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Erin Schenk



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    P2.01 - Advanced NSCLC (ID 618)

    • Event: WCLC 2017
    • Type: Poster Session with Presenters Present
    • Track: Advanced NSCLC
    • Presentations: 1
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      P2.01-054 - Inclusion of Central Nervous System Metastasis in Lung Cancer Early Phase Clinical Trials (ID 8407)

      09:00 - 09:00  |  Author(s): Erin Schenk

      • Abstract

      Background:
      Central nervous system (CNS) metastases are commonly seen in lung cancer patients; up to 40% will have CNS involvement during the course of the disease. However, clinical trials often exclude this patient population due to the increased morbidity/mortality associated with CNS metastases, subsequent reduction of overall survival and poor CNS pharmacokinetics or uncertainty about CNS pharmacokinetics in humans. Therefore, we studied the effects of CNS metastases on the enrollment of lung cancer patients in early phase clinical trials.

      Method:
      Trials were extracted from ClinicalTrials.gov on April 1[st], 2017. Completed and active trials from 2000-2016 were included in the analysis. Exclusion of CNS metastasis was treated as a binary variable and grouped as strict exclusion vs. allowed. Logistic regressions were used for statistical analysis.

      Result:
      598 trials were reviewed, 308 (52%) were phase 2, 164 (27%) were phase 1, and 126 (21%) were combined phase 1/2 trials. 304 (51%) trials were conducted in the U.S., 82 (14%) in Asia, 74 (12%) in Europe and 138 (23%) internationally. Most trials were funded by industry (59%), followed by investigator initiated/institutional (23%) and NIH funded (18%). Patients with CNS metastasis were strictly excluded in 130 (22%) trials, allowed if controlled/asymptomatic in 156 (26%) and allowed with no prior treatment in 42 (7%) trials. Patient requiring steroids for their CNS metastasis were excluded in 156 (26%) trials. CNS criteria were not referenced in 114 (19%) trials and these were excluded from further analysis. Of the 194 trials that included survival as one of their end points, 121 (62%) excluded patients with CNS disease. On univariate analysis, the odds of CNS metastasis exclusion were significantly higher in immunotherapy trials (OR: 1.26, 95%CI: 1.07-1.50, p<0.006) and significantly lower in NIH funded trials (OR: 0.35 95% CI: 0.17-0.73, p<0.005). In multivariate analysis, U.S. based trials had higher odds of exclusion of CNS disease (OR: 1.18, 95%CI: 1.06-1.31, p<0.001) compared to European, Asian and International trials. 58 phase 1 trials were followed by phase 2 trials, when comparing exclusion criteria, no changes were made regarding CNS metastasis.

      Conclusion:
      Many patients with lung cancer and brain metastases are excluded from participation in early phase clinical trials. Broader inclusion of patients with CNS metastasis, or separate clinical trials for those with CNS disease would help determine the efficacy of novel agents for those with CNS metastasis and provide clinical trial options for this patient population.

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    P2.02 - Biology/Pathology (ID 616)

    • Event: WCLC 2017
    • Type: Poster Session with Presenters Present
    • Track: Biology/Pathology
    • Presentations: 1
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      P2.02-037 - CD14<Sup>+</Sup> Cell Tumor Microenvironment Infiltration Correlates with Poor Overall Survival in Patients with Early Stage Lung Cancer (ID 9322)

      09:30 - 09:30  |  Presenting Author(s): Erin Schenk

      • Abstract

      Background:
      Despite undergoing curative-intent therapy, patients with early stage non-small cell lung cancer (NSCLC) have reduced survival rates of 43-73% due to the risk of distant metastasis(1-3). This underscores the acute need to identify new biomarkers for improved prognostication and to better understand the underlying biology that drives poor outcomes.

      Method:
      Tumor tissue from 189 patients with NSCLC who underwent curative intent surgery was stained for CD14 by IHC and qualitatively scored for low, moderate, or high expression. CD14 expression groups for all patients and stage I patients alone were analyzed for overall survival. In vitro studies were performed utilizing a coculture system of human lung cancer cell lines and freshly isolated CD14[+ ]cells.

      Result:
      We found that the level of CD14[+ ]cells within the tumor microenvironment (TME) was strongly associated with overall survival in all patients (p<0.001) and stage I patients alone (p=0.006). Patients with high CD14 TME staining had a median overall survival of 5.5 years versus 8.3 years and 10.7 years for moderate or low CD14 staining, respectively. The intensity of CD14 TME infiltration was associated with an advanced stage at time of diagnosis (p=0.049) and more positive lymph nodes found at surgery (p=0.012). The potential advantages of TME CD14[+ ]cells were investigated through a coculture system. Tumor growth kinetics were not altered with coculture. Lung cancer cells cocultured with CD14[+ ]cells recovered more quickly after exposure to chemotherapy. This improved recovery was observed only after a 48 hour coculture of tumor cells and CD14[+ ]cells. Figure 1



      Conclusion:
      CD14[+] cells are a prognostic marker within the TME of patients with resected lung adenocarcinoma. Our data suggests crosstalk with the CD14[+] cell infiltration results in a tumor survival benefit that drives poor patient outcomes.