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Xiaomei Gong



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    MA01 - Early Stage Lung Cancer: Questions and Controversies (ID 894)

    • Event: WCLC 2018
    • Type: Mini Oral Abstract Session
    • Track: Treatment of Early Stage/Localized Disease
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/24/2018, 10:30 - 12:00, Room 202 BD
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      MA01.09 - Risk Factors of Radiation-Induced Lymphopenia (RIL) and Its Prognostic Significance in Small Lung Cancer Patients Treated with Stereotactic Body Radiation Therapy (ID 14426)

      11:30 - 11:35  |  Presenting Author(s): Xiaomei Gong

      • Abstract
      • Presentation
      • Slides

      Background

      The decrease in peripheral blood lymphocytes induced by radiation lessens the antitumour effect of the immune response, which might cause immunosuppression. This reduction might be affected by fractionation scheme. The purpose of this study was to assess the effect of fractionation scheme (consecutive daily fractions or nonconsecutive fractions) of SBRT on clinical outcomes in early-stage peripheral non-small cell lung cancer (NSCLC). We also analyzed the different effect of these two fractionation schemes in reducing peripheral blood lymphocytes during SBRT treatment period.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Data from a total of 61 early-stage peripheral NSCLC patients who had received SBRT were retrospectively analyzed. A total dose of 50 Gy in 5 fractions over 5-7 days was delivered for all patients. Peripheral blood lymphocytes were measured before and after SBRT. We used the Kaplan-Meier method, the log-rank test, and Cox proportional hazards regression to determine whether radiation treatment schedule associated with clinical outcomes.

      4c3880bb027f159e801041b1021e88e8 Result

      Figure 1 showed Kaplan–Meier estimates for progression free survival (PFS) (Figure A) and overall survival (OS) (Figure B) for entire cohort stratifying for fractionation regimen. Multivariate analysis showed that nonconsecutive fractionation was an independent predictor of a longer PFS (P = 0.002). OS trended toward improvement in the non-consecutive group, but this was not statistically significant (P = 0.181). Development of any grade 3 or higher toxicity was not significantly different between the two groups (P = 0.813). The average circulating lymphocyte counts of consecutive group patients significantly declined after RT (1977.27 versus 1368.18 cells/µl, P < 0.001) while the nonconsecutive group patients did not (1700.00 versus 1450.00 cells/µl, P = 0.155).
      figure 1.jpg

      8eea62084ca7e541d918e823422bd82e Conclusion

      Five-fraction SBRT delivered over non-consecutive days achieved superior clinical outcomes and similar toxicity compared to consecutive fractionation. Consecutive daily fractions of SBRT might cause worse immunosuppression by the more severe damage of peripheral lymphocytes.

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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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      P2.17-12 - Eliminating Radiation Resistance of Non-Small Cell Lung Cancer By DHA Trough Abrogating Immunity Escaping via Inhibiting PD-L1 Expression   (ID 11169)

      16:45 - 18:00  |  Presenting Author(s): Xiaomei Gong

      • Abstract
      • Slides

      Background

      Lung cancer is a highly immune-suppressing malignancy with numerous methods to evade antitumor immune responses, including deficiencies in antigen processing and presentation, release of immunomodulatory cytokines, and inhibition of T cell activation. Our previous research also demonstrate that radiation can induce a local inflammatory response and simultaneously induce programmed death ligand 1 (PD-L1) expression that attenuate the sensitivity of radiation response in NSCLC. Current data have implicated that the molecular mechanisms by which DHA functions as radiosensitizer are varied, such as inducing apoptosis, extracellular signal-regulated protein kinases 1/2 (Erk1/2) activity, nuclear factor-kappa-B (NF-ƘB), and so on. However, there is no research about the immunity system alterations after the treatment of DHA plus radiation.In the present study, we demonstrate that combined DHA and radiotherapy synergistically enhances the anti-tumor effect by inhibiting the expression of PD-L1, eradicating the local accumulation of tumor-infiltrating regulatory T cells (iTregs) and myeloid-derived suppressor cells (MDSCs) and stimulating CD8+ T cell infiltration in the tumor microenvironment. Furthermore, DHA may also through inhibiting TGF-β, p-AKT and p-STAT3 pathways, epithelial-mesenchymal transition (EMT) process, facilitating apoptosis, and regulating TRIM21 to induce the synergistic anti-tumor effect.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Radiation resistance cell lines (A549/X) was induced from A549 by conventionally fractionated radiation. The relationship between PD-L1 expression and the radiation resistance and the immune cell was investigated by immunohistochemistry (IHC) and western blot in vitro and vivo. Apoptosis was evaluated by flow cytometry. The signaling pathway proteins, epithelial-mesenchymal transition (EMT)-related protein were analyzed by western blot.

      4c3880bb027f159e801041b1021e88e8 Result

      PD-L1 was up-regulated after radiation in vivo and vitro. Concomitant with radiation-mediated tumor regression, combined DHA and radiotherapy synergistically enhances the anti-tumor effect by inhibiting the expression of PD-L1. DHA plus radiotherapy also reduced the local accumulation of tumor-infiltrating regulatory T cells (iTregs) and myeloid-derived suppressor cells (MDSCs) and stimulated CD8+ T cell infiltration in the tumor microenvironment. Furthermore, DHA may also through inhibiting TGF-β, p-AKT and p-STAT3 pathways, epithelial-mesenchymal transition (EMT) process, facilitating apoptosis, and regulating TRIM21 to induce the synergistic anti-tumor effect.

      8eea62084ca7e541d918e823422bd82e Conclusion

      Our study demonstrated a synergistic anti-tumor effect of DHA in combination with radiation trough abrogating immunity escaping via inhibiting PD-L1 expression, which establish a basis for the rational design of combination therapy of DHA plus radiotherapy in NSCLC.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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