Overview Masses in the anterior mediastinum include neoplasms (e.g., thymomas, lymphomas, thymic carcinomas, thymic carcinoids, thymolipomas, germ cell tumors, parathyroid adenomas) or nonneoplastic conditions (e.g., intrathoracic goiter, thymic cysts, lymphangiomas, aortic aneurysms).1,2 Thymomas are the most common tumor in the anterior mediastinum.1,3,4 Many mediastinal masses are benign, especially those occurring in asymptomatic patients; however, symptomatic patients often have malignant mediastinal lesions. These guidelines outline the evaluation, treatment, and management of thymomas and thymic carcinomas (see Thymic Masses, opposite column). The WHO histologic classification system can be used to distinguish among thymomas, thymic carcinomas, and thymic carcinoids.3 Lymphomas typically manifest as generalized disease but can also be primary anterior mediastinal lesions (i.e., nodular sclerosing Hodgkin disease and non-Hodgkin's lymphomas [large B-cell lymphoma and lymphoblastic lymphoma]); patients typically have lymphadenopathy [see the NCCN Clinical Practice Guidelines in Oncology {NCCN Guidelines} for Non-Hodgkin's Lymphomas and Hodgkin Lymphoma].2,5 Thymic carcinoids are rare tumors that are discussed in the NCCN Guidelines for Neuroendocrine Tumors. Teratomas are discussed in the NCCN Guidelines for Testicular Cancer. (To view the most recent version of these guidelines, visit the NCCN Web site at www.NCCN.org.) Thymic Masses All patients with a mediastinal mass should undergo studies to determine the type of mass and extent of disease; these tests should include chest CT with contrast, fludeoxyglucose (FDG)–PET, radiolabeled octreotide scan (optional), complete blood cell counts, and platelets. Pulmonary function tests and MRI of the chest can also be done if clinically indicated. On CT, thymoma can look like malignant mesothelioma; however,...

Overview

Masses in the anterior mediastinum include neoplasms (e.g., thymomas, lymphomas, thymic carcinomas, thymic carcinoids, thymolipomas, germ cell tumors, parathyroid adenomas) or nonneoplastic conditions (e.g., intrathoracic goiter, thymic cysts, lymphangiomas, aortic aneurysms).1,2 Thymomas are the most common tumor in the anterior mediastinum.1,3,4 Many mediastinal masses are benign, especially those occurring in asymptomatic patients; however, symptomatic patients often have malignant mediastinal lesions. These guidelines outline the evaluation, treatment, and management of thymomas and thymic carcinomas (see Thymic Masses, opposite column).

The WHO histologic classification system can be used to distinguish among thymomas, thymic carcinomas, and thymic carcinoids.3 Lymphomas typically manifest as generalized disease but can also be primary anterior mediastinal lesions (i.e., nodular sclerosing Hodgkin disease and non-Hodgkin's lymphomas [large B-cell lymphoma and lymphoblastic lymphoma]); patients typically have lymphadenopathy [see the NCCN Clinical Practice Guidelines in Oncology {NCCN Guidelines} for Non-Hodgkin's Lymphomas and Hodgkin Lymphoma].2,5 Thymic carcinoids are rare tumors that are discussed in the NCCN Guidelines for Neuroendocrine Tumors. Teratomas are discussed in the NCCN Guidelines for Testicular Cancer. (To view the most recent version of these guidelines, visit the NCCN Web site at www.NCCN.org.)

Thymic Masses

All patients with a mediastinal mass should undergo studies to determine the type of mass and extent of disease; these tests should include chest CT with contrast, fludeoxyglucose (FDG)–PET, radiolabeled octreotide scan (optional), complete blood cell counts, and platelets. Pulmonary function tests and MRI of the chest can also be done if clinically indicated. On CT, thymoma can look like malignant mesothelioma; however, pleural effusion does not typically occur with thymoma. Alpha-fetoprotein (AFP) and β–human chorionic gonadotropin (β-HCG) levels should be measured (if appropriate) to rule out germ cell tumors (see page 1304). Thyroid-stimulating hormone (TSH), triiodothyronine (T3), and thyroxine (T4) levels should also be measured, as clinically indicated, to rule out mediastinal goiter.

