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H. Asamura



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    MO03 - Thymic Malignancies (ID 123)

    • Event: WCLC 2013
    • Type: Mini Oral Abstract Session
    • Track: Medical Oncology
    • Presentations: 3
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      MO03.01 - Outcome of surgical treatment for thymic epithelial tumors based on the nationwide retrospective database of 3033 patients in Japan (ID 2284)

      10:30 - 12:00  |  Author(s): H. Asamura

      • Abstract
      • Presentation
      • Slides

      Background
      Thymic epithelial tumor, consisting of thymoma, thymic carcinoma and thymic neuroendocrine carcinoma, is a relatively rare neoplasm, and there is not a satisfying consensus in the treatment strategy. Because of lack of TNM staging system and global consensus on pathological classification, global research in these research has been difficult. To participate in movement of establishing the global database, Japanese Association for research of the Thymus (JART) conducted the project of Japanese nation-wide database in 2012.

      Methods
      Patients undergoing surgical treatment during 20 years between 1991 and 2010 in Japan were collected from 32 institutes. 3182 patients were first enrolled, but after exclusion of cases with insufficient information, 3033 cases remained for analysis finally.

      Results
      1435 patients (44%) were male, and 1595 were female (not identified in 3 patients). The age at operation was 13 to 88 years (mean 57 years old). Pathological diagnosis was thymoma in 2505 patients (Type A: 203, Type AB: 710, Type B1: 599, Type B2: 669, Type B3: 329), thymic carcinoma in 381 patients (Squamous cell carcinoma: 223, neuroendocrine carcinomas 66), and unclassified or unknown in 147 patients. According to Masaoka staging system, 1063 patients were in stage I, 1084 were in stage II, 477 in stage III, 197 in stage IVA, 57 in stage IVB (undetermined in 155 patients). Complete resection was achieved in 2753 patients (92%), subtotal resection (mass reduction of more than 80%) in 157 patients (5%), partial resection including biopsy in 86 patients (unknown in 37 patients). 249 patients were alive with tumor. 316 patients were dead during the observation period, and 161 patients died from tumor. Among 2557 patients who underwent complete resection (R0), 269 patients (10.5%) had tumor recurrence. In the patients who underwent complete or subtotal resection, 10-year overall survival rate was 89% in thymoma, 56% in squamous cell carcinoma, 30% in non-squamous thymic carcinoma, 72% in well-differentiated neuroendocrine carcinoma and 29% in poorly-differentiated neuroendocrine carcinoma. According to Masaoka stage, 10-year overall survival rate was 94% in stage I, 93% in stage II, 74% in stage III, 59% in stage IVA and 44% in stage IVB. In thymoma patients who underwent complete resection, recurrence-free survival rate at 10 years was 96% in type A, 99% in type AB, 92% in type B1, 80% in type B2, 72% in type B3. By Cox’ proportional hazard model, involvement of the mediastinal pleura (p=0.01), involvement of the lung (p=0.01), pleural dissemination (p=0.0009), distant metastasis (p=0.01) and WHO histological subtype (p<0.0001) were found to be independent factors for tumor recurrence after complete resection, while nodal metastasis, intrapericardial dissemination, involvement of pericardium, pulmonary artery, SVC, brachiocephalic vein, aorta, or brachiocephalic artery were not.

      Conclusion
      Japanese nation-wide database revealed the oncological difference among thymoma, thymic carcinoma and thymic neuroendocrine carcinoma. In thymoma, involvement of pleura and lung, pleural dissemination, distant metastasis and WHO histological classification were significant factors of tumor recurrence. These results are supposed to contribute to clinical practice for tumor treatment as well as establishment of global TNM classification.

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      MO03.02 - Surgical Outcome of Patients with Stage III Thymoma in the Japanese Nationwide Database (ID 2842)

      10:30 - 12:00  |  Author(s): H. Asamura

      • Abstract
      • Presentation
      • Slides

      Background
      Stage III thymoma has a variety characteristics in terms of involved organs, complex surgery and multimodal strategy, and a careful consideration is required in choices of treatments. Recently the Japanese Association for Research on the Thymus (JART) conducted a nationwide large cohort analysis for thymic epithelial tumors. The aim of this study is to clarify clinical characteristics and therapeutic outcome of patients who underwent surgical resection for stage III thymoma using this database.

