Childhood Thymoma and Thymic Carcinoma Treatment (PDQ®)

NCI PDQ Summaries for Patients

General Information About Childhood Thymoma and Thymic Carcinoma
Childhood Thymoma
Childhood Thymic Carcinoma
Special Considerations for the Treatment of Children With Cancer
Changes to This Summary (10/02/2019)
About This PDQ Summary

Childhood Thymoma and Thymic Carcinoma Treatment

General Information About Childhood Thymoma and Thymic Carcinoma

Thymoma and thymic carcinoma originate within the epithelial cells of the thymus, resulting in an anterior mediastinal mass. The term thymoma is customarily used to describe neoplasms that show no overt atypia of the epithelial component, whereas, a thymic epithelial tumor that exhibits clear-cut cytologic atypia and histologic features no longer specific to the thymus is known as thymic carcinoma or type C thymoma. Thymic carcinomas have a higher incidence of capsular invasion and metastases. Other tumors that involve the thymus gland include lymphomas, germ cell tumors, carcinomas, and carcinoids. Hodgkin lymphoma and non-Hodgkin lymphoma may also involve the thymus and must be differentiated from true thymomas and thymic carcinomas.

Carretto E, Inserra A, Ferrari A, et al.: Epithelial thymic tumours in paediatric age: a report from the TREP project. Orphanet J Rare Dis 6: 28, 2011.

Kelly RJ, Petrini I, Rajan A, et al.: Thymic malignancies: from clinical management to targeted therapies. J Clin Oncol 29 (36): 4820-7, 2011.

Suster S, Moran CA: Thymoma classification: current status and future trends. Am J Clin Pathol 125 (4): 542-54, 2006.

Childhood Thymoma

Incidence and Outcome

Primary tumors of the thymus are exceptionally rare in children; very few pediatric series have been reported.

The following studies have reported on outcomes associated with thymoma:

  • A review of the Surveillance, Epidemiology, and End Results (SEER) registry from 1973 to 2008 identified 73 cases of malignant anterior mediastinal tumors in patients younger than 20 years. Of these cases, 32% were thymoma, 29% were non-Hodgkin lymphoma, and 22% were Hodgkin lymphoma. Patients with thymoma had a worse survival at 10 years than did patients with lymphoma. Patients with thymoma who were treated in an earlier era from 1973 to 1989 had a 10-year survival rate of 18%; patients who were treated between 1991 and 2008 had a 75% survival rate. Presence of metastatic disease and treatment without surgery were associated with a worse outcome.
  • A review of 48 published cases of thymoma in patients younger than 18 years, excluding thymic carcinoma, found an association between stage of disease and survival; it also suggested guidelines for treatment. The overall 2-year survival in this series was 71%.
  • The European Cooperative Study Group for Pediatric Rare Tumors identified 16 children with thymoma between 2000 and 2012. Complete resection was achieved in 11 of 16 patients with thymoma. Fourteen of the 16 patients with thymoma were alive and well at a median of 5 years from diagnosis.

Clinical Presentation

These neoplasms are usually located in the anterior mediastinum and discovered during a routine chest x-ray. Symptoms may include the following:

  • Cough.
  • Difficulty with swallowing.
  • Tightness of the chest.
  • Chest pain.
  • Shortness of breath
  • Superior vena cava syndrome.

About 40% of adults with thymoma have one or more paraneoplastic disorders during their lifetime. The most common associated disorder is myasthenia gravis, which occurs in approximately 30% of adult patients. This disorder has also been reported in children and is important to recognize it before a thoracotomy of a suspected thymoma. Various other paraneoplastic syndromes have been found to be associated with thymoma. These include pure red cell aplasia, hypogammaglobulinemia, nephrotic syndrome, and autoimmune or immune disorders such as scleroderma, dermatomyositis, systemic lupus erythematosus, rheumatoid arthritis, and thyroiditis. Endocrine disorders associated with thymoma include hyperthyroidism, Addison disease, and panhypopituitarism.

