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T. Otani



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    MINI 32 - Topics in Localized Lung Cancer (ID 166)

    • Event: WCLC 2015
    • Type: Mini Oral
    • Track: Treatment of Localized Disease - NSCLC
    • Presentations: 1
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      MINI32.01 - Computed Tomography Lymphography by Transbronchial Injection of Iopamidol for Preoperative Non-Small Cell Lung Cancer Patients (ID 3009)

      18:30 - 20:00  |  Author(s): T. Otani

      • Abstract
      • Presentation
      • Slides

      Background:
      Sentinel node (SN) is defined as the first node draining a tumor, and should be the first site affected in lymphatic dissemination. Recently, with the increased incidence of small sized non-small cell lung cancer (NSCLC), segmentectomy is again under evaluation for clinical T1a N0 NSCLC patients. In the ongoing trial regarding segmentectomy (JCOG0802), the eligibility criteria for segmentectomy include a prerequisite of no lymph node metastasis by intraoperative findings because node-positive cases have a chance to be locoregionaly controlled and to be correctly staged by converting to lobectomy. Therefore, intraoperative sampling and frozen sectioning of true SNs is important in ensuring the radicality of segmentectomy. The objective of this study was to assess the safety and the feasibility of computed tomography (CT) lymphography by transbronchial injection of a water-soluble extracellular CT contrast agent which was developed as a new method for identifying SNs in patient with NSCLC.

      Methods:
      Between April, 2010 and January, 2015, clinical stage I NSCLC patients who were candidates for lobectomy or segmentectomy were enrolled in this study. An ultrathin bronchoscope was inserted to the target bronchus under the guidance of virtual bronchoscopic navigation images. CT images of the chest were obtained 30 seconds after 2 or 3ml of iopamidol was injected through a microcatheter. SNs were identified when the maximum CT attenuation value of the lymph nodes in postcontrast CT images increased by 30 Hounsfield units or more compared to precontrast images. Patients underwent video-assisted thoracic surgery lobectomy with standard lymph node dissection. SNs were harvested according to findings of CTLG and to intraoperative findings of near-infrared fluorescence imaging with indocyanine green. All lymph nodes, including SNs, were histopathologically examined by standard hematoxylin and eosin staining.

      Results:
      The ultrathin bronchoscope could access targeted bronchus, and iopamidol was delivered into the peritumoral area in all 41 patients without any complications. SNs were identified in 38 of 41 patients (92.7%), and the average number of SNs was 1.4 (range: 1-4). Lymph node metastases were found in 6 cases, including one false-negative case. Enlargement of lymphatic vessel was seen in 3 out of 6 (50%) cases with lymph node metastases, whereas it was seen in 6 out of 35 cases (17%) without lymph node metastases.

      Conclusion:
      CT lymphography by transbronchial injection of iopamidol was a safe and feasible method to identify SNs in clinical stage I NSCLC patients. Lymphatic remodeling including peritumoral lymphangiogenesis and enlargement of lymphatic vessel has been reported to one of the crucial step of lymph node metastasis of cancer. Enlargement of lymphatic vessel seen in CT lymphography may be a risk factor for lymph node metastasis of NSCLC.

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    P1.04 - Poster Session/ Biology, Pathology, and Molecular Testing (ID 233)

    • Event: WCLC 2015
    • Type: Poster
    • Track: Biology, Pathology, and Molecular Testing
    • Presentations: 1
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      P1.04-108 - Non-Invasive Assessment of Cisplatin and Erlotinib Efficacy in Lung Cancer by Monitoring an Orthotopic SCID Mouse Model with Computed Tomography (ID 1317)

      09:30 - 17:00  |  Author(s): T. Otani

      • Abstract
      • Slides

      Background:
      Orthotopic models are likely to provide more relevant pharmacokinetic and pharmacodynamic information than subcutaneous models. We established an orthotopically implanted SCID mouse model of lung cancer without thoracotomy. This model is simple and reproducible and many transplanted mice can be produced at once. The main disadvantage of the orthotopic model is that tumor size and volume changes are difficult to continuously monitor reproducibly and can only be assessed at necropsy. In this study, we evaluated the usefulness of small-animal computed tomography (CT) to non-invasively and repeatedly monitored the inhibitory effect of cisplatin and erlotinib on lung cancer in an orthotopic SCID mouse model. Our goal was to establish a standard model to evaluate efficacy of novel treatment regimens in lung cancer.

      Methods:
      We created an orthotopic lung cancer transplantation model in mice. Suspensions of 2.0 × 10[4] cancer cells were injected into the left lung of SCID mice. We tested several non-small cell lung cancer cell lines, A549, FT821 and PC9 cells—only PC9 cells have an epidermal growth factor receptor (EGFR) mutation. We treated mice with cisplatin or erlotinib. When tumor volume had reached 1–3 mm[3], mice were divided into three groups: control, cisplatin and erlotinib. After treatment had begun, tumor volumes were evaluated by CT measurement every 3 days. All mice were sacrificed for histopathological analysis on day 18 after treatment began.

      Results:
      Mice implanted with A549, FT821 and PC9 cells were treated beginning on day 21, 50 and 35, respectively, after implantation. In mice transplanted with PC9 cells, tumor volume in the cisplatin group measured by CT was lower than in the control group, though not achieving statistical significance. In mice with A549 cells, tumor volume in the cisplatin group was similar to that in the control group. In mice with FT821 cells, tumor volume in the cisplatin group was significantly lower than in the control group. The mice in the cisplatin group showed temporarily decreased body weights. Histopathological analysis on day 18 after treatment showed necrotic lesions in lungs of mice transplanted with PC9 and FT821 cells but not in those with A549 cells. In mice with PC9 cells, which have a deletion of exon 19 in the EGFR gene, tumor volume in the erlotinib group was significantly lower than in the control group. In mice with A549 and FT821 cells, tumor volume in the erlotinib group was similar to that in the control group. There were no body weight changes in the erlotinib group. Histopathological analysis on day 18 after treatment showed necrotic lesions in lungs of mice implanted with PC9 cells but not in those with A549 and FT821 cells.

      Conclusion:
      This study supports using CT to monitor, non-invasively and repeatedly, tumor progression and therapeutic response of lung cancer in an orthotopic mouse model. This model is more analogous to the clinical condition than subcutaneously transplanted tumor models. Therefore, orthotopic tumor models have potential value as fundamental tools for the design and development of new therapies for cancer treatment.

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