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Yang-Si Li



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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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      P2.01-52 - Identification of Leptomeningeal Metastasis-Specific Exosomal miRNA Signatures in Cerebrospinal Fluids of NSCLC Patients (ID 13074)

      16:45 - 18:00  |  Author(s): Yang-Si Li

      • Abstract
      • Slides

      Background

      Leptomeningeal metastasis (LM) is a devastating complication with poor prognosis in non-small-cell lung cancer (NSCLC) patients. The confirmed diagnosis of LM usually involves neurological evaluation, MRI imaging, and cytopathology analysis of limited tumor cells from cerebrospinal fluid (CSF). Exosomes are extracellular vesicles in body fluids enriched with microRNAs (miRNAs), which have been implicated to participate in brain metastasis. Here, we aimed to identify LM-specific exosomal miRNA signatures in NSCLC patients to elucidate their potential role in LM mechanism and to predict LM via liquid biopsy.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Exosomes prepared from CSF and plasma samples of 39 advanced NSCLC patients with (LM+) or without (LM-) LM as well as 12 non-cancer individuals (NC) were underwent small RNA next-generation sequencing. For patients in the LM+ group, paired plasma samples were taken before (PLM+pre) and upon (PLM+post) LM diagnosis. Exosomal miRNA profiles were subjected for differential expression analysis, pathway enrichment analysis, and signature discovery.

      4c3880bb027f159e801041b1021e88e8 Result

      Unsupervised hierarchical clustering of the miRNA expression profiles clearly separated CSF samples into LM+ and LM free groups (LM- and NC). Interestingly, these samples were stratified based on their LM status only, regardless of their intraparenchymal metastasis status. In total, 247 (185 up and 62 down-regulated) miRNAs were identified differentially presented in the LM+ CSF exosome samples compared to the LM- and NC groups. Top altered miRNAs include dramatically up-regulated miR-200 family and down-regulated miR-144/451 cluster. Predicted gene targets of these top-regulated miRNAs were significantly enriched in Ras/MAPK/PI3K-AKT signaling, endocytosis pathways, and so on. Promisingly, a signature of five CSF exosomal miRNAs (let-7e-5p, miR-28-3p, miR-375, miR-200a-3p, and miR-486-5p) was identified for classification of LM+ patients with 100% sensitivity and 100% specificity. Due to the higher background complexity, we only identified one miRNA (miR-24-3p) was significantly up-regulated and one miRNA (miR-92b-5p) was significantly down-regulated in LM+ patients’ plasma-derived exosomes (PLM+pre and PLM+post) compared with the LM free group (PLM- and PNC). However, a combined signature of seven miRNAs (miR-24-3p, miR-223-3p, miR-340-5p, miR-27a-3p, miR-423-5p, miR-2110 and miR-342-5p) from PLM+pre samples was identified for the prediction of future LM with 81% sensitivity and 76% specificity.

      8eea62084ca7e541d918e823422bd82e Conclusion

      NSCLC patients with LM present a remarkably distinct CSF exosomal miRNA signature, which may involve in the progression of LM, and can be used as diagnostic biomarkers for LM. Furthermore, the identification miRNA signature in the pre-LM plasma samples suggests the potential use of liquid biopsy to predict LM for better patient care.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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    P3.01 - Advanced NSCLC (Not CME Accredited Session) (ID 967)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/26/2018, 12:00 - 13:30, Exhibit Hall
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      P3.01-64 - Preliminary Data of Diverse Therapies in Patients with Advanced Non–Small-Cell Lung Cancer Harbouring RET-Rearrangement (ID 13677)

      12:00 - 13:30  |  Author(s): Yang-Si Li

      • Abstract
      • Slides

      Background

      Activating RET-rearrangement has been discovered to play a crucial role in NSCLC tumorigenesis. However, the lack of specificity narrowed efficacy of multi-kinase inhibitors (MKIs) and the optimal treatment remains unknown. In this study, we compared chemotherapy, immunotherapy and MKIs in this group of patients.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      We retrospectively evaluated the efficacy of these three treatments in advanced, RET-rearranged NSCLC patients between January 2013 and April 2018 at our institution. RET-rearrangements were assessed by Next-generation sequencing (NGS) or any of FISH, IHC, RT-PCR. Treatment data were collected after the patients had been diagnosed with RET-rearranged advanced NSCLC. Progression-free survival (PFS) was measured from treatment start to disease progression, all-cause mortality or last follow up. Median follow-up time was 5.1months. NGS was performed to assess somatic mutation of available samples.

      4c3880bb027f159e801041b1021e88e8 Result

      A total of 30 patients with RET-rearrangement were investigated in this study. After the diagnosis, 15 patients, genetic profiles confirmed by NGS, received chemotherapy (n=10), checkpoint-inhibitors (n=7) and RET targeted MKI (n=6) with evaluable response. Several patients take any two of these three treatments as different line therapies. The disease control rate of chemotherapy, immunotherapy, MKI group was 70.0%, 71.43% and 50%, respectively. While the median PFS of three groups was 2.50 months, 2.70 months, 0.30 months, respectively, which of no significance. The NGS data of 10 patients showed that RET-rearrangement co-occurred with several other genes, including TP53, NTRK, CDK4, ERBB4. A low mutation burden (mean 4.5 mutations) was observed (Figure 1).

      figure of abstract 13677.jpg

      8eea62084ca7e541d918e823422bd82e Conclusion

      We confirmed relatively low PFS in advanced RET-rearranged NSCLC with MKIs reported in previous studies. But further investigation is warranted. Treatment with checkpoint-inhibitors seemed to encouragingly prolong PFS but a larger group of patients is needed to draw a definite conclusion.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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