Treatment of Childhood Thymoma

Treatment options for childhood thymoma include the following:

  • Surgery. Surgery is the mainstay of therapy and an attempt should be made to resect all disease.
  • Radiation therapy. Thymoma is relatively radiosensitive, and radiation therapy is recommended for patients with unresectable or incompletely resected invasive disease. Radiation dosage recommendations are based on the age of the child and the extent of tumor invasion. Total doses of 45 Gy to 50 Gy are recommended for control of clear or close margins, 54 Gy for microscopically positive margins, and doses of at least 60 Gy for patients with bulky residual disease.
  • Chemotherapy. Chemotherapy is usually reserved for patients with advanced-stage disease who have not responded to radiation therapy or corticosteroids. Agents that have been effective include doxorubicin, cyclophosphamide, etoposide, cisplatin, ifosfamide, and vincristine. Responses to regimens containing combinations of some of these agents have ranged from 26% to 100%, and survival rates have been as high as 50%.
  • Octreotide. Because thymoma shows high uptake of indium In 111–labeled octreotide, trials using this somatostatin analogue have been conducted in patients with refractory disease. In an Eastern Cooperative Oncology Group phase II trial of 42 patients, 4 patients had partial responses to octreotide alone and 8 patients responded with the addition of prednisone to octreotide.
  • Sunitinib. In an open-label phase II study of sunitinib in adult patients with refractory thymoma, partial responses were observed in 6% of patients with thymoma, and stable disease was achieved in 75% of patients with thymoma.
  • (Refer to the PDQ summary on Thymoma and Thymic Carcinoma Treatment [Adult] for more information about the treatment of thymoma.)

    Treatment Options Under Clinical Evaluation for Childhood Thymoma

    Information about National Cancer Institute (NCI)–supported clinical trials can be found on the NCI website. For information about clinical trials sponsored by other organizations, refer to the ClinicalTrials.gov website.

    The following is an example of a national and/or institutional clinical trial that is currently being conducted:

    • APEC1621 (NCT03155620) (Pediatric MATCH: Targeted Therapy Directed by Genetic Testing in Treating Pediatric Patients with Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphomas, or Histiocytic Disorders): NCI-COG Pediatric Molecular Analysis for Therapeutic Choice (MATCH), referred to as Pediatric MATCH, will match targeted agents with specific molecular changes identified using a next-generation sequencing targeted assay of more than 4,000 different mutations across more than 160 genes in refractory and recurrent solid tumors. Children and adolescents aged 1 to 21 years are eligible for the trial.

      Tumor tissue from progressive or recurrent disease must be available for molecular characterization. Patients with tumors that have molecular variants addressed by treatment arms included in the trial will be offered treatment on Pediatric MATCH. Additional information can be obtained on the NCI website and ClinicalTrials.gov website.

    Carretto E, Inserra A, Ferrari A, et al.: Epithelial thymic tumours in paediatric age: a report from the TREP project. Orphanet J Rare Dis 6: 28, 2011.

    Allan BJ, Thorson CM, Davis JS, et al.: An analysis of 73 cases of pediatric malignant tumors of the thymus. J Surg Res 184 (1): 397-403, 2013.

    Fonseca AL, Ozgediz DE, Christison-Lagay ER, et al.: Pediatric thymomas: report of two cases and comprehensive review of the literature. Pediatr Surg Int 30 (3): 275-86, 2014.

    Stachowicz-Stencel T, Orbach D, Brecht I, et al.: Thymoma and thymic carcinoma in children and adolescents: a report from the European Cooperative Study Group for Pediatric Rare Tumors (EXPeRT). Eur J Cancer 51 (16): 2444-52, 2015.

    Thomas CR, Wright CD, Loehrer PJ: Thymoma: state of the art. J Clin Oncol 17 (7): 2280-9, 1999.

    Tormoehlen LM, Pascuzzi RM: Thymoma, myasthenia gravis, and other paraneoplastic syndromes. Hematol Oncol Clin North Am 22 (3): 509-26, 2008.

    Cowen D, Richaud P, Mornex F, et al.: Thymoma: results of a multicentric retrospective series of 149 non-metastatic irradiated patients and review of the literature. FNCLCC trialists. Fédération Nationale des Centres de Lutte Contre le Cancer. Radiother Oncol 34 (1): 9-16, 1995.

