Journal of Thoracic Oncology:
IASLC Staging Committee Article
The IASLC/ITMIG Thymic Malignancies Staging Project: Development of a Stage Classification for Thymic Malignancies
Detterbeck, Frank C. MD*; Asamura, Hisao MD†; Crowley, John PhD‡; Falkson, Conrad MBChB§; Giaccone, Giuseppe MD‖; Giroux, Dori MS‡; Huang, James MD¶; Kim, Jhingook MD#; Kondo, Kazuya MD**; Lucchi, Marco MD††; Marino, Mirella MD‡‡; Marom, Edith M. MD§§; Nicholson, Andrew MD‖‖; Okumura, Meinoshin MD¶¶; Ruffini, Enrico MD##; van Schil, Paul MD***; Stratton, Kelly MS‡; on behalf of the Staging and Prognostic Factors Committee; Members of the Advisory Boards; Participating Institutions of the Thymic Domain
*Department of Thoracic Surgery, Yale New Haven Hospital, Yale University School of Medicine, New Haven, Connecticut; †Thoracic Surgery, National Cancer Center Hospital, Tokyo, Japan; ‡Biostatistics, Cancer Research And Biostatistics, Seattle, Washington; §Radiation Oncology, Queen’s University, Ontario, Canada; ‖Medical Oncology, National Cancer Institute, Bethesda, Maryland; ¶Thoracic Surgery, Sloan-Kettering Cancer Center, New York, New York; #Thoracic Surgery, Samsung Medical Center, Seoul, South Korea; **Thoracic Surgery, University of Tokushima, Tokushima, Japan; ††Thoracic Surgery, University of Pisa, Pisa, Italy; ‡‡Pathology, Regina Elena National Cancer Institute, Rome, Italy; §§Radiology, MD Anderson Cancer Center, Houston, Texas; ‖‖Pathology, Royal Brompton Hospital, London, United Kingdom; ¶¶Thoracic Surgery, Osaka University, Osaka, Japan; ##Thoracic Surgery, University of Torino, Torino, Italy; ***Thoracic Surgery, Antwerp University Hospital, Antwerp, Belgium; ††† Members of the Staging and Prognostic Factors Committee are listed in the Appendix 1; ‡‡‡ Members of the Advisory Boards are listed in the Appendices 2, 3, and 4; and §§§ Members of the Participating Institutions of the Thymic Domain are listed in the Appendix 5.
Disclosure: The authors declare no conflict of interest.
Address for correspondence: Frank C. Detterbeck, MD, Department of Surgery, Division of Thoracic Surgery, Yale University School of Medicine, BB2 333 Cedar Street, New Haven, Connecticut 06510. E-mail: email@example.com
The lack of an official-stage classification system for thymic malignancies is an issue that hampers progress in this rare disease. A collaborative effort by the International Association for the Study of Lung Cancer and the International Thymic Malignancies Interest Group is underway to develop proposals for such a system. A database of more than 10,000 cases worldwide has been assembled to provide a solid basis for analysis. This report outlines the structure of the effort and the process that has been designed.
Thymic malignancies are relatively rare and are therefore classified as an orphan disease. Among many issues hampering the ability to make robust scientific progress is the fact that there is no official American Joint Committee on Cancer/Union for International Cancer Control (AJCC/UICC) stage classification for these tumors. The ability to describe the extent of disease through a consistent universal nomenclature is a fundamental requirement for comparison of clinical results between centers and for multi-institutional collaborative work.
At least 15 different stage classification systems have been proposed, beginning as far back as 1978. A review of the various classification systems and their differences is the subject of a recent article.1 The most widely known system, the Masaoka system, was proposed in 1981 on the basis of an experience with 91 patients.2 All of the other proposed systems have involved roughly similar, relatively small cohorts of patients.1,3–5
Although the Masaoka system and variations thereof like Masaoka-Koga6 have been what has been used most widely, in fact there are significant discrepancies between centers regarding how the relatively vague wording describing the stages is interpreted. Thus, not only is the lack of an official system a problem but also the lack of clear definitions and consistent application even when using the same system.
