更新情報
PDQ®日本語版の更新情報

PDQ®（Physician Data Query）

米国国立がん研究所（NCI）の
PDQ®トップページ

医療専門家向け Thymoma and Thymic Carcinoma Treatment (Adult) (PDQ®)

ご利用について

This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the treatment of adult thymoma and thymic carcinoma. It is intended as a resource to inform and assist clinicians who care for cancer patients. It does not provide formal guidelines or recommendations for making health care decisions.

This summary is reviewed regularly and updated as necessary by the PDQ Adult Treatment Editorial Board, which is editorially independent of the National Cancer Institute (NCI). The summary reflects an independent review of the literature and does not represent a policy statement of NCI or the National Institutes of Health (NIH).

CONTENTS 全て開く全て閉じる

General Information About Thymoma and Thymic Carcinoma Treatment

Thymoma and thymic carcinoma (collectively termed thymic epithelial tumors [TETs]) are relatively rare tumors arising from the thymus. Although infrequent, TETs are the most common tumors of the anterior mediastinum in adults. TETs, particularly thymomas, have unique biological properties and are associated with autoimmune paraneoplastic diseases. TETs have the lowest tumor mutational burden of all solid tumors in adults. All TETs have malignant potential and the ability to metastasize. The clinical behavior of TETs can vary from relatively indolent to aggressive, resulting in a range of clinical outcomes.

Surgery is the main treatment, especially for early-stage disease. Multimodality therapy, including chemotherapy and radiation therapy, is used to treat locally advanced disease, and systemic therapy alone is indicated for metastatic TETs.[ 1 ]

Incidence and Mortality

TETs are relatively rare tumors representing about 0.2% to 1.5% of all malignancies.[ 2 ] The overall incidence of thymoma is 0.13 cases per 100,000 person years, based on data from the National Cancer Institute Surveillance, Epidemiology, and End Results (SEER) Program.[ 3 ] Thymic carcinomas account for approximately 20% of all TETs.[ 4 ] Five-year survival for inoperable, locally advanced carcinoma is 36%; for metastatic thymoma and thymic carcinoma, the 5-year survival is 24%.[ 5 ]

Autoimmune Paraneoplastic Diseases Associated With Thymoma and Thymic Carcinomas

Autoimmune paraneoplastic diseases are associated with thymoma and are rarely associated with thymic carcinomas.[ 6 ][ 7 ][ 8 ][ 9 ]

The occurrence of autoimmune paraneoplastic diseases in patients with thymoma is related to defective negative selection of autoreactive T cells. Decreased expression of AIRE, the autoimmune regulator gene, contributes to this process.[ 10 ] Thymoma-associated autoimmune paraneoplastic disease also involves an alteration in circulating T-cell subsets.[ 11 ][ 12 ] The primary T-cell abnormality appears to be related to the acquisition of the CD45RA+ phenotype on naive CD4+ T cells during terminal intratumorous thymopoiesis, followed by the export of these activated CD4+ T cells into the circulation.[ 13 ]

In addition to T-cell defects, B-cell lymphopenia and the presence of anticytokine antibodies have been observed in patients with thymoma-related immunodeficiency, resulting in an increased risk of developing opportunistic infection.[ 6 ][ 14 ][ 15 ]

The most common autoimmune paraneoplastic diseases associated with thymoma are myasthenia gravis, hypogammaglobulinemia, and autoimmune pure red cell aplasia.

A variety of other autoimmune paraneoplastic diseases can be associated with TETs and include virtually any organ system.[ 7 ][ 9 ]

Thymoma patients with myasthenia gravis or other autoimmune paraneoplastic diseases are typically diagnosed with early-stage disease and are more likely to undergo complete surgical resection than are those who do not have myasthenia gravis or other autoimmune paraneoplastic diseases.[ 9 ][ 20 ] Thymectomy may not significantly improve the course of thymoma-associated autoimmune paraneoplastic disease in all cases.[ 21 ][ 22 ] The presence of autoimmune paraneoplastic disease also does not appear to be an independent prognostic factor in patients with TETs.[ 9 ]

Clinical Features

At the time of diagnosis, most patients with thymoma or thymic carcinoma are asymptomatic.[ 23 ] About one-third of patients present with symptoms that arise either from the underlying tumor or from the presence of associated autoimmune paraneoplastic diseases. Typical clinical signs and symptoms include cough, dyspnea, chest pain, hoarseness of voice, phrenic nerve palsy, or signs suggestive of superior vena cava syndrome.[ 24 ]

Diagnostic and Staging Evaluation

TETs are differentiated from a number of nonthymic neoplasms that can present with mediastinal masses, including the following:[ 25 ][ 26 ]

Nonneoplastic thymic conditions that can present with mediastinal masses include thymic hyperplasia and thymic cysts.

The following tests and procedures may be used in the diagnosis and staging of thymoma and thymic carcinoma:

Thymic carcinoma can metastasize to regional lymph nodes, bone, liver, or lungs. An evaluation for sites of metastases may be warranted.

Prognostic Factors and Prognosis

The World Health Organization (WHO) pathologic classification of tumors of the thymus and stage correlate with prognosis.[ 25 ] The degree of invasion or tumor stage is generally thought to be a more important indicator of overall survival (OS).[ 27 ][ 35 ][ 36 ]

Thymoma

Histologic classification of thymoma is not sufficient to distinguish biologically indolent thymomas from thymomas that exhibit aggressive clinical behavior. Although some thymoma histologic types are more likely to be clinically aggressive, treatment outcome and the likelihood of recurrence appear to correlate more closely with the invasive/metastasizing properties of the tumor cells.[ 25 ][ 35 ] Therefore, some thymomas that appear to be relatively benign by histologic criteria may behave very aggressively. Independent evaluations of both tumor invasiveness (using staging criteria) and tumor histology may be combined to predict the clinical behavior of a thymoma.

Both histologic classification of thymomas and stage may have independent prognostic significance.[ 35 ][ 36 ] A few series have reported the prognostic value of the WHO classifications. Two large retrospective analyses, one with 100 thymoma cases and the other with 178 thymoma cases, showed that disease-free survival at 10 years varied (refer to Table 1).[ 37 ][ 38 ] In these series, stage and complete resection were significant independent prognostic factors. Another analysis reported on 273 thymoma patients who were treated over a 44-year period. Refer to Table 1 for the 20-year survival rates.[ 35 ]

Table 1. Disease-free Survival (DFS) of Patients With Thymoma by Histologic Subtype
Study
A AB B1 B2 B3 C
a10-year DFS.
b20-year DFS.
[ 37 ] (N = 100)a 100% 100% 83% 83% 36% 28%
[ 38 ] (N = 178)a 95% 90% 85% 71% 40%  
[ 35 ] (N = 273)b 100% 87% 91% 59% 36%  

Thymic carcinoma

Thymic carcinomas are usually advanced when diagnosed.[ 39 ][ 40 ] Thymic carcinomas have a greater propensity for capsular invasion, metastases, and recurrence than thymomas. Patients with thymic carcinoma have a worse survival compared with thymoma (5-year survival rate, 30%–50%).[ 41 ] In a retrospective study of 40 patients with thymic carcinoma, the OS rates were 38% for 5 years and 28% for 10 years.[ 39 ] In another retrospective study evaluating 43 cases of thymic carcinoma, prognosis was found to be dependent solely on tumor invasion of the brachiocephalic artery.[ 40 ]

Follow-up After Treatment of Thymoma

Thymoma has been associated with an increased risk of second malignancies. Because of this risk and because thymoma can recur after a long interval, lifelong surveillance should be considered.[ 22 ] The measurement of interferon-alpha and interleukin-2 antibodies is helpful in identifying patients with a thymoma recurrence.[ 42 ]

In a study of 849 cases between 1973 and 1998, there was an excess risk of subsequent non-Hodgkin lymphoma and soft tissue sarcomas following thymoma.[ 43 ] Risk of second malignancy does not appear to be related to thymectomy, radiation therapy, or a clinical history of myasthenia gravis.[ 22 ][ 43 ][ 44 ]

Related Summary

Refer to the following PDQ summary for additional information related to thymoma:

