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S. Miyoshi



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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): S. Miyoshi

      • 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): S. Miyoshi

      • 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): S. Miyoshi

      • 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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    P2.07 - Poster Session 2 - Surgery (ID 190)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Surgery
    • Presentations: 2
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      P2.07-016 - Perioperative nutrition of induction chemoradiotherapy followed by surgery in locally advanced non-small lung cancer patients (ID 1411)

      09:30 - 16:30  |  Author(s): S. Miyoshi

      • Abstract

      Background
      Induction chemoradiotherapy (CRT) followed by surgery (iCRT) is one of treatment strategies for locally advanced non-small cell lung cancers (NSCLCs). We have previously reported its feasibility and good clinical outcome with approximately 60% of 5-year overall survival rate. .Perioperative nutritional status,is considered as one of important factors for improved clinical outcome after surgery and other treatments. Here, we investigated the perioperative nutritional status in NSCLC patients treated by iCRT (CRT group) to evaluate the influence of nutritional variables on clinical outcome by comparing that in NSCLC patients with simple pulmonary resection without CRT (non-CRT group) .

      Methods
      Thirty-three consecutive patients with locally adcanced NSCLC who underwent iCRT from January 1, 2009, until December 31, 2011 at our institute were included in this study. The regimen of CRT was two cycles of docetaxel (40 mg/m[2]) plus cisplatin (40 mg/m[2]) with concurrent radiotherapy (46 gray) and the surgery was performed within 6 weeks of completing induction CRT. We compared nutrition-related factors and clinical outcome in 33 iCRT patients with those in 58 consecutive NSCLC patients who underwent lobectomy during January 1 to December 31, 2011 at out institute. .As for blood nutritional factors, total lymphocyte count (TLC), albumin (Alb), total cholesterol (T-cho), choline esterase (ChE), were examined. The prognostic nutritional index (PNI) was also calculated by Alb and TLC. Each nutrition-relatd factors were examined 1) before CRT, 2) before surgery and 3) one month after surgery.

      Results
      Median age of CRT group (61 years old) was significantly younger than that of non-CRT group (69 years old). Twenty-one males and 12 females and 44 males and 14 females were enrolled in CRT and non-CRT groups, respectively. Before any treatment, no significant difference was observed in body mass index and any blood nutritional factors in both groups. After induction CRT, TLC was significantly decreased, and additionally, Alb, T-cho, and ChE were significantly decreased after surgery comparing with those before surgery (after CRT). As for preoperative status in both groups, TLC, Alb and PNI were significantly lower in CRT group than in non-CRT group. Regard with surgery, extended surgery, operating time, and blood loss was significantly heavier in CRT group than in non-CRT group. Perioperative mortality rate was 0% in both groups and the frequency of post-operative complication was similar in both groups (51% and 41% in CRT and non-CRT groups, respectively). The length of hospital stay after surgery was significantly longer in CRT group (median 23 days) than in non-CRT group (median 14 days). Among CRT group, patients with loiw PNI index could not administrate adjuvant chemotherapy.

      Conclusion
      Perioperative nutritional status, especially TLC, is suppressed after CRT and moreover after surgery. Suppression of nutritional status continued one month after surgery with induction CRT and severe suppression of nutritional status disturbs further treatment such as adjuvant chemotherapy.

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      P2.07-023 - Extended sleeve lobectomy after induction chemoradiotherapy for locally advanced non-small cell lung cancer (ID 2013)

      09:30 - 16:30  |  Author(s): S. Miyoshi

      • Abstract

      Background
      An extended sleeve lobectomy is a useful procedure so as to spare the lung parenchyma. However, the resection of the bronchus can cause an increment in the tension at the site of the anastomosis and mismatches in the size of the bronchial orifices. Induction chemoradiotherapy (CRT) followed by surgery is a therapeutic option for locally advanced non-small cell lung cancer (NSCLC). Induction CRT, especially radiotherapy, has a negative effect on bronchial healing in the bronchial stump or anastomosis in a pulmonary resection.