To at least address the issue of vague wording and inconsistent interpretation, the International Thymic Malignancies Interest Group (ITMIG) assembled an international team that proposed clarifications of the definitions of the Masaoka-Koga classification.7 This was endorsed by the vast majority of clinicians active in this disease as a standard to use going forward. Nevertheless, this represents merely a consensus regarding a clarification of heretofore vague wording of an existing stage classification system. In fact, the explicit task of the ITMIG effort was to not make any changes to the Masaoka-Koga system, and not to address whether the system is appropriate, but only to achieve greater consistency by applying a uniform consensus interpretation.
THE THYMIC MALIGNANCIES DOMAIN OF THE INTERNATIONAL ASSOCIATION FOR THE STUDY OF LUNG CANCER STAGING AND PROGNOSTIC FACTORS COMMITTEE
The need for a consistent, validated stage classification system for thymic malignancies is clear. ITMIG and International Association for the Study of Lung Cancer (IASLC) more or less independently and simultaneously set out to accomplish this, and then joined forces in 2010, with ITMIG providing the engagement of the vast majority of clinicians active in this disease and IASLC providing infrastructure and experience gained during the development of the seventh edition of the lung cancer stage classification.
The current lung cancer stage classification was led by a massive IASLC initiative that assembled an international database of more than 100,000 patients with lung cancer diagnosed in a defined 10-year span.8 In contrast, the previous classification system was based on approximately 5000 patients diagnosed over more than a 30-year span. IASLC led an extensive internal and external validation of the stage proposals, which was carried out by the Cancer Research And Biostatistics (CRAB) organization.9 The IASLC proposals formed the basis of the AJCC/UICC seventh edition lung cancer stage classification system. IASLC and CRAB are now providing their expertise to the development of a thymic stage classification system.
IASLC and ITMIG partnered to create a Thymic Malignancies Domain of the Staging and Prognostic Factors Committee (SPFC-TD), which is charged with the development of proposals for change to AJCC/UICC for the eighth edition of the stage classification system. Individuals were invited to participate in the SPFC-TD, based on expertise and interest. The members of the SPFC-TD are shown in Table 1.
Creation of a Database
To allow global collaboration in clinical science regarding thymic malignancies, ITMIG created a retrospective and a prospective database. Institutions were invited to participate; the overwhelming response is a testament to the worldwide engagement and culture of collaboration that ITMIG has achieved.
Among the initial uses of this database is the stage classification initiative. ITMIG assembled a retrospective global database of 6097 cases. The Japanese Association for Research in the Thymus also assembled a database of 2897 cases, and made this available to ITMIG for the stage classification project. Together this represents a retrospective database of 8994 cases from 77 centers in 16 countries. This retrospective database was cleaned and provided to CRAB; an additional 1814 cases were contributed by the European Society of Thoracic Surgeons thymic group directly to CRAB. Thus, the total sample size available for analysis by CRAB includes 10,808 patients with thymic malignancies from 105 sites worldwide. A map of participating centers is shown in Figure 1.
The retrospective database has some limitations, which include the amount of detail that is available, varying interpretations of how a particular dataelement is defined by different institutions, changing definitions and policies over the course of the data collection, and questions about the comparability of data from different centers despite bearing the same data labels. ITMIG has also launched a prospective database, which is based on clear definitions developed by an international consensus, and contains many details that should provide another quantum leap forward over the already impressive retrospective database. The timing of the AJCC/UICC, however, limits the availability of sufficient prospective data to substantially contribute to the eighth edition of the stage classification.
Characteristics of a Thymic Stage Classification System
The SPFC-TD thought that a thymic stage classification should ideally have several characteristics (Table 2). First of all, the stage classification should be a nomenclature that describes the anatomic extent of disease only. Other factors that contribute to prognosis will be included in a prognostic prediction model but will not be a part of the stage classification (see later discussion of prognostic factors). This is consistent with the primary purpose of stage classification. This also recognizes the inherent complexity of prediction of prognosis and the inherent fundamental differences between an anatomic extent of disease classification and prognostication.10 Classification of the anatomic disease is concrete, grounded in actual findings that can be applied to an individual patient. Prediction of prognosis is inherently speculative, multifactorial (including factors that cannot be assessed at the time), dynamic and fluid, and applies to a patient population. Prognostication is inherently associated with uncertainty, which becomes greater and greater as one moves closer to predicting prognosis for an individual.