参考文献
  1. Kelly RJ, Petrini I, Rajan A, et al.: Thymic malignancies: from clinical management to targeted therapies. J Clin Oncol 29 (36): 4820-7, 2011.[PUBMED Abstract]
  2. Fornasiero A, Daniele O, Ghiotto C, et al.: Chemotherapy of invasive thymoma. J Clin Oncol 8 (8): 1419-23, 1990.[PUBMED Abstract]
  3. Engels EA: Epidemiology of thymoma and associated malignancies. J Thorac Oncol 5 (10 Suppl 4): S260-5, 2010.[PUBMED Abstract]
  4. Carter BW, Benveniste MF, Madan R, et al.: IASLC/ITMIG Staging System and Lymph Node Map for Thymic Epithelial Neoplasms. Radiographics 37 (3): 758-776, 2017 May-Jun.[PUBMED Abstract]
  5. Kondo K, Monden Y: Therapy for thymic epithelial tumors: a clinical study of 1,320 patients from Japan. Ann Thorac Surg 76 (3): 878-84; discussion 884-5, 2003.[PUBMED Abstract]
  6. Levy Y, Afek A, Sherer Y, et al.: Malignant thymoma associated with autoimmune diseases: a retrospective study and review of the literature. Semin Arthritis Rheum 28 (2): 73-9, 1998.[PUBMED Abstract]
  7. Marx A, Willcox N, Leite MI, et al.: Thymoma and paraneoplastic myasthenia gravis. Autoimmunity 43 (5-6): 413-27, 2010.[PUBMED Abstract]
  8. Bernard C, Frih H, Pasquet F, et al.: Thymoma associated with autoimmune diseases: 85 cases and literature review. Autoimmun Rev 15 (1): 82-92, 2016.[PUBMED Abstract]
  9. Padda SK, Yao X, Antonicelli A, et al.: Paraneoplastic Syndromes and Thymic Malignancies: An Examination of the International Thymic Malignancy Interest Group Retrospective Database. J Thorac Oncol 13 (3): 436-446, 2018.[PUBMED Abstract]
  10. Kisand K, Lilic D, Casanova JL, et al.: Mucocutaneous candidiasis and autoimmunity against cytokines in APECED and thymoma patients: clinical and pathogenetic implications. Eur J Immunol 41 (6): 1517-27, 2011.[PUBMED Abstract]
  11. Hoffacker V, Schultz A, Tiesinga JJ, et al.: Thymomas alter the T-cell subset composition in the blood: a potential mechanism for thymoma-associated autoimmune disease. Blood 96 (12): 3872-9, 2000.[PUBMED Abstract]
  12. Buckley C, Douek D, Newsom-Davis J, et al.: Mature, long-lived CD4+ and CD8+ T cells are generated by the thymoma in myasthenia gravis. Ann Neurol 50 (1): 64-72, 2001.[PUBMED Abstract]
  13. Ströbel P, Helmreich M, Menioudakis G, et al.: Paraneoplastic myasthenia gravis correlates with generation of mature naive CD4(+) T cells in thymomas. Blood 100 (1): 159-66, 2002.[PUBMED Abstract]
  14. Martinez B, Browne SK: Good syndrome, bad problem. Front Oncol 4: 307, 2014.[PUBMED Abstract]
  15. Burbelo PD, Browne SK, Sampaio EP, et al.: Anti-cytokine autoantibodies are associated with opportunistic infection in patients with thymic neoplasia. Blood 116 (23): 4848-58, 2010.[PUBMED Abstract]
  16. Morgenthaler TI, Brown LR, Colby TV, et al.: Thymoma. Mayo Clin Proc 68 (11): 1110-23, 1993.[PUBMED Abstract]
  17. Souadjian JV, Enriquez P, Silverstein MN, et al.: The spectrum of diseases associated with thymoma. Coincidence or syndrome? Arch Intern Med 134 (2): 374-9, 1974.[PUBMED Abstract]
  18. Voltz RD, Albrich WC, Nägele A, et al.: Paraneoplastic myasthenia gravis: detection of anti-MGT30 (titin) antibodies predicts thymic epithelial tumor. Neurology 49 (5): 1454-7, 1997.[PUBMED Abstract]
  19. Gautel M, Lakey A, Barlow DP, et al.: Titin antibodies in myasthenia gravis: identification of a major immunogenic region of titin. Neurology 43 (8): 1581-5, 1993.[PUBMED Abstract]
  20. Kondo K, Monden Y: Thymoma and myasthenia gravis: a clinical study of 1,089 patients from Japan. Ann Thorac Surg 79 (1): 219-24, 2005.[PUBMED Abstract]
  21. Budde JM, Morris CD, Gal AA, et al.: Predictors of outcome in thymectomy for myasthenia gravis. Ann Thorac Surg 72 (1): 197-202, 2001.[PUBMED Abstract]
  22. Evoli A, Minisci C, Di Schino C, et al.: Thymoma in patients with MG: characteristics and long-term outcome. Neurology 59 (12): 1844-50, 2002.[PUBMED Abstract]
  23. Schmidt-Wolf IG, Rockstroh JK, Schüller H, et al.: Malignant thymoma: current status of classification and multimodality treatment. Ann Hematol 82 (2): 69-76, 2003.[PUBMED Abstract]
  24. Rajan A, Giaccone G: Treatment of advanced thymoma and thymic carcinoma. Curr Treat Options Oncol 9 (4-6): 277-87, 2008.[PUBMED Abstract]
  25. Rosai J: Histological Typing of Tumours of the Thymus. New York, NY: Springer-Verlag, 2nd ed., 1999.[PUBMED Abstract]
  26. Strollo DC, Rosado-de-Christenson ML: Tumors of the thymus. J Thorac Imaging 14 (3): 152-71, 1999.[PUBMED Abstract]
  27. Sperling B, Marschall J, Kennedy R, et al.: Thymoma: a review of the clinical and pathological findings in 65 cases. Can J Surg 46 (1): 37-42, 2003.[PUBMED Abstract]
  28. Rendina EA, Venuta F, Ceroni L, et al.: Computed tomographic staging of anterior mediastinal neoplasms. Thorax 43 (6): 441-5, 1988.[PUBMED Abstract]
  29. Tomiyama N, Johkoh T, Mihara N, et al.: Using the World Health Organization Classification of thymic epithelial neoplasms to describe CT findings. AJR Am J Roentgenol 179 (4): 881-6, 2002.[PUBMED Abstract]
  30. Sasaki M, Kuwabara Y, Ichiya Y, et al.: Differential diagnosis of thymic tumors using a combination of 11C-methionine PET and FDG PET. J Nucl Med 40 (10): 1595-601, 1999.[PUBMED Abstract]
  31. Kageyama M, Seto H, Shimizu M, et al.: Thallium-201 single photon emission computed tomography in the evaluation of thymic carcinoma. Radiat Med 12 (5): 237-9, 1994 Sep-Oct.[PUBMED Abstract]
  32. Adams S, Baum RP, Hertel A, et al.: Metabolic (PET) and receptor (SPET) imaging of well- and less well-differentiated tumours: comparison with the expression of the Ki-67 antigen. Nucl Med Commun 19 (7): 641-7, 1998.[PUBMED Abstract]
  33. Kubota K, Yamada S, Kondo T, et al.: PET imaging of primary mediastinal tumours. Br J Cancer 73 (7): 882-6, 1996.[PUBMED Abstract]
  34. Carter BW, Lichtenberger JP, Benveniste MF: MR Imaging of Thymic Epithelial Neoplasms. Top Magn Reson Imaging 27 (2): 65-71, 2018.[PUBMED Abstract]
  35. Okumura M, Ohta M, Tateyama H, et al.: The World Health Organization histologic classification system reflects the oncologic behavior of thymoma: a clinical study of 273 patients. Cancer 94 (3): 624-32, 2002.[PUBMED Abstract]
  36. Chen G, Marx A, Wen-Hu C, et al.: New WHO histologic classification predicts prognosis of thymic epithelial tumors: a clinicopathologic study of 200 thymoma cases from China. Cancer 95 (2): 420-9, 2002.[PUBMED Abstract]
  37. Kondo K, Yoshizawa K, Tsuyuguchi M, et al.: WHO histologic classification is a prognostic indicator in thymoma. Ann Thorac Surg 77 (4): 1183-8, 2004.[PUBMED Abstract]
  38. Rena O, Papalia E, Maggi G, et al.: World Health Organization histologic classification: an independent prognostic factor in resected thymomas. Lung Cancer 50 (1): 59-66, 2005.[PUBMED Abstract]
  39. Ogawa K, Toita T, Uno T, et al.: Treatment and prognosis of thymic carcinoma: a retrospective analysis of 40 cases. Cancer 94 (12): 3115-9, 2002.[PUBMED Abstract]
  40. Blumberg D, Burt ME, Bains MS, et al.: Thymic carcinoma: current staging does not predict prognosis. J Thorac Cardiovasc Surg 115 (2): 303-8; discussion 308-9, 1998.[PUBMED Abstract]
  41. Eng TY, Fuller CD, Jagirdar J, et al.: Thymic carcinoma: state of the art review. Int J Radiat Oncol Biol Phys 59 (3): 654-64, 2004.[PUBMED Abstract]
  42. Buckley C, Newsom-Davis J, Willcox N, et al.: Do titin and cytokine antibodies in MG patients predict thymoma or thymoma recurrence? Neurology 57 (9): 1579-82, 2001.[PUBMED Abstract]
  43. Engels EA, Pfeiffer RM: Malignant thymoma in the United States: demographic patterns in incidence and associations with subsequent malignancies. Int J Cancer 105 (4): 546-51, 2003.[PUBMED Abstract]
  44. Pan CC, Chen PC, Wang LS, et al.: Thymoma is associated with an increased risk of second malignancy. Cancer 92 (9): 2406-11, 2001.[PUBMED Abstract]
Cellular Classification and Molecular Characteristics of Thymoma and Thymic Carcinomas

The histological classification of thymic epithelial tumors (TETs) has evolved and is largely based on the third edition of the World Health Organization (WHO) classification of tumors of the lung, pleura, thymus, and heart that was published in 2004. The fourth edition of the WHO classification, published in 2015, contains refined histological and immunohistochemical diagnostic criteria and is the most widely accepted cellular classification of TETs.[ 1 ][ 2 ] Thymomas arise from the thymic epithelium and consist of epithelial cells mixed with varying proportions of immature T cells. Thymic carcinomas are epithelial tumors with overt cytological atypia and without organotypic (i.e., thymus-like) features.