    Tomaszek S, Wigle DA, Keshavjee S, et al.: Thymomas: review of current clinical practice. Ann Thorac Surg 87 (6): 1973-80, 2009.

    National Comprehensive Cancer Network: NCCN Clinical Practice Guidelines in Oncology: Thymomas and Thymic Carcinoma. Version 2.2018. Fort Washington, Pa: National Comprehensive Cancer Network, 2018 . Available online with free subscription. Last accessed June 04, 2019.

    Casey EM, Kiel PJ, Loehrer PJ: Clinical management of thymoma patients. Hematol Oncol Clin North Am 22 (3): 457-73, 2008.

    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.

    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.

    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.

    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.

    Childhood Thymic Carcinoma

    The European Cooperative Study Group for Pediatric Rare Tumors identified 20 patients with thymic carcinoma between 2000 and 2012. Complete resection was achieved in 1 of 20 patients with thymic carcinoma. Five patients with thymic carcinoma survived. Five-year overall survival (OS) for patients with thymic carcinoma was 21.0%.

    Treatment of Childhood Thymic Carcinoma

    Treatment options for childhood thymic carcinoma include the following:

  • Surgery. Surgery is the mainstay of therapy and an attempt should be made to resect all disease.
  • Radiation therapy. Thymic carcinoma is relatively radiosensitive, and radiation therapy is recommended for patients with unresectable or incompletely resected invasive disease. Radiation dosage recommendations are based on the age of the child and the extent of tumor invasion. Total doses of 45 Gy to 50 Gy are recommended for control of clear or close margins, 54 Gy for microscopically positive margins, and doses of at least 60 Gy for patients with bulky residual disease.
  • Chemotherapy (as described for thymoma). Response rates are lower for patients with thymic carcinoma, but 2-year survival rates have been reported to be as high as 50%.
  • Sunitinib. In an open-label phase II study of sunitinib in adult patients with refractory thymic carcinoma, partial responses were observed in 26% of patients with thymic carcinoma and stable disease was achieved in 65% of patients with thymic carcinoma.
  • (Refer to the PDQ summary on Thymoma and Thymic Carcinoma Treatment [Adult] for more information about the treatment of thymic carcinoma.)

    Treatment Options Under Clinical Evaluation for Childhood Thymic Carcinoma

    Information about National Cancer Institute (NCI)–supported clinical trials can be found on the NCI website. For information about clinical trials sponsored by other organizations, refer to the ClinicalTrials.gov website.

    The following is an example of a national and/or institutional clinical trial that is currently being conducted:

    • APEC1621 (NCT03155620) (Pediatric MATCH: Targeted Therapy Directed by Genetic Testing in Treating Pediatric Patients with Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphomas, or Histiocytic Disorders): NCI-COG Pediatric Molecular Analysis for Therapeutic Choice (MATCH), referred to as Pediatric MATCH, will match targeted agents with specific molecular changes identified using a next-generation sequencing targeted assay of more than 4,000 different mutations across more than 160 genes in refractory and recurrent solid tumors. Children and adolescents aged 1 to 21 years are eligible for the trial.

      Tumor tissue from progressive or recurrent disease must be available for molecular characterization. Patients with tumors that have molecular variants addressed by treatment arms included in the trial will be offered treatment on Pediatric MATCH. Additional information can be obtained on the NCI website and ClinicalTrials.gov website.

    Stachowicz-Stencel T, Orbach D, Brecht I, et al.: Thymoma and thymic carcinoma in children and adolescents: a report from the European Cooperative Study Group for Pediatric Rare Tumors (EXPeRT). Eur J Cancer 51 (16): 2444-52, 2015.

    Tomaszek S, Wigle DA, Keshavjee S, et al.: Thymomas: review of current clinical practice. Ann Thorac Surg 87 (6): 1973-80, 2009.

    Cowen D, Richaud P, Mornex F, et al.: Thymoma: results of a multicentric retrospective series of 149 non-metastatic irradiated patients and review of the literature. FNCLCC trialists. Fédération Nationale des Centres de Lutte Contre le Cancer. Radiother Oncol 34 (1): 9-16, 1995.