The thymic stage classification system should ideally apply to all types of thymic malignancies, e.g., thymoma, thymic carcinoma, and thymic carcinoid tumors. A strong argument for this position is the simplicity of having only one system, which is particularly important in a rare disease that is encountered by many clinicians only sporadically. Furthermore, there are grey areas in the distinction between some histologic types,11 and this is especially true when only limited biopsy material is available such as in the clinical (pretreatment) phase of stage classification. It can be argued that the behavior of different types of thymic tumors is disparate, but there is precedent for a stage classification system to nevertheless be applicable (e.g., consider that the lung stage classification system is validated for small-cell lung cancer, non–small-cell lung cancer, and lung carcinoid tumors).12,13
The SPFC-TD thinks that it would be best to conform to a T (tumor), N (node), and M (metastasis) structure, which is used for the vast majority of malignancies (although there are exceptions). A tumor, node, metastasis–based system is more likely to be applicable to all thymic malignancies. Furthermore, node involvement may be more relevant, even for thymoma, than has been appreciated. A recent report involving node dissection found nodal metastases in 29% of stage III thymomas (thymic carcinoma was excluded).14 Although node involvement is traditionally thought to be rare with thymoma, a careful node assessment has generally not been carried out.
Guiding Principles for the Development of the Stage Classification System
What criteria should be used to establish a particular point as a good boundary between T, N, and M classes or between stage groupings? It is possible to consider many different arguments, and how much weight is given to a particular argument is influenced by the nature of the tumor, characteristics of the data available, and the primary purpose of the stage classification system. The SPFC-TD decided on a series of guiding principles, which are summarized in Table 2.
A fundamental goal of a classification system is to be able to consistently classify patients at many centers. If the classification system cannot be applied consistently, none of the other considerations will make up for this fundamental deficiency. ITMIG is launching studies of intra- and interobserver variability of particular boundaries to guide the SPFC-TD process.
Pathologic stage is generally viewed as more accurate, incorporating both any information available from clinical (pretreatment) staging and from the results of a surgical resection and pathologic examination of the tissues. Nevertheless, clinical staging is of more practical value, because this is when major decisions regarding treatment strategy must be made. Therefore, a high priority must be the ability to apply stage classification clinically and pathologically. Few articles have addressed clinical staging in thymoma15,16; ITMIG is developing a prospective imaging repository that can provide a basis for future validation of clinical staging proposals.
The stage classification should be applicable to all types of thymic malignancies. It seems likely that this will not be a major stumbling block. Compatibility with an existing system is desirable but of lower priority because of the lack of a widespread, consistently applied system. The number of different systems and the variability in how the wording in these systems has been interpreted inherently limit backwards compatibility.
Prognosis has been widely used as a tool to separate T, N, and M classes and stage groups, and there is no question that this should be considered in the development of a thymic stage classification system. Nevertheless, some aspects of prognosis need to be taken into account—both fundamental issues with the use of prognosis for classification and specific issues for thymic malignancies. First of all, prognosis is complex and multifactorial, reflecting many confounding factors and not just the impact of tumor characteristics per se (e.g., comorbidities, treatment received). This confounding cannot be easily disentangled, even with multivariate analysis; only natural history data (no active treatment) in patients without comorbidities can provide information about the impact of the tumor characteristics themselves. In the IASLC lung cancer database, this confounding was apparent in the marked variability of overall survival outcomes among different geographic regions, data sources, and other subgroups. This was indirectly accounted for during development of the seventh edition of the lung cancer stage classification by requiring that a valid boundary between T, N, and M classes or stage groupings had to show differences in prognosis (not prognosis per se) that were consistent in terms of magnitude and direction within multiple subgroup analyses. Nevertheless, such subgroup analyses are more difficult to carry out in thymic malignancies because of the much more limited number of patients. A requirement of statistically significant differences within subgroups is unlikely to be able to be met.
Prognosis in thymic malignancies is also more difficult to assess because of the poor correlation between recurrence and death, in contrast to many other malignancies. Thus the influence of other factors, unrelated to the thymic malignancy, on overall survival is large. A better measure of the effect of anatomic extent of disease may be the recurrence rate,17 but data on this outcome and how it was assessed are more limited. In addition, longer-term outcomes is likely influenced by treatment received; little data are available on how much variability there has been among centers.18
The Process of Developing a Thymic Stage Classification System
The planned process for the SPFC-TD is to gather data that inform the stage classification from whatever sources are available. This includes assessment of prognosis in the SPFC-TD retrospective database, studies of intra- and interobserver variability, and suggested factors in the publications of institutions or other organizations. These will be evaluated and synthesized according to the priorities stated above.