Thymoma

The epithelial component of thymomas exhibit no or minimal overt atypia and retain histologic features specific to the normal thymus.[ 1 ] Immature nonneoplastic lymphocytes are present in variable numbers depending on the histologic type of thymoma.

Table 2, Table 3, Table 4, Table 5, and Table 6 describe morphologic, molecular, and clinical characteristics of various subtypes of thymoma.

Table 2. Characteristics of Subtype A Thymoma
OS = overall survival.
Histologic subtype percentage of all thymomas in study cited.[ 3 ][ 4 ] Approximately 4%–7%.
Myasthenia gravis association.[ 3 ] Approximately 17%.
Morphologic characteristics.[ 2 ] Composed of bland, spindle-shaped epithelial cells (at least focally) with a paucity or absence of immature (TdT+) T cells throughout the tumor.
Molecular characteristics.[ 5 ][ 6 ] Chromosome abnormalities, when present, may correlate with an aggressive clinical course and may include the following: chromosome 6q25 loss, chromosome 6p23 loss (FOXC1), C19MC overexpression, GTF2I mutations, HRAS (G13V) mutations, and miR-515 upregulation.
Prognosis and survival.[ 3 ][ 4 ] Excellent, with a ≥15-year OS rate of 100%.
Table 3. Characteristics of Subtype AB Thymoma
OS = overall survival.
Histologic subtype percentage of all thymomas in study cited.[ 3 ][ 4 ] Approximately 28%–34%.
Myasthenia gravis association.[ 3 ] Approximately 16%.
Morphologic characteristics.[ 2 ] Composed of bland, spindle-shaped epithelial cells (at least focally), with an abundance of immature (TdT+) T cells focally or throughout the tumor.
Molecular characteristics.[ 5 ][ 6 ] Include chromosome 6q25 loss, chromosome 6p23 loss (FOXC1), chromosome 7p15 loss, C19MC overexpression, and GTF2I mutations.
Prognosis and survival.[ 3 ][ 4 ] Good, with a ≥15-year OS rate of approximately 90%.
Table 4. Characteristics of Subtype B1 Thymoma
OS = overall survival.
Histologic subtype percentage of all thymomas in study cited.[ 3 ][ 4 ] Approximately 9%–20%.
Myasthenia gravis association.[ 3 ] Approximately 57%.
Morphologic characteristics.[ 2 ] Tumors exhibit thymus-like architecture and cytology including the abundance of immature T cells, areas of medullary differentiation (medullary islands), and a paucity of polygonal or dendritic epithelia cells without clustering (i.e., <3 contiguous epithelial cells).
Molecular characteristics.[ 5 ] Include chromosome 1p, 2q, 3q, 6q losses.
Prognosis and survival.[ 3 ][ 4 ] Good, with a ≥20-year OS rate of approximately 90%.
Table 5. Characteristics of Subtype B2 Thymoma
OS = overall survival.
Histologic subtype percentage of all thymomas in study cited.[ 3 ][ 4 ] Approximately 20%–36%.
Myasthenia gravis association.[ 3 ] Approximately 71%.
Morphologic characteristics.[ 2 ] Tumors consist of increased numbers of single or clustered polygonal or dendritic epithelial cells intermingled with abundant immature T cells.
Molecular characteristics.[ 5 ] Include chromosome 6q25 loss, chromosome 6p23 loss (FOXC1), chromosome 1q gain, and KRAS (G12A) mutations.
Prognosis and survival.[ 3 ] Is worse than for thymoma types A, AB, and B1, with a 20-year OS rate (as defined by freedom from tumor death) of approximately 60%.
Table 6. Characteristics of Subtype B3 Thymoma
OS = overall survival.
Histologic subtype percentage of all thymomas in study cited.[ 3 ][ 4 ] Approximately 10%–14%.
Myasthenia gravis association.[ 3 ] Approximately 46%.
Morphologic characteristics.[ 2 ] Predominantly composed of sheets of polygonal, slightly-to-moderately atypical epithelial cells, absent or rare intercellular bridges, and paucity or absence of intermingled TdT+ T cells.
Molecular characteristics.[ 5 ] Include chromosome 6q25 loss, chromosome 6p23 loss (FOXC1), chromosome 11q4 loss, chromosome 1q gain, chromosomal translocation t(11;X), BCL2 copy number gains (18q21.33), MCL1 copy number gain, CDKN2A/B copy number losses (9p21.3), and BCOR and PHF15 mutations.
Prognosis and survival.[ 3 ] A 20-year OS rate (as defined by freedom from tumor death) of approximately 40%.

Thymic Carcinoma

Thymic carcinoma is a TET that exhibits a definite cytologic atypia and a set of histologic features no longer specific to the thymus but similar to histologic features observed in carcinomas of other organs. Unlike type A and B thymomas, thymic carcinomas lack immature lymphocytes. Any lymphocytes that are present are mature and usually admixed with plasma cells.[ 1 ]

The characteristics of thymic carcinoma subtypes are described in Table 7.

Table 7. Characteristics of Thymic Carcinoma Subtypesa
Subtype Characteristics
CEA = carcinoembryonic antigen; CK = cytokeratin; EMA = epithelial membrane antigen; PAS = periodic acid-Schiff; PLAP = placental alkaline phosphatase.
aAdapted from [ 7 ][ 8 ].
Squamous cell carcinoma (SCC) The most common subtype of thymic carcinoma, SCC exhibits clear-cut cytologic atypia and resembles SCC arising in other organs. Not all cases have clear evidence of keratinization. SCC lacks immature T lymphocytes. CD5, CD70, CD117, FoxN1, and CD205 are expressed by most thymic SCCs.
Basaloid carcinoma Composed of compact lobules of tumor cells that exhibit peripheral palisading and an overall basophilic staining pattern caused by the high nucleocytoplasmic ratio. Basaloid carcinoma tends to originate from multilocular thymic cysts, expresses keratin and EMA, can express CD5 but does not express S-100 and neuroendocrine markers.
Lymphoepithelioma-like carcinoma Syncytial growth of undifferentiated carcinoma cells accompanied by a lymphoplasmacytic infiltration is like undifferentiated carcinoma of the respiratory tract. Lymphoepithelioma-like carcinoma may or may not be Epstein-Barr virus positive. Tumor cells are strongly positive for AE1-defined acidic CKs, and negative for AE3-defined basic CKs. CK7 and CK20 are also negative. BCL-2 expression is common. CD5 is focally expressed or absent. Lymphoid cells are CD3+, CD5+, CD1a-, CD99-, and TdT-mature T cells. CD20+ B cells are present in small numbers in the stroma.
Sarcomatoid thymic carcinoma Part or all of the tumor resembles one of the types of soft tissue sarcoma. Sarcomatoid carcinoma includes spindle cell carcinoma (i.e., malignant transformation of type A thymoma), sarcomatoid transformation of preexisting thymic carcinoma, and true carcinosarcoma with heterologous component(s).
Clear cell thymic carcinoma Composed predominantly or exclusively of cells with optically clear cytoplasm. Tumor cells usually show strong cytoplasmic diastase-labile PAS positivity. Clear cell carcinomas are keratin positive. EMA is expressed in 20% of cases. CD5 expression is present in some cases. PLAP, vimentin, CEA, and S-100 are negative.
Mucoepidermoid thymic carcinoma Consists of squamous cells, mucus-producing cells, and cells of intermediate type and resembles mucoepidermoid carcinoma of other organs. Translocation of the MAML2 gene is present and can help distinguish this tumor from adenosquamous carcinomas and adenocarcinomas.
Papillary thymic adenocarcinoma Grows in a papillary fashion. Histology may be accompanied by psammoma body formation, which may result in a marked similarity with papillary carcinoma of the thyroid gland. Variable expression of Leu M1 and BerEP4 is observed. CEA and CD5 may also be positive. CD20, thyroglobulin, pulmonary surfactant apoprotein, and calretinin are absent.
Undifferentiated thymic carcinoma A rare type of thymic carcinoma that grows in a solid undifferentiated fashion but without exhibiting sarcomatoid (spindle cell or pleomorphic) features.
Carcinoma with t(15;19) translocation (NUT carcinoma) A rare, aggressive carcinoma of unknown histogenesis. The presence of undifferentiated, intermediate-sized, vigorously mitotic cells is characteristic. Pan-cytokeratin markers are expressed. Focal positivity of vimentin, EMA, and CEA is observed. CD30, CD45, PLAP, HMB45, S100, and neuroendocrine markers are negative. t(15;19)-translocation is observed with the generation of a BRD4–NUT fusion oncogene. Immunohistochemistry for NUT is highly sensitive and should be considered in any undifferentiated cancer, especially if focal squamous differentiation is seen.

