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T. Ohira



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    ORAL 34 - Quality/Survival/Prognosis in Localized Lung Cancer (ID 153)

    • Event: WCLC 2015
    • Type: Oral Session
    • Track: Treatment of Localized Disease - NSCLC
    • Presentations: 1
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      ORAL34.03 - Prognostic Factors in Early Stage NSCLC: Analysis of the Placebo Group in the MAGRIT Study (ID 24)

      16:45 - 18:15  |  Author(s): T. Ohira

      • Abstract
      • Presentation
      • Slides

      Background:
      The MAGRIT study was a worldwide, multicenter, phase-3 double-blind, randomized trial evaluating efficacy of the MAGE-A3 Cancer Immunotherapeutic in resected non-small cell lung cancer (NSCLC) (www.clinicaltrials.gov NCT00480025). We examined baseline patient and disease characteristics associated with overall survival (OS) and disease-free survival (DFS) among patients assigned to placebo.

      Methods:
      Study participants were ≥18 years, with histologically proven, MAGE-A3-positive stage IB, II or IIIA NSCLC (AJCC 6.0). Participants had undergone complete anatomical resection of the tumor (lobectomy or pneumectomy) with mediastinal lymph node (LN) dissection or sampling according to standard of care. Up to four cycles of platinum-based adjuvant chemotherapy were allowed. Cox regression models were used to explore characteristics that could predict DFS and OS. Factors statistically significant in univariate analysis (p<0.05) were included in multivariate models using a stepwise approach (p<0.05 to enter/remain in the model).

      Results:
      There were 757 placebo patients in the total treated population; median age 63 years, 76% male, 53% with squamous cell carcinoma (SCC), 34% with adenocarcinoma, 98% with performance status 0-1, 52% had received adjuvant chemotherapy.In univariate analyses, SCC, lower N-category and earlier disease stage were associated with improved DFS. Lower N-category, earlier stage and smaller tumor size were associated with improved OS. In multivariate analysis, N-category (HR 1.34, 95%CI [1.16-1.55]) and histological type (HR for SCC vs non-SCC 0.64, 95%CI [0.51-0.81]) remained significant for DFS. N-category (HR 1.47, 95%CI [1.21-1.79]) and tumor size (HR by unit increase 1.08, 95%CI [1.01-1.15]) did so for OS. No association was found between DFS or OS and age, gender, race, region, baseline performance status, quantitative MAGE-A3 expression, chemotherapy administration or type of chemotherapy, smoking status or type of LN sampling (minimal/systematic). Among patients with SCC, univariate analysis identified increased number of chemotherapy cycles and operative technique (pneumectomy) as associated with improved DFS (p<0.05). Only operative technique remained in the multivariate model. When including N-category (p<0.10 in univariate analysis) in the multivariate model, N-category and number of chemotherapy cycles were also selected. Lower N-category and smaller tumor size were significantly associated with improved OS, in univariate and multivariate analyses. Among patients with non-SCC, univariate analysis identified younger age, being female, lower N-category and earlier disease stage with improved DFS, and lower N-category, earlier disease stage and region (East Asia) with improved OS. N-category and gender, and N-category and region remained significant in the multivariate analysis for DFS and OS, respectively.

      Conclusion:
      This is the first prognostic factor analysis in resected NSCLC performed on data from a large, prospective randomized study. It highlighted that in terms of DFS, SCC patients have a better prognosis than non-SCC patients. N-category plays a major role in determining prognosis. Operative technique (pneumectomy), number of chemotherapy cycles (SCC) and gender (non-SCC) are also associated with outcome. Variables predictive for OS are N-category and tumor size (all) and region (non-SCC). These results confirm retrospective studies done within the context of TNM classification, but add that histopathology subtype is a strong determinant for DFS in resected 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: 2
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      P1.04-030 - Intra-Operative Pleural Lavage Cytology after Thoracotomy for Lung Cancer (ID 2906)

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

      • Abstract

      Background:
      Pleural lavage cytology (PLC) is the microscopic study of cells obtained from saline instilled into and retrieved from the chest cavity (in patients without preoperative pleural effusion) during surgery for non–small-cell lung cancer. The solution is aspirated, and cytologic analysis is performed to screen for malignant cells. Results from this procedure have been published from Japan as early as 1989,1 and internationally, an increasing number of centers have adopted this practice.

      Methods:
      Between 1995 and 2013, 2616 patients underwent surgical pulmonary resection for primary lung cancer without disseminated disease at our institute. Cytology of pleural lavage immediately after thoracotomy before any manipulation of the lung was examined in 1563consecutive patients with lung cancer with no pleural effusion. The macroscopic status of the pleural cavity was evaluated before any manipulation, and when no malignant findings were noted, the pleural cavity was washed with 100 ml of physiologic saline solution.

