UpToDate - Thymoma

Question 1

About what percentage of mediastinal neoplasms are thymomas?

Answer 1

20%

Question 2

What age range and sex do thymomas present? What are risk factors? Any associations?

Answer 2

40-60, similar incidence of males to females.
No known risk factors.
Strong association with myasthenia gravis and other paraneoplastic syndromes.

Question 3

What is myasthenia gravis?

Answer 3

autoimmune dz, auto-ab to ACh receptors at the NMJ -> diplopia, ptosis, dysphagia, weakness, and fatigue

Question 4

What percentage of patients w/ thymoma have sx consistent w/ MG?

Answer 4

1/2.
Myasthenia gravis is common with all types of thymoma, but is rare in thymic carcinoma. Males and females are equally affected.

Question 5

Does thymectomy cure MG?

Answer 5

In patients with thymoma and myasthenia gravis, thymectomy usually results in an attenuation of the severity of myasthenia gravis, although some symptoms persist in most patients.

Question 6

What is pure red cell aplasia?

Answer 6

Autoimmune-mediated hypoproliferation of erythrocyte precursors in the bone marrow. This paraneoplastic disorder occurs in 5 to 15 percent of patients with thymoma and is more common in older adult females. Pure red cell aplasia is usually seen with tumors that have spindle cell morphology.

Question 7

Other than MG and pure red cell aplasia, what other paraneoplastic syndromes can be associated with thymoma?

Answer 7

Immunodeficiency – Hypogammaglobulinemia and pure white blood cell aplasia are present in fewer than 5 percent of patients with thymoma, most commonly in older adult females. Conversely, up to 10 percent of patients with acquired hypogammaglobulinemia have an associated thymoma (Good syndrome), typically of spindle cell histology.

Thymoma-associated multiorgan autoimmunity – Several case reports have described a syndrome of thymoma-associated multiorgan autoimmunity (TAMA) that is similar to graft-versus-host disease. Patients presented with variable combinations of a morbilliform skin eruption, chronic diarrhea, and liver enzyme abnormalities. Histopathology of the skin or bowel mucosa is similar to that seen with graft-versus-host disease.

Question 8

What are some differences b/w thymoma and thymic carcinoma?

Answer 8

Thymic carcinomas are more aggressive than thymomas; evidence of invasion of mediastinal structures is present in the majority of these patients. As with thymomas, most patients present with cough, chest pain, phrenic nerve palsy, or superior vena cava syndrome.

Extrathoracic metastases are seen in fewer than 7 percent of patients at presentation, most commonly to the liver and bone, but may virtually develop in any site, including the brain, kidney, extrathoracic lymph nodes, adrenals, and thyroid.

Carcinomas often contain necrotic, cystic, or calcified areas. Contour is often irregular. PET scans are often negative in more well-differentiated thymomas but are highly positive in carcinomas.

Question 9

Other than thymoma/thymic carcinoma, what else should be on the differential dx for anterior mediastinal masses?

Answer 9

Retrosternal thyroid, lymphoma, and mediastinal germ cell tumor.
Should get - GCT markers (beta-hCG, AFP, LDH), as well as PFTs.

Question 10

A patient is thought to have thymoma after workup rules out other diagnosis and imaging is typical. The patient is otherwise healthy, and the anatomy is favorable. What is the next step?

Answer 10

For patients thought to have a thymoma that will be amenable to complete resection, the initial step in management is surgical resection, which can definitively establish the diagnosis.

For patients with a tumor that is not considered amenable to complete resection or in whom surgery is contraindicated because of age or comorbidity, a tissue diagnosis with a core needle biopsy or an open biopsy is required prior to therapy.

Question 11

Know thymic tumor staging. What imaging should be obtained preop?

Answer 11

Staging of thymic neoplasms, including both thymomas and thymic carcinoma, is based upon the extent of the primary tumor and the presence of invasion into adjacent structures and/or dissemination. In approximately two-thirds of thymomas and thymic carcinomas, preoperative chest CT can accurately predict the pathologic TNM stage.

Question 12

Manage localized disease for thymic tumors.

Answer 12

Surgery is indicated as the initial treatment for patients in whom a complete, R0 resection is considered feasible, ie, those with completely encapsulated tumors or those with tumors invading readily resectable structures, such as the mediastinal pleura, pericardium, or adjacent lung. Histopathologic examination of the resection specimen is required for definitive staging and determines whether postoperative RT or chemotherapy are recommended.

Question 13

How do you manage MG prior to thymectomy?

Answer 13

Because of the increased surgical risks, patients with myasthenia gravis should be carefully evaluated preoperatively; if signs or symptoms of myasthenia gravis are present, these should be treated medically prior to surgery, and care should be taken by the anesthesiology team during and after the operation in order to avoid respiratory failure due to myasthenia gravis.

Question 14

Is there a role for neoadjuvant therapy in thymic tumors?
What extra preop workup is necessary in these patients?

Answer 14

For patients in whom a complete resection is not considered feasible as the initial treatment (eg, those with tumor invasion into the innominate vein, phrenic nerve(s), or heart/great vessels), multimodality therapy incorporating preoperative chemotherapy and postoperative RT is indicated.
Biopsy is required before neoadjuvant therapy.
Re-evaluate after neoadjuvant treatment to determine resectability.

Question 15

A patient undergoes neoadjuvant therapy for potentially resectable localized thymic tumor, but complete resection cannot be accomplished at the time of surgery. What should be done?
What if it’s a thymic carcinoma?

Answer 15

Patients should undergo maximum debulking followed by postoperative RT if technically feasible, which may control residual disease and provide long-term, disease-free survival for some patients.

For those with thymic carcinoma and residual disease after surgery, chemotherapy may be recommended as well.

