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D. Steinfort



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    P1.05 - Poster Session 1 - Preclinical Models of Therapeutics/Imaging (ID 156)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Biology
    • Presentations: 1
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      P1.05-009 - Development of small cell lung cancer primary xenografts using specimens obtained by endobronchial-ultrasound transbronchial needle aspiration: a novel pre-clinical model (ID 1549)

      09:30 - 16:30  |  Author(s): D. Steinfort

      • Abstract

      Background
      Lung cancer has the highest cancer incidence and mortality worldwide. Small cell lung cancer (SCLC) accounts for 15% of all cases. Platinum-based chemotherapy induces responses in up to 70%. However, treatment-resistant recurrence is near universal, and 5-year survival remains poor at 1-2%. Therefore, there is urgent need for pre-clinical models that accurately recapitulate the parent tumour and allow testing for predictive biomarkers of response and resistance to drugs, and also screening of novel anticancer agents. Furthermore, as the vast majority of SCLC are inoperable, it is crucial that the mode of tumour tissue acquisition be minimally invasive and repeatable in cases of recurrence. Here we describe a novel pre-clinical model using samples obtained by the minimally invasive technique of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) to develop primary xenografts of SCLC.

      Methods
      Cell suspensions from samples of SCLC obtained by EBUS-TBNA were implanted directly into the flanks of NSG (Non-Obese Diabetic, Severe Combined Immune Deficient, IL2Rγ knockout) mice to generate primary xenografts. The mice were monitored for tumour growth, and if engraftment was successful, pre-graft and post-graft tumours were compared in terms of morphology, immunohistochemistry and molecular characteristics.

      Results
      Thus far, 14 SCLC specimens have been implanted, with 7 cases completing 6 months of tumour monitoring. Of these, 6 have undergone successful engraftment (86%). Samples typically contained over 1 million tumour cells with minimal stromal contamination. Mean engraftment lag time was 96 days. In all cases of engraftment, histological and molecular fidelity to the original tumour was demonstrated.

      Conclusion
      This is the first report of the generation of a primary xenograft model of lung cancer using a new method of tissue acquisition by EBUS-TBNA. Furthermore, it is the largest reported group of primary xenografts of SCLC. The primary xenograft lines from these specimens may provide the much-needed basis for more accurate pre-clinical modeling of SCLC, and hold great translational promise for novel therapeutic agents.

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    P1.17 - Poster Session 1 - Bronchoscopy, Endoscopy (ID 182)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Pulmonology + Endoscopy/Pulmonary
    • Presentations: 1
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      P1.17-009 - What is the rate of surgical upstaging following negative EBUS-TBNA of mediastinal lymph nodes for NSCLC? (ID 2621)

      09:30 - 16:30  |  Author(s): D. Steinfort

      • Abstract

      Background
      Mediastinal lymph node evaluation is a critical determinant of treatment strategy in NSCLC. Many staging modalities, both invasive and non-invasive, have been evaluated over the past few decades with varying degrees of accuracy. Despite the fact that CT imaging is the preliminary investigation for diagnosis of lung cancer, various studies have shown that CT scanning is less accurate (sensitivity of 41% to 63%, a specificity of 43% to 57%, and an accuracy of 39% to 59%) for the detection of mediastinal nodal metastasis. According to a meta analysis looking at nodal disease, the sensitivity for PET is 79% to 84% and its specificity is 89% to 91%.The ability of PET CT to provide morphologic and functional information enhances the diagnostic accuracy of mediastinal nodal staging in NSCLC . Most guidelines would however need tissue confirmation which can be obtained by EBUS- TBNA. This procedure has the advantage that it can be performed under sedation , however , the downside to this is the small samples without accurate anatomical definition. In our institute we perform PET-CT scan followed by EBUS TBNA for pre operative staging of the mediastinal lymph node {in selected cases}. However, in cases where EBUS-TBNA of mediastinal lymph nodes is negative for malignancy, there is still a possibility that metastases to these lymph nodes are found at surgery. This will result in an upstaging of the NSCLC following surgery. We aimed to determine the rate of surgical upstaging following negative EBUS-TBNA of mediastinal lymph nodes for NSCLC.

      Methods
      This is a retrospective study. From January 2009 till May 2013, we identified 304 patients who underwent surgery for NSCLC. All the patients who were planned for surgical resection underwent a staging CT scan thorax or a PET CT scan. Only those patients with suspicious lymph nodes on either of the imaging, were subjected to EBUS TBNA. These lymph nodes were then re-evaluated by histopathology following surgery. Of these 65 patients who had EBUS-TBNA prior to surgery , fifty-three patients had negative EBUS-TBNA and they formed the basis of this report.

      Results
      Out of the 53 patients with a negative EBUS-TBNA, nine of them (17%) demonstrated positive lymph nodes in surgery, giving a negative predictive value of 83% for EBUS-TBNA in this selected group. The negative predictive value of PET CT was around 77% whereas negative predictive value for EBUS TBNA was 83%.

      Conclusion
      Our study confirms a negative predictive value (83%) of EBUS-TBNA in excluding N2/3 disease in patients diagnosed with NSCLC which is higher than PET CT scan (77%). The slightly lower negative predictive value of EBUS TBNA may be attributed to the fact that not all the surgical candidates were staged with a pre operative histological confirmation of the mediastinal lymph nodes. However a combination of PET CT scan and EBUS TBNA is a reasonable pre operative staging for mediastinal lymph nodes with low complication rates.