Masses in the anterior mediastinum can be neoplasms (eg, thymomas, thymic carcinomas, or lung metastases) or non-neoplastic conditions (eg, intrathoracic goiter). Thymomas are the most common primary tumor in the anterior mediastinum, although they are rare. Thymic carcinomas are very rare. Thymomas and thymic carcinomas originate in the thymus. Although thymomas can spread locally, they are much less invasive than thymic carcinomas. Patients with thymomas have 5-year survival rates of approximately 78%. However, 5-year survival rates for thymic carcinomas are only approximately 40%. These guidelines outline the evaluation, treatment, and management of these mediastinal tumors.

Abstract

Masses in the anterior mediastinum can be neoplasms (eg, thymomas, thymic carcinomas, or lung metastases) or non-neoplastic conditions (eg, intrathoracic goiter). Thymomas are the most common primary tumor in the anterior mediastinum, although they are rare. Thymic carcinomas are very rare. Thymomas and thymic carcinomas originate in the thymus. Although thymomas can spread locally, they are much less invasive than thymic carcinomas. Patients with thymomas have 5-year survival rates of approximately 78%. However, 5-year survival rates for thymic carcinomas are only approximately 40%. These guidelines outline the evaluation, treatment, and management of these mediastinal tumors.

NCCN Categories of Evidence and Consensus

Category 1: Based upon high-level evidence, there is uniform NCCN consensus that the intervention is appropriate.

Category 2A: Based upon lower-level evidence, there is uniform NCCN consensus that the intervention is appropriate.

Category 2B: Based upon lower-level evidence, there is NCCN consensus that the intervention is appropriate.

Category 3: Based upon any level of evidence, there is major NCCN disagreement that the intervention is appropriate.

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.

Overview

Thymomas are the most common primary tumor in the anterior mediastinum, although they are rare (1.5 cases/million).1-3 Thymic carcinomas are very rare. Thymomas and thymic carcinomas originate in the thymus. Although thymomas can spread locally, they are much less invasive than thymic carcinomas.1 Patients with thymomas have 5-year survival rates of approximately 78%.4 However, 5-year survival rates for thymic carcinomas are only approximately 40%.5,6 These guidelines outline the evaluation, treatment, and management of these mediastinal tumors.

Mediastinal Masses

Masses in the anterior mediastinum can be neoplasms (eg, thymomas, lymphomas, thymic carcinomas, thymic carcinoids, thymolipomas, germ cell tumors, lung metastases) or nonneoplastic conditions (eg, intrathoracic goiter, thymic cysts, lymphangiomas, aortic aneurysms).2,7,8 Many mediastinal masses are benign, especially those occurring in asymptomatic patients; however, symptomatic patients often have malignant mediastinal lesions. All patients with a mediastinal mass should be evaluated to determine the type of mass and the extent of disease before treatment (see “Initial Evaluation,” page 4). It is essential to differentiate between thymic malignancies and other conditions (eg, lung metastases, lymphoma, goiter, and germ cell tumors) before treatment, because management differs for these conditions.9 Most masses in the mediastinum are metastases from a primary lung cancer (eg, non-small cell lung cancer). However, most primary cancers in the anterior mediastinum are thymomas.

Patients with thymomas often have an indolent presentation, whereas those with lymphoma or germ cell tumors have a rapid onset of symptoms.9 Lymphomas typically manifest as generalized disease but can also be primary anterior mediastinal lesions (ie, nodular sclerosing Hodgkin disease, non-Hodgkin’s lymphomas [diffuse large B-cell lymphoma and acute lymphoblastic lymphoma]); patients typically have lymphadenopathy (see the NCCN Clinical Practice Guidelines in Oncology [NCCN Guidelines] for Non-Hodgkin’s Lymphomas and Hodgkin Lymphoma; to view the most recent version of these guidelines, visit NCCN.org).8,10 Thymic carcinoids are rare tumors that are discussed in the NCCN Guidelines for Neuroendocrine Tumors (available at NCCN.org); they are associated with multiple endocrine neoplasia type 1 syndrome (MEN1).11,12 Lung carcinoids are discussed in the NCCN Guidelines for Small Cell Lung Cancer (see “Lung Neuroendocrine Tumors”; available at NCCN.org). Extragonadal germ cell tumors are rare tumors that occur in teenagers and young adults (http://www.cancer.gov/cancertopics/types/extragonadal-germ-cell). Recommended tests for assessing mediastinal masses include chest CT with contrast and blood chemistry studies (see “Initial Evaluation,” page 564).13-15 On CT, a thymoma is usually a well-defined round or oval mass in the thymus.13,16 Recently, low-dose CT (LDCT) was found to be useful for detecting lung cancer in high-risk individuals (see the NCCN Guidelines for Lung Cancer Screening; available at NCCN.org).17 Mediastinal masses (eg, thymomas, thymic carcinomas) may be detected in individuals undergoing lung cancer screening.

F1NCCN Clinical Practice Guidelines in Oncology: Thymomas and Thymic Carcinomas, Version 2.2013

Version 2.2013, 10-10-12 ©2012 National Comprehensive Cancer Network, Inc. All rights reserved. The NCCN 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 11, 5; 10.6004/jnccn.2013.0072

F2NCCN Clinical Practice Guidelines in Oncology: Thymomas and Thymic Carcinomas, Version 2.2013

Version 2.2013, 10-10-12 ©2012 National Comprehensive Cancer Network, Inc. All rights reserved. The NCCN 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 11, 5; 10.6004/jnccn.2013.0072

F3NCCN Clinical Practice Guidelines in Oncology: Thymomas and Thymic Carcinomas, Version 2.2013

Version 2.2013, 10-10-12 ©2012 National Comprehensive Cancer Network, Inc. All rights reserved. The NCCN 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 11, 5; 10.6004/jnccn.2013.0072

In patients who cannot tolerate iodinated contrast, MRI of the chest may be useful.13 Combined PET/CT may be useful for determining whether distant metastases are present.18 PET/CT provides better correlation with anatomic structures than PET alone. Alpha-fetoprotein (AFP) levels and beta-human chorionic gonadotropin (β-hCG) levels may be measured to rule out germ cell tumors (see “Initial Evaluation,” page 564). Thyroid-stimulating hormone (TSH), triiodothyronine (T3), and thyroxine (T4) levels may be measured to rule out mediastinal goiter.

Thymic Masses

All patients with thymic malignancies should be evaluated by radiation oncologists, surgeons, medical oncologists, diagnostic imaging specialists, and pulmonologists to determine the optimal plan of care before treatment.19 It is critical to determine whether the mass can be surgically resected; a board certified thoracic surgeon should make this decision. Total thymectomy and complete surgical excision of the tumor are the gold standard of treatment and are recommended whenever possible for most resectable tumors (see “Principles of Surgical Resection,” page 567).4,5,9,20,21 During thymectomy, the pleural surfaces should be examined for metastases. To achieve a complete gross resection, removal of pleural metastases may be appropriate in some patients.22-24 Core-needle or open biopsy is recommended for locally advanced unresectable thymic masses.7

Minimally invasive procedures are not typically recommended, because long-term data are not available regarding recurrence and survival. However, minimally invasive procedures may be considered if standard oncologic goals can be met (as described previously) and if performed in specialized centers with surgeons with expertise in these techniques.25-28 Although several staging systems exist, the Masaoka staging system is the most widely accepted system for management and determination of prognosis for both thymomas and thymic carcinomas (see Table 1 in the complete version of these guidelines, available at NCCN.org [ST-1]).4,5,29-35 The International Thymic Malignancy Interest Group (ITMIG) suggests using the Masaoka-Koga stage classification.29 The TNM staging system is less commonly used (see Table 2 in the complete version of these guidelines, available at NCCN.org [ST-1]).36 Patients with stage I to III thymomas have a 5-year survival rate of approximately 85% versus 65% for stage IV disease.4,37,38 In approximately 50% of patients, mortality is not related to thymoma.30 In approximately 20% of patients, mortality is related to myasthenia gravis.