One analysis will be an assessment of how well the Masaoka stage classification performs in separating prognostically distinct groups. The fact that prognosis is confounded by nonanatomic disease-extent characteristics will be addressed by subgroup analysis, similar to what was done in the development of the seventh edition of the lung cancer stage classification system. The two most important confounding factors are likely to be competing causes of death (e.g., comorbidities) and treatment given. To account for this, the analysis will include a specific focus on recurrence and on patients who underwent resection. Because the ability to differentiate between an R0 and R1 resection in the past is in question, this aspect will also be investigated.
Size is an appealing parameter to explore, because (at least one dimension) is usually available, there is some precedent for prognostic significance, and it can be applied clinically and pathologically. Nevertheless, larger thymic malignancies are not round, raising issues about how size was and should be measured and how well pathologic measurements (assessed in planes dictated by the tumor shape) correlate with clinical measurements (typically based on the greatest dimension on a transverse computed tomography image).
Finally, as many factors as possible will be investigated that can serve as T, N, and M descriptors (e.g., invasion into specific mediastinal structures, pleural, or pericardial implants). To address the issue of prognostic confounding by nonanatomic disease-extent factors, a focus on recurrence and resected patients is needed as described above.
Because thymic malignancies are a rare disease, the available data have some limitations. It is anticipated that enough data will be available to provide a basis for a thoughtful proposal. Nevertheless, it is also recognized that some aspects will be more empiric and will require further study. The initiation of the ITMIG prospective database, which contains much more detail, will provide a solid basis for this. The development of a thymic stage classification system for the eighth edition of the stage classification represents only the beginning of an ongoing process.
Although the eighth edition is not scheduled for publication until 2016, the AJCC/UICC mandates that ITMIG/IASLC completes its work in developing proposals in 2014. Assessment of outcomes for many thymic malignancies takes time with respect to overall survival; nevertheless, the median time to recurrence for stage ≥III is 3 to 4 years. This may allow some preliminary validation of a classification developed from the retrospective database against recurrence data in the prospective database before the stage classification takes effect.
The initial focus of the SPFC-TD is clearly on developing proposals for classification of the anatomic extent of disease. Nevertheless, there is a need for a prognostic model for thymic malignancies, as is true for cancers in general. In some ways, this is more difficult in thymic malignancies because much less data are available, but in other ways, this facilitates development of a structure to build upon. Several ITMIG initiatives will help the development of a prognostic model, including the prospective database, the use of Bayesian analysis, and development of adaptive models to guide treatment. This work will take some time, and therefore a prognostic model is not a planned deliverable together with the eighth edition of the stage classification.
Thymic malignancies are an orphan disease; one of the many things that hampers progress is the lack of a well-defined stage classification system. ITMIG and IASLC have partnered in a formal, structured process to develop this for the next (eighth) edition of the stage classification. This involves an international committee of experts, creation of a large (by thymic standards) database, and careful analysis of data regarding multiple aspects that influence the definition of stage descriptors and grouping. This article outlines the status of this project and the process that is planned.
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Appendix 1. International Association for the Study of Lung Cancer Staging and Prognostic Factors Committee