Question 16

A thymic tumor patient has unresectable localized disease. What do you do?

Answer 16

Systemic therapy, RT, or chemoradiotherapy may be indicated for patients who present with extensive pleural and/or pericardial metastases, unreconstructable great vessel, heart, or tracheal involvement or otherwise technically unresectable disease, including those with distant metastases. Additionally, such treatments are offered to those who are medically unfit for surgery due to age or comorbidity. Treatments are individualized according to the patient’s extent of disease, symptoms, and performance status. Debulking surgery may also provide benefit to select patients with initially unresectable disease, so continued involvement of a multidisciplinary team, including a thoracic surgeon, is important.

As examples:
Patients with locally advanced, unresectable disease (American Joint Committee on Cancer [AJCC] stage IIIB), thymoma, or thymic carcinoma should be treated with chemoradiotherapy when feasible. Extrapolating from treatment paradigms for locally advanced lung cancer, RT doses of 60 Gy are appropriate.

Chemoradiotherapy can improve long-term survival benefit and control the symptoms of the disease in a subset of patients with AJCC stage IVA disease, including those with nodal or localized metastatic disease. For example, if pleural metastases are the only site of metastatic disease in patients with thymoma, an aggressive multimodality approach may still be possible and may achieve prolonged disease control.

For patients with initially unresectable disease, it is appropriate to evaluate select patients for debulking surgery, as this approach may improve survival outcomes.

RT alone can be particularly useful to palliate thoracic symptoms. Patients with unresectable disease are generally given a total dose of 60 Gy or more.

Chemotherapy is the primary palliative treatment modality for patients with more widespread disease.

Question 17

In patients with thymoma, who would benefit from postoperative radiation therapy?

Answer 17

For patients with Stage I thymoma and invasion into the mediastinal fat or pleura and microscopic or grossly positive surgical margins, we suggest the addition of PORT, as this approach reduces the risk of recurrence to that of patients with R0 resections and lower-risk features. However, observation is an appropriate alternative given limited data.

Stage II to III thymoma (Masaoka stage III) – PORT is indicated in such patients given a higher risk of local recurrence.

Stage IV thymoma (Masaoka stage IV) – RT should be individualized to the needs of the patient. RT can be used for palliation and possibly as curative therapy in oligometastatic disease.

Question 18

In patients with thymic cancer, who would benefit from postop radiation?

Answer 18

Patients with stage I to III thymic carcinoma (Masaoka stage I to III) are at a higher risk of local recurrence than those with thymoma. Retrospective data suggest a survival advantage with PORT for resected thymic carcinoma, and PORT is recommended, regardless of the presence of other risk factors or stage. It should be recognized, however, that data are limited in regard to which particular stages derive benefit. In the presence of a positive margin or residual disease, PORT may be supplemented with systemic chemotherapy, although the evidence in favor is weak.

Stage IV (Masaoka stage IV) thymic carcinoma – The use of PORT should be restricted to palliation of local symptoms.

Question 19

How do you manage thymic tumor patients with metastatic disease?

Answer 19

For patients with thymomas or thymic carcinomas who have inoperable recurrent disease or disseminated metastases, we suggest initial treatment with a platinum-based chemotherapy regimen rather than other systemic regimens.
* CAP – Cyclophosphamide (500 mg/m2 intravenous [IV] day 1), doxorubicin (50 mg/m2 IV day 1), and cisplatin (50 mg/m2 IV day 1), repeated every three weeks. In a United States intergroup study, 29 patients with metastatic or progressive thymoma were treated with CAP. The overall and complete response rates were 50 and 10 percent, respectively, and the median survival was 38 months.

• PE – Cisplatin (60 mg/m2 IV day 1) and etoposide (120 mg/m2 IV days 1 to 3), repeated every three weeks [60]. In a European Organization for Research and Treatment of Cancer (EORTC) study, 16 patients with advanced thymoma received etoposide plus cisplatin every three weeks [60]. The overall and complete response rates were 56 and 31 percent, respectively, and the median progression-free and overall survival durations were 2.2 and 4.3 years, respectively.
• CAP with prednisone – Cyclophosphamide (500 mg/m2 IV day 1), doxorubicin (20 mg/m2/day as a continuous infusion, days 1 to 3), cisplatin (30 mg/m2 IV days 1 to 3), and prednisone (100 mg/day on days 1 to 5), repeated every three weeks. In a series of 22 patients given induction chemotherapy with the CAP with prednisone regimen, partial responses were observed in 14 cases and complete responses in three cases for an overall 77 percent response rate.
• Carboplatin (area under the curve [AUC] 6) and paclitaxel (225 mg/m2 IV) every three weeks – In a prospective, multicenter study of patients with advanced disease, three complete responses and six partial responses were observed in 21 patients with thymoma (overall response rate, 43 percent). There were five partial responses and no complete responses among the 23 patients with thymic carcinoma (overall response rate, 22 percent).
• ADOC – Cisplatin (50 mg/m2 IV day 1), doxorubicin (40 mg/m2 IV day 1), vincristine (0.6 mg/m2 IV day 3), and cyclophosphamide (700 mg/m2 IV day 4), repeated every three weeks. In another series, 37 patients with advanced disease were treated with ADOC. The overall and complete response rates were 92 and 43 percent, respectively, and the median survival was 15 months.
• VIP – Etoposide (75 mg/m2 IV days 1 to 4), ifosfamide (1.2 g/m2 IV on days 1 to 4), and cisplatin (20 mg/m2 IV days 1 to 4), repeated every three weeks. In an intergroup trial that included 28 patients with advanced thymoma or thymic carcinoma, nine partial responses (32 percent) were observed.