F1NCCN Clinical Practice Guidelines in Oncology: Thymic Malignancies

Version 2.2010, 02-23-10 ©2010 National Comprehensive Cancer Network, Inc. All rights reserved. These guidelines and this illustration may not be reproduced in any form without the express written permission of NCCN.

Citation: Journal of the National Comprehensive Cancer Network J Natl Compr Canc Netw 8, 11; 10.6004/jnccn.2010.0096

F2NCCN Clinical Practice Guidelines in Oncology: Thymic Malignancies

Version 2.2010, 02-23-10 ©2010 National Comprehensive Cancer Network, Inc. All rights reserved. These guidelines and this illustration may not be reproduced in any form without the express written permission of NCCN.

Citation: Journal of the National Comprehensive Cancer Network J Natl Compr Canc Netw 8, 11; 10.6004/jnccn.2010.0096

F3NCCN Clinical Practice Guidelines in Oncology: Thymic Malignancies

Version 2.2010, 02-23-10 ©2010 National Comprehensive Cancer Network, Inc. All rights reserved. These guidelines and this illustration may not be reproduced in any form without the express written permission of NCCN.

Citation: Journal of the National Comprehensive Cancer Network J Natl Compr Canc Netw 8, 11; 10.6004/jnccn.2010.0096

F4NCCN Clinical Practice Guidelines in Oncology: Thymic Malignancies

Version 2.2010, 02-23-10 ©2010 National Comprehensive Cancer Network, Inc. All rights reserved. These guidelines and this illustration may not be reproduced in any form without the express written permission of NCCN.

Citation: Journal of the National Comprehensive Cancer Network J Natl Compr Canc Netw 8, 11; 10.6004/jnccn.2010.0096

Thymomas

Thymomas typically occur in adults older than 40 years, and are rare in children or adolescents. Although some patients are asymptomatic, others present with chest pain, cough, or dyspnea. Thymomas are usually encapsulated. Some clinicians believe that surgical biopsy should be avoided if a resectable thymoma is strongly suspected based on clinical and radiologic features, and that a transpleural approach should be avoided during biopsy of a possible thymoma (category 2B for both). However, others feel that development of pleural metastases is most likely not the result of biopsies, because many patients who have never been biopsied have pleural disease at diagnosis. Total thymectomy and complete surgical excision are generally appropriate for most patients.68 Before surgery, all patients should be evaluated by radiation oncologists, surgeons, medical oncologists, diagnostic imaging specialists, and pulmonologists to determine the optimal plan of care.

Although thymomas can be locally invasive (pleura, lung), they rarely spread to regional lymph nodes or distant sites. The Masaoka staging system is useful for managing patients and determining prognosis (available online, in these guidelines, at www.NCCN.org [ST1]).911 Patients with stage I–III thymomas have a 5-year survival rate of approximately 70% compared with 50% for those with stage IV disease.12,13

For incompletely resected thymomas, postoperative radiation therapy (RT) is recommended (see page 1306). Note that extensive elective nodal radiation is not recommended, because thymomas do not typically metastasize to regional lymph nodes.14 CT-based planning is highly recommended (see pages 1309 and 1310). RT should be given using 3-dimensional conformal technique to reduce surrounding normal tissue damage (e.g., heart, lungs, esophagus, spinal cord). Use of intensity-modulated RT (IMRT) may further improve the dose distribution and may decrease the dose to the normal tissue. However, if IMRT is applied, the American Society for Radiation Oncology (ASTRO) IMRT guidelines should be followed strictly (http://www.astro.org/Research/ResearchHighlights/documents/Imrt.pdf). In addition to following the normal tissue constraints recommendation (see Principles of Radiation Therapy in the NCCN Guidelines for Non–Small Cell Lung Cancer, available at www.NCCN.org), special attention should be paid to minimizing the dose volumes to all the normal structures (see NCCN Guidelines for Non–Small Cell Lung Cancer, available at www.NCCN.org).15,16 Because these patients are younger and usually long-term survivors, the total dose to the heart should be limited to 30 Gy or less.

