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H. Chang



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    MINI 05 - EGFR Mutant Lung Cancer 1 (ID 103)

    • Event: WCLC 2015
    • Type: Mini Oral
    • Track: Treatment of Advanced Diseases - NSCLC
    • Presentations: 1
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      MINI05.01 - A Progression Free Survival Score for EGFR Mutant Non-Small Cell Lung Cancer Patients Treat with First Line EGFR Tyrosine Kinase Inhibitors (ID 493)

      16:45 - 18:15  |  Author(s): H. Chang

      • Abstract
      • Presentation
      • Slides

      Background:
      As epidermal growth factor receptor (EGFR) mutation a strong predictor of EGFR tyrosine kinase inhibitor (TKI) responsiveness, there are still around 10% TKI-naïve patients early refractory to first line TKIs. We aimed to find clinical predictors of TKIs responsiveness in EGFR-mutant non-small cell lung cancer (NSCLC) patients and create a scoring system as progression free survival (PFS) prediction.

      Methods:
      This retrospective study evaluated 262 patients harboring EGFR mutation received TKIs as first line therapy for NSCLC between January 2011 and December 2013. Patients were assigned to test (N=131) and validation (N=131) by time sequence. Patients with age ≤ 40, uncommon EGFR mutation, poor performance status, more sites of distal metastasis, and lymphocyte to monocyte ratio ≤3 were independently associated with poor progression free survival. These five factors were included in the scoring system and 3 predictive groups were formed by total score. Table. 1 Univariate and Cox regression analysis of progression free survival

      Univariate analysis Multivariate analysis
      PFS (M) P value P value
      Age >40 ≤40 11.6 3.3 0.001 0.002
      BMI >24 ≤24 14.9 9.1 0.027 0.928
      Gender Male Female 9.3 12.0 0.292
      DM YES NO 9.1 11.5 0.500
      Smoking Never Former / current 11.5 7.6 0.413
      Performance status ECOG 0-2 ECOG 3-4 11.5 2.7 0.009 0.012
      Mutation Common Uncommon 11.5 4.1 <0.001 <0.001
      Tumor type Adenocarcinoma Non-adenocarcinoma 11.1 9.8 0.789
      No. of distal metastasis 0 1-2 >2 21.4 11.3 6.1 <0.001 <0.001 0.015 <0.001
      Malignant effusion Yes No 9.1 11.6 0.031 0.946
      Lymphocyte to monocyte ratio >3 ≤3 13.4 7.4 <0.001 0.047


      Results:
      Progression free survival in the test group were 15.7 months(m) for 0-1 points, 9.3 m for 2 points, 4.0 m for 3-6 points (p <0.001). In the validation test, Progression free survival in there predictive groups each were 13.7 m, 9.5 m, 4.8 m (p <0.001). Between the test and validation groups, no significant differences were found in each one of the three predictive groups. Figure 1



      Conclusion:
      The score appears valid and reproducible. It can stratify NSCLC patients harboring EGFR mutation using first line EGFR-TKIs into long, intermediate and short PFS groups.

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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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      P2.01-018 - Baseline Lymphocyte-Monocyte Ratio Is a Prognostic Marker in EGFR Mutant NSCLC Patients Receiving First Line EGFR TKIs (ID 909)

      09:30 - 17:00  |  Author(s): H. Chang

      • Abstract
      • Slides

      Background:
      Patients with higher lymphocyte to monocyte ratio (LMR) has shown to have favorable prognostic in early stage lung cancer, non-metastatic renal cell carcinoma, gastric cancer, colon cancer, pancreatic cancer and breast cancer. However, prognostic significance of LMR in patients with advanced stage, epidermal growth factor receptor (EGFR) mutant non-small cell lung cancer receiving first line EGFR tyrosine kinase inhibitors is not well known. We conducted a retrospective analysis to investigate the influence of baseline LMR on clinical outcomes including progression free survival (PFS) and overall survival (OS) in EGFR mutant NSCLC patients.

      Methods:
      This retrospective study evaluated 253 patients harboring EGFR mutation received TKIs as first line therapy for advanced NSCLC between January 2011 and October 2013. The cut- off value determined by Receiver operating characteristic (ROC) curves for LMR was 3.29. Patients were divided into high and low LMR ratio based on above cut-off level. Kaplan–Meier analysis was used for PFS and OS estimation; and the log-rank test was utilized to examine the significance of the differences of survival distributions between groups.

      Results:
      Among 253 patients mean age was 65.2 years, 41% were male, medium PFS was 10.3 months, medium OS was 22 months. Low baseline LMR patients had shorter PFS (low vs. high: 8.2 vs 11.6m, HR: 1.508, p=0.003), and OS (low vs. high: 14.3m vs. 32.1m HR: 2.23, p<0.001) Figure 1



      Conclusion:
      Our results suggest baseline LMR is a prognostic marker for EGFR mutant NSCLC patients receiving first line EGFR-TKIs.

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    P3.04 - Poster Session/ Biology, Pathology, and Molecular Testing (ID 235)

    • Event: WCLC 2015
    • Type: Poster
    • Track: Biology, Pathology, and Molecular Testing
    • Presentations: 1
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      P3.04-095 - Intensity Expression of DOK2 as a Prognostic Marker in Patients with Advanced Stage of Lung Adenocarcinoma (ID 1199)

      09:30 - 17:00  |  Author(s): H. Chang

      • Abstract
      • Slides

      Background:
      DOK family is an adaptor proteins that function in feedback loops to modulate tyrosine kinase signaling, including epidermal growth factor receptor, c-Kit and platelet-derived growth factor receptor. Our previous study has shown that DOK2 was up-regulated in PBMC of NSCLC patients, and partially reversed after chemotherapy. We speculated that DOK2 levels in tumor tissue may be used to predict outcome of non-small cell lung cancer. The aim of this study is to determine the significance of DOK2 in advanced stage of lung adenocarcinoma.

      Methods:
      We retrospectively reviewed the data of 87 advanced stage of lung adenocarcinoma patients from Kaohsiung Chang Gung Memorial Hospital, Taiwan between Jan 2008 and Dec 2009. Tumor tissue was analyzed for DOK2 protein expressions detected via immunohistochemistry and specimens were classified into high or low DOK2 expression groups. Correlation with survival and clinicopathological parameters were undertaken.

      Results:
      DOK2 expression was confirmed in the advanced stage of lung adenocarcinoma tissue. Considerable differences in the protein expression were noted among the lung adenocarcinoma tissue. Patients were classified to high intensity DOK2 stained expression (n=53, 60.9%) or low intensity stained DOK2 expression (n=34, 39.1%), There were no significant correlation was found between DOK2 expression and clinicopathologic factor such as TNM stage, tumor size, performance status, comorbidity and treatment. Patients with low intensity DOK2 expression were significant and independent determinants of poor progressive free survival (9.5ms vs 4.3ms, P= 0.018) and overall survival (19.9ms vs 6.8ms, P= 0.013).

      Conclusion:
      Our study suggests the potential usefulness of DOK2 as a clinical marker for evaluating the advanced stage of lung adenocarcinoma progression and prognostic value. Prospective survey and mechanism studies are needed for further confirmation.

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