      Methods
      Clinical data of 3,033 thymic epithelial tumor patients of 1991 to 2010 were collected rom 32 Japanese institutes. Medical information registered included patients’ characteristics, types of surgery, pathological diagnosis, perioperative therapy, and clinical outcomes were registered. In this study, stage III thymoma patients who underwent surgery were extracted from the database, and retrospectively analyzed for clinical characteristics and surgical outcome.

      Results
      A total of 340 records of patients were analyzed in this study, which comprised 186 males (54.7%) and 153 females (45.0%), 83 (24.4%) with myasthenia gravis, 42 (12.4%) with induction chemotherapy, 18 (5.3%) with preoperative radiotherapy, and 29 (8.5%) with adjuvant chemotherapies. WHO histologic types comprised 16 A (4.7%), 40 AB (11.8%), 47 B1 (13.8%), 118 B2 (34.7%) and 97 B3 (28.5%). Involved organs were lung in 209 (61.4%), pericardium in 167 (49.1%), chest wall in 7 (2.1%), phrenic nerve in 88 (25.9%) and great vessels in 134 (39.4%). Completeness of resection was R0 in 268 (78.8%), R1 in 35 (10.3%) and R2 in 20 (5.9%). Complications were observed in 85 (25.0%) including arterial fibrillation, phrenic nerve palsy, bleeding and crisis of myasthenia gravis, and 30-day mortality rate was 1.8% (6 cases). Tumor recurrence was experienced in 96 (28.2%), and 39 (11.5%) died during the observation. Overall and disease-free 10-year survival rates were 81.0% and 56.7%, respectively. Involved organs except for chest wall, completeness of resection or myasthenia gravis did not affect the survivals. Number of involved organs (1 vs. >2) and tumor length (<7cm vs. >7cm) affected disease-free survival but not overall survival. Among factors suggested to affect overall survival by univariate analyses such as male, surgical complication, WHO histologic type B1-3, chest wall invasion, induction treatments, and recurrence, independent adverse predictors were revealed by a multivariate analysis to be male (p=0.031, HR=2.47), induction chemotherapy (p=0.034, HR=2.39), postoperative complication (p=0.018, HR=2.41) and recurrence of disease (p=0.041, HR=2.15). Of 96 patients with recurrence, 47 patients who underwent salvage resection showed better prognosis than 49 patients who did not (p=0.009).

      Conclusion
      This nationwide registry study exhibited favorable surgical outcome in Japanese patients with stage III thymoma. Effectiveness of multimodal treatments need to be further investigated in prospective controlled trials.

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      MO03.04 - Analysis of lymphatic metastases of thymic epithelial tumors on Japanese database (ID 3196)

      10:30 - 12:00  |  Author(s): H. Asamura

      • Abstract
      • Presentation
      • Slides

      Background
      Thymic epithelial tumors sometimes metastasize to lymph nodes (LNs). The frequency of lymph node metastasis, the pattern of node metastasis and the relationship between prognosis and node metastasis are still unclear.

      Methods
      We registered patients with thymic epithelial tumors who had undergone resection between 1991 and 2010 from 29 institutes in Japan by the Japanese Association for Research on the Thymus (JART). We investigated the collected data according to the site of lymphatic metastasis. Yamakawa-Masaoka's paper (Cancer 1991;68:1984–7.) tentatively classified the N factor to 3 groups: metastasis to anterior mediastinal lymph nodes around the thymus were defined as N1, metastasis to intrathoracic lymph nodes other than anterior mediastinal lymph nodes as N2, and metastasis to extrathoracic lymph nodes as N3.