The WHO histologic classification system can be used to distinguish among thymomas, thymic carcinomas, and thymic carcinoids (see Table 3 in the complete version of these guidelines, available at NCCN.org [ST-2]).36,39 The WHO classification is also used to differentiate among different histologic types of thymomas (ie, A, AB, B1, B2, B3); however, thymomas are difficult to classify.40 Thymic carcinomas are type C in the WHO classification, although they are very different from thymomas and are not advanced thymomas (see “Thymic Carcinomas,” page 572).41 However, the histologic subtype is less important for management than the extent of resection (ie, R0, R1, R2) (see “Postoperative Management,” page 565).5,42-45 For stage III to IV thymomas, 5-year survival rates have been reported to be 90% in patients with total resection.5 For thymic carcinomas, 5-year survival rates are lower, even in those with total resection.46

Thymomas

Thymomas typically occur in adults 40 to 70 years of age; they are rare in children or adolescents.9 Although some patients are asymptomatic, others present with chest pain, cough, or dyspnea. Approximately 30% to 50% of patients with thymomas have myasthenia gravis; therefore, patients should be evaluated for myasthenia gravis (eg, by history and/or measuring serum antiacetylcholine receptor antibody levels).37 Although thymomas can be locally invasive (eg, pleura, lung), they uncommonly spread to regional lymph nodes or distant sites.4,37 Surgery (ie, total thymectomy and complete excision of tumor) is recommended for all resectable thymomas for patients who can tolerate the surgery. For resected stage I and II thymomas, the 10-year survival rate is excellent (approximately 90% and 70%, respectively).9,47 Completeness of resection is the most important predictor of outcome.

Surgical biopsy is not necessary if a resectable thymoma is strongly suspected based on clinical and radiologic features (eg, patients have myasthenia gravis and a characteristic mass on CT).9 A transpleural approach should be avoided during biopsy of a possible thymoma.48,49 Small biopsy sampling (fine-needle or core-needle biopsy) does not always indicate whether invasion is present.50 The ITMIG has established procedures for reporting the surgical and pathologic findings from resection specimens.51

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. Symptoms suggestive of myasthenia gravis include drooping eyelids, double vision, drooling, difficulty climbing stairs, hoarseness, and/or dyspnea. If patients have myasthenia gravis, they should receive treatment by a neurologist with experience in myasthenia gravis before undergoing surgical resection.48,52-54

Adjuvant therapy is not recommended for completely resected (R0) stage I thymomas.20,55,56 For incompletely resected thymomas, postoperative radiation therapy (RT) is recommended (see “Postoperative Management,” page 565).20,57 Note that extensive elective nodal radiation is not recommended, because thymomas do not typically metastasize to regional lymph nodes.4,58 CT-based treatment planning is highly recommended before RT (see “Principles of Radiation Therapy,” page 568).59 RT should be given using the 3D conformal technique to reduce damage to surrounding normal tissue (eg, heart, lungs, esophagus, spinal cord).

Use of intensity-modulated RT (IMRT) may decrease the dose to the normal tissues.59,60 However, if IMRT is used, guidelines from the Advanced Technology Consortium (ATC)/NCI and American Society for Radiation Oncology/American College of Radiology (ASTRO/ACR) should be followed (http://rrp.cancer.gov/content/docs/imrt.doc).61-64 Although the normal tissue constraints recommendations for lung cancer may be used (see the “Principles of Radiation Therapy” in the NCCN Guidelines for Non-Small Cell Lung Cancer; to view the most recent version of these guidelines, visit NCCN.org), more conservative limits are recommended to minimize the dose volumes to all of the normal structures.65,66 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 recommended for patients with unresectable disease. For adjuvant treatment, a total dose of 45 to 50 Gy is recommended for clear or close margins; a total dose of 54 Gy is recommended for microscopically positive resection margins (see “Principles of Radiation Therapy,” page 568).59,60 However, a total dose of 60 Gy or more (1.8-2.0 Gy/fraction per day) is recommended for patients with gross residual disease after surgery.67,68

Postoperative RT can be considered in patients with thymoma and thymic carcinoma who have capsular invasion after an R0 resection, although this is a category 2B recommendation (see “Postoperative Management,” page 565).56,59,69-71 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 is recommended to maximize local control.72,73 Increasing evidence suggests that patients with stage II thymoma may not benefit from postoperative radiation.20,55,56,70 Postoperative chemotherapy is also not beneficial.74

For advanced disease, chemotherapy with (or without) RT is recommended (see “Principles of Chemotherapy for Thymic Malignancies,” page 569).56,75-87 Although 6 different combination regimens are provided in the NCCN algorithm, cisplatin/doxorubicin-based regimens seem to yield the best outcomes; the panel feels that cisplatin/doxorubicin/cyclophosphamide is the preferred regimen for thymoma.20,88,89 However, nonanthracycline regimens (eg, cisplatin/etoposide [with or without ifosfamide], carboplatin/paclitaxel) may be useful for patients who cannot tolerate the more aggressive regimens.89,90 For thymic carcinoma, the panel recommends carboplatin/paclitaxel.90,91 Induction therapy followed by surgery may be useful for thymic malignancies initially considered unresectable.46,83,92,93

Second-line systemic therapy includes etoposide, ifosfamide, pemetrexed, octreotide (long-acting release [LAR]; with or without prednisone), 5-FU, gemcitabine, and paclitaxel.75,76,89,94-97 However, none of these agents have been assessed in randomized trials. Octreotide may be useful in patients with thymoma who have a positive octreotide scan or symptoms of carcinoid syndrome. After resection, surveillance for recurrence should include annual chest CT.13 Given the risk of later recurrence for thymoma, surveillance should continue for at least 10 years. Patients with thymoma also have an increased risk for second malignancies, although no particular screening studies are recommended.98

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, 30%-50%).2,5,6,8,44,45,99,100 These tumors can be distinguished from thymomas because of their malignant histologic features and their different immunohistochemical and genetic features.7,36,41 However, thymic carcinomas should be differentiated from primary lung malignancies that metastasize to the thymus and have a similar histologic appearance.101,102 Thymic carcinomas often cause pericardial and pleural effusions. The Masaoka staging system can also be used to stage thymic carcinomas (see Table 1 in the complete version of these guidelines, available at NCCN.org [ST-1]).29,103,104 It is important to note that thymic carcinomas are very different from thymomas.41

Similar to thymomas, patients with completely resected thymic carcinomas have longer survival than those with either incompletely resected or are unresectable disease.44,46 Thus, management depends on the extent of resection. After resection of thymic carcinomas, postoperative management includes RT with (or without) chemotherapy, depending on the completeness of resection (see “Postoperative Management,” page 565).44,45,59 For unresectable or metastatic thymic carcinomas, chemotherapy with (or without) RT is recommended (see “Principles of Radiation Therapy” and “Principles of Chemotherapy for Thymic Malignancies,” pages 568 and 569).88

Unfortunately, thymic carcinomas respond poorly to chemotherapy; carboplatin/paclitaxel is recommended, because it has the highest response rate among thymic carcinomas in clinical trials.86,90,105-112 Data suggest that the ADOC (cisplatin, doxorubicin, vincristine, and cyclophosphamide) regimen is also effective, but it is more toxic than carboplatin/paclitaxel.110 Data are lacking regarding second-line chemotherapy for thymic carcinomas.75 Most of the second-line agents in the NCCN algorithm are appropriate for thymomas.76 However, S-1 (an oral fluorouracil) appears to be active in patients with thymic carcinomas.113,114 Targeted therapy (eg, sunitinib, sorafenib) may be useful for patients with c-Kit mutations; however, these mutations are rare in thymic carcinomas (<10%).115-118 Patients with thymomas do not have c-Kit mutations.101

Individual Disclosures for the NCCN Thymomas and Thymic Carcinomas Panel

T1

References

  • 1.

    Proceedings of the First International Conference on Thymic Malignancies. August 20-21, 2009. Bethesda, Maryland, USA. J Thorac Oncol2010;5:S259370.

    • Search Google Scholar
    • Export Citation
  • 2.

    StrolloDCRosado de ChristensonMLJettJR. Primary mediastinal tumors. Part 1: tumors of the anterior mediastinum. Chest1997;112:511522.

    • Search Google Scholar
    • Export Citation
  • 3.

    EngelsEAPfeifferRM. Malignant thymoma in the United States: demographic patterns in incidence and associations with subsequent malignancies. Int J Cancer2003;105:546551.

    • Search Google Scholar
    • Export Citation
  • 4.

    MasaokaA. Staging system of thymoma. J Thorac Oncol2010;5:S304312.

