THYMIC CARCINOMA- TREATMENT

Thymic carcinomas have a greater propensity to capsular invasion and metastases than thymomas. Patients more often present with advanced disease and have a 5-year survival rate of 30% to 50%.[1] Owing to the paucity of cases, optimal management of thymic carcinoma has yet to be defined. As with thymoma, in most published series, carefully selected patients with clearly resectable, well-defined disease, have received complete surgical extirpation. For clinically borderline or frankly unresectable lesions, induction chemotherapy, thoracic radiation therapy, or both, have been used.

In most published studies, surgery has been followed by adjuvant radiation therapy. A prescriptive dose range has yet to be identified; most studies use 40 Gy to 70 Gy with standard fractionation scheme (1.8 Gy–2.0 Gy/fraction).

In the largest series reported to date, data was obtained from 1,320 Japanese patients.[2] The Masaoka clinical stage was found to correlate well with prognosis of thymoma and thymic carcinoma. Patients with thymic carinoma were treated with radiation therapy or chemotherapy. For patients with thymic carcinoma, the 5-year survival rates were 67% for patients treated with total resection, 30% for patients treated with subtotal resection, and 24% for patients whose disease was inoperable. Adjuvant therapy including radiation or chemotherapy did not appear to improve the prognosis in patients with thymic carcinoma.[2]

A multi-institutional retrospective outcome analysis of 186 patients with thymic carcinoma has been reported.[2] This study failed to detect a long-term survival benefit in patients treated with subtotal resection nor any statistically significant survival augmentation from the addition of adjuvant radiation to surgical resection. The authors stipulated that no definitive conclusions could be made regarding the role of adjuvant radiation therapy in thymic carcinoma as a result of sample size limitations.

The 5-year survival rates for patients with totally resected thymic carcinoma were 81.5% for patients treated with chemotherapy; 46.6% for patients treated with radiation chemotherapy; 73.6% for patients treated with radiation therapy alone; and, 72.2% for patients who received no adjuvant treatment.[2]

The results from this study call into question conventional thinking regarding the efficacy of an aggressive multimodality approach including debulking, radiation therapy, and cisplatin-based chemotherapy.[3-5] While other studies support the addition of adjuvant radiation and chemotherapy, optimum treatment regimens are undetermined.

Chemotherapy is also utilized in the management of patients with inoperable thymic carcinoma. Most regimens used are similar to those used to treat thymoma and include cisplatin.[6-10]

Objective responses and improved outcomes compared to historical data have been reported from small uncontrolled studies. Combinations of doxorubicin, cyclophosphamide, and vincristine and cisplatin have also shown favorable responses in studies.[6-8] Etoposide, ifosfamide, and cisplatin (VIP) was utilized in a prospective North American Intergroup trial.[9] There was a 25% (2 of 8 patients) partial response rate. The 1-year and 2-year survival rates were 75% and 50%, respectively.

Standard treatment options for patients with operable disease include the following:

1.     En bloc surgical resection.

2.     Postoperative radiation therapy may be considered whether or not the surgical resection has been complete, and especially for stage III and stage IVA patients.

Standard treatment options for patients with inoperable disease (stage III and stage IV with vena caval obstruction, pleural involvement, pericardial implants, etc.) include the following:

1.     Radiation therapy.

2.     Chemotherapy with or without surgery and/or radiation therapy.

3.     Chemoradiation therapy.

4.     Chemotherapy.

Treatment options under clinical evaluation:

Areas of active clinical evaluation for patients with thymic carcinoma include the following:

·         New drug regimens.

·         Variation of drug doses in current regimens.

·         New radiation therapy schedules.

