Standard Treatment Options

Surgery

The classical surgical approach for thymic epithelial tumors is a sternotomy providing a wide access to the prevascular (anterior) mediastinum where the tumor is located. For very large tumors a so-called clamshell approach may be used to remove the tumor completely; this transverse incision extends on both sides of the chest giving broad access to the heart, mediastinum and both lungs.

During the last decade minimally invasive approaches have been more widely used. These include video-assisted thoracic surgery (VATS) and robotic-assisted thoracic surgery (RATS). The operation is performed by several small incisions (thoracoports) reducing the amount of pain and allowing more rapid recovery, especially in patients with myasthenia gravis. Several variations of VATS and RATS exist, also depending on the specific center and the experience of the individual surgeon. Depending on the location of the tumor, a left-sided or right-sided approach is used and more recently, the operation has been performed by an incision below the sternum (subxiphoid). The robotic approach provides a magnified 3-dimensional view with highly flexible robotic arms allowing a very precise dissection. However, the cost of RATS is much higher compared to the other techniques.

Minimally invasive approaches are generally used for clearly resectable tumors until 5 cm without invasion of neighbouring organs or structures.

More about minimally invasive surgery of the thymus you can find in a special series published in Mediastinum: Minimally Invasive Thymectomy.

For unresectable tumors only a biopsy is taken after discussion in a multidisciplinary tumor board. This is mostly performed by a 3-4 cm incision on the left or right side of the sternum (anterior mediastinoscopy) which provides immediate access to an anteriorly located tumor allowing large incisional biopsies which are essential to provide a definite diagnosis. For these, stage III or IV tumors multimodality therapy is indicated.

Oncological treatment

Chemotherapy

Chemotherapy is the definitive treatment for inoperable or recurrent thymoma and thymic carcinoma. It can also be used to decrease the size of potentially operable tumors in order to increase the chances of successful surgery. Several chemotherapy drugs are active against thymic cancers. These include cisplatin, carboplatin, doxorubicin, cyclophosphamide, paclitaxel, etoposide, pemetrexed, gemcitabine, capecitabine and ifosfamide.

In general, a combination of chemotherapy drugs is used for treatment of newly diagnosed inoperable thymic cancers or for pre-surgical treatment of locally advanced disease. Recurrent thymic cancers are usually treated with a single drug, although combination chemotherapy can also be considered in select cases. Commonly used combinations for treatment of newly diagnosed advanced thymoma or thymic carcinoma include cisplatin with doxorubicin and cyclophosphamide (commonly referred to as the PAC or CAP regimen), cisplatin with etoposide, or carboplatin with paclitaxel. These regimens can be used for pre-surgical treatment as well. Recurrent thymoma is often treated with single-agent pemetrexed, gemcitabine, capecitabine or a taxane drug, if not previously used (taxanes include paclitaxel, docetaxel or nab-paclitaxel). Recurrent thymic carcinoma can be treated with gemcitabine, capecitabine or a taxane. Pemetrexed is not as effective against recurrent thymic carcinoma as it is against recurrent thymoma. A combination of gemcitabine with capecitabine has also been evaluated in patients with recurrent thymoma or thymic carcinoma and found to be effective.

With the exception of capecitabine, all the chemotherapy drugs listed above are administered intravenously with appropriate ancillary medicines to decrease the risk of side effects. Intravenous hydration is also required for some forms of chemotherapy, such as cisplatin. Administration of chemotherapy is usually performed in the outpatient setting, although this is dependent on local practice patterns.

Side effects of chemotherapy

Side effects of treatment depend on the type of chemotherapy, although several drugs have overlapping side effects. In addition, there can be considerable variation in the severity of side effects experienced by patients due to individual variability. Common side effects include:

  • fatigue,
  • loss of appetite,
  • nausea,
  • vomiting
  • and a decrease in blood cell counts.

Side effects such as nausea and vomiting can be managed effectively with supportive therapy.

A few examples of side effects specific to certain chemotherapy drugs include:

  • tingling and/or numbness of the extremities, hearing loss and an effect on kidney function with cisplatin,
  • an effect on the pumping capacity of the heart and heart rhythm with doxorubicin,
  • tingling and/or numbness of the extremities with paclitaxel,
  • and a skin rash, especially over the palms and soles, with capecitabine.

Patients should talk to their doctors to learn more about all potential side effects associated with a particular chemotherapy drug. 

Biological drugs

In addition to chemotherapy, other biological drugs are available for treatment of recurrent thymoma and thymic carcinomas. These drugs have not been evaluated for treatment of newly diagnosed thymic cancers and for use in the pre-surgical setting. Examples of non-chemotherapy drugs include sunitinib, everolimus and a class of drugs known as somatostatin analogs.

Sunitinib and everolimus are available in tablet form and are associated with unique side effect profiles. Sunitinib can be used for treatment of recurrent thymic carcinoma. Everolimus has demonstrated activity against recurrent thymoma and thymic carcinoma. Results from a recent clinical trial describe the clinical activity of lenvatinib, an orally administered drug, in patients with recurrent thymic carcinoma.

Somatostatin analogs are injectable, non-chemotherapy drugs that are potentially active against recurrent thymomas that express somatostatin receptors, which can be detected by performing special scans, such as an Octreoscan or a Gallium-68 Dotatate scan. The route of administration depends on the specific type of somatostatin analog, and these drugs can be used individually or in combination with corticosteroids (prednisone).

Immunotherapy

Immunotherapy has also emerged as an option for treatment of advanced cancers. However, treatment of thymic cancers with immunotherapy can be associated with development of severe toxicity due to activation of the immune system.

Potentially life-threatening side effects have been described such as inflammation of skeletal and cardiac muscle and onset of autoimmune neuromuscular weakness (myasthenia gravis).

Immunotherapy for inoperable thymic cancers should be considered in the context of a clinical trial. Routine clinical use of these drugs is not recommended, especially for patients with recurrent thymoma.    

Patients with thymic cancers can also consider participating in clinical trials. Various drugs such as chemotherapy, biologic therapies and immunotherapy are under evaluation in clinical trials, either individually or in combination.
Disclaimer: The information provided here is intended to serve as an overview of treatment options for thymoma and thymic carcinoma. It is not intended as a treatment recommendation for an individual patient. Since practice patterns vary between treatment centers and internationally, treatment options mentioned in this monograph may or may not be applicable to a given individual and treatment decisions should not be based exclusively on the information mentioned here. Patients should discuss their specific circumstances and treatment plan with their physicians.