Molecular Characteristics of Thymoma and Thymic Carcinomas

TETs have the lowest mutational burden of all adult cancers. Multiplatform analyses have revealed four molecular subtypes that are associated with survival and WHO histological subtypes. Mutations in HRAS, NRAS, TP53, and GTF2I have been observed. Targetable mutations are uncommon. Tumor overexpression of muscle autoantigens and increased aneuploidy have also been identified and provide a molecular link between thymoma and myasthenia gravis.[ 6 ]

参考文献
  1. Travis WD, Brambilla E, Burke E, et al.: WHO Classification of Tumours of the Lung, Pleura, Thymus and Heart. 4th ed., Lyon, France: International Agency for Research on Cancer, 2015.[PUBMED Abstract]
  2. Marx A, Chan JK, Coindre JM, et al.: The 2015 World Health Organization Classification of Tumors of the Thymus: Continuity and Changes. J Thorac Oncol 10 (10): 1383-95, 2015.[PUBMED Abstract]
  3. Hirabayashi H, Fujii Y, Sakaguchi M, et al.: p16INK4, pRB, p53 and cyclin D1 expression and hypermethylation of CDKN2 gene in thymoma and thymic carcinoma. Int J Cancer 73 (5): 639-44, 1997.[PUBMED Abstract]
  4. Sasaki H, Kobayashi Y, Tanahashi M, et al.: Ets-1 gene expression in patients with thymoma. Jpn J Thorac Cardiovasc Surg 50 (12): 503-7, 2002.[PUBMED Abstract]
  5. Rajan A, Girard N, Marx A: State of the art of genetic alterations in thymic epithelial tumors. J Thorac Oncol 9 (9 Suppl 2): S131-6, 2014.[PUBMED Abstract]
  6. Radovich M, Pickering CR, Felau I, et al.: The Integrated Genomic Landscape of Thymic Epithelial Tumors. Cancer Cell 33 (2): 244-258.e10, 2018.[PUBMED Abstract]
  7. Travis W, Brambilla E, Müller-Hermelink H, et al., eds.: Pathology and Genetics of Tumours of the Lung, Pleura, and Thymus. Lyon, France: IARC Press, 2004. World Health Organization Classification of Tumours.[PUBMED Abstract]
  8. Marx A, Chan J, Coindre J-M, et al.: The 2015 WHO classification of tumors of the thymus: continuity and changes. J Thorac Oncol 10 (10): 1383–95, 2015.[PUBMED Abstract]
Stage Information for Thymoma and Thymic Carcinoma

Evaluating the invasiveness of a thymoma involves the use of staging criteria that indicate the presence and degree of contiguous invasion, the presence of tumor implants, and lymph node or distant metastases regardless of histologic type. The staging system, proposed by Masaoka in 1981 and modified by Koga in 1994, is most commonly used, with the modified system being recommended for use by the International Thymic Malignancies Interest Group (ITMIG) (refer to Table 8).[ 1 ][ 2 ] To establish consistency in the staging of thymic epithelial tumors (TETs), the American Joint Committee on Cancer (AJCC) and the Union for International Cancer Control (UICC) adopted a new TNM (tumor, node, metastasis) classification system developed by the International Association for the Study of Lung Cancer (IASLC) and ITMIG.[ 3 ][ 4 ][ 5 ]

Table 8. Masaoka-Koga Staging System for Thymoma, 1994a
Stage Description
I Macroscopically, completely encapsulated; microscopically, no capsular invasion.
II Macroscopic invasion into surrounding fatty tissue or mediastinal pleura; microscopic invasion into capsule.
III Macroscopic invasion into neighboring organs (pericardium, lung, and great vessels).
IVa Pleural or pericardial dissemination.
IVb Lymphogenous or hematogenous metastases.

AJCC Stage Groupings and TNM Definitions

Table 9. Definition of TNM Stage Ia
Stage T Description
T = primary tumor; N = regional lymph node; M = distant metastasis.
aAdapted from AJCC: Thymus. In: Amin MB, Edge SB, Greene FL, et al., eds.: AJCC Cancer Staging Manual. 8th ed. New York, NY: Springer, 2017, pp. 423–9.
The explanations for superscripts b and c are at the end of Table 12.
I T1a,b, N0, M0 T1 = Tumor encapsulated or extending into the mediastinal fat; may involve the mediastinal pleura.
–T1a = Tumor with no mediastinal pleura involvement.
–T1b = Tumor with direct invasion of mediastinal pleura.
N0 = No regional lymph node metastasis.
M0 = No pleural, pericardial, or distant metastasis.
Table 10. Definition of TNM Stage IIa
Stage T Description
T = primary tumor; N = regional lymph node; M = distant metastasis.
aAdapted from AJCC: Thymus. In: Amin MB, Edge SB, Greene FL, et al., eds.: AJCC Cancer Staging Manual. 8th ed. New York, NY: Springer, 2017, pp. 423–9.
The explanations for superscripts b and c are at the end of Table 12.
II T2, N0, M0 T2 = Tumor with direct invasion of the pericardium (either partial or full thickness).
N0 = No regional lymph node metastasis.
M0 = No pleural, pericardial, or distant metastasis.
Table 11. Definition of TNM Stages IIIA and IIIBa
Stage T Description
T = primary tumor; N = regional lymph node; M = distant metastasis.
aAdapted from AJCC: Thymus. In: Amin MB, Edge SB, Greene FL, et al., eds.: AJCC Cancer Staging Manual. 8th ed. New York, NY: Springer, 2017, pp. 423–9.
The explanations for superscripts b and c are at the end of Table 12.
IIIA T3, N0, M0 T3 = Tumor with direct invasion into any of the following: lung, brachiocephalic vein, superior vena cava, phrenic nerve, chest wall, or extrapericardial pulmonary artery or veins.
N0 = No regional lymph node metastasis.
M0 = No pleural, pericardial, or distant metastasis.
IIIB T4, N0, M0 T4 = Tumor with invasion into any of the following: aorta (ascending, arch, or descending), arch vessels, intrapericardial pulmonary artery, myocardium, trachea, esophagus.
N0 = No regional lymph node metastasis.
M0 = No pleural, pericardial, or distant metastasis.
Table 12. Definition of TNM Stages IVA and IVBa
Stage T Description
T = primary tumor; N = regional lymph node; M = distant metastasis.
aAdapted from AJCC: Thymus. In: Amin MB, Edge SB, Greene FL, et al., eds.: AJCC Cancer Staging Manual. 8th ed. New York, NY: Springer, 2017, pp. 423–9.
bInvolvement must be microscopically confirmed in pathological staging, if possible.
cT categories are defined by levels of invasion; they reflect the highest degree of invasion regardless of how many other (lower-level) structures are invaded. T1, level 1 structures: thymus, anterior mediastinal fat, mediastinal pleura; T2, level 2 structures: pericardium; T3, level 3 structures: lung, brachiocephalic vein, superior vena cava, phrenic nerve, chest wall, hilar pulmonary vessels; T4, level 4 structures: aorta (ascending, arch, or descending), arch vessels, intrapericardial pulmonary artery, myocardium, trachea, esophagus.
IVA Any T, N1, M0 TX = Primary tumor cannot be assessed.
T0 = No evidence of primary tumor.
T1 = Tumor encapsulated or extending into the mediastinal fat; may involve the mediastinal pleura.
–T1a = Tumor with no mediastinal pleura involvement.
–T1b = Tumor with direct invasion of mediastinal pleura.
T2 = Tumor with direct invasion of the pericardium (either partial or full thickness).
T3 = Tumor with direct invasion into any of the following: lung, brachiocephalic vein, superior vena cava, phrenic nerve, chest wall, or extrapericardial pulmonary artery or veins.
T4 = Tumor with invasion into any of the following: aorta (ascending, arch, or descending), arch vessels, intrapericardial pulmonary artery, myocardium, trachea, esophagus.
N1 = Metastasis in anterior (perithymic) lymph nodes.
M0 = No pleural, pericardial, or distant metastasis.
Any T, N0,1, M1a Any T = See descriptions (stage IVA) in this table.
N0 = No regional lymph node metastasis.
N1 = Metastasis in anterior (perithymic) lymph nodes.
M1a = Separate pleural or pericardial nodule(s).
IVB Any T, N2, M0, M1a Any T = See descriptions (stage IVA) in this table.
N2 = Metastasis in deep intrathoracic or cervical lymph nodes.
M0 = No pleural, pericardial, or distant metastasis.
M1a = Separate pleural or pericardial nodule(s).
Any T, Any N, M1b Any T = See descriptions (stage IVA) in this table.
NX = Regional lymph nodes cannot be assessed.
N0 = No regional lymph node metastasis.
N1 = Metastasis in anterior (perithymic) lymph nodes.
N2 = Metastasis in deep intrathoracic or cervical lymph nodes.
M1b = Pulmonary intraparenchymal nodule or distant organ metastasis.