Current Clinical Trials

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients withthymic carcinoma. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

References

1.     Eng TY, Fuller CD, Jagirdar J, et al.: Thymic carcinoma: state of the art review. Int J Radiat Oncol Biol Phys 59 (3): 654-64, 2004. [PUBMED Abstract]

2.     Kondo K, Monden Y: Therapy for thymic epithelial tumors: a clinical study of 1,320 patients from Japan. Ann Thorac Surg 76 (3): 878-84; discussion 884-5, 2003. [PUBMED Abstract]

3.     Ogawa K, Toita T, Uno T, et al.: Treatment and prognosis of thymic carcinoma: a retrospective analysis of 40 cases. Cancer 94 (12): 3115-9, 2002. [PUBMED Abstract]

4.     Greene MA, Malias MA: Aggressive multimodality treatment of invasive thymic carcinoma. J Thorac Cardiovasc Surg 125 (2): 434-6, 2003. [PUBMED Abstract]

5.     Lucchi M, Mussi A, Ambrogi M, et al.: Thymic carcinoma: a report of 13 cases. Eur J Surg Oncol 27 (7): 636-40, 2001. [PUBMED Abstract]

6.     Koizumi T, Takabayashi Y, Yamagishi S, et al.: Chemotherapy for advanced thymic carcinoma: clinical response to cisplatin, doxorubicin, vincristine, and cyclophosphamide (ADOC chemotherapy). Am J Clin Oncol 25 (3): 266-8, 2002. [PUBMED Abstract]

7.     Weide LG, Ulbright TM, Loehrer PJ Sr, et al.: Thymic carcinoma. A distinct clinical entity responsive to chemotherapy. Cancer 71 (4): 1219-23, 1993. [PUBMED Abstract]

8.     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. [PUBMED Abstract]

9.     Loehrer PJ Sr, 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. [PUBMED Abstract]

10.                       Igawa S, Murakami H, Takahashi T, et al.: Efficacy of chemotherapy with carboplatin and paclitaxel for unresectable thymic carcinoma. Lung Cancer 67 (2): 194-7, 2010. [PUBMED Abstract]

THYMOMA- TREATMENT

Thymoma

Stage I and Stage II Thymoma

Excellent long-term survival can be obtained following complete surgical excision for a pathologic stage I thymoma. There appears to be no benefit to adjuvant radiation therapy following complete resection of encapsulated noninvasive tumors.[1,2] For patients with stage II thymomas with pathologically demonstrated capsular invasion, adjuvant radiation therapy following complete surgical excision has been considered a standard of care despite the lack of prospective clinical trials.[3,4]

Most studies use 40 Gy to 70 Gy with standard fractionation scheme (1.8–2.0 Gy/fraction). Some, but not all, retrospective clinical studies show improved local control and survival with the addition of postoperative radiation therapy (PORT).[5-8][Level of evidence: 3iiiDiv] More recent retrospective studies have found no outcome difference in patients treated with or without PORT following complete resection of the thymic tumor.[8-12]

In the largest series reported to date, data was obtained from 1,320 Japanese patients.[8] The Masaoka clinical stage was found to correlate well with prognosis of thymoma and thymic carcinoma. Patients with stage I thymoma were treated with surgery only, and patients with stage II thymoma underwent surgery and additional radiation therapy. Prophylactic mediastinal radiation therapy did not appear to prevent local recurrences effectively in patients with totally resected stage II thymoma.

The role and risks of adjuvant radiation therapy for patients with completely resected stage II thymomas need further study. To avoid the potential morbidity and costs associated with thoracic radiation, PORT may be reserved for stage II patients where adjacent organs are within a few millimeters or involve of the surgical margin as determined by both pathological and intraoperative findings.

Operable or Potentially Operable Stage III and Stage IVA Thymoma

Stage III thymoma may be difficult to identify prior to surgery as subtle invasion to the adjacent organs may only be identified at the time of mediastinal exploration. Such patients often receive aggressive surgical resection including wide surgical margins with consideration of adjuvant radiation therapy. Invasion of local organs can be apparent on pretreatment computed tomographic imaging. Such patients may be offered combined modality treatment with chemotherapy followed by surgery and/or radiation therapy.[13-20] The optimal strategy for induction therapy, which minimizes operative morbidity and mortality and optimizes resectability rates and ultimately survival, currently remains unknown.