Peter Goldstraw, Past Chair, Royal Brompton Hospital and Imperial College, London, United Kingdom; Ramón Rami-Porta, Chair, Hospital Universitari Mutua Terrassa, Terrassa, Spain; Hisao Asamura, Chair Elect, National Cancer Center, Tokyo, Japan; David Ball, Peter MacCallum Cancer Institute, Melbourne, Australia; David Beer, University of Michigan, Ann Arbor, MI; Ricardo Beyruti, University of Sao Paulo, Sao Paulo, Brazil; Vanessa Bolejack, Cancer Research And Biostatistics, Seattle, WA; Kari Chansky, Cancer Research And Biostatistics, Seattle, WA; John Crowley, Cancer Research And Biostatistics, Seattle, WA; Frank Detterbeck, Yale University, New Haven, CT; Wilfried Eberhardt, University of Essen, Essen, Germany; John Edwards, Northern General Hospital, Sheffield, United Kingdom; Françoise Galateau-Sallé, Centre Hospitalier Universitaire, Caen, France; Dorothy Giroux, Cancer Research And Biostatistics, Seattle, WA; Fergus Gleeson, Churchill Hospital, Oxford, United Kingdom; Patti Groome, Queen’s Cancer Research Institute, Kingston, Ontario, Canada; James Huang, Memorial Sloan-Kettering Cancer Center, New York, NY; Catherine Kennedy, University of Sydney, Sydney, Australia; Jhingook Kim, Samsung Medical Center, Seoul, Korea; Y. T. Kim, Seoul National University, Seoul, South Korea; Laura Kingsbury, Cancer Research And Biostatistics, Seattle, WA; Haruhiko Kondo, Kyorin University Hospital, Tokyo, Japan; Mark Krasnik, Gentofte Hospital, Copenhagen, Denmark; Kaoru Kubota, Nippon Medical School Hospital, Tokyo, Japan; Antoon Lerut, University Hospitals, Leuven, Belgium; Gustavo Lyons, British Hospital, Buenos Aires, Argentina; Mirella Marino, Regina Elena National Cancer Institute, Rome, Italy; Edith Marom, MD Anderson Cancer Center, Houston, TX; Jan van Meerbeeck, University Hospital, Ghent, Belgium; Alan Mitchell, Cancer Research And Biostatistics, Seattle, WA; Takashi Nakano, Hyogo College of Medicine, Hyogo, Japan; Jennifer Newman, Cancer Research And Biostatistics, Seattle, WA; Andrew Nicholson, Royal Brompton Hospital, London, United Kingdom; Anna Nowak, University of Western Australia, Subiaco, Australia; Michael Peake, Glenfield Hospital, Leicester, United Kingdom; Thomas Rice, Cleveland Clinic, Cleveland, OH; Kenneth Rosenzweig, Mount Sinai Hospital, New York, NY; Enrico Ruffini, University of Torino, Torino, Italy; Valerie Rusch, Memorial Sloan-Kettering Cancer Center, New York, NY; Paul van Schil, University Hospital of Antwerp, Aartselaar, Belgium; Jean-Paul Sculier, Institut Jules Bordet, Brussels, Belgium; Kelly Stratton, Cancer Research And Biostatistics, Seattle, WA; Kenji Suzuki, Juntendo University, Tokyo, Japan; Yuji Tachimori, National Cancer Center, Tokyo, Japan; Charles F. Thomas Jr, Mayo Clinic, Rochester, MN; William Travis, Memorial Sloan-Kettering Cancer Center, New York, NY; Ming Tsao, The Princess Margaret Hospital, Toronto, Ontario, Canada; Andrew Turrisi, Sinai-Grace Hospital, Detroit, MI; Johan Vansteenkiste, University Hospitals, Leuven, Belgium; Hirokazu Watanabe, National Cancer Center Hospital, Tokyo, Japan; Yi-Iong Wu, Guangdong General Hospital, Guangzhou, People’s Republic of China; and Marcin Zielinski, Pulmonary Hospital, Zakopane, Poland.
Appendix 2. Advisory Board of the International Association for the Study of Lung Cancer Thymic Malignancies Domain
Conrad Falkson, Queen’s University, Ontario, Canada; Pier Luigi Filosso, University of Torino, Torino, Italy; Giuseppe Giaccone, National Cancer Institute, Bethesda, MD; Kazuya Kondo, University of Tokushima, Tokushima, Japan; Marco Lucchi, University of Pisa, Pisa, Italy; and Meinoshin Okumura, Osaka University, Osaka, Japan.
Appendix 3. Advisory Board of the International Association for the Study of Lung Cancer Mesothelioma Domain
Paul Baas, The Netherlands Cancer Institute, Amsterdam, The Netherlands; Jeremy Erasmus, MD Anderson Cancer Center, Houston, TX; Seiki Hasegawa, Hyogo College of Medicine, Hyogo, Japan; Kouki Inai, Hiroshima University Postgraduate School, Hiroshima, Japan; Kemp Kernstine, City of Hope, Duarte, CA; Hedy Kindler, The University of Chicago Medical Center, Chicago, IL; Lee Krug, Memorial Sloan-Kettering Cancer Center, New York, NY; Kristiaan Nackaerts, University Hospitals, Leuven, Belgium; Harvey Pass, New York University, New York, NY; and David Rice, MD Anderson Cancer Center, Houston, TX.
Appendix 4. Advisory Board of the International Association for the Study of Lung Cancer Esophageal Cancer Domain
Eugene Blackstone, Cleveland Clinic, OH.