When the Masaoka staging system was applied to a series of 85 surgically treated thymoma patients, its value in determining prognosis was confirmed, with 5-year survival rates of 96% for stage I disease, 86% for stage II disease, 69% for stage III disease, and 50% for stage IV disease.[ 1 ] In a large, retrospective study involving 273 patients with thymoma, 20-year survival rates (as defined by freedom from tumor death) according to the Masaoka staging system were reported to be 89% for stage I disease, 91% for stage II disease, 49% for stage III disease, and 0% for stage IV disease.[ 6 ]

The TNM staging system, applicable to thymoma and thymic carcinoma, is based on a large, global database of more than 10,000 subjects, as opposed to smaller series of fewer than 100 patients that were used to develop older staging systems. The TNM system also benefits from rigorous statistical analysis of a large pool of data and input from a multidisciplinary panel of experts. The rate of disease recurrence was 5% in patients with stage I disease, 18% for stage II disease, 32% for stage III disease, 59% for stage IVA disease, and 49% for stage IVB disease. The death rate was 7% in patients with stage I disease, 16% for stage II disease, 18% for stage III disease, 30% for stage IVA disease, and 33% for stage IVB disease.[ 5 ]

参考文献
  1. Masaoka A, Monden Y, Nakahara K, et al.: Follow-up study of thymomas with special reference to their clinical stages. Cancer 48 (11): 2485-92, 1981.[PUBMED Abstract]
  2. Koga K, Matsuno Y, Noguchi M, et al.: A review of 79 thymomas: modification of staging system and reappraisal of conventional division into invasive and non-invasive thymoma. Pathol Int 44 (5): 359-67, 1994.[PUBMED Abstract]
  3. Thymus. In: Amin MB, Edge SB, Greene FL, et al., eds.: AJCC Cancer Staging Manual. 8th ed. New York, NY: Springer, 2017, pp. 423–9.[PUBMED Abstract]
  4. Carter BW, Benveniste MF, Madan R, et al.: IASLC/ITMIG Staging System and Lymph Node Map for Thymic Epithelial Neoplasms. Radiographics 37 (3): 758-776, 2017 May-Jun.[PUBMED Abstract]
  5. Detterbeck FC, Stratton K, Giroux D, et al.: The IASLC/ITMIG Thymic Epithelial Tumors Staging Project: proposal for an evidence-based stage classification system for the forthcoming (8th) edition of the TNM classification of malignant tumors. J Thorac Oncol 9 (9 Suppl 2): S65-72, 2014.[PUBMED Abstract]
  6. Okumura M, Ohta M, Tateyama H, et al.: The World Health Organization histologic classification system reflects the oncologic behavior of thymoma: a clinical study of 273 patients. Cancer 94 (3): 624-32, 2002.[PUBMED Abstract]
Treatment Option Overview for Thymoma and Thymic Carcinoma

Standard primary treatment for patients with thymoma or thymic carcinoma is surgical resection with en bloc resection for invasive tumors, if possible.[ 1 ][ 2 ][ 3 ] Depending on tumor stage, multimodality treatment options—which include the use of radiation therapy and chemotherapy with or without surgery—may be used.[ 4 ][ 5 ] The optimal strategy for induction therapy, which minimizes operative morbidity and mortality and optimizes resectability rates and ultimately survival, remains unknown. A review of the management of thymic epithelial tumors has been published.[ 1 ]

13. Standard Treatment Options for Thymoma and Thymic Carcinoma
Standard Treatment Options
Stage I and II thymoma Surgery
Surgery with or without radiation therapy (PORT)
Stage III and IV thymoma (operable) Surgery followed by radiation therapy
Induction chemotherapy followed by surgery and radiation therapy
Stage III and IV thymoma (inoperable) Chemotherapy
Chemotherapy followed by radiation therapy
Chemotherapy followed by surgery (if operable) and radiation therapy
Thymic carcinoma (operable) Surgery (en bloc surgical resection) followed by postoperative radiation therapy with or without postoperative chemotherapy.
Thymic carcinoma (inoperable) Chemotherapy
Chemoradiation therapy
Chemotherapy followed by surgery (if operable) and radiation therapy
Recurrent thymoma and thymic carcinoma Chemotherapy
Biologic therapies
Surgery or radiation therapy in carefully selected cases
参考文献
  1. Girard N, Ruffini E, Marx A, et al.: Thymic epithelial tumours: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 26 (Suppl 5): v40-55, 2015.[PUBMED Abstract]
  2. Ruffini E, Filosso PL, Guerrera F, et al.: Optimal surgical approach to thymic malignancies: New trends challenging old dogmas. Lung Cancer 118: 161-170, 2018.[PUBMED Abstract]
  3. Cameron RB, Loehrer Sr, Marx A: Neoplasms of the mediastinum. In: DeVita VT Jr, Lawrence TS, Rosenberg SA, et al., eds.: DeVita, Hellman, and Rosenberg’s Cancer : Principles & Practice of Oncology. 11th ed. Philadelphia, Pa: Wolters Kluwer, 2019, pp 700-12.[PUBMED Abstract]
  4. Rimner A, Yao X, Huang J, et al.: Postoperative Radiation Therapy Is Associated with Longer Overall Survival in Completely Resected Stage II and III Thymoma-An Analysis of the International Thymic Malignancies Interest Group Retrospective Database. J Thorac Oncol 11 (10): 1785-92, 2016.[PUBMED Abstract]
  5. Rajan A, Giaccone G: Chemotherapy for thymic tumors: induction, consolidation, palliation. Thorac Surg Clin 21 (1): 107-14, viii, 2011.[PUBMED Abstract]
Treatment of Thymoma

For patients presenting with a mediastinal mass that is highly suspicious for an early-stage thymic epithelial tumor (TET) and is potentially completely resectable, surgical resection is the preferred initial treatment.[ 1 ] Under these circumstances, surgical resection serves as a diagnostic and therapeutic procedure. Complete resection of the tumor can be achieved in nearly all patients with stage I and stage II TETs.

Postoperative radiation therapy (PORT) is associated with survival benefit and is generally recommended for patients with stage II or stage III disease.[ 2 ] Patients with stage IVA disease are usually offered multimodality therapy consisting of induction chemotherapy followed by surgery (if the disease is considered resectable) and PORT.[ 3 ][ 4 ][ 5 ][ 6 ] Patients with stage IVB disease are treated with definitive chemotherapy.[ 7 ][ 8 ][ 9 ][ 9 ][ 10 ] Surgery and radiation therapy usually do not have a role as primary treatment modalities for advanced disease.

Stage I and Stage II Thymoma

Standard treatment options for stages I and II thymoma

Standard treatment options for stage I and stage II thymoma (operable disease) include the following:

  1. Surgery (stage I).
  2. Surgery with or without radiation therapy (PORT) (stage II).

Surgery (stage I)

Excellent long-term survival can be obtained after complete surgical excision for a pathologic stage I thymoma. There appears to be no benefit to adjuvant radiation therapy after complete resection of encapsulated noninvasive tumors.[ 1 ][ 11 ]

Surgery with or without radiation therapy (PORT) (stage II)

For patients with stage II thymomas with pathologically demonstrated capsular invasion, adjuvant radiation therapy after complete surgical excision has been considered a standard of care despite the lack of prospective clinical trials.[ 12 ][ 13 ] Most studies use 40 Gy to 70 Gy with a standard fractionation scheme (1.8–2.0 Gy per fraction).

The role and risks of adjuvant radiation therapy for patients with completely resected stage II thymomas need further study. To avoid the potential morbidity and costs associated with thoracic radiation, PORT may be reserved for stage II patients when adjacent organs are within a few millimeters or involve the surgical margin (close or positive surgical margins) as determined by both pathological and intraoperative findings.

Evidence (surgery followed by PORT):

  1. Data were obtained from a clinical study of 1,320 Japanese patients.[ 14 ] Patients with stage I thymoma were treated with surgery only, and patients with stage II thymoma underwent surgery and additional radiation therapy.
  2. Some, but not all, retrospective clinical studies show improved local control and survival with the addition of PORT.[ 2 ][ 14 ][ 15 ][ 16 ][ 17 ][Level of evidence: 3iiiDiv]
  3. Other retrospective studies have found no outcome difference in patients treated with or without PORT after complete resection of the thymic tumor.[ 18 ][ 19 ][ 20 ][ 21 ]

Current Clinical Trials

Use our advanced clinical trial search to find NCI-supported cancer clinical trials that are now enrolling patients. The search can be narrowed by location of the trial, type of treatment, name of the drug, and other criteria. General information about clinical trials is also available.

Stage III and Stage IV Thymoma

Treatment options for operable or potentially operable stages III and IV thymoma

Advances in imaging techniques have resulted in more accurate staging of TETs. However, on occasion, stage III thymoma may be difficult to identify before surgery, and invasion of adjacent mediastinal structures may be identified only at the time of surgery.

Surgical resection with curative intent should be considered for all patients deemed to have resectable stage III thymoma after the initial work-up. PORT is offered to all patients regardless of surgical margin status because it is associated with longer overall survival (OS).[ 2 ]

Combined-modality treatment consisting of induction chemotherapy followed by surgery and radiation therapy should be considered for all patients with unresectable stage III thymoma. The optimal strategy for induction therapy, which optimizes resectability rates and ultimately survival, is not defined. However, commonly used induction chemotherapy regimens include combinations of cisplatin, doxorubicin, and cyclophosphamide, or cisplatin and etoposide. Rates of response to induction chemotherapy ranged from 79% to 100%, with subsequent resectability rates of 36% to 69%.[ 3 ][ 4 ][ 5 ][ 6 ][ 7 ][ 22 ][ 23 ][ 24 ][ 25 ]

Treatment options for operable or potentially operable stage III and stage IV thymoma include the following:

  1. Surgery followed by radiation therapy (PORT).
  2. Induction chemotherapy followed by surgery and radiation therapy.

Evidence (treatment of stage III and IV operable or potentially operable thymoma):

  1. Data were obtained from a large clinical study of 1,320 Japanese patients.[ 14 ] Patients with stage III and stage IV thymoma underwent surgery and multimodality therapy with surgical resection followed by adjuvant therapy consisting of radiation therapy and/or chemotherapy.
  2. In a large retrospective study, 1,334 patients diagnosed with malignant thymoma and treated between 1973 and 2005 were identified in a Surveillance, Epidemiology, and End Results (SEER) database.[ 25 ]
  3. In a retrospective study, 476 patients with stage III thymoma who underwent surgical resection were identified using the SEER database. PORT was administered to 322 patients (67.6%).[ 26 ]
  4. Long-term survival rates following induction chemotherapy and surgery with or without radiation therapy and consolidation chemotherapy have ranged from 50% at 4 years, to 77% at 7 years, to 86% for stage III patients and 76% for stage IV patients at 10 years, in different published series.[ 5 ][ 22 ][ 23 ][ 27 ]
  5. Similar survival rates have been reported with preoperative radiation therapy without chemotherapy, particularly if great vessels are involved; results showed a 5-year OS rate of 77% and a 10-year OS rate of 59%.[ 28 ][ 29 ]

Treatment options for inoperable stages III and IV thymoma

Treatment options for patients with inoperable stage III and stage IV thymoma include the following:

  1. Chemotherapy.
  2. Chemotherapy followed by radiation therapy.
  3. Chemotherapy followed by surgery (if operable) and radiation therapy.