      Results
      The rate of lymphatic metastasis in thymoma was 1.75% (44 cases of 2508). Most of metastatic nodes were located in anterior mediastinal lymph nodes (N1, 78%). There is a significant difference of overall survival between thymomas with LN metastasis and those without LN metastasis (p<0.0001, 10-year survival: 89.8% vs 63.6%). Thymomas with N1 metastasis showed a good prognosis than those with other node metastasis, although there is no significant relationship (5-year survival: 64.4% vs 52.5%). The rate of lymphatic metastasis in thymic carcinoma including thymic carcinoid was 22% (84 cases of 380). Most of metastatic nodes were located in anterior mediastinal lymph nodes (N1, 69%). There is a significant difference of overall survival between thymic carcinomas with LN metastasis and those without LN metastasis (p<0.0001, 10-year survival: 59.5% vs 18.4%). Thymic carcimomas with N1 metastasis showed good prognosis than those with other node metastases, although there was no significant relationship (5-year survival: 55.5% vs 27.5%).

      Conclusion
      The rate of lymphatic metastasis in thymoma and thymic carcinoma was 1.75% and 22%, respectively. Both tumors frequently metastasized to the anterior mediastinal nodes. There was a significant difference of overall survival between tumors with LN metastasis and without LN metastasis in both tumors. And both tumors with N1 metastasis showed good prognoses than those with other node metastases, although there was no significant relationship. We think that it may be reasonable to consider the anterior mediastinal lymph node group (N1) to be a primary lymph node of thymic epithelial tumor.

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    O09 - General Thoracic Surgery (ID 100)

    • Event: WCLC 2013
    • Type: Oral Abstract Session
    • Track: Surgery
    • Presentations: 1
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      O09.02 - Clinicopathological characteristics and surgical results of lung cancer patients aged up to 50 years: the Japanese Lung Cancer Registry Study 2004 (ID 83)

      16:15 - 17:45  |  Author(s): H. Asamura

      • Abstract
      • Presentation
      • Slides

      Background
      Since the incidence of lung cancer death increases from 50 years-old, the surgical results of young lung cancer patients remains unclear.

      Methods
      Seven hundred and four patients with lung cancer, aged up to 50 years, were enrolled from among the 11,663 patients registered in the Japanese Lung Cancer Registry Study 2004, and their clinical data were compared with those of 10959 patients older than 50 years.

      Results
      In the young/old groups, pneumonectomy was performed in 5.7%/3.2%; adjuvant therapies were given preoperatively in 10.4%/4.7% (p<0.001) and postoperatively in 31.4%/24.5% (p<0.001). The proportions of patients with p-stage IIIA and adenocarcinoma histology were higher in the young group. The 5-year overall survival rate (5Y-OS) was 94.8%/86.2% for p-stage IA (p<0.001), 87.0%/73.2% for p-stage IB (p=0.001), 61.0%/61.6% for p-stage IIA (p=0.595), 71.0%/48.4% for p-stage IIB (p=0.003), 49.6%/39.4% for p-stage IIIA (p=0.020), and 80.0%/24.8% for p-stage IIIB (p=0.012); it was 83.5%/80.7% for females (p=0.106) and 75.1%/62.3% for males (p<0.001) in the young/old groups. The postoperative survival was significantly better with all operative procedures in the young group. The 5Y-OS after recurrence was better in the young group (17.9%, p=0.016). In the young group, the 5Y-OS was better in females (83.5%) than in males (75.1%, p=0.002), and for patients with adenocarcinoma (80.3%) than for those with squamous cell carcinoma (68.5%, p=0.013). Age up to 50 years was identified as an independent prognostic factor on multivariate analysis. Figure 1

      Conclusion
      The postoperative survival in lung cancer patients aged up to 50 years was better than that in patients older than 50 years.

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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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      P1.20-003 - Lung Cancers Detected Using Low-dose CT Screening: Results of an Eight-year Observational Study (ID 1779)

      09:30 - 16:30  |  Author(s): H. Asamura

      • Abstract

      Background
      To evaluate lung cancers detected using low-dose CT screening between February 2004 and March 2012.

      Methods
      The number of screenees analyzed in the observational study was 12,116. Screenees were classified into three groups based on their smoking index (SI): SI ≥ 600, SI < 600, and never-smokers. Overall, 147 lung cancers in 132 cases treated at the National Cancer Center Hospital and the National Cancer Center Hospital East were evaluated according to the smoking index. Adenocarcinomas were evaluated based on the following classification: group A (adenocarcinoma in situ and minimally invasive adenocarcinoma), and group B (invasive adenocarcinoma). Statistical analyses were performed using the chi-square test.