Two large series have reported outcomes. In the first study, data was obtained from 1,320 Japanese patients.[8] The Masaoka clinical stage was found to correlate well with prognosis of thymoma and thymic carcinoma. Patients with stage III thymoma underwent surgery and additional radiation therapy. Patients with stage IV thymoma were treated with radiation therapy or chemotherapy. For patients with stage III or stage IV thymoma, the 5-year survival rates were 93% for patients treated with total resection, 64% for patients treated with subtotal resection, and 36% for patients whose disease was inoperable. Prophylactic mediastinal radiation therapy did not appear to prevent local recurrences effectively in patients with totally resected stage III thymoma. Adjuvant therapy including radiation or chemotherapy did not appear to improve the prognosis in patients with totally resected stage III or stage IV thymoma.[8]

In the second study, 1,334 patients diagnosed and treated between 1973 and 2005 were identified in a SEER database. At a relatively short median follow-up of 65 months, radiation therapy did not appear to increase the risk of cardiac mortality or secondary malignancy. Routine use of PORT did not appear to improve long-term survival.[20]

Most invasive thymomas have been found to be relatively sensitive to cisplatin-based combination chemotherapy regimens. The combinations that follow have reported objective response rates from 79% to 100% with subsequent resectability rates ranging between 36% and 69%:[13-19,21]

·         The combination of cisplatin, doxorubicin, and cyclophosphamide (PAC) with or without prednisone.

·         The combination of cisplatin, doxorubicin, vincristine, and cyclophosphamide (ADOC).

·         The combination of cisplatin, etoposide, and epirubicin.

Long-term survival rates following induction chemotherapy and surgery with or without radiation therapy and consolidation chemotherapy have ranged from 50% at 4 years, 77% at 7 years and, respectively, 86% and 76% for stage III and IV patients at 10 years in different published series.[14,16,17,22]

However, similar results have been reported with preoperative radiation therapy without chemotherapy, particularly if great vessels are involved (5-year overall survival rate of 77% and 10-year OS rate of 59%).[23,24]

An intergroup trial conducted in the United States reported a predicted 5-year OS rate of 52% in 26 patients receiving the PAC chemotherapy regimen followed by radiation therapy without surgery.[18]

The role of surgical debulking for patients with either stage III or stage IVA disease is controversial. Phase II data suggests that prolonged survival can be accomplished with chemotherapy and radiation therapy alone in many patients presenting with locally advanced or even metastatic thymoma.[18] Therefore, the value of surgery may be questioned if complete, or at the very least, near complete extirpation cannot be accomplished.

Standard treatment options for patients with operable disease include the following:

1.     En bloc surgical resection.

2.     PORT may be considered, especially for patients with close or involved surgical margins and for stage III and stage IVA patients.

3.     Induction chemotherapy followed by surgery with or without radiation.

Standard treatment options for patients with inoperable disease (stage III and stage IV with vena caval obstruction, pleural involvement, pericardial implants, etc.) include the following:

1.     Induction chemotherapy followed by surgery or radiation.

2.     Induction chemotherapy followed by surgery and radiation.

3.     Radiation therapy.

4.     Chemotherapy.

Treatment options under clinical evaluation:

Areas of active clinical evaluation for patients with thymoma include the following:

·         New drug regimens.

·         Variation of drug doses in current regimens.

·         New radiation therapy schedules and techniques.