      Results:
      The results of the cytologic examination were divided into two categories, positive and negative PLC group. Papanicolaou classes I to IIIa were regarded as negative, classes IIIb, IV and V as positive. Of the 83 patients (6.8%) whose specimens were positive for PLC. Of the 83 patients in the positive PLC group, 74 (4.7%) had adenocarcinoma, with a significantly higher ratio of adenocarcinoma compared with the negative PLC group. Survival in the positive PLC group was significantly worse than in the negative PLC group (p = 0.001), especially in pathologic stage II (p = 0.001). We assume that the PLC positive cases have a T4 status. All PLC positive cases are reassigned Stage III. The result showed almost similar curves was shown between PLC negative Stage III and the adjusted PLC positive Stage III. We propose that positive PLC positive disease should be classified to pathologic T4 and managed similarly to dissemination.

      Conclusion:
      A positive PLC result was a strong unfavorable prognostic factor, and almost all patients with positive PLC relapsed within 5 years. PLC should be considered in all patients with early stage lung cancer suitable for resection ,especially, done when assessing the final stage in patients with adenocarcinoma of the lung. A positive result is an independent predictor of adverse survival and carries a prognosis. That suggests it may be appropriate to upstage patients by 1 T category or consider as T4 disease.

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      P1.04-035 - Clinicopathologic and Biological Characteristics of Young Age Non-Small Cell Lung Cancer (ID 2421)

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

      • Abstract

      Background:
      The Japan Lung Cancer Society, Japanese Association for Chest Surgery, and Japanese Respiratory Society jointly established the Japanese Joint Committee for Lung Cancer Registration. The Japanese Joint Committee reported that number of resected lung cancer patients under 40 years of age in Japan was 101 cases of 11663 registered patients in 2004. Apparently there are many people on their 50s to 70s who was resected for treatment of lung cancer. Lung cancer in patients under 40 years old is rare. Young lung cancer patients should have specific characteristics.

      Methods:
      We performed 2835 operations for lung cancer for 15years from 2000 through 2014 in our hospital. Among 2835 patients with lung cancer, 47 patients were younger than 40. Among 47 patients 26 patients were male and 21 patients were female. We examined characteristics of young lung cancer patients by clinicopathologic and molecular biologic characteristics.

      Results:
      Among patients with operation, pathological stage IA, IB, IIA, IIB, IIIA, IIIB were 24, 6, 3, 2, 6, 5 cases, respectively. 36 cases were diagnosed as adenocarcinoma. Squamous cell carcinoma was only one case. 3 cases were diagnosed as large cell carcinoma. Most of young lung cancer cases were diagnosed as adenocarcinoma. 5-year survival of resected lung cancer patients was 74%. 5-year survival of inoperable cases was 23.8%. We will show the biological characteristics of young age lung cancer patients. 9cases showed EGFR sensitive mutation. 4 cases showed the transforming EML4-ALK fusion gene.

      Conclusion:
      Young lung cancer patients showed specific clinicopathologic and molecular biologic characteristics compared with the older age patients.

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    P2.02 - Poster Session/ Treatment of Localized Disease – NSCLC (ID 210)

    • Event: WCLC 2015
    • Type: Poster
    • Track: Treatment of Localized Disease - NSCLC
    • Presentations: 1
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      P2.02-006 - Development of the New Photodynamic Therapy for Peripheral Type Lung Cancer (ID 2322)

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

      • Abstract
      • Slides

      Background:
      In Japan, photodynamic therapy (PDT) has been recommended for the treatment of centrally located early lung cancers (CLELC). With recent advances in the diagnosis lung cancer, we continually attempt to expand the indications of PDT, not only for CLELC but also for peripheral type lung cancer. PDT for peripheral lung cancer could be one of the desirable treatment options for patients without surgical indication such as poor pulmonary function. To perform PDT for peripheral lung nodules, it is necessary to use a thin and flexible laser fiber that can sufficiently reach the peripheral lung parenchyma. In this study, we evaluated the feasibility and efficacy of a plastic laser fiber for peripheral PDT.

      Methods:
      A plastic fiber (cylindrical light diffuser Model RD [Medlight, Switzerland]) was used as a laser fiber for peripheral PDT. The laser output and the light irradiation distribution of the RD cylindrical light diffuser were measured and compared with those of the Panasonic cylindrical probe currently used for PDT. NPe6-PDT was performed for peripheral pig lung. One week after PDT, the pigs were dissected and the lung was removed. The efficacy of NPe6-PDT was evaluated by the pathological findings.

      Results:
      The mean difference in laser output and the laser source output was 17.7±1.6% for the Panasonic cylindrical fiber and 11.6±3.1% for the RD cylindrical light diffuser. For the light irradiation distribution, the RD cylindrical light diffuser was able to produce more uniform irradiation than the Panasonic cylindrical fiber. The pathological findings showed necrotic tissue and infiltration of lymphoid cells at the laser irradiation area. Around the necrotic tissue, thickening of the alveolar walls and obstruction of the vessels due to thickening of the vascular endothelium were observed.

