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T. Leong



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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): T. Leong

      • 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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    P3.17 - Poster Session 3 - Bronchoscopy, Endoscopy (ID 185)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track:
    • Presentations: 1
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      P3.17-007 - Rapid On-Site Cytologic Evaluation (ROSE) of bronchial brushings during bronchoscopic investigation of peripheral pulmonary lesions: diagnostic accuracy and impact on procedure time (ID 2749)

      09:30 - 16:30  |  Author(s): T. Leong

      • Abstract

      Background
      Rapid on-site evaluation (ROSE) of transbronchial needle aspirates is cost-effective due to its ability to reduce biopsy number and complication rates without compromising diagnostic yield. Use of ROSE during sampling of peripheral pulmonary lesions (PPLs) has not previously been examined. We aimed to determine the ability of ROSE performed on transbronchial brushings of peripheral pulmonary lesions to accurately determine final procedural diagnosis. To determine if use of ROSE impacts on procedural time or procedural complication rates.

      Methods
      Prospective cohort of patients undergoing radial probe endobronchial ultrasound-guided bronchoscopy for investigation of PPLs. ROSE was performed using a Rapid Romanowsky stain. If ROSE demonstrated diagnostic malignant material the procedure was determined to be successful and no further sampling was undertaken. Non-diagnsotic ROSE assessment resulted in further sampling including transbronchial lung biopsy, and possibly sampling from different locations.

      Results
      Specimens obtained from 128 lesions in 118 consecutive patients in whom radial EBUS successfully localized a peripheral pulmonary lesion. Final procedural diagnoses included non-small cell lung cancer (n=76), carcinoid (3), metastatic malignancy (n=3), benign inflammatory/infective infiltrate (n=46). Positive predictive value of ROSE for a malignant bronchoscopic diagnosis was 97% (63/65). Two patients had positive diagnoses made on ROSE but final procedural diagnosis was “reactive bronchial cells” however both of these patients were subsequently confirmed to have NSCLC following alternate biopsy procedures. Procedure times were significantly shorter in those in whom ROSE specimens demonstrated malignancy than in those in whom ROSE was non-diagnostic (19+8 minutes vs. 31+11 minutes, respectively. p<0.0001) In four procedures, initial negative ROSE results prompted redirection of sampling from alternate bronchial segments resulting in positive diagnostic tissue being obtained.

      Conclusion
      ROSE examination of brushings specimen had high positive predictive value for bronchoscopic diagnosis of cancer. ROSE of brushings specimens has the potential to shorten bronchoscopy times, reduce complications and is likely to be cost-effective. It may also improve diagnostic performance via live feedback, allowing proceduralists to redirect subsequent sampling procedures.