References

1.     Maggi G, Casadio C, Cavallo A, et al.: Thymoma: results of 241 operated cases. Ann Thorac Surg 51 (1): 152-6, 1991. [PUBMED Abstract]

2.     Masaoka A, Monden Y, Nakahara K, et al.: Follow-up study of thymomas with special reference to their clinical stages. Cancer 48 (11): 2485-92, 1981. [PUBMED Abstract]

3.     Pollack A, Komaki R, Cox JD, et al.: Thymoma: treatment and prognosis. Int J Radiat Oncol Biol Phys 23 (5): 1037-43, 1992. [PUBMED Abstract]

4.     Ogawa K, Uno T, Toita T, et al.: Postoperative radiotherapy for patients with completely resected thymoma: a multi-institutional, retrospective review of 103 patients. Cancer 94 (5): 1405-13, 2002. [PUBMED Abstract]

5.     Ariaratnam LS, Kalnicki S, Mincer F, et al.: The management of malignant thymoma with radiation therapy. Int J Radiat Oncol Biol Phys 5 (1): 77-80, 1979. [PUBMED Abstract]

6.     Penn CR, Hope-Stone HF: The role of radiotherapy in the management of malignant thymoma. Br J Surg 59 (7): 533-9, 1972. [PUBMED Abstract]

7.     Curran WJ Jr, Kornstein MJ, Brooks JJ, et al.: Invasive thymoma: the role of mediastinal irradiation following complete or incomplete surgical resection. J Clin Oncol 6 (11): 1722-7, 1988. [PUBMED Abstract]

8.     Kondo K, Monden Y: Therapy for thymic epithelial tumors: a clinical study of 1,320 patients from Japan. Ann Thorac Surg 76 (3): 878-84; discussion 884-5, 2003. [PUBMED Abstract]

9.     Mangi AA, Wright CD, Allan JS, et al.: Adjuvant radiation therapy for stage II thymoma. Ann Thorac Surg 74 (4): 1033-7, 2002. [PUBMED Abstract]

10.                       Singhal S, Shrager JB, Rosenthal DI, et al.: Comparison of stages I-II thymoma treated by complete resection with or without adjuvant radiation. Ann Thorac Surg 76 (5): 1635-41; discussion 1641-2, 2003. [PUBMED Abstract]

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

12.                       Berman AT, Litzky L, Livolsi V, et al.: Adjuvant radiotherapy for completely resected stage 2 thymoma. Cancer 117 (15): 3502-8, 2011. [PUBMED Abstract]

13.                       Macchiarini P, Chella A, Ducci F, et al.: Neoadjuvant chemotherapy, surgery, and postoperative radiation therapy for invasive thymoma. Cancer 68 (4): 706-13, 1991. [PUBMED Abstract]

14.                       Berruti A, Borasio P, Gerbino A, et al.: Primary chemotherapy with adriamycin, cisplatin, vincristine and cyclophosphamide in locally advanced thymomas: a single institution experience. Br J Cancer 81 (5): 841-5, 1999. [PUBMED Abstract]

15.                       Rea F, Sartori F, Loy M, et al.: Chemotherapy and operation for invasive thymoma. J Thorac Cardiovasc Surg 106 (3): 543-9, 1993. [PUBMED Abstract]

16.                       Shin DM, Walsh GL, Komaki R, et al.: A multidisciplinary approach to therapy for unresectable malignant thymoma. Ann Intern Med 129 (2): 100-4, 1998. [PUBMED Abstract]

17.                       Kim ES, Putnam JB, Komaki R, et al.: Phase II study of a multidisciplinary approach with induction chemotherapy, followed by surgical resection, radiation therapy, and consolidation chemotherapy for unresectable malignant thymomas: final report. Lung Cancer 44 (3): 369-79, 2004. [PUBMED Abstract]

18.                       Loehrer PJ Sr, Chen M, Kim K, et al.: Cisplatin, doxorubicin, and cyclophosphamide plus thoracic radiation therapy for limited-stage unresectable thymoma: an intergroup trial. J Clin Oncol 15 (9): 3093-9, 1997. [PUBMED Abstract]