      Results
      The ages of the patients with lung cancer ranged between 42 and 85 years (mean, 61 years). Thirty-two of the 2989 male screenees (1.48%) and 2 of the 149 female screenees (1.34%) in the SI≥600 group, 22 of the 2989 male screenees (0.74%) and 10 of the 796 female screenees (1.26%) in the SI<600 group, and 16 of the 2148 male screenees (0.74%) and 50 of the 3878 female screenees (1.29%) in the never-smoker group were diagnosed as having lung cancer. Among the 147 lung cancers, 8 lesions (5.4%) did not present as nodules and instead appeared as a partial thickening of the bulla wall, a funicular-like shadow, a pneumonia-like shadow, etc. Among the remaining 139 lung cancers, 35 lesions (25.2%) presented as pure ground-glass nodules (GGNs), 64 lesions (46%) presented as part-solid nodules, and 40 lesions (28.8%) presented as solid nodules. The histology of the lung cancers was adenocarcinoma in 132 cases (89.8%), squamous cell carcinoma in 8 cases (5.4%), small cell carcinoma in 3 cases (2%), adenosquamous carcinoma in 1 case (0.7%), carcinoid tumor in 2 cases (1.4%), and NSCLC in 1 case (0.7%). The disease stages were as follows: IA, 127 (86.4%); IB, 11 (7.5%); IIA, 2 (1.4%); IIB, 1 (0.7%); IIIA, 3 (2.0%); and IIB, 3 (2.0%). Among the 147 cancers, the number of incident cases was 8 in the SI≥600 group (median follow-up period, 3.1 years), 3 in the SI<600 group (median follow-up period, 2.9 years), and none in the never-smoker group (median follow-up period, 3.0 years). Lung cancer cases in smokers (including ex-smokers) occurred predominantly in men (male, 54; female, 12), while lung cancer cases in never-smokers occurred predominantly in women (female, 50; male, 16) (P < 0.0001). The number of adenocarcinomas in smokers (including ex-smokers) was 29 in group A and 24 in group B, while the number of adenocarcinomas in never-smokers was 42 in group A and 23 in group B (P = 0.274). In the never-smoker group, the number of adenocarcinomas in men was 7 in group A and 9 in group B, while the number of adenocarcinomas in women was 35 in group A and 14 in group B (P < 0.05).

      Conclusion
      The number of invasive adenocarcinomas was not statistically different between smokers (including ex-smokers) and never-smokers. Never-smokers should also be a target population of CT lung cancer screening. Adenocarcinoma may be overdiagnosed among female never-smokers.

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    P2.20 - Poster Session 2 - Early Detection and Screening (ID 173)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Imaging, Staging & Screening
    • Presentations: 1
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      P2.20-005 - Volume Doubling Times of Subsolid Nodules Detected Using Low-dose CT Lung Cancer Screening based on an Eight-year Prospective Observation (ID 1798)

      09:30 - 16:30  |  Author(s): H. Asamura

      • Abstract

      Background
      To evaluate the volume doubling times (VDTs) of subsolid nodules (SNs) detected using low-dose CT lung cancer screening.

      Methods
      Patients with SNs detected between February 2004 and January 2005 were enrolled. Among the SNs that were detected after February 2005, increasing SNs and resected SNs after follow-up were also included in this study. After confirming the persistency of the SNs at 3 months after screening, a follow-up thin-section CT examination was performed every year, in principle. Dedicated software was developed to analyze the SNs. The volumes of the subsolid nodules were calculated based on the summation of the area of each CT slice multiplied by the CT slice thickness (i.e., 1 mm). The area of a SN on each CT slice was determined semiautomatically. The measurement of each area was performed twice, and the average of the first and second measurements was used for the volume calculation. VDTs were calculated using the following formula; (T1-T0)*log2/log(V1/V0).