  • 5.

    KondoKMondenY. Therapy for thymic epithelial tumors: a clinical study of 1,320 patients from Japan. Ann Thorac Surg2003;76:878884; discussion 884-875.

    • Search Google Scholar
    • Export Citation
  • 6.

    EngTYFullerCDJagirdarJ. Thymic carcinoma: state of the art review. Int J Radiat Oncol Biol Phys2004;59:654664.

  • 7.

    MarchevskyAMarxAStrobelP. Policies and reporting guidelines for small biopsy specimens of mediastinal masses. J Thorac Oncol2011;6:S17241729.

    • Search Google Scholar
    • Export Citation
  • 8.

    StrolloDCRosado-de-ChristensonMLJettJR. Primary mediastinal tumors: part II. Tumors of the middle and posterior mediastinum. Chest1997;112:13441357.

    • Search Google Scholar
    • Export Citation
  • 9.

    DetterbeckFCParsonsAM. Management of stage I and II thymoma. Thorac Surg Clin2011;21:5967vi-vii.

  • 10.

    BarthTFELeithäuserFJoosS. Mediastinal (thymic) large B-cell lymphoma: where do we stand?Lancet Oncol2002;3:229234.

  • 11.

    FerollaPFalchettiAFilossoP. Thymic neuroendocrine carcinoma (carcinoid) in multiple endocrine neoplasia type 1 syndrome: the Italian series. J Clin Endocrinol Metab2005;90:26032609.

    • Search Google Scholar
    • Export Citation
  • 12.

    TehBT. Thymic carcinoids in multiple endocrine neoplasia type 1. J Intern Med1998;243:501504.

  • 13.

    MaromEM. Imaging thymoma. J Thorac Oncol2010;5:S296303.

  • 14.

    Rosado-de-ChristensonMLStrolloDCMaromEM. Imaging of thymic epithelial neoplasms. Hematol Oncol Clin North Am2008;22:409431.

  • 15.

    SadoharaJFujimotoKMullerNL. Thymic epithelial tumors: comparison of CT and MR imaging findings of low-risk thymomas, high-risk thymomas, and thymic carcinomas. Eur J Radiol2006;60:7079.

    • Search Google Scholar
    • Export Citation
  • 16.

    MaromEMRosado-de-ChristensonMLBruzziJF. Standard report terms for chest computed tomography reports of anterior mediastinal masses suspicious for thymoma. J Thorac Oncol2011;6:S17171723.

    • Search Google Scholar
    • Export Citation
  • 17.

    AberleDRAdamsAMBergCD. Reduced lung-cancer mortality with low-dose computed tomographic screening. N Engl J Med2011;365:395409.

  • 18.

    SungYMLeeKSKimBT. 18F-FDG PET/CT of thymic epithelial tumors: usefulness for distinguishing and staging tumor subgroups. J Nucl Med2006;47:16281634.

    • Search Google Scholar
    • Export Citation
  • 19.

    RuffiniEVan RaemdonckDDetterbeckF. Management of thymic tumors: a survey of current practice among members of the European Society of Thoracic Surgeons. J Thorac Oncol2011;6:614623.

    • Search Google Scholar
    • Export Citation
  • 20.

    KondoK. Optimal therapy for thymoma. J Med Invest2008;55:1728.

  • 21.

    DetterbeckFCParsonsAM. Thymic tumors. Ann Thorac Surg2004;77:18601869.

  • 22.

    WrightCD. Stage IVA thymoma: patterns of spread and surgical management. Thorac Surg Clin2011;21:9397vii.

  • 23.

    WrightCD. Extended resections for thymic malignancies. J Thorac Oncol2010;5:S344347.

  • 24.

    HuangJRizkNPTravisWD. Feasibility of multimodality therapy including extended resections in stage IVA thymoma. J Thorac Cardiovasc Surg2007;134:14771483; discussion 1483-1484.

    • Search Google Scholar
    • Export Citation
  • 25.

    TokerASonettJZielinskiM. Standard terms, definitions, and policies for minimally invasive resection of thymoma. J Thorac Oncol2011;6:S17391742.

    • Search Google Scholar
    • Export Citation
  • 26.

    PennathurAQureshiISchuchertMJ. Comparison of surgical techniques for early-stage thymoma: feasibility of minimally invasive thymectomy and comparison with open resection. J Thorac Cardiovasc Surg2011;141:694701.

    • Search Google Scholar
    • Export Citation
  • 27.

    KomanapalliCBCohenJISukumarMS. Extended transcervical video-assisted thymectomy. Thorac Surg Clin2010;20:235243.

  • 28.

    LimmerKKKernstineKH. Minimally invasive and robotic-assisted thymus resection. Thorac Surg Clin2011;21:6983vii.

  • 29.

    DetterbeckFCNicholsonAGKondoK. The Masaoka-Koga stage classification for thymic malignancies: clarification and definition of terms. J Thorac Oncol2011;6:S17101716.

    • Search Google Scholar
    • Export Citation
  • 30.

    HuangJDetterbeckFCWangZLoehrerPJSr.Standard outcome measures for thymic malignancies. J Thorac Oncol2011;6:S16911697.

  • 31.

    MoranCAWalshGSusterSKaiserL. Thymomas II: a clinicopathologic correlation of 250 cases with a proposed staging system with emphasis on pathologic assessment. Am J Clin Pathol2012;137:451461.

    • Search Google Scholar
    • Export Citation
  • 32.

    KondoK. Tumor-node metastasis staging system for thymic epithelial tumors. J Thorac Oncol2010;5:S352356.

  • 33.

    LeeHSKimSTLeeJ. A single institutional experience of thymic epithelial tumours over 11 years: clinical features and outcome and implications for future management. Br J Cancer2007;97:2228.

    • Search Google Scholar
    • Export Citation
  • 34.

    MasaokaAMondenYNakaharaKTaniokaT. Follow-up study of thymomas with special reference to their clinical stages. Cancer1981;48:24852492.

    • Search Google Scholar
    • Export Citation
  • 35.

    WrightCD. Management of thymomas. Crit Rev Oncol Hematol2008;65:109120.

  • 36.

    TravisWBrambillaEMuller-HermelinkHHarrisC. Pathology and genetics of tumours of the lung pleura thymus and heart. WHO Classification of Tumors3rd ed.Lyon: IARC Press; 2004:145197.

    • Search Google Scholar
    • Export Citation
  • 37.

    LewisJEWickMRScheithauerBW. Thymoma. A clinicopathologic review. Cancer1987;60:27272743.

  • 38.

    ParkHSShinDMLeeJS. Thymoma. A retrospective study of 87 cases. Cancer1994;73:24912498.

  • 39.

    KondoKYoshizawaKTsuyuguchiM. WHO histologic classification is a prognostic indicator in thymoma. Ann Thorac Surg2004;77:11831188.

  • 40.

    MoranCAWeissferdtAKalhorN. Thymomas I: a clinicopathologic correlation of 250 cases with emphasis on the World Health Organization schema. Am J Clin Pathol2012;137:444450.

    • Search Google Scholar
    • Export Citation
  • 41.

    MarxARiekerRTokerA. Thymic carcinoma: is it a separate entity? From molecular to clinical evidence. Thorac Surg Clin2011;21:2531v-vi.

    • Search Google Scholar
    • Export Citation
  • 42.

    MargaritoraSCesarioACusumanoG. Thirty-five-year follow-up analysis of clinical and pathologic outcomes of thymoma surgery. Ann Thorac Surg2010;89:245252; discussion 252.

    • Search Google Scholar
    • Export Citation
  • 43.

    RegnardJFMagdeleinatPDromerC. Prognostic factors and long-term results after thymoma resection: a series of 307 patients. J Thorac Cardiovasc Surg1996;112:376384.

    • Search Google Scholar
    • Export Citation
  • 44.

    YanoMSasakiHYokoyamaT. Thymic carcinoma: 30 cases at a single institution. J Thorac Oncol2008;3:265269.

  • 45.

    OgawaKToitaTUnoT. Treatment and prognosis of thymic carcinoma: a retrospective analysis of 40 cases. Cancer2002;94:31153119.

  • 46.

    OkerekeICKeslerKAFreemanRK. Thymic carcinoma: outcomes after surgical resection. Ann Thorac Surg2012;93:16681672; discussion 1672-1673.

