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J. Nakajima



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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 - 10:35  |  Author(s): J. Nakajima

      • 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)

      10:35 - 10:40  |  Author(s): J. Nakajima

      • 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)

      10:45 - 10:50  |  Author(s): J. Nakajima

      • 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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    O20 - Staging and Advanced Disease (ID 102)

    • Event: WCLC 2013
    • Type: Oral Abstract Session
    • Track: Surgery
    • Presentations: 1
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      O20.02 - A novel nodal classification for resected non-small cell lung cancer: comparison between location-based and number-based systems (ID 881)

      16:25 - 16:35  |  Author(s): J. Nakajima

      • Abstract
      • Presentation
      • Slides

      Background
      The current UICC/WHO nodal classification system is based on the location of metastatic lymph nodes, while some studies have revealed that the number or ratio of metastatic lymph nodes may work as more effective prognostic indicators. The Japan Lung Cancer Society proposed a new tumor site-based classification for mediastinal nodal metastases according to the tumor-bearing lobe. This study aimed to compare the prognostic power of location-based and number-based classification systems and elucidate the optimal classification.

      Methods
      Of 511 patients with non-small cell lung cancer (NSCLC) who underwent lung lobectomy and complete hilar and mediastinal lymph node dissection with curative intent at our institute between 1998 and 2009, 119 with confirmed lymph node metastases were retrospectively analyzed. Ten classifications were compared using a log-rank test. Four classifications were location-based: the current system, the tumor site-based classification, the classification based on presence or absence of clinical N2 disease, and the classification based on presence or absence of non-skip N2 disease. The other 6 classifications were number-based: the classifications based on the number or ratio of metastatic lymph nodes, the classifications based on that of metastatic stations, and the classifications based on that of metastatic mediastinal lymph nodes.

      Results
      Compared with the current system [hazard ratio (HR), 1.4; p = 0.29], the tumor site-based classification (HR, 2.8; p = 3.0E-4), the classification based on the number of metastatic lymph nodes (HR, 2.8; p = 1.7E-4), and the classification based on the number of metastatic mediastinal lymph nodes (HR, 2.3; p = 3.3E-3) were considered to be stronger predictors of overall survival. Similar results were obtained in terms of disease-free survival (current system: HR, 1.6; p = 0.047; tumor site-based classification: HR, 2.7; p = 2.3E-5; number of metastatic lymph nodes, HR, 2.3; p = 4.0E-4; number of metastatic mediastinal lymph nodes: HR, 2.4; p = 1.4E-4). A combination of the tumor site-based classification with the classification based on the number of metastatic lymph nodes (p = 9.0E-4) or the classification based on the number of metastatic mediastinal lymph nodes (p = 9.5E-4) further increased predictive efficiency.

      Conclusion
      The tumor site-based classification as well as the classifications based on the number of metastatic lymph nodes and the number of metastatic mediastinal lymph nodes was more predictive of surgical outcomes compared with the current nodal system. The results need to be further validated in a new set of patients. Figure 1

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    P2.21 - Poster Session 2 - Diagnosis and Staging (ID 170)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Prevention & Epidemiology
    • Presentations: 1
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      P2.21-001 - Solitary pulmonary squamous cell carcinoma in patients with a history of squamous cell carcinoma: metastasis or second primary tumour? (ID 315)

      09:30 - 09:30  |  Author(s): J. Nakajima

      • Abstract

      Background
      Primary and metastatic squamous cell carcinomas (SCC) in the lung are often histologically indistinguishable, and the differential diagnosis between them is primarily dependent on clinical information such as the location of the lung lesion, the tumour stage, and the disease-free interval, particularly when the pulmonary nodule is solitary. The management of solitary pulmonary SCC in patients with a history of SCC may pose diagnostic and therapeutic challenges.

      Methods
      A retrospective chart review analysis was conducted. The study included 244 consecutive patients with antecedent cancer histories who subsequently underwent pulmonary resections for newly discovered solitary pulmonary nodules (new SPNs) from January 1998 to December 2007 at our institute.

      Results
      Of the 244 patients, 36 had a history of SCC (neck: 14, oesophagus: 9, neck and oesophagus: 3, lung: 5, anal canal: 1, unknown: 1, uterine cervix: 3), and 208 had no history of SCC. A history of SCC was significantly associated with the squamous pathology of new SPNs (22 of 36, p < 0.0001). Of the 22 new SPNs with a squamous pathology, 14 of them were diagnosed as metastatic (mSCC), and 8 were diagnosed as primary carcinomas (pSCC). The mSCC showed a more advanced initial disease (p = 0.0109) and a marginally shorter disease-free interval (p= 0.0818) than the pSCC. The overall survival (OS) and recurrence-free survival (RFS) of patients with pSCC were superior to those of patients with mSCC (OS: p = 0.0413, RFS: p = 0.0282) (Figure 1). Notably, 6 intra-thoracic recurrences were observed in the mSCC group.Figure 1

      Conclusion
      The current policy for differentiation between mSCC and pSCC, which is based on clinical information, appears to be acceptable. In cases in which the origin of the pulmonary lesion is unclear, it might be better to treat solitary lung SCC as a primary lung cancer because it might offer the best chance for a cure.