Clinicopathological analysis of thymic malignancies with a consistent retrospective database in a single institution: From Tokyo Metropolitan Cancer Center

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Clinicopathological analysis of thymic malignancies with a consistent retrospective database in a single institution: From Tokyo Metropolitan Cancer Center

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Thymic epithelial tumors (TETs), which comprise thymoma and thymic carcinoma, are rare cancers with specific morphological and clinical features. Their clinical characteristics and outcomes have gradually been clarified by assessing large-scale, retrospective data obtained with international cooperation.

Okuma et al BMC Cancer 2014, 14:349 http://www.biomedcentral.com/1471-2407/14/349 RESEARCH ARTICLE Open Access Clinicopathological analysis of thymic malignancies with a consistent retrospective database in a single institution: from Tokyo Metropolitan Cancer Center Yusuke Okuma1,5*, Yukio Hosomi1, Kageaki Watanabe1, Yuko Yamada2, Hirotoshi Horio3, Yoshiharu Maeda4, Tatsuru Okamura1 and Tsunekazu Hishima2 Abstract Background: Thymic epithelial tumors (TETs), which comprise thymoma and thymic carcinoma, are rare cancers with specific morphological and clinical features Their clinical characteristics and outcomes have gradually been clarified by assessing large-scale, retrospective data obtained with international cooperation Methods: The study is a retrospective review of 187 Japanese patients with TETs who attended our institution from 1976 to 2012 Relevant clinical features of patients with TETs and their tumors, including histology, staging, treatment strategies, and overall survival, were investigated Differences in survival were assessed by the Kaplan–Meier method and uni- and multi-variate Cox proportional hazards regression analyses Results: The 187 patients included 52 patients with stage I, 37 with stage II, 22 with stage III, and 76 with stage IVa/IVb tumors according to the Masaoka–Koga Staging System As to histological type, five patients had type A, 33 type AB, 19 type B1, 39 type B2, and 15 type B3 thymomas, whereas 68 patients had thymic carcinoma, including 11 with neuroendocrine carcinomas according to the 2004 WHO classification Either insufficient data were available to classify the tumors of the remaining eight patients or they had rare types Immunological abnormalities were present in 26 patients, most of whom had thymomas (21.8% of the thymoma group) Most of the patients who presented with symptoms had myasthenia gravis or extensive thymic carcinoma Secondary cancers were present in 25 patients (13.3%) The overall 5- and 10-year survival rates for thymoma were 85.4 and 71.5%, respectively, and those for thymic carcinoma were 33.8 and 2.3%, respectively OS differed significantly between stage IVa thymomas and thymic carcinomas The stage and whether the tumors were thymomas or thymic carcinomas were significant determinants of survival according to multivariate analysis Conclusion: The efficacy of treatments for thymoma and thymic carcinoma should be investigated separately because these tumors differ in their clinical features and prognosis Keywords: Thymoma, Thymic carcinoma, Thymic epithelial tumor, World Health Organization classification, Treatment, Prognostic factor, Rare cancer * Correspondence: y-okuma@cick.jp Department of Thoracic Oncology and Respiratory Medicine, Tokyo Metropolitan Cancer and Infectious diseases Center Komagome Hospital, 3-18-22 Honkomagome, Bunkyo, Tokyo 113-8677, Japan Division of Oncology, Research Center for Medical Science, The Jikei University School of Medicine, Minato, Tokyo, Japan Full list of author information is available at the end of the article © 2014 Okuma et al.; licensee BioMed Central Ltd This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated Okuma et al BMC Cancer 2014, 14:349 http://www.biomedcentral.com/1471-2407/14/349 Background Thymic epithelial tumors (TETs, or thymic malignancies) which comprise thymoma and thymic carcinoma, are rare cancers according to the definition of the RARECARE project, which is supported by the European Commission Their annual incidence is approximately 0.15 cases in the United States [1] and 0.32 cases in the Netherlands [2] per 100,000 person-years Thymic malignancies are extremely heterogeneous, with an exceedingly broad spectrum of morphological appearances and immunological abnormalities Because thymomas are bioactive and have organotypic features that lead to autoimmune manifestations, whereas thymic carcinomas are not immunologically active and lack organotypic features, patients with thymic carcinoma usually have symptoms associated with tumor extension or metastasis Because of their rarity, the clinical characteristics and prognostic indicators in patients with thymic malignancies have not been well characterized [3] Therefore, the International Thymic Malignancy Interest Group (ITMIG) was organized Despite the paucity of evidence, this group has reached consensus agreements in support of some treatment modalities, having conducted some single-arm phase II studies and a few retrospective studies of small groups of treated patients with diverse backgrounds [4] However, the optimal therapeutic strategy remains controversial In previous studies, patients with thymoma and thymic carcinoma have basically received the same treatment However, it has recently been suggested that the two types of tumors should be considered separate entities [5] In addition, the ITMIG has proposed using the Masaoka–Koga staging system [6] and the 2004 World Health Organization (WHO) histological classification; both proposals have been accepted [7] Thus, we believe it is necessary to review and clarify the