A definitive total dose of 60 to 70 Gy is given to patients with unresectable disease. For adjuvant treatment, a total dose of 45 to 50 Gy is used for clear or close margins; a total dose of 54 Gy is used for microscopically positive resection margins (see pages 1309 and 1310). However, a total dose of 60 Gy or more (1.8–2.0 Gy per daily fraction) is given for patients with gross residual disease after surgery.17,18

Postoperative RT can be considered in some higher-risk patients after an R0 resection, although this is a category 2B recommendation (see page 1306).1922 Patients with stage III (with macroscopic invasion into neighboring organs) thymoma or those with thymic carcinoma have higher risks of recurrent disease, and therefore postoperative radiation can be used to maximize local control. Growing evidence shows that patients with stage II thymoma may not benefit from postoperative radiation. For advanced disease, chemotherapy with (or without) RT is recommended (see page 1311).2232 Although 6 different combination regimens are provided, cisplatin/doxorubicin-based regimens seem to yield the best outcomes. For patients who have complete resection, surveillance should include annual chest CT. Given the risk of later recurrence for thymoma, this surveillance should continue for at least 10 years.

Because approximately 30% to 50% of patients with thymomas have myasthenia gravis, patients should be evaluated for this disease. Before any surgical procedure, all patients suspected of having thymomas (even those without symptoms) should have their serum antiacetylcholine receptor antibody levels measured to determine whether they have myasthenia gravis to avoid respiratory failure during surgery. In patients who have myasthenia gravis, the disease should be medically controlled before surgical resection is performed (see page 1308).33,34 Less frequently, patients may have hypogammaglobulinemia and red cell aplasia.

During thymectomy, the pleural surfaces should be examined for pleural metastases. In some cases, resection of pleural metastases to achieve complete gross resection may be appropriate.35 Minimally invasive procedures are not routinely recommended because of lack of long-term data.

Thymic Carcinomas

Thymic carcinomas are rare aggressive tumors that often metastasize to regional lymph nodes and distant sites; thus, they have a worse prognosis than thymomas (5-year survival rates, 20%–30%).1,2,36,37 These tumors can be distinguished from thymomas because of their malignant histologic features.3 However, thymic carcinomas should be differentiated from primary lung malignancies that metastasize to the thymus, which can be similar histologically. Thymic carcinomas often cause pericardial and pleural effusions. The Masaoka staging system can also be used to stage thymic carcinomas, although this is controversial (available online, in these guidelines, at www.NCCN.org [ST1]).38

After resection of thymic carcinomas, postoperative management includes RT with (or without) chemotherapy, depending on the completeness of resection (see page 1306). For unresectable or metastatic thymic carcinomas, patients should undergo chemotherapy with (or without) RT.31,3945

Individual Disclosures for the NCCN Thymic Malignancies Panel

T1

NCCN Clinical Practice Guidelines in Oncology for Thymic Malignancies*

NCCN Categories of Evidence and Consensus

Category 1: The recommendation is based on high-level evidence (e.g., randomized controlled trials) and there is uniform NCCN consensus.

Category 2A: The recommendation is based on lower-level evidence and there is uniform NCCN consensus.

Category 2B: The recommendation is based on lower-level evidence and there is nonuniform NCCN consensus (but no major disagreement).

Category 3: The recommendation is based on any level of evidence but reflects major disagreement.

All recommendations are category 2A unless otherwise noted.

Clinical trials: NCCN believes that the best management for any cancer patient is in a clinical trial. Participation in clinical trials is especially encouraged.

*Note: For 2011 and ongoing, these NCCN Guidelines have been renamed to Thymomas and Thymic Carcinomas.

Please Note

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines™) are a statement of consensus of the authors regarding their views of currently accepted approaches to treatment. Any clinician seeking to apply or consult the NCCN Guidelines is expected to use independent medical judgment in the context of individual clinical circumstances to determine any patient's care or treatment. The National Comprehensive Cancer Network®(NCCN®) makes no representation or warranties of any kind regarding their content, use, or application and disclaims any responsibility for their applications or use in any way.