    • Search Google Scholar
    • Export Citation
  • 47.

    DetterbeckFYoussefSRuffiniEOkumuraM. A review of prognostic factors in thymic malignancies. J Thorac Oncol2011;6:S1698–-1704.

  • 48.

    MehranRGhoshRMaziakD. Surgical treatment of thymoma. Can J Surg2002;45:2530.

  • 49.

    MurakawaTNakajimaJKohnoT. Results from surgical treatment for thymoma. 43 years of experience. Jpn J Thorac Cardiovasc Surg2000;48:8995.

    • Search Google Scholar
    • Export Citation
  • 50.

    WakelyPEJr.Fine needle aspiration in the diagnosis of thymic epithelial neoplasms. Hematol Oncol Clin North Am2008;22:433442.

  • 51.

    DetterbeckFCMoranCHuangJ. Which way is up? Policies and procedures for surgeons and pathologists regarding resection specimens of thymic malignancy. J Thorac Oncol2011;6:S17301738.

    • Search Google Scholar
    • Export Citation
  • 52.

    GilhusNEOweJFHoffJM. Myasthenia gravis: a review of available treatment approaches. Autoimmune Dis2011;2011:847393.

  • 53.

    Autoantibodies to acetylcholine receptors in myasthenia gravis. N Engl J Med1983;308:402403.

  • 54.

    HowardFMLennonVAFinleyJ. Clinical correlations of antibodies that bind, block, or modulate human acetylcholine receptors in myasthenia gravis. Ann N Y Acad Sci1987;505:526538.

    • Search Google Scholar
    • Export Citation
  • 55.

    UtsumiTShionoHKadotaY. Postoperative radiation therapy after complete resection of thymoma has little impact on survival. Cancer2009;115:54135420.

    • Search Google Scholar
    • Export Citation
  • 56.

    KorstRJKanslerALChristosPJMandalS. Adjuvant radiotherapy for thymic epithelial tumors: a systematic review and meta-analysis. Ann Thorac Surg2009;87:16411647.

    • Search Google Scholar
    • Export Citation
  • 57.

    ForquerJARongNFakirisAJ. Postoperative radiotherapy after surgical resection of thymoma: differing roles in localized and regional disease. Int J Radiat Oncol Biol Phys2010;76:440445.

    • Search Google Scholar
    • Export Citation
  • 58.

    RuffiniEMancusoMOliaroA. Recurrence of thymoma: analysis of clinicopathologic features, treatment, and outcome. J Thorac Cardiovasc Surg1997;113:5563.

    • Search Google Scholar
    • Export Citation
  • 59.

    GomezDKomakiRYuJ. Radiation therapy definitions and reporting guidelines for thymic malignancies. J Thorac Oncol2011;6:S17431748.

  • 60.

    GomezDKomakiR. Technical advances of radiation therapy for thymic malignancies. J Thorac Oncol2010;5:S336343.

  • 61.

    HartfordACPaliscaMGEichlerTJ. American Society for Therapeutic Radiology and Oncology (ASTRO) and American College of Radiology (ACR) Practice Guidelines for Intensity-Modulated Radiation Therapy (IMRT). Int J Radiat Oncol Biol Phys2009;73:914.

    • Search Google Scholar
    • Export Citation
  • 62.

    MoranJMDempseyMEisbruchA. Safety considerations for IMRT: executive summary. Med Phys2011;38:50675072.

  • 63.

    GregoireVMackieTR. State of the art on dose prescription, reporting and recording in intensity-modulated radiation therapy (ICRU report No. 83). Cancer Radiother2011;15:555559.

    • Search Google Scholar
    • Export Citation
  • 64.

    HolmesTDasRLowD. American Society of Radiation Oncology recommendations for documenting intensity-modulated radiation therapy treatments. Int J Radiat Oncol Biol Phys2009;74:13111318.

    • Search Google Scholar
    • Export Citation
  • 65.

    KongFMPanCEisbruchATen HakenRK. Physical models and simpler dosimetric descriptors of radiation late toxicity. Semin Radiat Oncol2007;17:108120.

    • Search Google Scholar
    • Export Citation
  • 66.

    MilanoMTConstineLSOkunieffP. Normal tissue tolerance dose metrics for radiation therapy of major organs. Semin Radiat Oncol2007;17:131140.

    • Search Google Scholar
    • Export Citation
  • 67.

    MyojinMChoiNCWrightCD. Stage III thymoma: pattern of failure after surgery and postoperative radiotherapy and its implication for future study. Int J Radiat Oncol Biol Phys2000;46:927933.

    • Search Google Scholar
    • Export Citation
  • 68.

    MornexFResbeutMRichaudP. 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 Phys1995;32:651659.

    • Search Google Scholar
    • Export Citation
  • 69.

    SinghalSShragerJBRosenthalDI. Comparison of stages I-II thymoma treated by complete resection with or without adjuvant radiation. Ann Thorac Surg2003;76:16351641; discussion 1641-1642.

    • Search Google Scholar
    • Export Citation
  • 70.

    RenaOPapaliaEOliaroA. Does adjuvant radiation therapy improve disease-free survival in completely resected Masaoka stage II thymoma?Eur J Cardiothorac Surg2007;31:109113.

    • Search Google Scholar
    • Export Citation
  • 71.

    MangiAAWrightCDAllanJS. Adjuvant radiation therapy for stage II thymoma. Ann Thorac Surg2002;74:10331037.

  • 72.

    SugieCShibamotoYIkeya-HashizumeC. Invasive thymoma: postoperative mediastinal irradiation, and low-dose entire hemithorax irradiation in patients with pleural dissemination. J Thorac Oncol2008;3:7581.

    • Search Google Scholar
    • Export Citation
  • 73.

    OgawaKUnoTToitaT. Postoperative radiotherapy for patients with completely resected thymoma: a multi-institutional, retrospective review of 103 patients. Cancer2002;94:14051413.

    • Search Google Scholar
    • Export Citation
  • 74.

    CowenDRichaudPMornexF. Thymoma: results of a multicentric retrospective series of 149 non-metastatic irradiated patients and review of the literature. FNCLCC trialists. Federation Nationale des Centres de Lutte Contre le Cancer. Radiother Oncol1995;34:916.

    • Search Google Scholar
    • Export Citation
  • 75.

    GirardNLalRWakeleeH. Chemotherapy definitions and policies for thymic malignancies. J Thorac Oncol2011;6:S17491755.

  • 76.

    GirardN. Chemotherapy and targeted agents for thymic malignancies. Expert Rev Anticancer Ther2012;12:685695.

  • 77.

    LoehrerPJSr.ChenMKimK. Cisplatin, doxorubicin, and cyclophosphamide plus thoracic radiation therapy for limited-stage unresectable thymoma: an Intergroup trial. J Clin Oncol1997;15:30933099.

    • Search Google Scholar
    • Export Citation
  • 78.

    LoehrerPJKimKAisnerSC. 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 Oncol1994;12:11641168.

    • Search Google Scholar
    • Export Citation
  • 79.

    GiacconeGArdizzoniAKirkpatrickA. 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 Oncol1996;14:814820.

    • Search Google Scholar
    • Export Citation
  • 80.

    ShinDMWalshGLKomakiR. A multidisciplinary approach to therapy for unresectable malignant thymoma. Ann Intern Med1998;129:100104.

  • 81.

    FornasieroADanieleOGhiottoC. Chemotherapy for invasive thymoma. A 13-year experience. Cancer1991;68:3033.

  • 82.

    LoehrerPJJiroutekMAisnerS. Combined etoposide, ifosfamide, and cisplatin in the treatment of patients with advanced thymoma and thymic carcinoma: an intergroup trial. Cancer2001;91:20102015.

    • Search Google Scholar
    • Export Citation
  • 83.

    KimESPutnamJBKomakiR. 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 Cancer2004;44:369379.

    • Search Google Scholar
    • Export Citation
  • 84.

    LucchiMMelfiFDiniP. Neoadjuvant chemotherapy for stage III and IVA thymomas: a single-institution experience with a long follow-up. J Thorac Oncol2006;1:308313.

    • Search Google Scholar
    • Export Citation
  • 85.