Appendix 5. Participating Institutions in the International Association for the Study of Lung Cancer/International Thymic Malignancies Interest Group Thymic Malignancies Staging Project
S. Call Caja, Hospital Universitari Mutua Terrassa, Terrassa, Spain; U. Ahmad and F. Detterbeck, Yale Cancer Center, New Haven, CT; N. Girard, Louis Pradel Hospital, Lyon, France; Seok Jin Haam, Gangnam Severance Hospital, Seoul, Korea; Mi Kyung Bae, Severance Hospital, Seoul, Korea; D.R. Gomez and E. Marom, MD Anderson Cancer Center, Houston, TX; P. van Schil, Antwerp University Hospital, Antwerp, Belgium; P. Ströbel, University Medical Center Göttingen, Göttingen, Germany; A. Marx, University Medical Center Mannheim, Mannheim, Germany; S. Saita, Azienda Ospedaliero-Universitaria Policlinico V.Emanuele, Catania, Italy; H. Wakelee, Stanford University, Stanford, CA; L. Bertolaccini, Thoracic Surgery, Azienda Ospedaliera S.Croce e Carle, Cuneo, Italy; E. Vallieres, Swedish Cancer Institute, Seattle, WA; W. Scott and S. Su, Fox Chase Cancer Center, Philadelphia, PA; B. Park and J. Marks, Hackensack University Medical Center, Hackensack, NJ; S. Khella, Penn Presbyterian Medical Center, Philadelphia, PA; R. Shen, Mayo Clinic Rochester, Rochester, MN; M. Rosenberg, Alexander Fleming Institute, Buenos Aires, Argentina; M. Rosenberg, Maria Ferrer Institute, Buenos Aires, Argentina; V. Tomulescu, Fundeni Clinical Institute, Bucharest, Romania; J. Huang, Memorial Sloan-Kettering Cancer Center, New York, NY; C. Foroulis, AHEPA University Hospital, Aristotle University Medical School, Thessaloniki, Greece; L. Lang-Lazdunski and Andrea Billè, Guy’s & St. Thomas’ Hospital, London, United Kingdom; J.G. Maessen and M. Keijzers, Maastricht University Medical Centre, Maastricht, Netherlands; H. van Veer, University Hospitals Leuven, Leuven, Belgium; C. Wright, Massachusetts General Hospital, Boston, MA; M. Marino, Regina Elena National Cancer Institute, Rome, Italy; G. Palmieri and C. Buonerba, Università Degli Studi di Napoli Federico II, Napoli, Italy; M. Ferguson, University of Chicago, Chicago, IL; G. Marulli, University of Padua, Padua, Italy; M. Lucchi, University of Pisa, Pisa, Italy; P. Loehrer, Indiana University Simon Cancer Center, Indianapolis, IN; M. Kalkat, Birmingham Heartlands Hospital, Birmingham, United Kingdom; K. Rohrberg and G. Daugaard, Rigshospitalet, University Hospital of Copenhagen, Copenhagen, Denmark; A. Toker and S. Erus, Istanbul Medical University, Istanbul, Turkey; M. Kimmich, Klinik Schillerhoehe, Gerlingen, Germany; A. Brunelli and M. Refai, Ospedali Riuniti, Ancona, Italy; A. Nicholson and E. Lim, Royal Brompton Hospital/Harefield NHS Foundation Trust, London, United Kingdom; In Kyu Park, Seoul National Hospital, Seoul, Korea; J. Wagner and B. Tieu, Oregon Health and Science University, Portland, Oregon; Wentao Fang and Jie Zhang, Shanghai Chest Hospital, Jiaotong University Medical School, Shanghai, China; Zhentao Yu, Tianjin Medical University Cancer Hospital, Tianjin, China; Yongtao Han, Sichuan Cancer Hospital, Chengdu, China; Yin Li, Henan Cancer Hospital, Zhengzhou, China; Keneng Chen, Beijing University Cancer Hospital, Beijing, China; Gang Chen, Shanghai Pulmonary Hospital, Tongji University, Shanghai, China; Meinoshin Okumura, Osaka University, Osaka, Japan; Yoshitaka Fujii, Nagoya City University, Aichi, Japan; Hisao Asamura, National Cancer Center Hospital, Tokyo, Japan; Kanji Nagai, National Cancer Center Hospital East, Chiba, Japan; Jun Nakajima, University of