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P. Meldgaard



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    P2.04 - Poster Session/ Biology, Pathology, and Molecular Testing (ID 234)

    • Event: WCLC 2015
    • Type: Poster
    • Track: Biology, Pathology, and Molecular Testing
    • Presentations: 1
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      P2.04-096 - Liquid Biopsies in Patients with EGFR Mutated Non-Small Cell Lung Cancer Undergoing Curative Treatment (ID 1422)

      09:30 - 09:30  |  Author(s): P. Meldgaard

      • Abstract
      • Slides

      Background:
      A blood based test for detection of EGFR mutations has been developed. Studies have shown a correlation between level of mutations in the blood and course of the disease in stage IV patients, suggesting that the test could be used as a monitoring device. No studies have been conducted examining whether the blood test can be used to monitor patients who undergo curative treatment.

      Methods:
      Six patients with EGFR mutated tumors were monitored with continuous blood samples from the time of diagnosis until relapse, death or present date. The blood samples were tested for the level of EGFR mutations using the Cobas® EGFR Mutation Test developed for plasma DNA (Roche Molecular Systems, Inc.). Results were compared to the clinical course of the disease.

      Results:
      Operated without adjuvant chemotherapy (n=3, all patients with T1N0M0 disease). In two patients there were no measurable mutations in the blood samples at any point. One patient is at present date without sign of relapse after 3 years and attends follow up. The other patient died of non-cancer related causes. The third patient had declining level of mutations the first two years after the operation but the mutated DNA has never reached zero. Operated with adjuvant chemotherapy (n=1, T2N2M0). Mutations were measurable before operation and declined to zero after. One year after the operation, metastatic disease (CNS) was discovered along with a rise in mutation level, which again declined after local irradiation and initiation of erlotinib treatment. Chemoradiotherapy (n=2, T2N2-3M0). One of these patients had measurable levels of mutations initially, which declined to zero during the course of treatment with chemoradiotherapy and a supplement of erlotinib. Metastatic disease (CNS) was found during the treatment, and the patient proceeded with erlotinib treatment and cerebral irradiation. The patient died due to disease progression 9 months later, no measurable mutated DNA was identified. In contrast, another patient had no measurable mutations until after relapse was detected.

      Conclusion:
      Our results suggest that in some cases monitoring the level of EGFR mutations in the blood might be a valuable tool in the detection of relapse in patients who have undergone curative treatment for their lung cancer. Further investigations are warranted to elucidate the subject. We have initiated a project, where we prospectively follow all patients with EGFR mutated NSCLC regardless of stage and treatment modality and we examine their blood for EGFR mutations every time a blood sample is drawn.

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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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      P3.04-023 - Exosomes and Their Potential for Detection of Lung Cancer (ID 831)

      09:30 - 09:30  |  Author(s): P. Meldgaard

      • Abstract
      • Slides

      Background:
      A recent study showed that advanced lung adenocarcinoma patients have a distinct exosomal protein-profile compared to a matched group without cancer (Jakobsen et al., 2015, JEV). To improve the overall survival, it is however crucial to develop tools capable of detecting early stages of lung cancer as well. In addition, it is unsettled if different histologic subclasses result in distinct exosomal protein profiles. The aim of this study is to explore the potential of using exosomal proteins as biomarkers in lung cancer patients of all stages and of different histology histology.

      Methods:
      Plasma was isolated from patients suspected of having lung cancer. Patients diagnosed to be cancer free were defined as controls. Based on previous experiments a panel of 47 antibodies were selected for exosome-capture using a highly sensitive extracellular vesicle protein array (EV Array). 10 µl unpurified plasma was applied to the EV Array and captured exosomes were visualised by binding of biotin-conjugated CD9, CD63 and CD81 antibodies. The information from all 47 markers was investigated by multivariate analysis by partial least squares discriminant analysis (PLS-DA).

      Results:
      The study included 504 patients; 153 control patients and 351 patients with NSCLC (adenocarcinoma 70%, squamous cell 24%, other 6%). 51% had locally advanced or advanced disease and 49% had local disease. Multivariate analysis produced a combined marker model separating cancer patients from controls regardless of stage and histology. Area under the curve (AUC) was for each stage: I: 0.74 (0.68-0.82), II: 0.68 (0.57-0.79), III: 0.77 (0.62-0.91) and IV 0.79 (0.73-0.83). For all stages AUC was 0.755, CI (0.72-0.81) with sensitivity 0.70 and specificity 0.66. The accuracy of the test was 0.69.

      Conclusion:
      We demonstrate that the EV array is able to lung cancer in advanced as well as low stages regardless of histology.

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