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J. Zhao



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    MINI 24 - Epidemiology, Early Detection, Biology (ID 140)

    • Event: WCLC 2015
    • Type: Mini Oral
    • Track: Thymoma, Mesothelioma and Other Thoracic Malignancies
    • Presentations: 1
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      MINI24.12 - Assessment of PD-L1, TGF-β Expression and Tumor-Infiltrating CD8+ T Cells in Advanced Thymic Epithelial Tumors (ID 2373)

      16:45 - 18:15  |  Author(s): J. Zhao

      • Abstract
      • Presentation
      • Slides

      Background:
      “Avoiding immune destruction” is one of the emerging hallmarks of cancer, as proposed by Weinburg and Hanahan. High expressions of immunosuppresive proteins strongly links to prognosis and cancer treatment. This study aimed to exam the expressions of immunosuppressors programmed death receptor ligand-1 (PD-L1) and transforming growth factor –β (TGF-β), and CD8+ tumor-infiltrating lymphocytes (TILs) in pre-treatment specimens from patients with advanced thymic epithelial tumors (TETs) including advanced thymic carcinoma and advanced invasive thymoma. To our knowledge, this is the first report to demonstrate the expression of PD-L1, TGF-β and CD8 and their clinical relevance in advanced TETs in Chinese population.

      Methods:
      Retrospective analysis was performed using tumor specimens from 20 patients with stage IV thymic carcinoma and 13 patients with stage III/IV invasive thymoma. Tissue biopsies were obtained before the first-line chemotherapy with (or without radiotherapy). The expression level of PD-L1, TGF-β and the prevalence of CD8+ TILs were assessed using immunohistochemistry (IHC). Their prognostic value for predicting overall survival (OS) and progression-free survival (PFS) were statistically analyzed using the SPSS software.

      Results:
      Higher expression levels of PD-L1 and TGF-β were detected in advanced thymic carcinoma than in advanced invasive thymoma (65.0% vs. 46.2%, 65.0% vs. 15.4%, respectively). Low level of CD8+ TILs was presented in 45.0% cases with advanced thymic carcinoma. In advanced thymic carcinoma, higher TGF-β expression was strongly associated with worse OS, with a p-value almost reaching statistical significance (p = 0.052). Median OS of patients with TGF-β high and low expression was 29.5 ms (95%CI: 18.6-40.4) and 62.9 ms (95%CI: 15.6-110.1), respectively. Higher PD-L1 expressions significantly predicted worse PFS after firs-line chemotherapy with (or without) radiotherapy (p =0.043). Median PFS was not estimable in PD-L1 low expression group. Mean PFS of patients with PD-L1 high and low expression was 13.3ms (95%CI: 8.0-18.6) and 23.5ms (95%CI: 13.9-33.2), respectively. An additional radiation treatment was particularly needed for CD8 low expression patients, in which first-line treatment with “chemotherapy + radiotherapy” significantly prolonged PFS compared to “chemotherapy-alone” (median PFS = 6.8ms, 95%CI: 0.0-2.7 vs. 3.5ms, 95%CI: NE, p = 0.015).

      Conclusion:
      Our results documented the clinical relevance of PD-L1, TGF-β, and CD8 in advanced TETs, with the prognostic value of predicting OS and PFS, as well as a potential association of immune conditions with therapeutic benefits.

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    P2.01 - Poster Session/ Treatment of Advanced Diseases – NSCLC (ID 207)

    • Event: WCLC 2015
    • Type: Poster
    • Track: Treatment of Advanced Diseases - NSCLC
    • Presentations: 1
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      P2.01-062 - Efficacy and Safety of Weekly Albumin-Bound Paclitaxel for Non-Small-Cell Lung Cancer Patients Who Have Failed ≥ 2 Prior Systemic Regimens (ID 2375)

      09:30 - 17:00  |  Author(s): J. Zhao

      • Abstract
      • Slides

      Background:
      To evaluate the efficacy and safety of weekly intravenous Nanoparticle albumin-bound paclitaxel (NAB-paclitaxel) for the patients with advanced non-small-cell lung cancer (NSCLC) who have failed prior multilines treatments, and to investigate the association of status of secreted protein, acidic and rich in cysteine (SPARC) expression and clinipathological factors with clinical outcome.

      Methods:
      We retrospectively analyzed the efficacy and toxicities of NAB-paclitaxel monotherapy in treating 84 patients who had progression disease after at least two lines standard chemotherapy from May 1, 2011 to June 31, 2014. All patients were treated with NAB-paclitaxel 130mg/m2 on days 1 and 8 of a 21-day cycle. Radiologic tumor assessment was performed every 6 weeks or when the patient’s symptoms deteriorated obviously. We also detected the SPARC status expression (by immunohistochemistry) in 35 patients who had tumor tissue available. 76 of 84 patients had EGFR mutation status. The date of last follow-up was March 31, 2015.

      Results:
      Of these 84 patients, 76 patients had complete follow-up data, 5 patients lost of follow-up for overall survival, and 3 patients couldn’t tolerate the continuous NAB-paclitaxel therapy due to serious adverse events and had only the evaluation of safety data.. EGFR mutation were found in 22 of 76 patients and their median PFS and OS were 4.4 months and 11.5months. The median treatment line of weekly NAB-paclitaxel therapy was 4 line (range: 2~7 line). The median follow-up interval time was 11.2 months. The objective response rate (ORR) and disease control rate (DCR) (N=81) were 14.8% (12/81) and 67.9% (55/81), respectively. The median progression-free survival (PFS) and overall survival (OS) were 3.9 months (95% CI: 2.8~5.0 months) and 11.0 months (95%CI: 7.6~14.4 months), respectively. Pearson’s correlation analysis showed that previous treatment with Solvent-based Paclitaxel or Docetaxel didn’t affect the response to NAB-paclitaxel. However, the patients who reached disease control after previous Solvent-based Paclitaxel or Docetaxel presented better DCR than the patients who failed to previous Solvent-based Paclitaxel or Docetaxel (DCR: 77.1% vs 47.6%, p=0.040) (by Fisher’s Exact Test). Cox regression analysis showed that ORR was related with both PFS and OS. The common adverse events (N=84) included leukopenia (36.1%), neutropenia (29.2%), peripheral neurotoxicity (23.6%), et al. The main grade 3/4 toxicities included neutropenia (9.7%) and leukopenia (6.9%). 3 patients had discontinued chemotherapy due to drug induced lung injury, serious fatigue and serious anorexia, separately. In this study, no association between SPARC expression and efficacy was observed.

      Conclusion:
      Advanced NSCLC patients who have experienced multiline chemotherapy with disease progression could benefit from weekly NAB-paclitaxel therapy with good safety and clinical outcome. It seemed that SPARC expression could not predict efficacy to NAB-paclitaxel.

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