The role of surgical debulking for patients with either stage III or stage IVA disease is controversial. Phase II data suggest that prolonged survival can be accomplished with chemotherapy and radiation therapy alone in many patients who present with locally advanced or even metastatic thymoma.[ 24 ] The value of surgery may be questioned if complete or, at the very least, near-complete extirpation cannot be accomplished.

Evidence (treatment of stage III and IV inoperable thymoma):

  1. An intergroup trial conducted in the United States reported a predicted 5-year OS rate of 52% in 26 patients who received the PAC chemotherapy regimen (cisplatin, doxorubicin, cyclophosphamide) followed by radiation therapy without surgery.[ 24 ]
  2. In a series of 30 patients with stage IV or locally progressive recurrent tumor after radiation therapy, the PAC regimen was administered.[ 7 ][Level of evidence: 3iiiDiv]
  3. The ADOC regimen (doxorubicin, cisplatin, vincristine, cyclophosphamide) was administered to 37 patients.[ 8 ][Level of evidence: 3iiiDiv]
  4. A study of combined chemotherapy with cisplatin and etoposide reported the following:[ 30 ][Level of evidence: 3iiiDiv]
  5. Patients with invasive thymoma or thymic carcinoma were treated with four cycles of etoposide, ifosfamide, and cisplatin (VIP) at 3-week intervals.[ 9 ][Level of evidence: 3iiiDiv]
  6. A phase II study evaluated the activity of a combination of carboplatin and paclitaxel in 46 patients with unresectable TETs, including 21 patients with unresectable thymoma.[ 10 ][Level of evidence: 3iiiDiv]
参考文献
  1. Maggi G, Casadio C, Cavallo A, et al.: Thymoma: results of 241 operated cases. Ann Thorac Surg 51 (1): 152-6, 1991.[PUBMED Abstract]
  2. Rimner A, Yao X, Huang J, et al.: Postoperative Radiation Therapy Is Associated with Longer Overall Survival in Completely Resected Stage II and III Thymoma-An Analysis of the International Thymic Malignancies Interest Group Retrospective Database. J Thorac Oncol 11 (10): 1785-92, 2016.[PUBMED Abstract]
  3. Macchiarini P, Chella A, Ducci F, et al.: Neoadjuvant chemotherapy, surgery, and postoperative radiation therapy for invasive thymoma. Cancer 68 (4): 706-13, 1991.[PUBMED Abstract]
  4. Rea F, Sartori F, Loy M, et al.: Chemotherapy and operation for invasive thymoma. J Thorac Cardiovasc Surg 106 (3): 543-9, 1993.[PUBMED Abstract]
  5. Kim ES, Putnam JB, Komaki R, et al.: Phase II study of a multidisciplinary approach with induction chemotherapy, followed by surgical resection, radiation therapy, and consolidation chemotherapy for unresectable malignant thymomas: final report. Lung Cancer 44 (3): 369-79, 2004.[PUBMED Abstract]
  6. Yokoi K, Matsuguma H, Nakahara R, et al.: Multidisciplinary treatment for advanced invasive thymoma with cisplatin, doxorubicin, and methylprednisolone. J Thorac Oncol 2 (1): 73-8, 2007.[PUBMED Abstract]
  7. Loehrer PJ, Kim K, Aisner SC, et al.: Cisplatin plus doxorubicin plus cyclophosphamide in metastatic or recurrent thymoma: final results of an intergroup trial. The Eastern Cooperative Oncology Group, Southwest Oncology Group, and Southeastern Cancer Study Group. J Clin Oncol 12 (6): 1164-8, 1994.[PUBMED Abstract]
  8. Fornasiero A, Daniele O, Ghiotto C, et al.: Chemotherapy for invasive thymoma. A 13-year experience. Cancer 68 (1): 30-3, 1991.[PUBMED Abstract]
  9. Loehrer PJ, Jiroutek M, Aisner S, et al.: Combined etoposide, ifosfamide, and cisplatin in the treatment of patients with advanced thymoma and thymic carcinoma: an intergroup trial. Cancer 91 (11): 2010-5, 2001.[PUBMED Abstract]
  10. Lemma GL, Lee JW, Aisner SC, et al.: Phase II study of carboplatin and paclitaxel in advanced thymoma and thymic carcinoma. J Clin Oncol 29 (15): 2060-5, 2011.[PUBMED Abstract]
  11. Masaoka A, Monden Y, Nakahara K, et al.: Follow-up study of thymomas with special reference to their clinical stages. Cancer 48 (11): 2485-92, 1981.[PUBMED Abstract]
  12. Pollack A, Komaki R, Cox JD, et al.: Thymoma: treatment and prognosis. Int J Radiat Oncol Biol Phys 23 (5): 1037-43, 1992.[PUBMED Abstract]
  13. Ogawa K, Uno T, Toita T, et al.: Postoperative radiotherapy for patients with completely resected thymoma: a multi-institutional, retrospective review of 103 patients. Cancer 94 (5): 1405-13, 2002.[PUBMED Abstract]
  14. Kondo K, Monden Y: Therapy for thymic epithelial tumors: a clinical study of 1,320 patients from Japan. Ann Thorac Surg 76 (3): 878-84; discussion 884-5, 2003.[PUBMED Abstract]
  15. Ariaratnam LS, Kalnicki S, Mincer F, et al.: The management of malignant thymoma with radiation therapy. Int J Radiat Oncol Biol Phys 5 (1): 77-80, 1979.[PUBMED Abstract]
  16. Penn CR, Hope-Stone HF: The role of radiotherapy in the management of malignant thymoma. Br J Surg 59 (7): 533-9, 1972.[PUBMED Abstract]
  17. Curran WJ, Kornstein MJ, Brooks JJ, et al.: Invasive thymoma: the role of mediastinal irradiation following complete or incomplete surgical resection. J Clin Oncol 6 (11): 1722-7, 1988.[PUBMED Abstract]
  18. Mangi AA, Wright CD, Allan JS, et al.: Adjuvant radiation therapy for stage II thymoma. Ann Thorac Surg 74 (4): 1033-7, 2002.[PUBMED Abstract]
  19. Singhal S, Shrager JB, Rosenthal DI, et al.: Comparison of stages I-II thymoma treated by complete resection with or without adjuvant radiation. Ann Thorac Surg 76 (5): 1635-41; discussion 1641-2, 2003.[PUBMED Abstract]
  20. Thomas CR, Wright CD, Loehrer PJ: Thymoma: state of the art. J Clin Oncol 17 (7): 2280-9, 1999.[PUBMED Abstract]
  21. Berman AT, Litzky L, Livolsi V, et al.: Adjuvant radiotherapy for completely resected stage 2 thymoma. Cancer 117 (15): 3502-8, 2011.[PUBMED Abstract]
  22. Berruti A, Borasio P, Gerbino A, et al.: Primary chemotherapy with adriamycin, cisplatin, vincristine and cyclophosphamide in locally advanced thymomas: a single institution experience. Br J Cancer 81 (5): 841-5, 1999.[PUBMED Abstract]
  23. Shin DM, Walsh GL, Komaki R, et al.: A multidisciplinary approach to therapy for unresectable malignant thymoma. Ann Intern Med 129 (2): 100-4, 1998.[PUBMED Abstract]
  24. Loehrer PJ, Chen M, Kim K, et al.: Cisplatin, doxorubicin, and cyclophosphamide plus thoracic radiation therapy for limited-stage unresectable thymoma: an intergroup trial. J Clin Oncol 15 (9): 3093-9, 1997.[PUBMED Abstract]
  25. Fernandes AT, Shinohara ET, Guo M, et al.: The role of radiation therapy in malignant thymoma: a Surveillance, Epidemiology, and End Results database analysis. J Thorac Oncol 5 (9): 1454-60, 2010.[PUBMED Abstract]
  26. Weksler B, Shende M, Nason KS, et al.: The role of adjuvant radiation therapy for resected stage III thymoma: a population-based study. Ann Thorac Surg 93 (6): 1822-8; discussion 1828-9, 2012.[PUBMED Abstract]
  27. Lucchi M, Melfi F, Dini P, et al.: Neoadjuvant chemotherapy for stage III and IVA thymomas: a single-institution experience with a long follow-up. J Thorac Oncol 1 (4): 308-13, 2006.[PUBMED Abstract]
  28. Yagi K, Hirata T, Fukuse T, et al.: Surgical treatment for invasive thymoma, especially when the superior vena cava is invaded. Ann Thorac Surg 61 (2): 521-4, 1996.[PUBMED Abstract]
  29. Akaogi E, Ohara K, Mitsui K, et al.: Preoperative radiotherapy and surgery for advanced thymoma with invasion to the great vessels. J Surg Oncol 63 (1): 17-22, 1996.[PUBMED Abstract]
  30. Giaccone G, Ardizzoni A, Kirkpatrick A, et al.: Cisplatin and etoposide combination chemotherapy for locally advanced or metastatic thymoma. A phase II study of the European Organization for Research and Treatment of Cancer Lung Cancer Cooperative Group. J Clin Oncol 14 (3): 814-20, 1996.[PUBMED Abstract]
Treatment of Thymic Carcinoma

The optimal treatment of thymic carcinoma remains undefined because of its rarity. For patients with clearly resectable well-defined disease, surgical resection is often the initial therapeutic intervention. For patients with clinically borderline or frankly unresectable lesions, neoadjuvant (preoperative) chemotherapy, thoracic radiation therapy, or both, have been given.[ 1 ] Patients presenting with locally advanced disease are carefully evaluated and undergo multimodality therapy. Patients with poor performance status and high associated operative risks are generally not considered for these types of aggressive treatments. Patients with metastatic disease may respond to combination chemotherapy.