    YokoiKMatsugumaHNakaharaR. Multidisciplinary treatment for advanced invasive thymoma with cisplatin, doxorubicin, and methylprednisolone. J Thorac Oncol2007;2:7378.

    • Search Google Scholar
    • Export Citation
  • 86.

    LemmaGLLoehrerPJSr.LeeJW. A phase II study of carboplatin plus paclitaxel in advanced thymoma or thymic carcinoma: E1C99 [abstract]. J Clin Oncol2008;26(Suppl 15):Abstract 8018.

    • Search Google Scholar
    • Export Citation
  • 87.

    VenutaFRendinaEALongoF. Long-term outcome after multimodality treatment for stage III thymic tumors. Ann Thorac Surg2003;76:18661872; discussion 1872.

    • Search Google Scholar
    • Export Citation
  • 88.

    RajanAGiacconeG. Chemotherapy for thymic tumors: induction, consolidation, palliation. Thorac Surg Clin2011;21:107114viii.

  • 89.

    SchmittJLoehrerPJSr.The role of chemotherapy in advanced thymoma. J Thorac Oncol2010;5:S357360.

  • 90.

    LemmaGLLeeJWAisnerSC. Phase II study of carboplatin and paclitaxel in advanced thymoma and thymic carcinoma. J Clin Oncol2011;29:20602065.

    • Search Google Scholar
    • Export Citation
  • 91.

    FurugenMSekineITsutaK. Combination chemotherapy with carboplatin and paclitaxel for advanced thymic cancer. Jpn J Clin Oncol2011;41:10131016.

    • Search Google Scholar
    • Export Citation
  • 92.

    RielyGJHuangJ. Induction therapy for locally advanced thymoma. J Thorac Oncol2010;5:S323326.

  • 93.

    WrightCDChoiNCWainJC. Induction chemoradiotherapy followed by resection for locally advanced Masaoka stage III and IVA thymic tumors. Ann Thorac Surg2008;85:385389.

    • Search Google Scholar
    • Export Citation
  • 94.

    LongoFDe FilippisLZiviA. Efficacy and tolerability of long-acting octreotide in the treatment of thymic tumors: results of a pilot trial. Am J Clin Oncol2012;35:105109.

    • Search Google Scholar
    • Export Citation
  • 95.

    LoehrerPJSr.WangWJohnsonDH. Octreotide alone or with prednisone in patients with advanced thymoma and thymic carcinoma: an Eastern Cooperative Oncology Group Phase II Trial. J Clin Oncol2004;22:293299.

    • Search Google Scholar
    • Export Citation
  • 96.

    PalmieriGMerolaGFedericoP. Preliminary results of phase II study of capecitabine and gemcitabine (CAP-GEM) in patients with metastatic pretreated thymic epithelial tumors (TETs). Ann Oncol2010;21:11681172.

    • Search Google Scholar
    • Export Citation
  • 97.

    HighleyMSUnderhillCRParnisFX. Treatment of invasive thymoma with single-agent ifosfamide. J Clin Oncol1999;17:27372744.

  • 98.

    PanCCChenPCWangLS. Thymoma is associated with an increased risk of second malignancy. Cancer2001;92:24062411.

  • 99.

    SusterSRosaiJ. Thymic carcinoma. A clinicopathologic study of 60 cases. Cancer1991;67:10251032.

  • 100.

    HuangJRizkNPTravisWD. Comparison of patterns of relapse in thymic carcinoma and thymoma. J Thorac Cardiovasc Surg2009;138:2631.

  • 101.

    StrobelPHohenbergerPMarxA. Thymoma and thymic carcinoma: molecular pathology and targeted therapy. J Thorac Oncol2010;5:S286290.

  • 102.

    MoranCASusterS. Thymic carcinoma: current concepts and histologic features. Hematol Oncol Clin North Am2008;22:393407.

  • 103.

    HosakaYTsuchidaMToyabeS. Masaoka stage and histologic grade predict prognosis in patients with thymic carcinoma. Ann Thorac Surg2010;89:912917.

    • Search Google Scholar
    • Export Citation
  • 104.

    BlumbergDBurtMEBainsMS. Thymic carcinoma: current staging does not predict prognosis. J Thorac Cardiovasc Surg1998;115:303308; discussion 308-309.

    • Search Google Scholar
    • Export Citation
  • 105.

    MaruyamaRSuemitsuROkamotoT. Persistent and aggressive treatment for thymic carcinoma. Results of a single-institute experience with 25 patients. Oncology2006;70:325329.

    • Search Google Scholar
    • Export Citation
  • 106.

    WeideLGUlbrightTMLoehrerPJWilliamsSD. Thymic carcinoma. A distinct clinical entity responsive to chemotherapy. Cancer1993;71:12191223.

    • Search Google Scholar
    • Export Citation
  • 107.

    LucchiMMussiAAmbrogiM. Thymic carcinoma: a report of 13 cases. Eur J Surg Oncol2001;27:636640.

  • 108.

    YohKGotoKIshiiGI. Weekly chemotherapy with cisplatin, vincristine, doxorubicin, and etoposide is an effective treatment for advanced thymic carcinoma. Cancer2003;98:926931.

    • Search Google Scholar
    • Export Citation
  • 109.

    IgawaSMurakamiHTakahashiT. Efficacy of chemotherapy with carboplatin and paclitaxel for unresectable thymic carcinoma. Lung Cancer2010;67:194197.

    • Search Google Scholar
    • Export Citation
  • 110.

    KoizumiTTakabayashiYYamagishiS. Chemotherapy for advanced thymic carcinoma: clinical response to cisplatin, doxorubicin, vincristine, and cyclophosphamide (ADOC chemotherapy). Am J Clin Oncol2002;25:266268.

    • Search Google Scholar
    • Export Citation
  • 111.

    KandaSKoizumiTKomatsuY. Second-line chemotherapy of platinum compound plus CPT-11 following ADOC chemotherapy in advanced thymic carcinoma: analysis of seven cases. Anticancer Res2007;27:30053008.

    • Search Google Scholar
    • Export Citation
  • 112.

    KomatsuYKoizumiTTanabeT. Salvage chemotherapy with carboplatin and paclitaxel for cisplatin-resistant thymic carcinoma—three cases. Anticancer Res2006;26:48514855.

    • Search Google Scholar
    • Export Citation
  • 113.

    OkumaYShimokawaTTakagiY. S-1 is an active anticancer agent for advanced thymic carcinoma. Lung Cancer2010;70:357363.

  • 114.

    KoizumiTAgatsumaTKomatsuYKuboK. Successful S-1 monotherapy for chemorefractory thymic carcinoma. Anticancer Res2011;31:299301.

  • 115.

    StrobelPBargouRWolffA. Sunitinib in metastatic thymic carcinomas: laboratory findings and initial clinical experience. Br J Cancer2010;103:196200.

    • Search Google Scholar
    • Export Citation
  • 116.

    BisagniGRossiGCavazzaA. Long lasting response to the multikinase inhibitor bay 43-9006 (Sorafenib) in a heavily pretreated metastatic thymic carcinoma. J Thorac Oncol2009;4:773775.

    • Search Google Scholar
    • Export Citation
  • 117.

    StrobelPHartmannMJakobA. Thymic carcinoma with overexpression of mutated KIT and the response to imatinib. N Engl J Med2004;350:26252626.

    • Search Google Scholar
    • Export Citation
  • 118.

    GirardN. Targeted therapies for thymic malignancies. Thorac Surg Clin2011;21:115123viii.

If the inline PDF is not rendering correctly, you can download the PDF file here.

Article Sections

Figures

  • View in gallery
    NCCN Clinical Practice Guidelines in Oncology: Thymomas and Thymic Carcinomas, Version 2.2013

    Version 2.2013, 10-10-12 ©2012 National Comprehensive Cancer Network, Inc. All rights reserved. The NCCN 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: Thymomas and Thymic Carcinomas, Version 2.2013

    Version 2.2013, 10-10-12 ©2012 National Comprehensive Cancer Network, Inc. All rights reserved. The NCCN 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: Thymomas and Thymic Carcinomas, Version 2.2013

    Version 2.2013, 10-10-12 ©2012 National Comprehensive Cancer Network, Inc. All rights reserved. The NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN®.

References

  • 1.

    Proceedings of the First International Conference on Thymic Malignancies. August 20-21, 2009. Bethesda, Maryland, USA. J Thorac Oncol2010;5:S259370.

