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Chao Zhao



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    EP1.04 - Immuno-oncology (ID 194)

    • Event: WCLC 2019
    • Type: E-Poster Viewing in the Exhibit Hall
    • Track: Immuno-oncology
    • Presentations: 1
    • Now Available
    • Moderators:
    • Coordinates: 9/08/2019, 08:00 - 18:00, Exhibit Hall
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      EP1.04-40 - Extra-Thoracic Metastasis Indicated Worse Clinical Efficacy on Immune Checkpoint Inhibitors in Chinese Advanced NSCLC Patients (Now Available) (ID 995)

      08:00 - 18:00  |  Author(s): Chao Zhao

      • Abstract
      • Slides

      Background

      Immune checkpoint inhibitors (ICIs) have demonstrated inspiring effectiveness against lots of cancer types, including non-small-cell lung cancer (NSCLC). However, the individual therapeutic response varies and heterogeneous. The purpose of this study was to investigate the association of different metastatic sites with clinical outcomes after ICIs monotherapy in Chinese advanced NSCLC patients.

      Method

      We retrospectively analyzed all patients receiving more than two circles of ICIs monotherapy (anti-programmed death 1 or anti-PD-L1) in Shanghai pulmonary hospital from January 2016 to December 2018. Detailed clinical characteristics, metastasis status and progress-free survival (PFS, calculated from the first day receiving ICIs until the disease progressed) was recorded.

      Result

      76 patients were enrolled in this study. 10 of them received immunotherapy in the first-line and 46 of them in the second-line. The rate of extra-thoracic metastasis was 50% (38/76), including brain metastasis (10/38), liver metastasis (11/38), bone marrow metastasis (30/38), adrenal metastasis (4/38), extra-thoracic lymph node metastasis (10/38) and others (5/38). Patients with extra-thoracic metastasis had a significantly shorter PFS than those without (median PFS 4.20 VS 7.10months; hazard ratio [HR] 1.939, 95% CI 1.221-3.389; p=0.0072). In subgroup analysis, patients with brain metastasis, liver metastasis or bone marrow metastasis showed significantly shorter PFS than those without (3.35 vs 4.60m, p=0.0499; 2.50 vs 4.60m, p=0.0007; 3.70 vs 5.80m, p=0.0003 respectively). The disease control rate (DCR) is numerically lower in patients with extra-thoracic metastasis (66.7% vs 80%) comparing with those without, even though not statistically significant.

      Conclusion

      The current study suggested that advanced NSCLC patients with extra-thoracic metastasis indicated worse clinical outcomes on ICIs monotherapy and more clinical strategies should be considered to improving treatment efficacy for them.

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    P1.01 - Advanced NSCLC (ID 158)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Advanced NSCLC
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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      P1.01-42 - Whole-Exome Sequencing Identifies Novel Somatic Mutations Associated with Prognosis in Lung Cancer Metastatic to the Brain    (ID 988)

      09:45 - 18:00  |  Author(s): Chao Zhao

      • Abstract
      • Slides

      Background

      Lung cancer is the leading cause of cancer-related mortality in China and worldwide. Patients with lung cancer are the major origin of metastastatic brain tumor. Understanding the difference between primary lung lesion and brain metastases may contribute to the treatment strategy.

      Method

      To investigate the difference of somatic mutations in patients with non–small-cell lung cancer (NSCLC) and brain metastases. Whole-exome sequencing method were used in 13 paired lung cancer and brain metastasis samples from our institute.

      Result

      6,318 SNVs and 56,686 mutation events in 3864 genes were observed in 13 paired lung cancer and brain metastasis samples. We identified 46 driven gene mutations which are most frequently related to lung cancer. Several lung cancer metastases associated genes (KMT2C, BAGE2 and FER1L4) and epigenetic factors (CHEK2P2, miR-4436A, miR-6077) were found as well. A mean of 3.1 driver mutation events per tumor with the dN/dS of 2.06 (95%CI: 1.73-2.4) in these samples which indicating a significant enrichment of the cancer driven mutations. Mutation spectrum analysis found that these samples have more similar transition (Ti) and transversion (Tv) profile,in which C->T transitions is more frequently seen in brain metastasis samples, while lung primary tumor have a higher frequency of C->A transversion. Furthermore we found the most important tumor onset and metastasis pathways in these samples, such as focal adhesion,PI3K-Akt signaling pathway and MAPK signaling pathway. What’s more, Glioma pathway were also identified which highly indicating the solid finding of the study.

      figure 1.jpgfigure 2.jpg

      Conclusion

      In summary, we conducted an exome-wide sequencing through pairwised lung primary and brain metastasis samples and identified some novel cancer and metastasis related mutation which provided potential biomarkers for prognosis and novel therapeutics.

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    P1.04 - Immuno-oncology (ID 164)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Immuno-oncology
    • Presentations: 1
    • Now Available
    • Moderators:
    • Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
    • +

      P1.04-57 - Metronomic Dosing of Chemotherapy Alters Antitumor Immunity and Synergizes with PD-1/PD-L1 Inhibition in Non-Small Cell Lung Cancer (Now Available) (ID 1216)

      09:45 - 18:00  |  Author(s): Chao Zhao

      • Abstract
      • Slides

      Background

      The combination of immune checkpoint blockade with chemotherapy is currently under investigation as a promising strategy for the treatment of non-small cell lung cancer. Although it has been reported that metronomic dosing of cisplatin can be immune stimulating, the impact of its combination with anti-PD-1/PD-L1 immunotherapy for the treatment of lung cancer remains to be evaluated. Therefore, the current study aimed to explore whether combining low-dose continuous chemotherapy and anti-PD-L1 treatment can induce synergistic antitumor effect by enhancing antitumor immune response in murine lung cancer.

      Method

      We evaluated the antitumor effects of conventional dose of cisplatin and low-dose metronomic dose of cisplatin as monotherapy or in combination with anti-PD-L1 monoclonal antibody in a murine lung cancer model using Lewis lung cancer cells (LLC). And the changes of immune components in tumor were tested in different treatment groups by flow cytometry and immunohistochemistry.

      Result

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      The results showed that low-dose metronomic use of cisplatin could eradicate Foxp3+ regulatory T cells (Tregs) and myeloid derived suppressive cells (MDSCs). Furthermore, combining low-dose cisplatin and anti-PD-L1 therapy could not only increase the inflitration of CD8+ T cells ,especially IFN-γ+CD8+ T cells , but also significantly reduce the expression of PD-1 and PD-L1. In a syngeneic mouse model of NSCLC, we observed that concurrent use of low-dose cisplatin and anti–PD-L1 delayed tumor growth and enhanced survival.

      Conclusion

      Low-dose continuous cisplatin treatment can modify tumor immune microenvironment by eliminating immunosuppressive components like Tregs and MDSCs and enhance antitumor immune response, which can be enhanced by PD-1/PD-L1 blockade and therefore induced a synergistic anti-tumor effect.

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