19.                       Loehrer PJ Sr, Kim K, Aisner SC, et al.: Cisplatin plus doxorubicin plus cyclophosphamide in metastatic or recurrent thymoma: final results of an intergroup trial. The Eastern Cooperative Oncology Group, Southwest Oncology Group, and Southeastern Cancer Study Group. J Clin Oncol 12 (6): 1164-8, 1994. [PUBMED Abstract]

20.                       Fernandes AT, Shinohara ET, Guo M, et al.: The role of radiation therapy in malignant thymoma: a Surveillance, Epidemiology, and End Results database analysis. J Thorac Oncol 5 (9): 1454-60, 2010. [PUBMED Abstract]

21.                       Yokoi K, Matsuguma H, Nakahara R, et al.: Multidisciplinary treatment for advanced invasive thymoma with cisplatin, doxorubicin, and methylprednisolone. J Thorac Oncol 2 (1): 73-8, 2007. [PUBMED Abstract]

22.                       Lucchi M, Melfi F, Dini P, et al.: Neoadjuvant chemotherapy for stage III and IVA thymomas: a single-institution experience with a long follow-up. J Thorac Oncol 1 (4): 308-13, 2006. [PUBMED Abstract]

23.                       Yagi K, Hirata T, Fukuse T, et al.: Surgical treatment for invasive thymoma, especially when the superior vena cava is invaded. Ann Thorac Surg 61 (2): 521-4, 1996. [PUBMED Abstract]

24.                       Akaogi E, Ohara K, Mitsui K, et al.: Preoperative radiotherapy and surgery for advanced thymoma with invasion to the great vessels. J Surg Oncol 63 (1): 17-22, 1996. [PUBMED Abstract]

THYMOMA AND THYMIC CARCINOMA- TREATMENT OVERVIEW

Treatment Option Overview for Thymoma and Thymic Carcinoma Treatment

·      Thymoma

Most thymomas are diagnosed and staged at the time of surgical intervention. Surgical resection is the preferred treatment of patients who can tolerate surgery and have a mediastinal mass that is suspected of being a thymoma. A complete, surgical resection is recommended for patients with either stage I or stage II disease. A complete resection of all tumors can be achieved in nearly all stage I and stage II patients and in 27% to 44% of stage III patients. Postoperative radiation therapy (PORT) is generally employed for stage II and stage III patients. Patients with stage IVa disease can only rarely be resected completely and are usually offered debulking surgery and PORT with or without chemotherapy.

Thymic Carcinoma

The optimal treatment of thymic carcinoma remains undefined because of its rarity. Most patients with thymic carcinomas present initially with any of the following:

·         Cough.

·         Chest pain.

·         Phrenic nerve palsy.

·         Superior vena cava syndrome.

Most patients with thymic carcinoma have evidence of invasion of contiguous mediastinal structures at presentation.

Thymic carcinoma can metastasize to the following areas:

·         Regional lymph nodes.

·         Bone.

·         Liver.

·         Lungs.

Treatment options include the following:[1]

·         Surgery.

·         Radiation.

·         Multimodality approach, such as:

o    Surgical resection.

o    Radiation therapy.

o    Cisplatin-based chemotherapy.

For patients with clinically resectable disease, surgical resection is often the initial therapeutic intervention. For clinically borderline or frankly unresectable lesions, neoadjuvant (preoperative) chemotherapy or thoracic radiation therapy, or both, is given.[2] Patients presenting with locally advanced disease should be carefully evaluated and undergo multimodality therapy. Patients with poor performance status and high associated operative risks are generally not considered for these types of aggressive treatments. Patients with metastatic disease may respond to combination chemotherapy.