    • Search Google Scholar
    • Export Citation
  • 2.

    StrolloDCRosado de ChristensonMLJettJR. Primary mediastinal tumors. Part 1: tumors of the anterior mediastinum. Chest1997;112:511522.

    • Search Google Scholar
    • Export Citation
  • 3.

    EngelsEAPfeifferRM. Malignant thymoma in the United States: demographic patterns in incidence and associations with subsequent malignancies. Int J Cancer2003;105:546551.

    • Search Google Scholar
    • Export Citation
  • 4.

    MasaokaA. Staging system of thymoma. J Thorac Oncol2010;5:S304312.

  • 5.

    KondoKMondenY. Therapy for thymic epithelial tumors: a clinical study of 1,320 patients from Japan. Ann Thorac Surg2003;76:878884; discussion 884-875.

    • Search Google Scholar
    • Export Citation
  • 6.

    EngTYFullerCDJagirdarJ. Thymic carcinoma: state of the art review. Int J Radiat Oncol Biol Phys2004;59:654664.

  • 7.

    MarchevskyAMarxAStrobelP. Policies and reporting guidelines for small biopsy specimens of mediastinal masses. J Thorac Oncol2011;6:S17241729.

    • Search Google Scholar
    • Export Citation
  • 8.

    StrolloDCRosado-de-ChristensonMLJettJR. Primary mediastinal tumors: part II. Tumors of the middle and posterior mediastinum. Chest1997;112:13441357.

    • Search Google Scholar
    • Export Citation
  • 9.

    DetterbeckFCParsonsAM. Management of stage I and II thymoma. Thorac Surg Clin2011;21:5967vi-vii.

  • 10.

    BarthTFELeithäuserFJoosS. Mediastinal (thymic) large B-cell lymphoma: where do we stand?Lancet Oncol2002;3:229234.

  • 11.

    FerollaPFalchettiAFilossoP. Thymic neuroendocrine carcinoma (carcinoid) in multiple endocrine neoplasia type 1 syndrome: the Italian series. J Clin Endocrinol Metab2005;90:26032609.

    • Search Google Scholar
    • Export Citation
  • 12.

    TehBT. Thymic carcinoids in multiple endocrine neoplasia type 1. J Intern Med1998;243:501504.

  • 13.

    MaromEM. Imaging thymoma. J Thorac Oncol2010;5:S296303.

  • 14.

    Rosado-de-ChristensonMLStrolloDCMaromEM. Imaging of thymic epithelial neoplasms. Hematol Oncol Clin North Am2008;22:409431.

  • 15.

    SadoharaJFujimotoKMullerNL. Thymic epithelial tumors: comparison of CT and MR imaging findings of low-risk thymomas, high-risk thymomas, and thymic carcinomas. Eur J Radiol2006;60:7079.

    • Search Google Scholar
    • Export Citation
  • 16.

    MaromEMRosado-de-ChristensonMLBruzziJF. Standard report terms for chest computed tomography reports of anterior mediastinal masses suspicious for thymoma. J Thorac Oncol2011;6:S17171723.

    • Search Google Scholar
    • Export Citation
  • 17.

    AberleDRAdamsAMBergCD. Reduced lung-cancer mortality with low-dose computed tomographic screening. N Engl J Med2011;365:395409.

  • 18.

    SungYMLeeKSKimBT. 18F-FDG PET/CT of thymic epithelial tumors: usefulness for distinguishing and staging tumor subgroups. J Nucl Med2006;47:16281634.

    • Search Google Scholar
    • Export Citation
  • 19.

    RuffiniEVan RaemdonckDDetterbeckF. Management of thymic tumors: a survey of current practice among members of the European Society of Thoracic Surgeons. J Thorac Oncol2011;6:614623.

    • Search Google Scholar
    • Export Citation
  • 20.

    KondoK. Optimal therapy for thymoma. J Med Invest2008;55:1728.

  • 21.

    DetterbeckFCParsonsAM. Thymic tumors. Ann Thorac Surg2004;77:18601869.

  • 22.

    WrightCD. Stage IVA thymoma: patterns of spread and surgical management. Thorac Surg Clin2011;21:9397vii.

  • 23.

    WrightCD. Extended resections for thymic malignancies. J Thorac Oncol2010;5:S344347.

  • 24.

    HuangJRizkNPTravisWD. Feasibility of multimodality therapy including extended resections in stage IVA thymoma. J Thorac Cardiovasc Surg2007;134:14771483; discussion 1483-1484.

    • Search Google Scholar
    • Export Citation
  • 25.

    TokerASonettJZielinskiM. Standard terms, definitions, and policies for minimally invasive resection of thymoma. J Thorac Oncol2011;6:S17391742.

    • Search Google Scholar
    • Export Citation
  • 26.

    PennathurAQureshiISchuchertMJ. Comparison of surgical techniques for early-stage thymoma: feasibility of minimally invasive thymectomy and comparison with open resection. J Thorac Cardiovasc Surg2011;141:694701.

    • Search Google Scholar
    • Export Citation
  • 27.

    KomanapalliCBCohenJISukumarMS. Extended transcervical video-assisted thymectomy. Thorac Surg Clin2010;20:235243.

  • 28.

    LimmerKKKernstineKH. Minimally invasive and robotic-assisted thymus resection. Thorac Surg Clin2011;21:6983vii.

  • 29.

    DetterbeckFCNicholsonAGKondoK. The Masaoka-Koga stage classification for thymic malignancies: clarification and definition of terms. J Thorac Oncol2011;6:S17101716.

    • Search Google Scholar
    • Export Citation
  • 30.

    HuangJDetterbeckFCWangZLoehrerPJSr.Standard outcome measures for thymic malignancies. J Thorac Oncol2011;6:S16911697.

  • 31.

    MoranCAWalshGSusterSKaiserL. Thymomas II: a clinicopathologic correlation of 250 cases with a proposed staging system with emphasis on pathologic assessment. Am J Clin Pathol2012;137:451461.

    • Search Google Scholar
    • Export Citation
  • 32.

    KondoK. Tumor-node metastasis staging system for thymic epithelial tumors. J Thorac Oncol2010;5:S352356.

  • 33.

    LeeHSKimSTLeeJ. A single institutional experience of thymic epithelial tumours over 11 years: clinical features and outcome and implications for future management. Br J Cancer2007;97:2228.

    • Search Google Scholar
    • Export Citation
  • 34.

    MasaokaAMondenYNakaharaKTaniokaT. Follow-up study of thymomas with special reference to their clinical stages. Cancer1981;48:24852492.

    • Search Google Scholar
    • Export Citation
  • 35.

    WrightCD. Management of thymomas. Crit Rev Oncol Hematol2008;65:109120.

  • 36.

    TravisWBrambillaEMuller-HermelinkHHarrisC. Pathology and genetics of tumours of the lung pleura thymus and heart. WHO Classification of Tumors3rd ed.Lyon: IARC Press; 2004:145197.

    • Search Google Scholar
    • Export Citation
  • 37.

    LewisJEWickMRScheithauerBW. Thymoma. A clinicopathologic review. Cancer1987;60:27272743.

  • 38.

    ParkHSShinDMLeeJS. Thymoma. A retrospective study of 87 cases. Cancer1994;73:24912498.

  • 39.

    KondoKYoshizawaKTsuyuguchiM. WHO histologic classification is a prognostic indicator in thymoma. Ann Thorac Surg2004;77:11831188.

  • 40.

    MoranCAWeissferdtAKalhorN. Thymomas I: a clinicopathologic correlation of 250 cases with emphasis on the World Health Organization schema. Am J Clin Pathol2012;137:444450.

    • Search Google Scholar
    • Export Citation
  • 41.

    MarxARiekerRTokerA. Thymic carcinoma: is it a separate entity? From molecular to clinical evidence. Thorac Surg Clin2011;21:2531v-vi.

    • Search Google Scholar
    • Export Citation
  • 42.

    MargaritoraSCesarioACusumanoG. Thirty-five-year follow-up analysis of clinical and pathologic outcomes of thymoma surgery. Ann Thorac Surg2010;89:245252; discussion 252.

    • Search Google Scholar
    • Export Citation
  • 43.