© National Comprehensive Cancer Network, Inc. 2010, All rights reserved. The NCCN Guidelines and the illustrations herein may not be reproduced in any form without the express written permission of NCCN.

Disclosures for the NCCN Guidelines Panel for Thymic Malignancies

At the beginning of each NCCN Guidelines panel meeting, panel members disclosed any financial support they have received from industry. Through 2008, this information was published in an aggregate statement in JNCCN and online. Furthering NCCN's commitment to public transparency, this disclosure process has now been expanded by listing all potential conflicts of interest respective to each individual expert panel member.

Individual disclosures for the NCCN Guidelines for Thymic Malignancies panel members can be found on page 1315. (The most recent version of these guidelines and accompanying disclosures, including levels of compensation, are available on the NCCN Web site at www.NCCN.org.)

These guidelines are also available on the Internet. For the latest update, please visit www.NCCN.org.

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    NCCN Clinical Practice Guidelines in Oncology: Thymic Malignancies

    Version 2.2010, 02-23-10 ©2010 National Comprehensive Cancer Network, Inc. All rights reserved. These guidelines and this illustration may not be reproduced in any form without the express written permission of NCCN.

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    Version 2.2010, 02-23-10 ©2010 National Comprehensive Cancer Network, Inc. All rights reserved. These guidelines and this illustration may not be reproduced in any form without the express written permission of NCCN.

  • View in gallery
    NCCN Clinical Practice Guidelines in Oncology: Thymic Malignancies

    Version 2.2010, 02-23-10 ©2010 National Comprehensive Cancer Network, Inc. All rights reserved. These guidelines and this illustration may not be reproduced in any form without the express written permission of NCCN.

  • View in gallery
    NCCN Clinical Practice Guidelines in Oncology: Thymic Malignancies

    Version 2.2010, 02-23-10 ©2010 National Comprehensive Cancer Network, Inc. All rights reserved. These guidelines and this illustration may not be reproduced in any form without the express written permission of NCCN.

  • 1.

    Strollo DC, Rosado de Christenson ML, Jett JR. Primary mediastinal tumors. Part 1: tumors of the anterior mediastinum. Chest 1997;112:511522.

    • Search Google Scholar
    • Export Citation
  • 2.

    Strollo DC, Rosado-de-Christenson ML, Jett JR. Primary mediastinal tumors: part II. Tumors of the middle and posterior mediastinum. Chest 1997;112:13441357.

    • Search Google Scholar
    • Export Citation
  • 3.

    Travis W, Brambilla E, Muller-Hermelink H, Harris C. Pathology and Genetics of Tumours of the Lung, Pleura, Thymus and Heart. WHO Classification of Tumors, 3rd ed. Lyon, France: IARC Press; 2004.

    • Search Google Scholar
    • Export Citation
  • 4.

    Okumura M, Shiono H, Minami M. Clinical and pathological aspects of thymic epithelial tumors. Gen Thorac Cardiovasc Surg 2008;56:1016.

  • 5.

    Barth TF, Leithäuser F, Joos S. Mediastinal (thymic) large B-cell lymphoma: where do we stand? Lancet Oncol 2002;3:229234.

  • 6.

    Kondo K, Monden Y. Therapy for thymic epithelial tumors: a clinical study of 1,320 patients from Japan. Ann Thorac Surg 2003;76:878884.

  • 7.

    Kondo K. Optimal therapy for thymoma. J Med Invest 2008;55:1728.

  • 8.

    Detterbeck FC, Parsons AM. Thymic tumors. Ann Thorac Surg 2004;77:18601869.

  • 9.

    Lee HS, Kim ST, Lee J. A single institutional experience of thymic epithelial tumours over 11 years: clinical features and outcome and implications for future management. Br J Cancer 2007;97:2228.

    • Search Google Scholar
    • Export Citation
  • 10.

    Masaoka A, Monden Y, Nakahara K, Tanioka T. Follow-up study of thymomas with special reference to their clinical stages. Cancer 1981;48:24852492.

    • Search Google Scholar
    • Export Citation
  • 11.