References

1.     Hsu HC, Huang EY, Wang CJ, et al.: Postoperative radiotherapy in thymic carcinoma: treatment results and prognostic factors. Int J Radiat Oncol Biol Phys 52 (3): 801-5, 2002. [PUBMED Abstract]

2.     Koizumi T, Takabayashi Y, Yamagishi S, et al.: Chemotherapy for advanced thymic carcinoma: clinical response to cisplatin, doxorubicin, vincristine, and cyclophosphamide (ADOC chemotherapy). Am J Clin Oncol 25 (3): 266-8, 2002. [PUBMED Abstract]

THYMOMA AND THYMIC CARCINOMA- STAGING

Stage Information for Thymoma and Thymic Carcinomas

Computed tomography (CT) with intravenous contrast may be useful in the diagnosis and clinical staging of thymoma, especially for noninvasive tumors. CT is usually accurate in predicting the following:

·         Tumor size.

·         Location.

·         Invasion into vessels, the pericardium, and the lungs.

However, CT cannot predict invasion or resectability with accuracy.[1,2] Appearance of the tumor on CT may be related to the World Health Organization (WHO) histologic type.[3] A retrospective study involving 53 patients who underwent thymectomy for thymic epithelial tumors indicated that smooth contours with a round shape were most suggestive of type A thymomas, and irregular contours were most suggestive of thymic carcinomas. Calcification was suggestive of type B thymomas. In this study, however, CT was found to be of limited value differentiating type AB, B1, B2, and B3 thymomas.[4]

Most patients with thymic carcinomas present initially with any of the following:

·         Cough.

·         Chest pain.

·         Phrenic nerve palsy.

·         Superior vena cava syndrome.

Patients may have evidence of invasion of contiguous mediastinal structures at presentation. Thymic carcinoma can metastasize to any of the following:

·         Regional lymph nodes.

·         Bone.

·         Liver.

·         Lungs.

An evaluation for sites of metastases may be warranted for these patients.

Positron emission tomography of 18-flouro-deoxyglucose (FDG-PET) as well as thallium single-photon emission computed tomography have been reported in small series for diagnosis and evaluation of therapeutic outcomes in thymic carcinoma.[5-8] Two small series reported that FDG uptake was related to the invasiveness of thymic carcinoma.[7,8] This raises the possibility of FDG-PET utilization for diagnosis, treatment planning, and monitoring for recurrence. Sensitivity, specificity impact on clinical therapeutic decisions, remains to be defined.

Histologic classification of thymoma is not sufficient to distinguish biologically benign thymomas from malignant thymomas. The degree of invasion or tumor stage is generally thought to be a more important indicator of overall survival.[1,9,10]

Evaluating the invasiveness of a thymoma involves the use of staging criteria that indicate the presence and degree of contiguous invasion, the presence of implants, and lymph node or distant metastases regardless of histologic type. Although no standardized staging system exists, the one proposed by Masaoka in 1981 is commonly employed.[11] It was revised in 1994 and is shown below.[11]

Enlarge

Thymoma Staging System of Masaoka 1994a
Stage	Description
a[12]
I	Macroscopically, completely encapsulated; microscopically, no capsular invasion.
II	Macroscopic invasion into surrounding fatty tissue or mediastinal pleura; microscopic invasion into capsule.
III	Macroscopic invasion into neighboring organs (pericardium, lung, and great vessels).
IVa	Pleural or pericardial dissemination.
IVb	Lymphogenous or hematogenous metastases.

Application of this staging system to a series of 85 surgically treated patients confirmed its value in determining prognosis, with 5-year survival rates of 96% for stage I disease, 86% for stage II disease, 69% for stage III disease, and 50% for stage IV disease.[11,13] In a large, retrospective study involving 273 patients with thymoma, 20-year survival rates (as defined by freedom from tumor death) according to the Masaoka staging system were reported to be 89% for stage I disease, 91% for stage II disease, 49% for stage III disease, and 0% for stage IV disease.[9]

In a retrospective analysis of 130 resected, thymoma patients, the WHO pathological classification was tightly correlated with stage and by multivariate analysis, tumor size, completeness of resection, histologic subtype, and stage were significant prognostic factors for survival. Of note, only four patients received neoadjuvant cisplatin-based chemotherapy and complete resection was possible in 95% of cases. The 5-year survival rate of the 11 stage IV patients was 47%.[12]