nature and characteristics of these clinical entities in light of the proposed criteria Furthermore, the National Comprehensive Cancer Network has updated its guidelines for the clinical management and treatment of thymic malignancies, despite their rarity [8] The objective of the present study was to retrospectively clarify the clinical characteristics, prognosis, and prognostic indicators of patients with thymoma and thymic carcinoma according to the 2004 WHO classification [7] who had attended our institution over a 30-year period Methods Database This is a retrospective review of patients diagnosed with thymic malignancies between January 1976 and December 2012 identified from the databases at Tokyo Metropolitan Cancer and Infectious diseases Center Komagome Hospital (Tokyo, Japan) The codes of the International Classification of Diseases (9th edition) were used Page of This retrospective study was approved by the Ethics Committee of the Tokyo Metropolitan Cancer and Infectious diseases Center Komagome Hospital (#1049) Patients and histological evaluation A retrospective review of relevant clinical features and treatment-related data of 187 consecutive Japanese patients with diagnoses of thymic malignancies was performed Their pathology was reviewed by a thoracic pathologist (TH) according to the 2004 WHO classification and Masaoka–Koga staging system [6] Diagnoses of thymic carcinoma were confirmed by hematoxylin-eosin staining and immunohistochemistry for CD5 and/or CD117 (c-KIT) and/or p63 to exclude other malignant thoracic tumors, as well as supplemental testing for terminal deoxynucleotidyl transferase to distinguish carcinomas from thymomas Clinical factors were also examined Data were collected in accordance with the Standard Definitions and Policies of the ITMIG [4] Clinical factors including age, sex, histological subtype, stage, immunological abnormalities, secondary malignancies, initial treatment -intent of modality, and survival were examined, relevant data having been obtained from medical records and laboratory data Staging had been determined according to the Masaoka–Koga staging system by computed tomography, magnetic resonance imaging, positron emission tomography, or bone scanning Histology was also classified according to the 2004 WHO classification The patients had been treated with curativeintent or palliative-intent surgery, radiotherapy, chemotherapy, and best supportive care, or a combination of these modalities Statistical analysis Descriptive statistics were used to summarize the patients’ baseline characteristics Survival time was defined as the period from the date of initiation of initial treatment (surgery, radiotherapy, chemotherapy, or best supportive care) to the date of death from any cause or last follow-up The Kaplan–Meier method was used to assess overall survival and 5- and 10-year survival rates Patients who had been lost to follow-up were censored at the time of last contact These end points reflected clinical practice because of the retrospective nature of the data In accordance with the ITMIG Standard Definitions and Policies, the 5-year survival rate of patients with thymic carcinomas and 10-year survival rate of those with thymoma were calculated Correlations between histological subtype according to the 2004 WHO classification and Masaoka–Koga stage were evaluated using a nonparametric measure of statistical dependence between the two variables The log-rank test was used to identify prognostic indicators by uni- and multi-variate analysis Candidate variables Okuma et al BMC Cancer 2014, 14:349 http://www.biomedcentral.com/1471-2407/14/349 Page of Table Characteristics of patients and tumors in patients with thymic malignancies Characteristics Median age, Thymoma Thymic carcinoma n = 119 (%) n = 68 (%) 58 [26–81] - 63 [14–83] - Male 52 43.7 38 55.9 Female 67 56.3 30 44.1 Thymomas Thymic carcinomas 68 100.0 Squamous cell carcinoma 46 67.6 Mucoepidermoid carcinoma 7.4 Lymphoepithelioma-like carcinoma 1.5 Undifferentiated carcinoma 4.4 Neuroendocrine carcinomas 11 16.2 Small cell carcinoma 4.4 LCNEC 2.9 Carcinoid 8.8 Not classified in WHO classification 2.9 Years [range] Gender Histology 119 100.0 Type A 4.2 Type B1 19 16.1 Type B2 39 32.8 Type B3 15 12.6 Type AB 33 27.7 Other subtypes or missing data of thymoma 6.7 Staging I 52 43.7 0 II 31 26.1 8.8 III 12 10.1 10 14.7 IVa 18 15.1 16 23.5 IVb 5.0 36 52.9 20 16.8 1.5 13 19.1 Complications Immunological abnormalities (overlapped) Myasthenia gravis Pure red cell aplasia 3.3 Hypogammaglobulinemia 4.2 Secondary malignancies 12 10.1 Initial treatment-intent of modalities Curative-intent treatment 116 97.5 43 63.2 Surgery 109 91.6 30 44.1 Surgery alone 89 74.8 10 14.7 Surgery with perioperative treatment 20 16.8 20 29.4 Radiotherapy 5.9 13 19.1 Definitive radiotherapy alone 0.8 1.5 Okuma et al BMC Cancer 2014, 14:349 http://www.biomedcentral.com/1471-2407/14/349 Page of Table Characteristics of patients and tumors in patients with thymic malignancies (Continued) Chmoradiotherapy (sequential/concurrent) 5.1 12 17.6 Palliative-intent treatment 2.5 25 36.8 Chemotherapy alone 1.7 24 35.3 Best supportive care 0.8 1.5 analyzed included age (

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Mục lục

    Patients and histological evaluation

    Characteristics of patients with thymoma and thymic carcinoma and their tumors

    Treatment modalities and strategies for thymoma and thymic carcinoma

    Clinical outcomes of thymoma and thymic carcinoma by stage and histological classification

    Correlation between tumor type according to the 2004 WHO classification and Masaoka–Koga stage

    Prognostic factors affecting survival according to uni- and multi-variate analysis

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