      Results
      As of June 14, 2013, the measurements of 81 SNs in 72 cases had been completed. The interim results were as follows. VDTs were classified into positive values (n = 56) and negative values (n = 25). VDTs with positive values ranged from 333 to 83384 days (median, 1981 days; VDT >4500 days, n = 13), while the VDTs with negative values ranged from -110007 to -1014 days (median, -13317 days; VDT <-4500 days, n = 20). The initial volumes for the positive VDTs ranged from 45 to 3486 mm[3 ](median, 199 mm[3]), while the initial volumes for the negative VDTs ranged from 45 to 1037 mm[3 ](median, 189 mm[3]); the difference in initial volume between the positive VDTs and the negative VDTs was not statistically significant (P = 0.468)[. ]Among the 72 cases, 9 SNs in 9 cases (12.5%) were resected and diagnosed as adenocarcinomas (adenocarcinoma in situ [AIS], n = 4; minimally invasive adenocarcinoma [MIA], n = 3; and invasive adenocarcinoma [IA], n = 2). The VDTs for AIS ranged between 726 and 1723 days (median, 1154 days), the VDTs for MIA ranged between 333 and 806 days (median, 536 days), and the VDTs for IA ranged between 348 and 448 days (median, 398 days). The measurements of other SNs are ongoing.

      Conclusion
      The interim results showed that adenocarcinomas with a higher degree of invasiveness had a shorter VDT. Tentatively assuming that absolute values of VDTs >4500 days indicate clinical stability in volume despite the inherent variability of semiautomatic volumetry, 40% of the SNs were stable after an eight-year observation period.

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    P2.22 - Poster Session 2 - Epidemiology, Etiology (ID 167)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Prevention & Epidemiology
    • Presentations: 1
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      P2.22-001 - Japanese Nation Wide Lung Cancer Registries conducted by the Japanese Joint Committee of Lung Cancer Registry (JJCLCR) (ID 66)

      09:30 - 16:30  |  Author(s): H. Asamura

      • Abstract

      Background
      The Japanese Joint Committee of Lung Cancer Registry (JJCLCR) is jointly established by the Japan Lung Cancer Society, the Japanese Respiratory Society, the Japanese Association for Chest Surgery and the Japan Society for Respiratory Endoscopy, conducting Japanese nation-wide registries of lung cancer patients

      Methods
      In 1999, 2004 and 2009, registries were conducted for surgical patients in 1994, 1999 and 2004, respectively. In 2002, both surgical and non-surgical (non-biased) patients in 2002 were registered with a follow up period of 3 years or more. In 2012, a registry has been conducted for non-surgical patients in 2012 with a follow up period of 3 years. In 2016, surgical patients in 2010 will be registered. These registries were observationally assessed.

      Results
      Registries for surgical cases in 1994, 1999 and 2004 which were conducted in 1999, 2004 and 2009 revealed the trend of increase in mean age, rates of female, the aged, small sized lesion, adenocarcinoma and stage I, and that of decrease in the rate of perioperative death. Furthermore proposals for TNM classification were stated as peer reviewed papers- invasion to visceral pleura, chest wall and fat tissue in the mediastinum for T factor. In addition, status of N2 disease were assessed resulting in that highly selected cases (3.8%) were subjected to surgery or surgery-included multimodal therapy with a 5-year survival rate of 30.1% in cN2/pN2-Stage IIIA and it was better than previous registries. Registry for surgical and non-surgical patients in 2002 revealed that stage-specific prognosis was within a range similar to other reports and stage, gender, surgery and performance status were independent prognostic indicator of both non-small and small cell lung cancer. Registry of non-surgical cases in 2012 was conducted and greater than 8,000 cases were registered. In this study, status of usage of FDG-PET scan for staging, EGFR gene mutation and individual therapy were, and prognosis of patients will be registered. In up-coming registry for surgical cases in 2010 which will be performed in 2016, new parameters- the size of tumor regarding non-invasive regions in adenocarcinoma (ground grass opacity in computed tomography), quantitative assessment of lymph node metastasis (the number of metastasized lymph node) as a prognostic indicator, which may be assessed as factors of TNM classification in the future. Besides, the TNM classification will be revised in 2016 according to the proposal from IASLC staging project, to which the JJCLCR offered data of 47,306 cases (approximately 25% of whole world wide cases) from the recent 4 registries.

      Conclusion
      The JJCLCR conducted nation-wide lung cancer registry in Japan, revealing the condition of the treatment of lung cancer and contributing to the TNM staging program.