    National Comprehensive Cancer Network: NCCN Clinical Practice Guidelines in Oncology: Thymomas and Thymic Carcinoma. Version 2.2018. Fort Washington, Pa: National Comprehensive Cancer Network, 2018 . Available online with free subscription. Last accessed June 04, 2019.

    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.

    Carlson RW, Dorfman RF, Sikic BI: Successful treatment of metastatic thymic carcinoma with cisplatin, vinblastine, bleomycin, and etoposide chemotherapy. Cancer 66 (10): 2092-4, 1990.

    Stachowicz-Stencel T, Bien E, Balcerska A, et al.: Thymic carcinoma in children: a report from the Polish Pediatric Rare Tumors Study. Pediatr Blood Cancer 54 (7): 916-20, 2010.

    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.

    Special Considerations for the Treatment of Children With Cancer

    Cancer in children and adolescents is rare, although the overall incidence of childhood cancer has been slowly increasing since 1975. Referral to medical centers with multidisciplinary teams of cancer specialists experienced in treating cancers that occur in childhood and adolescence should be considered for children and adolescents with cancer. This multidisciplinary team approach incorporates the skills of the following health care professionals and others to ensure that children receive treatment, supportive care, and rehabilitation that will achieve optimal survival and quality of life:

    • Primary care physicians.
    • Pediatric surgeons.
    • Radiation oncologists.
    • Pediatric medical oncologists/hematologists.
    • Rehabilitation specialists.
    • Pediatric nurse specialists.
    • Social workers.
    • Child-life professionals.
    • Psychologists.

    (Refer to the PDQ Supportive and Palliative Care summaries for specific information about supportive care for children and adolescents with cancer.)

    Guidelines for pediatric cancer centers and their role in the treatment of pediatric patients with cancer have been outlined by the American Academy of Pediatrics. At these pediatric cancer centers, clinical trials are available for most types of cancer that occur in children and adolescents, and the opportunity to participate in these trials is offered to most patients and their families. Clinical trials for children and adolescents diagnosed with cancer are generally designed to compare potentially better therapy with therapy that is currently accepted as standard. Most of the progress made in identifying curative therapy for childhood cancers has been achieved through clinical trials. Information about ongoing clinical trials is available from the NCI website.

    Dramatic improvements in survival have been achieved for children and adolescents with cancer. Between 1975 and 2010, childhood cancer mortality decreased by more than 50%. Childhood and adolescent cancer survivors require close monitoring because cancer therapy side effects may persist or develop months or years after treatment. (Refer to the PDQ summary on Late Effects of Treatment for Childhood Cancer for specific information about the incidence, type, and monitoring of late effects in childhood and adolescent cancer survivors.)

    Childhood cancer is a rare disease, with about 15,000 cases diagnosed annually in the United States in individuals younger than 20 years. The U.S. Rare Diseases Act of 2002 defines a rare disease as one that affects populations smaller than 200,000 persons. Therefore, all pediatric cancers are considered rare.

    The designation of a rare tumor is not uniform among pediatric and adult groups. Adult rare cancers are defined as those with an annual incidence of fewer than six cases per 100,000 people, and they are estimated to account for up to 24% of all cancers diagnosed in the European Union and about 20% of all cancers diagnosed in the United States. Also, the designation of a pediatric rare tumor is not uniform among international groups, as follows:

    • The Italian cooperative project on rare pediatric tumors (Tumori Rari in Eta Pediatrica [TREP]) defines a pediatric rare tumor as one with an incidence of less than two cases per 1 million population per year and is not included in other clinical trials.
    • The Children's Oncology Group has opted to define rare pediatric cancers as those listed in the International Classification of Childhood Cancer subgroup XI, which includes thyroid cancer, melanoma and nonmelanoma skin cancers, and multiple types of carcinomas (e.g., adrenocortical carcinoma, nasopharyngeal carcinoma, and most adult-type carcinomas such as breast cancer, colorectal cancer, etc.). These diagnoses account for about 4% of cancers diagnosed in children aged 0 to 14 years, compared with about 20% of cancers diagnosed in adolescents aged 15 to 19 years.