Some investigators maintain that the Masaoka staging system does not accurately predict outcome for thymic carcinoma.[14,15] In one retrospective study evaluating 43 cases of thymic carcinoma, prognosis was found to be dependent solely on tumor invasion of the innominate artery.[15]

References

1. Sperling B, Marschall J, Kennedy R, et al.: Thymoma: a review of the clinical and pathological findings in 65 cases. Can J Surg 46 (1): 37-42, 2003. [PUBMED Abstract]
2. Rendina EA, Venuta F, Ceroni L, et al.: Computed tomographic staging of anterior mediastinal neoplasms. Thorax 43 (6): 441-5, 1988. [PUBMED Abstract]
3. Rosai J: Histological Typing of Tumours of the Thymus. New York, NY: Springer-Verlag, 2nd ed., 1999.
4. Tomiyama N, Johkoh T, Mihara N, et al.: Using the World Health Organization Classification of thymic epithelial neoplasms to describe CT findings. AJR Am J Roentgenol 179 (4): 881-6, 2002. [PUBMED Abstract]
5. Sasaki M, Kuwabara Y, Ichiya Y, et al.: Differential diagnosis of thymic tumors using a combination of 11C-methionine PET and FDG PET. J Nucl Med 40 (10): 1595-601, 1999. [PUBMED Abstract]
6. Kageyama M, Seto H, Shimizu M, et al.: Thallium-201 single photon emission computed tomography in the evaluation of thymic carcinoma. Radiat Med 12 (5): 237-9, 1994 Sep-Oct. [PUBMED Abstract]
7. Adams S, Baum RP, Hertel A, et al.: Metabolic (PET) and receptor (SPET) imaging of well- and less well-differentiated tumours: comparison with the expression of the Ki-67 antigen. Nucl Med Commun 19 (7): 641-7, 1998. [PUBMED Abstract]
8. Kubota K, Yamada S, Kondo T, et al.: PET imaging of primary mediastinal tumours. Br J Cancer 73 (7): 882-6, 1996. [PUBMED Abstract]
9. Okumura M, Ohta M, Tateyama H, et al.: The World Health Organization histologic classification system reflects the oncologic behavior of thymoma: a clinical study of 273 patients. Cancer 94 (3): 624-32, 2002. [PUBMED Abstract]
10. Chen G, Marx A, Wen-Hu C, et al.: New WHO histologic classification predicts prognosis of thymic epithelial tumors: a clinicopathologic study of 200 thymoma cases from China. Cancer 95 (2): 420-9, 2002. [PUBMED Abstract]
11. Masaoka A, Monden Y, Nakahara K, et al.: Follow-up study of thymomas with special reference to their clinical stages. Cancer 48 (11): 2485-92, 1981. [PUBMED Abstract]
12. Nakagawa K, Asamura H, Matsuno Y, et al.: Thymoma: a clinicopathologic study based on the new World Health Organization classification. J Thorac Cardiovasc Surg 126 (4): 1134-40, 2003. [PUBMED Abstract]
13. Cameron RB, Loehrer PJ Sr, Thomas CR Jr: Neoplasms of the mediastinum. In: DeVita VT Jr, Hellman S, Rosenberg SA, eds.: Cancer: Principles and Practice of Oncology. 7th ed. Philadelphia, Pa: Lippincott Williams & Wilkins, 2005, pp 845-58.
14. Ritter JH, Wick MR: Primary carcinomas of the thymus gland. Semin Diagn Pathol 16 (1): 18-31, 1999. [PUBMED Abstract]
15. Blumberg D, Burt ME, Bains MS, et al.: Thymic carcinoma: current staging does not predict prognosis. J Thorac Cardiovasc Surg 115 (2): 303-8; discussion 308-9, 1998. [PUBMED Abstract]