    Wright CD. Management of thymomas. Crit Rev Oncol Hematol 2008;65:109120.

  • 12.

    Lewis JE, Wick MR, Scheithauer BW. Thymoma. A clinicopathologic review. Cancer 1987;60:27272743.

  • 13.

    Park HS, Shin DM, Lee JS. Thymoma. A retrospective study of 87 cases. Cancer 1994;73:24912498.

  • 14.

    Ruffini E, Mancuso M, Oliaro A. Recurrence of thymoma: analysis of clinicopathologic features, treatment, and outcome. J Thorac Cardiovasc Surg 1997;113:5563.

    • Search Google Scholar
    • Export Citation
  • 15.

    Kong FM, Pan C, Eisbruch A, Ten Haken RK. Physical models and simpler dosimetric descriptors of radiation late toxicity. Semin Radiat Oncol 2007;17:108120.

    • Search Google Scholar
    • Export Citation
  • 16.

    Milano MT, Constine LS, Okunieff P. Normal tissue tolerance dose metrics for radiation therapy of major organs. Semin Radiat Oncol 2007;17:131140.

    • Search Google Scholar
    • Export Citation
  • 17.

    Myojin M, Choi NC, Wright CD. Stage III thymoma: pattern of failure after surgery and postoperative radiotherapy and its implication for future study. Int J Radiat Oncol Biol Phys 2000;46:927933.

    • Search Google Scholar
    • Export Citation
  • 18.

    Mornex F, Resbeut M, Richaud P. Radiotherapy and chemotherapy for invasive thymomas: a multicentric retrospective review of 90 cases. The FNCLCC trialists. Federation Nationale des Centres de Lutte Contre le Cancer. Int J Radiat Oncol Biol Phys 1995;32:651659.

    • Search Google Scholar
    • Export Citation
  • 19.

    Singhal S, Shrager JB, Rosenthal DI. Comparison of stages I-II thymoma treated by complete resection with or without adjuvant radiation. Ann Thorac Surg 2003;76:16351641.

    • Search Google Scholar
    • Export Citation
  • 20.

    Rena O, Papalia E, Oliaro A. Does adjuvant radiation therapy improve disease-free survival in completely resected Masaoka stage II thymoma? Eur J Cardiothorac Surg 2007;31:109113.

    • Search Google Scholar
    • Export Citation
  • 21.

    Mangi AA, Wright CD, Allan JS. Adjuvant radiation therapy for stage II thymoma. Ann Thorac Surg 2002;74:10331037.

  • 22.

    Korst RJ, Kansler AL, Christos PJ, Mandal S. Adjuvant radiotherapy for thymic epithelial tumors: a systematic review and meta-analysis. Ann Thorac Surg 2009;87:16411647.

    • Search Google Scholar
    • Export Citation
  • 23.

    Loehrer PJ, Kim K, Aisner SC. 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 1994;12:11641168.

    • Search Google Scholar
    • Export Citation
  • 24.

    Giaccone G, Ardizzoni A, Kirkpatrick A. 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 1996;14:814820.

    • Search Google Scholar
    • Export Citation
  • 25.

    Shin DM, Walsh GL, Komaki R. A multidisciplinary approach to therapy for unresectable malignant thymoma. Ann Intern Med 1998;129:100104.

  • 26.

    Fornasiero A, Daniele O, Ghiotto C. Chemotherapy for invasive thymoma. A 13-year experience. Cancer 1991;68:3033.

  • 27.

    Loehrer PJ, Jiroutek M, Aisner S. Combined etoposide, ifosfamide, and cisplatin in the treatment of patients with advanced thymoma and thymic carcinoma: an intergroup trial. Cancer 2001;91:20102015.

    • Search Google Scholar
    • Export Citation
  • 28.

    Kim ES, Putnam JB, Komaki R. 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 2004;44:369379.

    • Search Google Scholar
    • Export Citation
  • 29.

    Lucchi M, Melfi F, Dini P. Neoadjuvant chemotherapy for stage III and IVA thymomas: a single-institution experience with a long follow-up. J Thorac Oncol 2006;1:308313.

    • Search Google Scholar
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