      Conclusion:
      The cylindrical light diffuser Model RD showed comparable laser irradiation to the Panasonic cylindrical fiber. The animal experiment showed the effect of PDT in peripheral lung. We conclude that PDT for peripheral lung using the new fiber is feasible and could become one treatment option for peripheral lung cancer.

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    P3.02 - Poster Session/ Treatment of Localized Disease – NSCLC (ID 211)

    • Event: WCLC 2015
    • Type: Poster
    • Track: Treatment of Localized Disease - NSCLC
    • Presentations: 1
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      P3.02-011 - Evaluation of a New Chest Tube Management Using Digital Air Leak Monitoring after Lung Resection (ID 2440)

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

      • Abstract

      Background:
      The use of digital drainage systems after thoracic surgery is becoming accepted as a safe method. The aim of this study was to assess the effectiveness of the digital drainage system versus traditional devices on chest tube removal and air leak duration after lung resection. We report the management of a digital drainage system in patients undergoing lung resection.

      Methods:
      This study is retrospective study of patients undergoing anatomical lung resection (segmentectomy, lobectomy, sleeve lobectomy, or bilobectomy).145 patients who underwent lung resections for lung cancer were evaluated. Chest tubes were removed when an air leak was not evident anymore and the drained fluid was less than 200 mL/day.

      Results:
      These series includes 140 lobectomies, 2 sleeve lobectomies, 1 bilobectomy and 2 anatomical segmentectomies. Patients who use digital drainage system had a significantly shorter air leak duration (0.9 versus 1.7 days; p=0.037), no significance of duration of chest tube placement (4.4 versus 5.5 days; p=0.112) and no significance of chest tube placement after the air leakage disappearance (3.5 versus 3.8 days; p=0.71).

      Conclusion:
      Patients managed with digital drainage system experienced a shorter duration of air leak compared with those managed with traditional devices. Digital devices appear to be safe and effective and may prove to be a useful tool in the management of lung resection.

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    P3.08 - Poster Session/ Thymoma, Mesothelioma and Other Thoracic Malignancies (ID 226)

    • Event: WCLC 2015
    • Type: Poster
    • Track: Thymoma, Mesothelioma and Other Thoracic Malignancies
    • Presentations: 1
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      P3.08-032 - Maximizing Use of Robot-Arms in the Robot-Assisted Thoracic Surgery (ID 875)

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

      • Abstract
      • Slides

      Background:
      We have previously reported on the importance of appropriate robot-arm settings and replacement of instrument-ports in robot-assisted thoracic surgery. Because the thoracic cavity requires a large space to access all lesions in various areas of the thoracic cavity from the apex to the diaphragm and mediastinum and the chest wall. Moreover it can be difficult manipulate the da Vinci[® ]Surgical System (Intuitive Surgical, Inc., Sunnyvale, CA) using only arms No. 1 and No. 2 depending on the tumor location. In this report, we show how robot-arm No. 3 can be used with maximum effectiveness in the da Vinci[®]-assisted thoracic surgery.

      Methods:
      Robot-arm No. 3 of the da Vinci® Surgical System was usually positioned on the same side of arm No. 2, and sometimes it was used as an assistant arm to avoid conflict with other arms in our previous report. We describe new effective application of robot-arm No. 3 for the da Vinci S®-assisted thoracic surgery. A 62-year-old man had an anterior mediastinal tumor suspected to be non-invasive thymoma. Instead of arm No. 1, arm No. 3 was placed in the 6th intercostal in the mid-axillary line inserted from reverse the side, rotating it behind the body of the da Vinci® Surgical System.

      Results:
      Robotic surgery enables access to tumors located throughout in the thoracic cavity. The time required for the da Vinci S ® -setting was 12 minutes and the console-time (the da Vinci S ®working time) was 75 minutes. Thymectomy was performed successfully, and the amount of bleeding was 68 ml, and there were no complications. The pathological findings were thymoma, Masaoka stage II.

      Conclusion:
      Arm No. 3 has wider range of motion than other arms because it has one more additional joint. That is the reason why arm No. 3 enables good operability and ability to reach remote lesions, such as in the apex, diaphragm, or costophrenic angle. Moreover, between the space of the camera-arm and arm No. 3 make enough working space than using arm No. 1 to avoid conflict between arms. This use of the da Vinci S ® arms should be helpful in robotic procedures for thoracic surgeons in manipulating the da Vinci S ® instrument arms. Our recent experience has taught us that arm No. 3 is extremely useful when used as the main arm instead of arm No. 1. This idea should facilitate the da Vinci S®-assisted thoracic surgery procedures as a new effective application of robot-arm No. 3.

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