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P. Zarogoulidis



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    P1.19 - Poster Session 1 - Imaging (ID 179)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Imaging, Staging & Screening
    • Presentations: 1
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      P1.19-001 - Inhaled Cisplatin Displayed with the CytoViva Technique in Stage II Non-Small Cell Lung Cancer Patients (ID 160)

      09:30 - 16:30  |  Author(s): P. Zarogoulidis

      • Abstract

      Background
      Lung cancer therapies during the last decade are targeting the genome of cancer cells. However, investigating the gene pathways of tumor has the disadvantage so far that mutations are found in a limited number of patients therefore limiting the production of targeting therapies. Novel routes for administering lung cancer therapies have been investigated for decades. Aerosol therapies for several systematic diseases and systemic infections have been introduced in the market for a decade. One of the main issues of aerosol therapies has been the investigation of the deposition of a drug compound throughout the systematic circulation and lymph node circulation. Until now none of the published studies have efficiently displayed the deposition of a chemotherapy pharmaceutical within the lymph node tissue.

      Methods
      The CytoViva[®] technique can be summarized to the following information. Optical and hyperspectral images along with hyperspectral data were captured utilizing a research grade optical microscope equipped with the CytoViva[®] advanced darkfield illumination system, dual mode fluorescence module and integrated hyperspectral imaging system. This integrated system builds hyperspectral image files via “push broom” method, enabling the creation of a high signal to noise spectral image file. Subsequent image analysis delineates the reflectance spectral response of the sample elements in each nanoscale pixel of the image file.

      Results
      Figure 1 First picture represents an optical image lymph node station 7 after inhaled cisplatin. Second image represents spectral image of lymph node station 7 red areas represent the cisplatin diffusion within the tissue. Third image spectral library of inhaled cisplatin (90minutes after aerosol cisplatin administration, 40mg) The concentration 90 minutes after the aerosol cisplatin administration (40mg) was 2.09 μg/g Pt. in lymph node station 7 as measured with biochemistry techniques in a second patient.

      Conclusion
      We have efficiently presented data correlating at the same time local deposition with diffusion of aerosol cisplatin and concentration within lymphnodes. Using an optical technique and a biochemistry technique. Aerosol chemotherapy is an efficient method of treatment and further investigation is warranted with or without additional carriers added to the drug formulation.

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    P1.20 - Poster Session 1 - Early Detection and Screening (ID 172)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Imaging, Staging & Screening
    • Presentations: 1
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      P1.20-006 - Non-invasive Detection of Lung Cancer from Cells in Sputum Using Cell-CT™ (ID 2624)

      09:30 - 16:30  |  Author(s): P. Zarogoulidis

      • Abstract

      Background
      Cell-CT is a fully-automated, single-cell analysis system that has been developed to enable non-invasive screening for lung cancer. We report the results of a pilot clinical study using Cell-CT for lung cancer detection from patient sputum, including the determination of criteria that define specimen adequacy, the detection of abnormal cells in adequate specimens (sensitivity), and the detection of normal cells (specificity), performed automatically or further enhanced with human evaluation.

      Methods
      Twenty-seven patients with biopsy-confirmed lung cancer produced spontaneous-cough sputa (three morning-pooled) that were fixed, stained with hematoxylin following mucus dissolution, then enriched for epithelial cells using the method of fluorescence-activated cell sorting. The specimens were analyzed using Cell-CT, which computes 3D digital images of single cells through tomographic reconstruction with isometric, sub-micron resolution (see figure). The 3D cell images were automatically interrogated to measure morphometric biosignatures for lung cancer. 3D feature measurements were combined to produce two probabilistic scores: one that identifies abnormal cell candidates (moderate, marked dysplasia, and cancer) and another that identifies normal bronchial epithelial cells to determine specimen adequacy. 3D images of the abnormal cell candidates were transmitted to a workstation for cytopathologist confirmation and final diagnosis, using a custom computer interface (Surveyor™). Figure 1

      Results
      Based on a stringent criterion for determining specimen adequacy, 12 of the 27 sputum specimens (or roughly 50%) were deemed adequate. In the adequate specimens, abnormal cells were automatically detected, correctly classified, and confirmed in 11 of the 12 cases. This result is statistically significant and demonstrates that the Cell-CT can achieve an abnormal cell detection rate for lung cancer cells in sputum nearing 92% sensitivity. The area under the receiver operator characteristic curve (aROC) for abnormal cell detection is 0.99 (see figure). We can estimate the specificity for normal specimens by examining the rate of correct normal cell detection and classification. With the detection of 9,683 normal cells, seven were falsely classified as abnormal (false positives). However, following human evaluation using Surveyor, the resulting specimen specificity was essentially 100%.

      Conclusion
      This first important study of Cell-CT shows there are sufficient abnormal cells in adequate, spontaneous sputa to achieve high-sensitivity lung cancer detection rates without false positives. The power of 3D single-cell morphometry supports the future potential impact of a non-invasive, sputum-based lung cancer screening test.

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    P2.10 - Poster Session 2 - Chemotherapy (ID 207)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Medical Oncology
    • Presentations: 1
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      P2.10-008 - Establishing the Optimal Nebulization system for Paclitaxel, Docetaxel, Cisplatin, Carboplatin and Gemcitabine; Back to Drawing the Residual Cup. (ID 690)

      09:30 - 16:30  |  Author(s): P. Zarogoulidis

      • Abstract

      Background
      Chemotherapy drugs have still the major disadvantage of non-specific cytotoxic effects. Although, new drugs targeting the genome of the tumor are already on the market, doublet chemotherapy regimens still remain the cornerstone of lung cancer treatment. Novel modalities of administration are under investigation such as; aerosol, intratumoral and intravascular.

      Methods
      In the present study five chemotherapy drugs; paclitaxel, docetaxel, gemcitabine, carboplatin and cisplatin were nebulized with three different jet nebulisers (Maxineb[®], Sunmist[®], Invacare[®]) and six different residual cups at different concentrations. The purpose of the study was to identify the ``ideal`` combination of nebulizer-residual cup design-drug-drug loading for a future concept of aerosol chemotherapy in lung cancer patients. The Mastersizer® 2000 was used to evaluate the aerosol droplet mass median aerodynamic diameter.

      Results
      The drug, nebulizer and residual cup design greatly influences the producing droplet size (p<0.005, in each case). However; the design of the residual cup is the most important factor affecting the produced droplet size (F=834.6, p<0,001). The drug loading plays a vital role in the production of the desired droplet size (F=10.42, p<0.001). The smallest droplet size was produced at 8ml loading (1.26μm), while it remained the same at 2, 4 and 6 mls of drug loading.

      Conclusion
      The ideal nebulizer would be Maxineb[®], with a large residual cup (10 ml maximum loading capacity) and 8 mls loading and the drug with efficient pulmonary deposition would be docetaxel.