Standard Treatment Options for Thymic Carcinoma

Standard treatment options for patients with operable thymic carcinoma include the following:[ 2 ]

  1. Surgery (en bloc surgical resection) followed by postoperative radiation therapy (PORT) with or without postoperative chemotherapy.

Standard treatment options for patients with inoperable thymic carcinoma (stage III and stage IV with vena caval obstruction, pleural involvement, pericardial implants, etc.) include the following:

  1. Chemotherapy.
  2. Chemoradiation therapy.
  3. Chemotherapy followed by surgery (if operable) and radiation therapy.

In most published studies, surgery has been followed by adjuvant radiation therapy.[ 3 ][ 4 ] A prescriptive dose range has yet to be identified. Most studies use 40 Gy to 70 Gy with a standard fractionation scheme (1.8–2.0 Gy per fraction).

Evidence (surgery followed by PORT with or without postoperative chemotherapy):

  1. In the largest series reported, data were obtained from a clinical study of 1,320 Japanese patients.[ 5 ] Patients with thymic carcinoma were treated with PORT or chemotherapy.
  2. A multi-institutional retrospective outcome analysis of 186 patients with thymic carcinoma has been reported.[ 5 ]

The results from these studies call into question conventional thinking regarding the efficacy of an aggressive multimodality approach including debulking, radiation therapy, and cisplatin-based chemotherapy.[ 6 ][ 7 ][ 8 ] While other studies support the addition of adjuvant radiation therapy and chemotherapy, optimum treatment regimens are undetermined.

Chemotherapy is the primary treatment modality for patients with inoperable thymic carcinoma. Most regimens used are similar to those used to treat thymoma and include a platinum compound with or without an anthracycline (PAC [cisplatin, doxorubicin, cyclophosphamide], VIP [etoposide, ifosfamide, and cisplatin], ADOC [doxorubicin, cisplatin, vincristine, cyclophosphamide], cisplatin/etoposide, carboplatin/paclitaxel).[ 1 ][ 9 ][ 10 ][ 11 ][ 12 ][ 13 ][ 14 ]

Evidence (chemotherapy):

  1. A phase II study evaluated the activity of a combination of carboplatin and paclitaxel in 46 patients with unresectable thymic epithelial tumors, including 23 patients with unresectable thymic carcinoma.[ 14 ][Level of evidence: 3iiiDiv]
  2. VIP was utilized in a prospective North American Intergroup trial.[ 11 ]

Current Clinical Trials

Use our advanced clinical trial search to find NCI-supported cancer clinical trials that are now enrolling patients. The search can be narrowed by location of the trial, type of treatment, name of the drug, and other criteria. General information about clinical trials is also available.

参考文献
  1. Koizumi T, Takabayashi Y, Yamagishi S, et al.: Chemotherapy for advanced thymic carcinoma: clinical response to cisplatin, doxorubicin, vincristine, and cyclophosphamide (ADOC chemotherapy). Am J Clin Oncol 25 (3): 266-8, 2002.[PUBMED Abstract]
  2. Hsu HC, Huang EY, Wang CJ, et al.: Postoperative radiotherapy in thymic carcinoma: treatment results and prognostic factors. Int J Radiat Oncol Biol Phys 52 (3): 801-5, 2002.[PUBMED Abstract]
  3. Omasa M, Date H, Sozu T, et al.: Postoperative radiotherapy is effective for thymic carcinoma but not for thymoma in stage II and III thymic epithelial tumors: the Japanese Association for Research on the Thymus Database Study. Cancer 121 (7): 1008-16, 2015.[PUBMED Abstract]
  4. Ahmad U, Yao X, Detterbeck F, et al.: Thymic carcinoma outcomes and prognosis: results of an international analysis. J Thorac Cardiovasc Surg 149 (1): 95-100, 101.e1-2, 2015.[PUBMED Abstract]
  5. Kondo K, Monden Y: Therapy for thymic epithelial tumors: a clinical study of 1,320 patients from Japan. Ann Thorac Surg 76 (3): 878-84; discussion 884-5, 2003.[PUBMED Abstract]
  6. Ogawa K, Toita T, Uno T, et al.: Treatment and prognosis of thymic carcinoma: a retrospective analysis of 40 cases. Cancer 94 (12): 3115-9, 2002.[PUBMED Abstract]
  7. Greene MA, Malias MA: Aggressive multimodality treatment of invasive thymic carcinoma. J Thorac Cardiovasc Surg 125 (2): 434-6, 2003.[PUBMED Abstract]
  8. Lucchi M, Mussi A, Ambrogi M, et al.: Thymic carcinoma: a report of 13 cases. Eur J Surg Oncol 27 (7): 636-40, 2001.[PUBMED Abstract]
  9. Weide LG, Ulbright TM, Loehrer PJ, et al.: Thymic carcinoma. A distinct clinical entity responsive to chemotherapy. Cancer 71 (4): 1219-23, 1993.[PUBMED Abstract]
  10. Loehrer PJ, Kim K, Aisner SC, et al.: Cisplatin plus doxorubicin plus cyclophosphamide in metastatic or recurrent thymoma: final results of an intergroup trial. The Eastern Cooperative Oncology Group, Southwest Oncology Group, and Southeastern Cancer Study Group. J Clin Oncol 12 (6): 1164-8, 1994.[PUBMED Abstract]
  11. Loehrer PJ, Jiroutek M, Aisner S, et al.: Combined etoposide, ifosfamide, and cisplatin in the treatment of patients with advanced thymoma and thymic carcinoma: an intergroup trial. Cancer 91 (11): 2010-5, 2001.[PUBMED Abstract]
  12. Fornasiero A, Daniele O, Ghiotto C, et al.: Chemotherapy for invasive thymoma. A 13-year experience. Cancer 68 (1): 30-3, 1991.[PUBMED Abstract]
  13. Giaccone G, Ardizzoni A, Kirkpatrick A, et al.: Cisplatin and etoposide combination chemotherapy for locally advanced or metastatic thymoma. A phase II study of the European Organization for Research and Treatment of Cancer Lung Cancer Cooperative Group. J Clin Oncol 14 (3): 814-20, 1996.[PUBMED Abstract]
  14. Lemma GL, Lee JW, Aisner SC, et al.: Phase II study of carboplatin and paclitaxel in advanced thymoma and thymic carcinoma. J Clin Oncol 29 (15): 2060-5, 2011.[PUBMED Abstract]
Recurrent Thymoma and Thymic Carcinoma

Standard Treatment Options for Recurrent Thymoma and Thymic Carcinoma

Standard treatment options for recurrent thymoma and thymic carcinoma include the following:

Chemotherapy

A number of studies have demonstrated that certain chemotherapy drugs can induce tumor responses as single-agent or combination therapy. These drugs include pemetrexed, gemcitabine, taxanes, capecitabine, or 5-fluorouracil and etoposide. In general, higher response rates have been reported with combinations, however, no randomized trials have been conducted. In most cases of inoperable disease recurrence, single-agent systemic therapy is preferred. Combination chemotherapy can be considered in selected cases where patients have demonstrated a good response previously, have had a long recurrence-free interval and good performance status, and in the case of anthracycline-containing regimen, have not received high cumulative doses previously, which can jeopardize safety, especially in relation to cardiac toxicity.[ 1 ]

Evidence (single-agent chemotherapy):

  1. A phase II trial of pemetrexed (500 mg/m2) was conducted in 27 patients with recurrent thymic epithelial tumors (TETs) (16 patients) and recurrent thymic carcinoma (11 patients).[ 2 ]
  2. Six of 16 patients achieved objective responses to octreotide (1.5 mg qd SQ) associated with prednisone (0.6 mg/kg qd PO for 3 months, 0.2 mg/kg qd PO during follow-up).[ 3 ]

Evidence (combination chemotherapy):

  1. Thirty patients (22 patients with recurrent thymoma and 8 patients with thymic carcinoma) were enrolled in a phase II trial and treated with capecitabine (650 mg/m2 twice daily on days 1–14) and gemcitabine (1,000 mg/m2 on days 1 and 8 every 3 weeks).[ 4 ]

Biologic therapies

Octreotide with or without prednisone may induce responses in patients with octreotide scan–positive thymoma. Objective responses have also been observed with sunitinib and everolimus in patients with recurrent TETs.