Tokyo, Tokyo, Japan; Norihiko Ikeda, Tokyo Medical University, Tokyo, Japan; Shuji Haraguchi, Nippon Medical School, Tokyo, Japan; Takamasa Onuki, Tokyo Women’s Medical University, Tokyo, Japan; Kenji Suzuki, Juntendo University, Tokyo, Japan; Ichiro Yoshino, Chiba University, Chiba, Japan; Masanori Tsuchida, Niigata University, Niigata, Japan; Shoji Takahashi, Shizuoka Cancer Center, Shizuoka, Japan; Kohei Yokoi, Nagoya University, Aichi, Japan; Masayuki Hanyuda, Aichi Medical University, Aichi, Japan; Hiroshi Niwa, Seirei Mikatahara General Hospital, Shizuoka, Japan; Hiroshi Date, Kyoto University, Kyoto, Japan; Yoshimasa Maniwa, Kobe University, Hyogo, Japan; Shinichiro Miyoshi, Okayama University, Okayama, Japan; Kazuya Kondo, Tokushima University, Tokushima, Japan; Akinori Iwasaki, Fukuoka University, Fukuoka, Japan; Tatsuro Okamoto, Kyusyu University, Fukuoka, Japan; Takeshi Nagayasu, Nagasaki University, Nagasaki, Japan; Fumihiro Tanaka, University of Occupational and Environmental Health, Fukuoka, Japan; Minoru Suzuki, Kumamoto University, Kumamoto, Japan; Kazuo Yoshida, Shinshu University, Nagano, Japan; Yusuke Okuma and Hirotoshi Horio, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Tokyo, Japan; Akihide Matsumura, Kinki-Chuo Chest Medical Center, Osaka, Japan; Masahiko Higashiyama, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan; Hiroshi Suehisa, Shikoku Cancer Center, Ehime, Japan; Takuya Onuki, Tsuchiura Kyodo Hospital, Ibaragi, Japan; Yoshifumi Sano, Ehime University, Ehime, Japan; Keishi Kondo, Hokkaido Cancer Center, Hokkaido, Japan; K. Al Kattan, King Khalid University Hospital, Riyadh, Saudi Arabia; R. Cerfolio, University of Alabama, Birmingham, AL; C. Gebitekin, Uludag University School of Medicine, Bursa, Turkey; D. Gomez de Antonio, Hospital Universitario Puerta de Hierro Majadahonda, Madrid, Spain; K.H. Kernstine, University of Texas, Southwestern Medical Center and School of Medicine (SW), Dallas; N. Altorki, The New York Hospital, Cornell Medical Centre, New York, NY; N. Novoa, Salamanca University Hospital, Salamanca, Spain; E. Ruffini and P.L. Filosso, University of Torino, Torino, Italy; S. Saita, University of Catania, Catania, Italy; M. Scarci, Papworth Hospital NHS Foundation Trust, Papworth Everard, Cambridge, United Kingdom; L. Voltolini, Università di Siena, Siena, Italy; W. Weder, University Hospital, Zurich, Switzerland; Wojciech Zurek, Medical University of Gdansk, Gdansk, Poland; A. Arame, Hopital Europeen Georges-Pompidou and Hopital Laennec, Paris, France; C. Casadio, Chirurgia Toracica, Novara, Italy; P. Carbognani, Università di Parma, Parma, Italy; G. Donati, Ospedale di Aosta, Aosta, Italy; S. Keshavjee, University of Toronto, Toronto, Canada; W. Klepetko and B. Moser, Medical University of Vienna, Vienna, Austria; C. Lequaglie, Thoracic Surgery, Rionero in Vulture, Italy; Moishe Liberman, Centre Hospitalier de l’Université de Montréal, Montréal, Canada; M. Mancuso, Ospedale Alessandria, Alessandria, Italy; M. Nosotti, Policlinico, Milan, Italy; L. Spaggiari, Istituto Europeo di Oncologia (IEO), Milan, Italy; P.A. Thomas, Hôpital Nord, Université de la Méditerranée, Marseille, France; E. Rendina, University La Sapienza, Ospedale Sant’ Andrea, Rome, Italy; F. Venuta and M. Anile, Policlinico Umberto I, Rome, Italy; J. Schützner, Teaching Hospital Motol, Prague, Czech Republic; and G. Rocco, Pascale Institute, Napoli, Italy.
Thymoma; Thymic carcinoma; Staging of stage classification
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