      Methods
      The medical records were reviewed for nine NSCLC patients who underwent extended sleeve lobectomy after CRT between December 2007 and January 2013. Disease stage was evaluated with imaging analyses, including enhanced chest computed tomography (CT) scan, brain magnetic resonance imaging, positron emission tomography-CT scan and bronchoscopy. Induction CRT was performed for eight cases using cisplatin and docetaxel with concurrent thoracic radiation. For one patient who had synchronous laryngeal cancer, 5-fluorouracil and nedaplatin were used as chemotherapy. The radiation dose was 46 or 40 Gy using a conventional fractionation (2 Gy/day). Patients without progressive disease or good general condition underwent surgery. The bronchial anastomosis was basically wrapped with an omental pedicled flap or pericardial fat pad with prophylactic intent. The pre- and postoperative first-second forced expiratory volume was measured. The overall survival (OS) and the disease-free survival (DFS) were calculated from the date of initialing induction CRT until the date of death or the last follow-up for OS and until confirmed death of any cause or recurrence at local or distant site for DFS. The survival curve was calculated by the Kaplan-Meier method.

      Results
      The median patient age was 60 years (range, 50 to 73 years). There were seven men and two women. The histological subtype was squamous cell carcinoma in six patients and adenocarcinoma in three patients. Five patients had clinical stage (c-stage) IIIA, two patients had c-stage IIIB, and two patients had c-stage IIB. The radiation dose was 46 Gy in seven patients and 40 Gy in two patients. An extended sleeve lobectomy was performed for the left lingular division and the lower lobe in four patients, the right upper lobe and trachea in one patient, the right upper lobe, carina and trachea in one patient, the right middle and lower lobe in one patient, the right upper and middle lobe and the carina in one patient, and the right upper lobe and superior segment of the lower lobe in one patient. While no postoperative 90-day deaths occurred in this series, one case developed a bronchopleural fistula on postoperative day (POD) 25 and one case developed a bronchovascular fistula on POD 163. No cases of local recurrence occurred. The first-second forced expiratory volume before surgery was 2.52 ± 0.58 L (mean ± standard deviation), while that after surgery was 1.80 ± 0.66 L. The 2-year overall survival and disease-free survival rates were 63.5% and 47.6%, respectively.

      Conclusion
      Our experience suggests that an extended sleeve lobectomy after induction CRT is feasible, but careful patient selection and perioperative management is mandatory.

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    P2.09 - Poster Session 2 - Combined Modality (ID 213)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Combined Modality
    • Presentations: 1
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      P2.09-011 - Tumor arising from lower lobes is a poor prognostic factor in non-small cell lung cancer patients with N2 disease treated with induction chemoradiotherapy (ID 2239)

      09:30 - 16:30  |  Author(s): S. Miyoshi

      • Abstract

      Background
      Trimodality therapy consisting of induction chemoradiotherapy (CRT) followed by surgery can be one of the treatment options for locally advanced non-small cell lung cancer (NSCLC). While recent randomized phase III trials failed to demonstrate a benefit from the addition of surgery in the entire population, the subset analysis of the intergroup trial 0139 indicates that trimodality therapy is beneficial for population who did not undergo pneumonectomy. This result strongly suggests that the status of disease may influence the prognosis even in same stage population. Thus, identifying prognostic factors and their inclusion in stratification are critical for the appropriate randomized study. In this study, we retrospectively examined the prognostic impact of tumor location in NSCLC patients with clinical (c-) N2 disease who underwent trimodality therapy in our institute.

      Methods
      Among patients who underwent induction CRT followed by surgery between 1999 and 2011 at our institution, a total of 76 NSCLC patients with c- N2/3 stage III were enrolled for this retrospective study. Induction CRT basically consisted of docetaxel and cisplatin with concurrent radiation at a dose of 40 - 60 Gray.

      Results
      A total of 76 patients consisted of 53 male and 23 female, 43 adenocarcinomas and 33 non-adenocarcinomas, and 44 c-Stage IIIA and 32 c-Stage IIIB. Primary tumors were located in right upper lobe for 33 patients, right middle lobe for 5, right lower lobe for 11, left upper lobe for 20, and left lower lobe for 7. For all population, lower lobe tumors showed significantly shorter overall survival (OS) and disease-free survival (DFS) times compared to non-lower lobe tumors (OS, p = 0.022; DFS, p = 0.0007). In a multivariate analysis, tumor location was independent prognostic factor for poor prognosis. Limited to pathologically proven N2/3 disease before induction CRT (n = 36), location of lower lobe tend to be poor prognosis compared to other location (OS, p = 0.068; DFS, p = 0.0075).

      Conclusion
      We showed that tumor arising from lower lobes is a poor prognostic factor in NSCLC patients with N2 disease treated with induction CRT. The status of tumor location should be considered in stratification in randomized trails that estimate the impact of the trimodality therapy.