Octreotide with or without prednisone

Evidence (octreotide with or without prednisone):

  1. In one study, six of 16 patients achieved objective responses to octreotide (1.5 mg qd SQ) associated with prednisone (0.6 mg/kg qd PO for 3 months, 0.2 mg/kg qd PO during follow-up).[ 3 ]
  2. In a study of octreotide with or without prednisone, two complete responses (5.3%) and ten partial responses (25%) were observed among 42 patients.[ 5 ]

Sunitinib

Evidence (sunitinib):

  1. Forty-one patients with recurrent TETs (25 thymic carcinoma, 16 thymoma) were enrolled in a phase II trial and treated with sunitinib at a dose of 50 mg per day administered in 6-week cycles (4 weeks on treatment followed by a 2-week break).[ 6 ][Level of evidence: 3iiiDiv]

Everolimus

Evidence (everolimus):

  1. Fifty-one patients with recurrent TETs (32 with thymoma and 19 with thymic carcinoma) were enrolled in a phase II trial and treated with oral everolimus at a dose of 10 mg per day.[ 7 ][Level of evidence: 3iiiDiv]

Surgery

Surgical resection may be repeated, particularly for local recurrences and, in some cases, pleural and pericardial implants. Patients with recurrent thymomas who undergo repeat resection of recurrent disease may have prolonged survival when complete resection is attained.[ 8 ] However, only a minority of patients may be candidates for resection.

Evidence (surgery):

  1. In a review of 395 patients who underwent resections for TETs, 67 had tumor recurrence and 22 underwent a repeat resection procedure.[ 9 ]
  2. In another study, 30 of 266 patients initially treated by total resection of the tumor had a recurrence; in all 30 patients, surgical resection was attempted.[ 10 ] Complete resection of the recurrent tumor was obtained in ten cases.

Of note, patients in these series may have received chemotherapy and/or radiation therapy in addition to surgery.

Radiation therapy

Postoperative radiation therapy has been used for patients with incomplete resections and has been employed in selected patients after complete resections of recurrent thymomas.[ 8 ] Radiation therapy is also indicated for palliation of symptoms such as pain due to chest wall invasion, and superior vena cava syndrome.

Treatment Options Under Clinical Evaluation for Recurrent Thymoma and Thymic Carcinoma

Pembrolizumab (anti-programmed death ligand 1 antibody) has been evaluated in patients with recurrent TETs.

  1. Thirty-three patients with refractory or relapsed TETs (26 with thymic carcinoma, 7 with thymoma) were enrolled in a phase II trial of pembrolizumab.[ 11 ]
  2. Forty-one patients with recurrent thymic carcinoma were enrolled in a single-arm phase II study of pembrolizumab.[ 12 ]

Immune checkpoint inhibitor therapy is under clinical evaluation and should be used in the context of a clinical trial.

Current Clinical Trials

Use our advanced clinical trial search to find NCI-supported cancer clinical trials that are now enrolling patients. The search can be narrowed by location of the trial, type of treatment, name of the drug, and other criteria. General information about clinical trials is also available.

参考文献
  1. Girard N, Ruffini E, Marx A, et al.: Thymic epithelial tumours: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 26 (Suppl 5): v40-55, 2015.[PUBMED Abstract]
  2. Gbolahan OB, Porter RF, Salter JT, et al.: A Phase II Study of Pemetrexed in Patients with Recurrent Thymoma and Thymic Carcinoma. J Thorac Oncol 13 (12): 1940-1948, 2018.[PUBMED Abstract]
  3. Palmieri G, Montella L, Martignetti A, et al.: Somatostatin analogs and prednisone in advanced refractory thymic tumors. Cancer 94 (5): 1414-20, 2002.[PUBMED Abstract]
  4. Palmieri G, Buonerba C, Ottaviano M, et al.: Capecitabine plus gemcitabine in thymic epithelial tumors: final analysis of a Phase II trial. Future Oncol 10 (14): 2141-7, 2014.[PUBMED Abstract]
  5. Loehrer PJ, Wang W, Johnson DH, et al.: Octreotide alone or with prednisone in patients with advanced thymoma and thymic carcinoma: an Eastern Cooperative Oncology Group phase II trial. J Clin Oncol 22 (2): 293-9, 2004.[PUBMED Abstract]
  6. Thomas A, Rajan A, Berman A, et al.: Sunitinib in patients with chemotherapy-refractory thymoma and thymic carcinoma: an open-label phase 2 trial. Lancet Oncol 16 (2): 177-86, 2015.[PUBMED Abstract]
  7. Zucali PA, De Pas T, Palmieri G, et al.: Phase II Study of Everolimus in Patients With Thymoma and Thymic Carcinoma Previously Treated With Cisplatin-Based Chemotherapy. J Clin Oncol 36 (4): 342-349, 2018.[PUBMED Abstract]
  8. Urgesi A, Monetti U, Rossi G, et al.: Aggressive treatment of intrathoracic recurrences of thymoma. Radiother Oncol 24 (4): 221-5, 1992.[PUBMED Abstract]
  9. Okumura M, Shiono H, Inoue M, et al.: Outcome of surgical treatment for recurrent thymic epithelial tumors with reference to world health organization histologic classification system. J Surg Oncol 95 (1): 40-4, 2007.[PUBMED Abstract]
  10. Ruffini E, Mancuso M, Oliaro A, et al.: Recurrence of thymoma: analysis of clinicopathologic features, treatment, and outcome. J Thorac Cardiovasc Surg 113 (1): 55-63, 1997.[PUBMED Abstract]
  11. Cho J, Kim HS, Ku BM, et al.: Pembrolizumab for Patients With Refractory or Relapsed Thymic Epithelial Tumor: An Open-Label Phase II Trial. J Clin Oncol 37 (24): 2162-2170, 2019.[PUBMED Abstract]
  12. Giaccone G, Kim C, Thompson J, et al.: Pembrolizumab in patients with thymic carcinoma: a single-arm, single-centre, phase 2 study. Lancet Oncol 19 (3): 347-355, 2018.[PUBMED Abstract]
Changes to This Summary (05/14/2020)

The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above.

Editorial changes were made to this summary.

This summary is written and maintained by the PDQ Adult Treatment Editorial Board, which is editorially independent of NCI. The summary reflects an independent review of the literature and does not represent a policy statement of NCI or NIH. More information about summary policies and the role of the PDQ Editorial Boards in maintaining the PDQ summaries can be found on the About This PDQ Summary and PDQ® - NCI's Comprehensive Cancer Database pages.

About This PDQ Summary

Purpose of This Summary

This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the treatment of adult thymoma and thymic carcinoma. It is intended as a resource to inform and assist clinicians who care for cancer patients. It does not provide formal guidelines or recommendations for making health care decisions.

Reviewers and Updates

This summary is reviewed regularly and updated as necessary by the PDQ Adult Treatment Editorial Board, which is editorially independent of the National Cancer Institute (NCI). The summary reflects an independent review of the literature and does not represent a policy statement of NCI or the National Institutes of Health (NIH).

Board members review recently published articles each month to determine whether an article should:

Changes to the summaries are made through a consensus process in which Board members evaluate the strength of the evidence in the published articles and determine how the article should be included in the summary.

Any comments or questions about the summary content should be submitted to Cancer.gov through the NCI website's Email Us. Do not contact the individual Board Members with questions or comments about the summaries. Board members will not respond to individual inquiries.

Levels of Evidence

Some of the reference citations in this summary are accompanied by a level-of-evidence designation. These designations are intended to help readers assess the strength of the evidence supporting the use of specific interventions or approaches. The PDQ Adult Treatment Editorial Board uses a formal evidence ranking system in developing its level-of-evidence designations.

Permission to Use This Summary

PDQ is a registered trademark. Although the content of PDQ documents can be used freely as text, it cannot be identified as an NCI PDQ cancer information summary unless it is presented in its entirety and is regularly updated. However, an author would be permitted to write a sentence such as “NCI’s PDQ cancer information summary about breast cancer prevention states the risks succinctly: [include excerpt from the summary].”

The preferred citation for this PDQ summary is:

PDQ® Adult Treatment Editorial Board. PDQ Thymoma and Thymic Carcinoma Treatment (Adult). Bethesda, MD: National Cancer Institute. Updated <MM/DD/YYYY>. Available at: https://www.cancer.gov/types/thymoma/hp/thymoma-treatment-pdq. Accessed <MM/DD/YYYY>. [PMID: 26389476]

Images in this summary are used with permission of the author(s), artist, and/or publisher for use within the PDQ summaries only. Permission to use images outside the context of PDQ information must be obtained from the owner(s) and cannot be granted by the National Cancer Institute. Information about using the illustrations in this summary, along with many other cancer-related images, is available in Visuals Online, a collection of over 2,000 scientific images.

Disclaimer

Based on the strength of the available evidence, treatment options may be described as either “standard” or “under clinical evaluation.” These classifications should not be used as a basis for insurance reimbursement determinations. More information on insurance coverage is available on Cancer.gov on the Managing Cancer Care page.

Contact Us

More information about contacting us or receiving help with the Cancer.gov website can be found on our Contact Us for Help page. Questions can also be submitted to Cancer.gov through the website’s Email Us.