    RegnardJFMagdeleinatPDromerC. Prognostic factors and long-term results after thymoma resection: a series of 307 patients. J Thorac Cardiovasc Surg1996;112:376384.

    • Search Google Scholar
    • Export Citation
  • 44.

    YanoMSasakiHYokoyamaT. Thymic carcinoma: 30 cases at a single institution. J Thorac Oncol2008;3:265269.

  • 45.

    OgawaKToitaTUnoT. Treatment and prognosis of thymic carcinoma: a retrospective analysis of 40 cases. Cancer2002;94:31153119.

  • 46.

    OkerekeICKeslerKAFreemanRK. Thymic carcinoma: outcomes after surgical resection. Ann Thorac Surg2012;93:16681672; discussion 1672-1673.

    • Search Google Scholar
    • Export Citation
  • 47.

    DetterbeckFYoussefSRuffiniEOkumuraM. A review of prognostic factors in thymic malignancies. J Thorac Oncol2011;6:S1698–-1704.

  • 48.

    MehranRGhoshRMaziakD. Surgical treatment of thymoma. Can J Surg2002;45:2530.

  • 49.

    MurakawaTNakajimaJKohnoT. Results from surgical treatment for thymoma. 43 years of experience. Jpn J Thorac Cardiovasc Surg2000;48:8995.

    • Search Google Scholar
    • Export Citation
  • 50.

    WakelyPEJr.Fine needle aspiration in the diagnosis of thymic epithelial neoplasms. Hematol Oncol Clin North Am2008;22:433442.

  • 51.

    DetterbeckFCMoranCHuangJ. Which way is up? Policies and procedures for surgeons and pathologists regarding resection specimens of thymic malignancy. J Thorac Oncol2011;6:S17301738.

    • Search Google Scholar
    • Export Citation
  • 52.

    GilhusNEOweJFHoffJM. Myasthenia gravis: a review of available treatment approaches. Autoimmune Dis2011;2011:847393.

  • 53.

    Autoantibodies to acetylcholine receptors in myasthenia gravis. N Engl J Med1983;308:402403.

  • 54.

    HowardFMLennonVAFinleyJ. Clinical correlations of antibodies that bind, block, or modulate human acetylcholine receptors in myasthenia gravis. Ann N Y Acad Sci1987;505:526538.

    • Search Google Scholar
    • Export Citation
  • 55.

    UtsumiTShionoHKadotaY. Postoperative radiation therapy after complete resection of thymoma has little impact on survival. Cancer2009;115:54135420.

    • Search Google Scholar
    • Export Citation
  • 56.

    KorstRJKanslerALChristosPJMandalS. Adjuvant radiotherapy for thymic epithelial tumors: a systematic review and meta-analysis. Ann Thorac Surg2009;87:16411647.

    • Search Google Scholar
    • Export Citation
  • 57.

    ForquerJARongNFakirisAJ. Postoperative radiotherapy after surgical resection of thymoma: differing roles in localized and regional disease. Int J Radiat Oncol Biol Phys2010;76:440445.

    • Search Google Scholar
    • Export Citation
  • 58.

    RuffiniEMancusoMOliaroA. Recurrence of thymoma: analysis of clinicopathologic features, treatment, and outcome. J Thorac Cardiovasc Surg1997;113:5563.

    • Search Google Scholar
    • Export Citation
  • 59.

    GomezDKomakiRYuJ. Radiation therapy definitions and reporting guidelines for thymic malignancies. J Thorac Oncol2011;6:S17431748.

  • 60.

    GomezDKomakiR. Technical advances of radiation therapy for thymic malignancies. J Thorac Oncol2010;5:S336343.

  • 61.

    HartfordACPaliscaMGEichlerTJ. American Society for Therapeutic Radiology and Oncology (ASTRO) and American College of Radiology (ACR) Practice Guidelines for Intensity-Modulated Radiation Therapy (IMRT). Int J Radiat Oncol Biol Phys2009;73:914.

    • Search Google Scholar
    • Export Citation
  • 62.

    MoranJMDempseyMEisbruchA. Safety considerations for IMRT: executive summary. Med Phys2011;38:50675072.

  • 63.

    GregoireVMackieTR. State of the art on dose prescription, reporting and recording in intensity-modulated radiation therapy (ICRU report No. 83). Cancer Radiother2011;15:555559.

    • Search Google Scholar
    • Export Citation
  • 64.

    HolmesTDasRLowD. American Society of Radiation Oncology recommendations for documenting intensity-modulated radiation therapy treatments. Int J Radiat Oncol Biol Phys2009;74:13111318.

    • Search Google Scholar
    • Export Citation
  • 65.

    KongFMPanCEisbruchATen HakenRK. Physical models and simpler dosimetric descriptors of radiation late toxicity. Semin Radiat Oncol2007;17:108120.

    • Search Google Scholar
    • Export Citation
  • 66.

    MilanoMTConstineLSOkunieffP. Normal tissue tolerance dose metrics for radiation therapy of major organs. Semin Radiat Oncol2007;17:131140.

    • Search Google Scholar
    • Export Citation
  • 67.

    MyojinMChoiNCWrightCD. Stage III thymoma: pattern of failure after surgery and postoperative radiotherapy and its implication for future study. Int J Radiat Oncol Biol Phys2000;46:927933.

    • Search Google Scholar
    • Export Citation
  • 68.

    MornexFResbeutMRichaudP. 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 Phys1995;32:651659.

    • Search Google Scholar
    • Export Citation
  • 69.

    SinghalSShragerJBRosenthalDI. Comparison of stages I-II thymoma treated by complete resection with or without adjuvant radiation. Ann Thorac Surg2003;76:16351641; discussion 1641-1642.

    • Search Google Scholar
    • Export Citation
  • 70.

    RenaOPapaliaEOliaroA. Does adjuvant radiation therapy improve disease-free survival in completely resected Masaoka stage II thymoma?Eur J Cardiothorac Surg2007;31:109113.

    • Search Google Scholar
    • Export Citation
  • 71.

    MangiAAWrightCDAllanJS. Adjuvant radiation therapy for stage II thymoma. Ann Thorac Surg2002;74:10331037.

  • 72.

    SugieCShibamotoYIkeya-HashizumeC. Invasive thymoma: postoperative mediastinal irradiation, and low-dose entire hemithorax irradiation in patients with pleural dissemination. J Thorac Oncol2008;3:7581.

    • Search Google Scholar
    • Export Citation
  • 73.

    OgawaKUnoTToitaT. Postoperative radiotherapy for patients with completely resected thymoma: a multi-institutional, retrospective review of 103 patients. Cancer2002;94:14051413.

    • Search Google Scholar
    • Export Citation
  • 74.

    CowenDRichaudPMornexF. Thymoma: results of a multicentric retrospective series of 149 non-metastatic irradiated patients and review of the literature. FNCLCC trialists. Federation Nationale des Centres de Lutte Contre le Cancer. Radiother Oncol1995;34:916.

    • Search Google Scholar
    • Export Citation
  • 75.

    GirardNLalRWakeleeH. Chemotherapy definitions and policies for thymic malignancies. J Thorac Oncol2011;6:S17491755.

  • 76.

    GirardN. Chemotherapy and targeted agents for thymic malignancies. Expert Rev Anticancer Ther2012;12:685695.

  • 77.

    LoehrerPJSr.ChenMKimK. Cisplatin, doxorubicin, and cyclophosphamide plus thoracic radiation therapy for limited-stage unresectable thymoma: an Intergroup trial. J Clin Oncol1997;15:30933099.

    • Search Google Scholar
    • Export Citation
  • 78.

    LoehrerPJKimKAisnerSC. 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 Oncol1994;12:11641168.

    • Search Google Scholar
    • Export Citation
  • 79.

    GiacconeGArdizzoniAKirkpatrickA. 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 Oncol1996;14:814820.

    • Search Google Scholar
    • Export Citation
  • 80.

    ShinDMWalshGLKomakiR. A multidisciplinary approach to therapy for unresectable malignant thymoma. Ann Intern Med1998;129:100104.

  • 81.

    FornasieroADanieleOGhiottoC. Chemotherapy for invasive thymoma. A 13-year experience. Cancer1991;68:3033.

  • 82.

    LoehrerPJJiroutekMAisnerS. Combined etoposide, ifosfamide, and cisplatin in the treatment of patients with advanced thymoma and thymic carcinoma: an intergroup trial. Cancer2001;91:20102015.

