, which is significantly (p=0.016) associated with poorer progression-free survival (PFS). More specifically, patients with chromosome 18q loss in the primary tumor showed a trend (p=0.107) towards poorer PFS. PTEN (p=0.002) and GNAS (p=0.002) mutations are enriched in the primary tumors of DP group, and are associated with poorer PFS. Furthermore, pleural metastatic tumors harbor a relatively higher level of mutation burden (p=0.105) and significantly increased SCNA (p=0.035) compared to the primary tumors.NSCLC patients in the attenuated progression group have more stable genomes. High level of genomic instability, GNAS and PTENmutations, as well as chromosome 18q loss are associated with rapid progression. a9ded1e5ce5d75814730bb4caaf49419

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    P2.01 - Advanced NSCLC (Not CME Accredited Session) (ID 950)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/25/2018, 16:45 - 18:00, Exhibit Hall
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      P2.01-18 - Differential Molecular Mechanisms Associated with Dramatic and Gradual Progression in NSCLC Patients with Intrathoracic Dissemination (ID 12979)

      16:45 - 18:00  |  Presenting Author(s): Ying Chen

      • Abstract
      • Slides

      Background

      Lung cancer is a highly heterogeneous disease with diverse clinical outcomes. The pleural cavity is a frequent metastasis site of proximal lung cancer. Better understanding of its underlining molecular mechanisms associated with dramatic and gradual progression of pleural metastasis in patients with non-small cell lung cancer (NSCLC) is essential for prognosis, intervention and new therapy development.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      We performed whole-exome sequencing (WES) of matched primary lung adenocarcinoma and pleural metastatic tumors from 26 lung cancer patients with dramatic progression (DP, n=13) or gradual progression (GP, n=13). Somatic alterations at both genome-wide level and gene level were detected. Kaplan-Meier survival analysis and multivariate Cox regression models were applied to analyze the association between different somatic alterations and clinical parameters.

      4c3880bb027f159e801041b1021e88e8 Result

      We first analyzed the differences in somatic alterations between AP and RP group in the primary tumors, and identified higher somatic copy number alteration (SCNA) level in DP group compared to GP group, which is significantly (p=0.016) associated with poorer progression-free survival (PFS). More specifically, patients with chromosome 18q loss in the primary tumor showed a trend (p=0.107) towards poorer PFS. PTEN (p=0.002) and GNAS (p=0.002) mutations are enriched in the primary tumors of DP group, and are associated with poorer PFS. Furthermore, pleural metastatic tumors harbor a relatively higher level of mutation burden (p=0.105) and significantly increased SCNA (p=0.035) compared to the primary tumors.

      8eea62084ca7e541d918e823422bd82e Conclusion

      NSCLC patients in the attenuated progression group have more stable genomes. High level of genomic instability, GNAS and PTEN mutations, as well as chromosome 18q loss are associated with rapid progression.
      scna&survival.jpg

      6f8b794f3246b0c1e1780bb4d4d5dc53

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    P2.17 - Treatment of Locoregional Disease - NSCLC (Not CME Accredited Session) (ID 966)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/25/2018, 16:45 - 18:00, Exhibit Hall
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      P2.17-32 - Dynamic Monitoring Before and After Neo-Adjuvant Crizotinib in Non-Small Cell Lung Cancer: A Brief Report (ID 11829)

      16:45 - 18:00  |  Author(s): Ying Chen

      • Abstract
      • Slides

      Background

      Neo-adjuvant therapy has been considered as an optional approach for locally advanced non-small-cell lung cancer (NSCLC) patients. While targeted therapy has been widely applied in advanced NSCLC, neo-adjuvant targeted therapy remains poorly explored.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      We describe four ALK-positive patients with pathological confirmed locally advanced NSCLC receiving neo-adjuvant Crizotinib. All patients received Crizotinib at a starting dose of 250mg twice daily for 1-3 months before surgical resection. One patients provided dynamic monitoring before and after neo-adjuvant therapy through next generation sequencing of plasma and tissue.

      4c3880bb027f159e801041b1021e88e8 Result

      Three patients were partial response without apparent adverse event before surgery while one received pathological complete response to neo-adjuvant Crizotinib but suffering from grade 4 hepatic damage. One of them had disease recurrence but achieved long duration of response (PFS=15m) through first-line Crizotinib. Dynamic monitoring with both plasma and tissue indicated simultaneously decrease of sensitive ALK-signaling in a patient with partial response (-51%) and no ALK-dependent resistant variants were captured.

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      8eea62084ca7e541d918e823422bd82e Conclusion

      Neo-adjuvant Crizotinib may be feasible and well-tolerated in locally advanced disease for complete resection. Crizotinib prior to surgery may provide thorough elimination of circulating molecular residual disease and it did not influence the response of reusing Crizotinib in first-line setting.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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