      Most cancers within subgroup XI are either melanomas or thyroid cancer, with the remaining subgroup XI cancer types accounting for only 1.3% of cancers in children aged 0 to 14 years and 5.3% of cancers in adolescents aged 15 to 19 years.

    These rare cancers are extremely challenging to study because of the low incidence of patients with any individual diagnosis, the predominance of rare cancers in the adolescent population, and the lack of clinical trials for adolescents with rare cancers.

    Information about these tumors may also be found in sources relevant to adults with cancer such as the PDQ summary on Thymoma and Thymic Carcinoma Treatment (Adult).

    Smith MA, Seibel NL, Altekruse SF, et al.: Outcomes for children and adolescents with cancer: challenges for the twenty-first century. J Clin Oncol 28 (15): 2625-34, 2010.

    Corrigan JJ, Feig SA; American Academy of Pediatrics: Guidelines for pediatric cancer centers. Pediatrics 113 (6): 1833-5, 2004.

    Smith MA, Altekruse SF, Adamson PC, et al.: Declining childhood and adolescent cancer mortality. Cancer 120 (16): 2497-506, 2014.

    Ward E, DeSantis C, Robbins A, et al.: Childhood and adolescent cancer statistics, 2014. CA Cancer J Clin 64 (2): 83-103, 2014 Mar-Apr.

    Gatta G, Capocaccia R, Botta L, et al.: Burden and centralised treatment in Europe of rare tumours: results of RARECAREnet-a population-based study. Lancet Oncol 18 (8): 1022-1039, 2017.

    DeSantis CE, Kramer JL, Jemal A: The burden of rare cancers in the United States. CA Cancer J Clin 67 (4): 261-272, 2017.

    Ferrari A, Bisogno G, De Salvo GL, et al.: The challenge of very rare tumours in childhood: the Italian TREP project. Eur J Cancer 43 (4): 654-9, 2007.

    Pappo AS, Krailo M, Chen Z, et al.: Infrequent tumor initiative of the Children's Oncology Group: initial lessons learned and their impact on future plans. J Clin Oncol 28 (33): 5011-6, 2010.

    Howlader N, Noone AM, Krapcho M, et al., eds.: SEER Cancer Statistics Review, 1975-2012. Bethesda, Md: National Cancer Institute, 2015. Also available online. Last accessed June 04, 2019.

    Changes to This Summary (10/02/2019)

    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.

    This is a new summary.

    This summary is written and maintained by the PDQ Pediatric 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 childhood 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 Pediatric 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:

    • be discussed at a meeting,
    • be cited with text, or
    • replace or update an existing article that is already cited.

    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.

    The lead reviewers for Childhood Thymoma and Thymic Carcinoma Treatment are:

    • Denise Adams, MD (Children's Hospital Boston)
    • Karen J. Marcus, MD, FACR (Dana-Farber Cancer Institute/Boston Children's Hospital)
    • Paul A. Meyers, MD (Memorial Sloan-Kettering Cancer Center)
    • Thomas A. Olson, MD (Aflac Cancer and Blood Disorders Center of Children's Healthcare of Atlanta - Egleston Campus)
    • Alberto S. Pappo, MD (St. Jude Children's Research Hospital)
    • Arthur Kim Ritchey, MD (Children's Hospital of Pittsburgh of UPMC)
    • Carlos Rodriguez-Galindo, MD (St. Jude Children's Research Hospital)
    • Stephen J. Shochat, MD (St. Jude Children's Research Hospital)

    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 Pediatric Treatment Editorial Board uses a formal evidence ranking system in developing its level-of-evidence designations.

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    The preferred citation for this PDQ summary is:

    PDQ® Pediatric Treatment Editorial Board. PDQ Childhood Thymoma and Thymic Carcinoma Treatment. Bethesda, MD: National Cancer Institute. Updated <MM/DD/YYYY>. Available at: https://www.cancer.gov/types/thymoma/hp/child-thymoma-treatment-pdq. Accessed <MM/DD/YYYY>.

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    Date last modified: 2019-10-02