    • Search Google Scholar
    • Export Citation
  • 83.

    KimESPutnamJBKomakiR. 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 Cancer2004;44:369379.

    • Search Google Scholar
    • Export Citation
  • 84.

    LucchiMMelfiFDiniP. Neoadjuvant chemotherapy for stage III and IVA thymomas: a single-institution experience with a long follow-up. J Thorac Oncol2006;1:308313.

    • Search Google Scholar
    • Export Citation
  • 85.

    YokoiKMatsugumaHNakaharaR. Multidisciplinary treatment for advanced invasive thymoma with cisplatin, doxorubicin, and methylprednisolone. J Thorac Oncol2007;2:7378.

    • Search Google Scholar
    • Export Citation
  • 86.

    LemmaGLLoehrerPJSr.LeeJW. A phase II study of carboplatin plus paclitaxel in advanced thymoma or thymic carcinoma: E1C99 [abstract]. J Clin Oncol2008;26(Suppl 15):Abstract 8018.

    • Search Google Scholar
    • Export Citation
  • 87.

    VenutaFRendinaEALongoF. Long-term outcome after multimodality treatment for stage III thymic tumors. Ann Thorac Surg2003;76:18661872; discussion 1872.

    • Search Google Scholar
    • Export Citation
  • 88.

    RajanAGiacconeG. Chemotherapy for thymic tumors: induction, consolidation, palliation. Thorac Surg Clin2011;21:107114viii.

  • 89.

    SchmittJLoehrerPJSr.The role of chemotherapy in advanced thymoma. J Thorac Oncol2010;5:S357360.

  • 90.

    LemmaGLLeeJWAisnerSC. Phase II study of carboplatin and paclitaxel in advanced thymoma and thymic carcinoma. J Clin Oncol2011;29:20602065.

    • Search Google Scholar
    • Export Citation
  • 91.

    FurugenMSekineITsutaK. Combination chemotherapy with carboplatin and paclitaxel for advanced thymic cancer. Jpn J Clin Oncol2011;41:10131016.

    • Search Google Scholar
    • Export Citation
  • 92.

    RielyGJHuangJ. Induction therapy for locally advanced thymoma. J Thorac Oncol2010;5:S323326.

  • 93.

    WrightCDChoiNCWainJC. Induction chemoradiotherapy followed by resection for locally advanced Masaoka stage III and IVA thymic tumors. Ann Thorac Surg2008;85:385389.

    • Search Google Scholar
    • Export Citation
  • 94.

    LongoFDe FilippisLZiviA. Efficacy and tolerability of long-acting octreotide in the treatment of thymic tumors: results of a pilot trial. Am J Clin Oncol2012;35:105109.

    • Search Google Scholar
    • Export Citation
  • 95.

    LoehrerPJSr.WangWJohnsonDH. Octreotide alone or with prednisone in patients with advanced thymoma and thymic carcinoma: an Eastern Cooperative Oncology Group Phase II Trial. J Clin Oncol2004;22:293299.

    • Search Google Scholar
    • Export Citation
  • 96.

    PalmieriGMerolaGFedericoP. Preliminary results of phase II study of capecitabine and gemcitabine (CAP-GEM) in patients with metastatic pretreated thymic epithelial tumors (TETs). Ann Oncol2010;21:11681172.

    • Search Google Scholar
    • Export Citation
  • 97.

    HighleyMSUnderhillCRParnisFX. Treatment of invasive thymoma with single-agent ifosfamide. J Clin Oncol1999;17:27372744.

  • 98.

    PanCCChenPCWangLS. Thymoma is associated with an increased risk of second malignancy. Cancer2001;92:24062411.

  • 99.

    SusterSRosaiJ. Thymic carcinoma. A clinicopathologic study of 60 cases. Cancer1991;67:10251032.

  • 100.

    HuangJRizkNPTravisWD. Comparison of patterns of relapse in thymic carcinoma and thymoma. J Thorac Cardiovasc Surg2009;138:2631.

  • 101.

    StrobelPHohenbergerPMarxA. Thymoma and thymic carcinoma: molecular pathology and targeted therapy. J Thorac Oncol2010;5:S286290.

  • 102.

    MoranCASusterS. Thymic carcinoma: current concepts and histologic features. Hematol Oncol Clin North Am2008;22:393407.

  • 103.

    HosakaYTsuchidaMToyabeS. Masaoka stage and histologic grade predict prognosis in patients with thymic carcinoma. Ann Thorac Surg2010;89:912917.

    • Search Google Scholar
    • Export Citation
  • 104.

    BlumbergDBurtMEBainsMS. Thymic carcinoma: current staging does not predict prognosis. J Thorac Cardiovasc Surg1998;115:303308; discussion 308-309.

    • Search Google Scholar
    • Export Citation
  • 105.

    MaruyamaRSuemitsuROkamotoT. Persistent and aggressive treatment for thymic carcinoma. Results of a single-institute experience with 25 patients. Oncology2006;70:325329.

    • Search Google Scholar
    • Export Citation
  • 106.

    WeideLGUlbrightTMLoehrerPJWilliamsSD. Thymic carcinoma. A distinct clinical entity responsive to chemotherapy. Cancer1993;71:12191223.

    • Search Google Scholar
    • Export Citation
  • 107.

    LucchiMMussiAAmbrogiM. Thymic carcinoma: a report of 13 cases. Eur J Surg Oncol2001;27:636640.

  • 108.

    YohKGotoKIshiiGI. Weekly chemotherapy with cisplatin, vincristine, doxorubicin, and etoposide is an effective treatment for advanced thymic carcinoma. Cancer2003;98:926931.

    • Search Google Scholar
    • Export Citation
  • 109.

    IgawaSMurakamiHTakahashiT. Efficacy of chemotherapy with carboplatin and paclitaxel for unresectable thymic carcinoma. Lung Cancer2010;67:194197.

    • Search Google Scholar
    • Export Citation
  • 110.

    KoizumiTTakabayashiYYamagishiS. Chemotherapy for advanced thymic carcinoma: clinical response to cisplatin, doxorubicin, vincristine, and cyclophosphamide (ADOC chemotherapy). Am J Clin Oncol2002;25:266268.

    • Search Google Scholar
    • Export Citation
  • 111.

    KandaSKoizumiTKomatsuY. Second-line chemotherapy of platinum compound plus CPT-11 following ADOC chemotherapy in advanced thymic carcinoma: analysis of seven cases. Anticancer Res2007;27:30053008.

    • Search Google Scholar
    • Export Citation
  • 112.

    KomatsuYKoizumiTTanabeT. Salvage chemotherapy with carboplatin and paclitaxel for cisplatin-resistant thymic carcinoma—three cases. Anticancer Res2006;26:48514855.

    • Search Google Scholar
    • Export Citation
  • 113.

    OkumaYShimokawaTTakagiY. S-1 is an active anticancer agent for advanced thymic carcinoma. Lung Cancer2010;70:357363.

  • 114.

    KoizumiTAgatsumaTKomatsuYKuboK. Successful S-1 monotherapy for chemorefractory thymic carcinoma. Anticancer Res2011;31:299301.

  • 115.

    StrobelPBargouRWolffA. Sunitinib in metastatic thymic carcinomas: laboratory findings and initial clinical experience. Br J Cancer2010;103:196200.

    • Search Google Scholar
    • Export Citation
  • 116.

    BisagniGRossiGCavazzaA. Long lasting response to the multikinase inhibitor bay 43-9006 (Sorafenib) in a heavily pretreated metastatic thymic carcinoma. J Thorac Oncol2009;4:773775.

    • Search Google Scholar
    • Export Citation
  • 117.

    StrobelPHartmannMJakobA. Thymic carcinoma with overexpression of mutated KIT and the response to imatinib. N Engl J Med2004;350:26252626.

    • Search Google Scholar
    • Export Citation
  • 118.

    GirardN. Targeted therapies for thymic malignancies. Thorac Surg Clin2011;21:115123viii.

Article Information

Cited By

PubMed

Google Scholar

Related Articles

Metrics

All Time Past Year Past 30 Days
Abstract Views 0 0 0
Full Text Views 289 288 38
PDF Downloads 99 99 16
EPUB Downloads 0 0 0